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Biomedical subjects

S Pucci

Publications and source records attributed to S Pucci.

13 recordsLinked to original sources

B-myb transcriptional regulation and mRNA stability during differentiation of neuroblastoma cells.

B-myb and c-myb expression is high in neuroblastoma cells and declines during retinoic acid-induced differentiation. We show here that B-myb down-regulation during retinoic acid-induced differentiation of LAN-5 neuroblastoma cells occurs at the transcriptional level. In addition, we measured B-myb and c-myb messenger RNA half-lives, and found that, unlike c-myb, B-myb messenger RNA was remarkably stable (> 10 h). Inhibition of protein synthesis by treatment with cycloheximide increased B-myb messenger RNA levels, suggesting that one or more labile proteins act as repressors of B-myb transcription. In the same cell line, blocking protein synthesis decreased the level of c-myb mRNA under both normal and differentiative conditions. Thus, B-myb and c-myb undergo similar transcriptional regulation, but there are specific differences in the stability of their messenger RNAs and in the mechanisms through which their transcription is controlled. These differences could reflect different functional roles played by c-myb and B-myb in neuroblastoma cells.

Cell Cycle Proteins

Requirement of b-myb function for survival and differentiative potential of human neuroblastoma cells.

The B-myb gene belongs to a family of transcription factors that also includes A-myb and c-myb. B-myb is expressed in many cell types including human neuroblastoma cells. Here we demonstrate that B-myb expression is down-regulated during retinoic acid-induced neural and glial differentiation of neuroblastoma cells. This modulation is an early event, is maintained at late times of induction, and is in part regulated at the transcriptional level. Constitutive expression of B-myb prevents retinoic acid-induced neural differentiation as reflected by morphological features and the expression of (or lack of) biochemical markers associated with the undifferentiated phenotype. Furthermore, the expression of antisense B-myb transcripts does not allow the rescue of viable cells, suggesting an important role for B-myb in the survival of neuroblastoma cells. These results indicate that B-myb plays a functional role in the differentiative potential of neuroblastoma cells, raising the possibility that this gene is one of the nuclear regulators in the cascade of events leading to cellular differentiation.

Base Sequence

Lack of correlation between N-myc and MAX expression in neuroblastoma tumors and in cell lines: implication for N-myc-MAX complex formation.

Detectable levels of MAX messenger RNA were found in a set of human neuroblastoma tumors and established cell lines. MAX mRNA levels were independent of tumor stage and N-myc genomic amplification. By contrast, N-myc mRNA transcripts were detectable only in tumors with amplification of N-myc gene and in cell lines. Analysis by reverse transcriptase polymerase chain reaction and hybridization to specific oligodeoxynucleotide probes revealed approximately equal amounts of two MAX transcripts in all cases analyzed. Immunoprecipitations with a specific antibody to MAX detected two proteins of M(r) 21,000 and 22,000 in approximately equal amounts in all neuroblastoma lines regardless of N-myc amplification and/or expression. On the other hand, protein binding to the myc DNA consensus sequence correlated with N-myc expression in neuroblastoma cells. Thus, N-myc expression might be a limiting factor in the formation of the N-myc-MAX heterodimer in neuroblastomas.

Amino Acid Sequence

Shortness of interval between two stings as risk factor for developing Hymenoptera venom allergy.

The aim of the study was to determine whether a short interval (< 2 months) between two consecutive stings influences the development of Hymenoptera venom allergy. The study compared the sting-interval distribution in 120 allergic patients who experienced a first-time systemic reaction to a Hymenoptera sting, and in 100 healthy controls. A significant difference in sting-interval distribution between the two groups was found (P = 0.0001). In 71 of 120 allergic patients, the sting that provoked the systemic reaction had been preceded by another, completely tolerated sting not more than 2 months before. However, in the control group only four subjects out of 100 had received two consecutive stings within less than 2 months. In conclusion, a short interval between two consecutive stings seems to be a risk factor for the onset of Hymenoptera venom allergy.

Adolescent

Inhibition of proliferation by c-myb antisense RNA and oligodeoxynucleotides in transformed neuroectodermal cell lines.

Transfection of a neuroblastoma cell line with expression vectors containing two different segments of human c-myb complementary DNA in antisense orientation yielded far fewer transfectant clones than did the transfection with the identical segments in sense orientation. In cell clones expressing c-myb antisense RNA, levels of the c-myb protein were down-regulated and the proliferation rate was slower than that of cells transfected with sense constructs or the untransfected parental cell line. Treatment of neuroblastoma and neuroepithelioma cell lines with a c-myb antisense oligodeoxynucleotide strongly inhibited cell growth. These data indicate a definite involvement of c-myb in the proliferation of neuroectodermal tumor cells extending the role of this protooncogene beyond the hematopoietic system. The availability of cell clones that transcribe c-myb antisense RNA provides a useful tool to study the involvement of other genes in the proliferation and differentiation of neuroblastoma cells.

Animals

Efficacy of an air-cleaning device equipped with a high efficiency particulate air filter in house dust mite respiratory allergy.

The efficacy of an air-cleaning device equipped with a high efficiency particulate air (HEPA) filter (without further avoidance measures) was studied in patients allergic to house dust mite. The effects of the air-cleaner on indoor Dermatophagoides sp. levels, symptom score and bronchial hyperresponsiveness in nine mite-allergic patients were assessed using a cross-over controlled study. No significant effect was demonstrated on indoor Dermatophagoides sp. levels when comparing the period of air-cleaner activity (2 months) with the control period (2 months). The Dermatophagoides sp. levels in the houses studied were lower than the risk level for asthmatic attacks, making it difficult to assess any effect on asthma; however, neither bronchial hyperresponsiveness nor rhinitis symptom score were changed by air-cleaner activity. During the trial period, however the mean level of Dermatophagoides sp. allergen in the houses changed spontaneously from 4.4 micrograms/g (mean level in the first 2 trial months) to 1.75 micrograms/g of dust (second 2 months) (P less than 0.05). Owing to this change, the mean rhinitis symptom score also decreased (P less than 0.05), even if no significant correlation was demonstrated (r = 0.4 P = 0.089). HEPA filter air-cleaners appear insufficient as substitutes for standard avoidance measures in mite allergic patients.

Adolescent

Hyposensitization therapy of Parietaria-sensitive patients with a tyrosine adsorbed allergoid, Pollinex Parietaria (Bencard Parietaria).

Thirty patients suffering from allergy to Parietaria pollen were treated with either a new tyrosine-adsorbed allergoid of Parietaria judaica pollen (Pollinex Parietaria) or a commercially available alum-adsorbed extract (Alavac) as control. A reduced response to nasal provocation was seen in 7 out of 11 patients following treatment with Pollinex and 1 out of 10 after control treatment. 9 out of 11 and 3 out of 10, respectively, showed reduced skin test activity. Patients who received Pollinex tended to have fewer nasal symptoms during the pollen season. Pollinex induced larger increases in P. judaica-specific IgG antibody than did the control product. Side effects of therapy were similar between the two groups of patients. Pollinex Parietaria thus shows good potential for the control of allergy to Parietaria pollen.

Adult

Lack of adverse cardiac effects of combined treatment with theophylline and albuterol in asthmatic children.

Our study was designed to assess potential cardiovascular adverse effects in clinically stable asthmatic children due either to oral sustained-release theophylline or theophylline in combination with an inhaled beta-2 adrenergic agonist. Twenty-five asthmatic children were evaluated while receiving no drugs, theophylline alone, and theophylline with an inhaled beta-2 adrenergic agonist. In each phase all patients underwent 24- to 48-hour Holter monitoring and a maximal treadmill exercise test. The results show that neither theophylline alone nor combined therapy was associated with any relevant cardiovascular adverse effect, including ectopic cardiac activity. A nonsignificant increase in mean heart rate was observed between each period of study. The data suggest that the use of theophylline either alone or in combination with a beta-2 adrenergic agonist in clinically stable asthmatic children is not associated with any serious cardiovascular effect.

Albuterol

[Autonomic neuropathy in type I diabetes in children].

We tested some cardiovascular reflexes (Valsalva ratio, deep-breathing, postural hypotension) in 53 subjects suffering from diabetes type I in childhood with an average disease length of 13 +/- 6 years, in order to estimate possible damage to the autonomic nervous system without clinical symptomatology. A rather high percentage of signs of neurovegetative involvement combined with the progressive increase of further complications during the course of the disease, suggests early neurologic damage. We confirm the sensitivity of adopted tests and deep-breathing in particular.

Adolescent

Flow cytometric and molecular analysis of proliferative activity and DNA content in neuroblastoma: presence of stationary cells in S-phase.

Twenty-nine previously untreated neuroblastomas were analyzed for DNA content and percentage of cells in S-phase, both determined by flow cytometry, and N-myc oncogene copy number. Twelve of them were also tested for histone H3 transcript levels as a marker of actual proliferative activity. A significantly higher S-phase fraction was associated with advanced stages of disease, unfavorable (i.e., near-diploid and near-tetraploid) DNA content, and N-myc amplification. The occurrence of six tumors with a remarkable (greater than or equal to 10%) S-phase fraction but lacking histone H3 transcripts suggests the presence of stationary S-phase cells in neuroblastoma.

Cell Division

Comparative study of terfenadine and cetirizine in hay fever: assessment of efficacy and central nervous system effects.

A daily dose of either terfenadine 120 mg or cetirizine 10 mg was compared in two parallel groups of patients suffering from hay fever. According to a double-blind, double-dummy, randomized design, 28 patients were treated with one of the two drugs once daily in the morning for 2 weeks during the 1990 grass pollen season. The severity of nasal congestion, rhinorrhea, sneezing, nasopharyngeal itching and itchy, watery, red eyes was evaluated by the investigator after a 1-week run-in period and at the end of the treatment. The patients made a daily record of the severity of symptoms on a diary card. In addition, drug-related central nervous system (CNS) effects were assessed at baseline and at the end of the treatment by neuropsychological tests aimed at investigating selective and sustained attention, visuomotor abilities and anxiety, and by quantitative, bit-mapped EEG. Both terfenadine and cetirizine produced a significant improvement in symptoms at endpoint without any significant difference between the two drugs. Drowsiness was referred by one patient in each treatment group. No significant impairment of psychomotor performance occurred with either drug. Quantitative EEG showed a significant power increase in the relative (%) delta band in both groups of treated patients. Although the difference was not statistically significant, a tendency towards greater involvement of the CNS was observed with the use of cetirizine. In conclusion, the results of this study confirm that terfenadine and cetirizine are equally effective in the management of hay fever. Some differentiated untoward EEG changes were also observed in relation to the drugs used, without any variation in neuropsychological performance.

Adolescent

Early decrease in skin reactivity after rush venom immunotherapy.

Previous studies have documented changes in skin reactivity after specific immunotherapy. The aim of this study was to evaluate the time course of this phenomenon after rush venom immunotherapy. According to the method of endpoint evaluation, the skin reactivity of 38 patients allergic to venom was studied 24 h before and after the end of a rush venom immunotherapy protocol (7 days). The results were compared with 13 controls. An early significant decrease in skin reactivity was documented (p < 0.001), which was not related to an increase in specific IgG. Thus, rush venom immunotherapy induces a very early decrease in skin reactivity.

Adolescent