Biomedical subjects

Ilona Benko

Publications and source records attributed to Ilona Benko.

7 recordsLinked to original sources

PubMed2007

Long-lasting partial remission by Interferon-alpha treatment in a child with essential thrombocythemia.

Essential thrombocythemia (ET) is a clonal myeloproliferative disorder characterized by sustained thrombocytosis, isolated hyperplasia of megakaryocytic lineage, and association with thrombotic or bleeding episodes. It is extremely rare in childhood and frequently presents without evident clinical signs. We describe a 3-year-old girl with severe headache and dizziness suffering from ET, who was treated with Interferon-alpha-2a (IFN) based on the potent effect of this agent to inhibit myeloid colonies induced by phytohemagglutinin A stimulated leukocyte conditioned medium (PHA-LCM). Bone-marrow-derived mononuclear cells of this patient did not exhibit spontaneous colony formation but responded to recombinant human (rh) erythropoietin (EPO), rh granulocyte-colony stimulating factor (G-CSF), granulocyte-macrophage (GM)-CSF, and stem-cell factor in addition to PHA-LCM. After 65 months of in vivo IFN treatment, the patient experienced a sustained partial remission with platelet counts varying between 400 and 600 x 10(3)/microl.

Bone Marrow Examination↗

PubMed2005

Effect of rosiglitazone, an insulin sensitizer, on myelotoxicity caused by repeated doses of 5-fluorouracil.

Haematopoietic colony-stimulating factors are used frequently to moderate myelotoxicity, but administration of granulocyte-colony-stimulating factor (G-CSF) prior to chemotherapy actually may worsen the toxic effects on bone marrow. This is important in the design of clinical cancer treatment protocols. Previously, we found that rosiglitazone may protect granulocyte-macrophage progenitor cells (CFU-GM) against damage caused by a single dose of 5-fluorouracil (5-FU). Our new studies are designed to evaluate whether rosiglitazone has similar beneficial effects on bone marrow preservation when administered concurrently with repeated, daily doses of 5-FU while restricting regeneration time. Myelotoxicity characterized by the decrease in cellularity, frequency of granulocyte-macrophage progenitor cells and CFU-GM content of femoral bone marrow in mice. Five-day oral rosiglitazone pre-treatment decreased the susceptibility of granulocyte-macrophage progenitors to 5-FU damage. Significantly, more CFU-GM cells survived after the single intraperitoneal dose of 5-FU (100 mg kg(-1)). The increased frequency of CFU-GM cells with their intensive proliferation allowed faster restoration of the damaged CFU-GM compartment than was seen in the case of repeated daily administration of the cytostatic drug (25 or 50 mg kg(-1)) together with rosiglitazone for 7 consecutive days. The expansion of the CFU-GM compartment was 3 times and 50 times greater in the combined-treated mice than in their counterparts treated with repeated doses of 5-FU alone, although differences in absolute neutrophil counts were not significant. In conclusion, our results indicated that rosiglitazone has protective effects on bone marrow progenitor cells even after daily 5-FU treatment but further studies are warranted to evaluate the optimal treatment schedules.

Animals↗

PubMed2005

Investigation of beta-Lactamases in clinical isolates of Staphylococcus aureus for further explanation of borderline methicillin resistance.

BACKGROUND: Borderline methicillin resistance in Staphylococcus aureus is due to beta-lactamase overproduction and/or specific methicillinases. METHODS: beta-Lactamase activity in culture supernatants and in cytoplasmic membrane fractions was estimated by bioassay and by SDS-PAGE combined with nitrocefin assay. RESULTS: During the investigation of borderline methicillin-resistant Staphylococcus aureus (BORSA) strains VU94 and 822 two beta-lactamases were detected in the membranes, with molecular weights of 13 and 30 kDa. The latter could be found in the culture supernatants, too. In the presence of globomycin, this enzyme disappeared from the membrane, and the oxacillin-hydrolyzing activity of the membrane decreased to the level of susceptible strains. Both beta-lactamases were detected in the methicillin-resistant Staphylococcus aureus strain studied, but the susceptible strains possessed only the first enzyme. CONCLUSIONS: The 30-kDa beta-lactamase proved to be a methicillinase, and it can be one of the main causes of the borderline phenotype of BORSA strains. The other enzyme is one of the smallest beta-lactamases published to date.

Humans↗

PubMed2005

Accelerated recovery of 5-fluorouracil-damaged bone marrow after rosiglitazone treatment.

Our preliminary data indicate that rosiglitazone may be myeloprotective. We investigated whether it can modify bone marrow recovery. Five-day pre-treatment with rosiglitazone significantly accelerated recovery of 5-fluorouracil-damaged bone marrow in mice. Frequency and femoral content of granulocyte-macrophage progenitors reached mean baseline faster in pre-treated groups than in 5-fluorouracil-treated controls. Consequently, neutropenia was milder. Five-day insulin pre-treatment had similar effects in vivo. Insulin supports in vitro hematopoiesis. The observed myeloprotection demonstrated the importance of insulin in vivo. Clinical use of insulin to moderate myelotoxicity is impractical but rosiglitazone, an insulin sensitizer, could offer hope. Although rosiglitazone tends to increase plasma insulin levels, the significant myeloprotection was partly due to direct effects on progenitors. In vitro rosiglitazone enhanced the survival of both murine progenitor and human mobilized blood stem cells in the presence of 5-fluorouracil, the effect of which was neutralized by a peroxisome-proliferator-activated receptor-gamma antagonist.

Administration, Oral↗

PubMed2005

Potent inhibition of HIV-1 entry by (s4dU)35.

We have previously reported the potent in vitro HIV-1 anti-reverse transcriptase activity of a 35-mer of 4-thio-deoxyuridylate [(s(4)dU)(35)]. In efforts to define its activity in a more physiological system, studies were carried out to determine the stage of viral infection that this compound mediates its anti-viral effect. Results of the studies reported herein show that (s(4)dU)(35) is nontoxic and is capable of inhibiting both single and multi-drug resistant HIV strains (IC(50): 0.8-25.4 microg/ml) in vitro. Besides its previously reported anti-RT activity, (s(4)dU)(35) mediated its antiviral action by preventing virus attachment (IC(50): 0.002-0.003 microg/ml), and was stable in vitro and slowly degraded by DNAses. Competition studies and fluorescence resonance energy transfer (FRET) experiments indicated that (s(4)dU)(35) preferentially binds to CD4 receptors, but not to CD48. Confocal laser scanning microscopy (CLSM) studies showed that (s(4)dU)(35) did not penetrate into the cells and colocalized with cell surface thioredoxin. Our studies identify (s(4)dU)(35) as a potential novel HIV entry inhibitor that may have utility as either a systemic antiretroviral or as a preventing agent for HIV transmission.

Anti-HIV Agents↗

PubMed2004

Leukemic cells and the cytokine patchwork.

BACKGROUND: In leukemia, the clonal population is characterized by a hierarchical organization. Although the majority of the leukemic population is generated after post-determinic divisions, a subset of cells retain undifferentiated "blast" morphology. In addition, leukemic cells often have numerical or structural chromosomal abnormalities, aberrant gene expression patterns, and abnormal cell surface marker profiles. Despite these differences when compared to normal bone marrow and blood cells, leukemic cell survival and proliferation, just like that of normal progenitor cells, is influenced by hematopoietic growth factors. A major issue is whether differential regulation of normal and leukemic hematopoietic cells by cytokines can be exploited in antileukemic treatment or, in contrast, whether in vivo cytokine therapy may even be harmful to the patients. PROCEDURE: Here we review the results of recent experimental and clinical observations that investigated the influence of cytokines on leukemic cell growth and differentiation in vitro and in vivo. RESULTS: The majority of studies indicate that hematopoietic growth factors are involved in the regulation of proliferation and terminal differentiation of leukemic blast cells. Genetic aberrations involving cytokines or their receptors may contribute to leukemogenesis. Abundant interactions, cross-lineage stimulation, and aberrant response patterns seem to transform the complex cytokine network regulation of normal hematopoiesis into an even more interlaced "patchwork" that controls leukemic hematopoiesis. CONCLUSIONS: Since hematopoietic growth factors are present in high serum concentrations in patients with acute leukemia and myelodysplastic syndromes, consequences of possible interactions should be kept in mind even when well-defined human recombinant factors in single application are to be involved in antileukemic protocols.

Animals↗

PubMed2003

Rosiglitazone-induced protection against myelotoxicity produced by 5-fluorouracil.

Insulin promotes survival of haemopoietic progenitors. We investigated if rosiglitazone, an insulin sensitizer, could confer protection against 5-fluorouracil (5-FU)-induced myelotoxicity in mice. The decrease in bone marrow cellularity, frequency and content of granulocyte-macrophage progenitors (CFU-GM) characterized myelotoxicity in mice, while insulin sensitivity was determined by hyperinsulinaemic euglycaemic glucose clamping. CFU-GM colony numbers increased in groups pre-treated with rosiglitazone (1.5-6 mg/kg, 5 days), compared to that in mice treated with 5-fluorouracil alone. Since rosiglitazone pre-treatment significantly promoted the clonal expansion of CFU-GM when given in the insulin sensitizing dose, we conclude that rosiglitazone had myeloprotective effects possibly by amplifying endogenous insulin action.

Administration, Oral↗