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A Ronchi

Publications and source records attributed to A Ronchi.

53 records · Page 3Linked to original sources
PubMed1989

The same nuclear proteins bind the proximal CACCC box of the human beta-globin promoter and a similar sequence in the enhancer.

Using in vitro assays, we show that nuclear proteins related to the Sp1 and GT-1 factors bind to a CACCC box sequence in the human beta-globin enhancer, adjacent to binding sites for the erythroid-specific factor NFE1 and the ubiquitous factor CP1. The same proteins are known to bind to the proximal, but not to the distal, CACCC, box in the human beta-globin promoter. A C G mutation in the promoter CACCC box, known to cause beta-thalassemia, greatly decreases protein binding to the CACCC box; the same effect is obtained when this mutation is introduced into the enhancer CACCC box.

Base Sequence↗
PubMed1989

Increased erythroid-specific expression of a mutated HPFH gamma-globin promoter requires the erythroid factor NFE-1.

The -175 T greater than C mutation in the promoter of the A gamma- or G gamma-globin gene causes a 50-100 fold increase of the expression of the respective gene in adult erythroid cells (Hereditary Persistence of Fetal Hemoglobin). We show here that this mutation increases 3-9 fold the expression of a gamma-CAT reporter plasmid transfected into the erythroid cells K562, but not that of the same plasmid in non erythroid cells. The overexpression of the mutant is abolished by the mutation of the binding site for the erythroid specific factor NFE1; inactivation of the adjacent binding site for the ubiquitous factor OTF1 does not cause overexpression of the normal gamma-globin promoter. Previous results demonstrated that the -175 mutation slightly increases the in vitro binding of NFE1 and almost abolishes that of OTF1; the present functional data indicate that altered binding of NFE1, but not of OTF1, is responsible for the observed overexpression of the mutated promoter.

Adult↗
PubMed1989

DNA sequences regulating human globin gene transcription in nondeletional hereditary persistence of fetal hemoglobin.

Strong genetic evidence supports the idea that point mutations in the promoter of gamma-globin genes overexpressed in adult age [hereditary persistence of fetal hemoglobin (HPFH)] are responsible for the observed phenotype. DNA binding sites for ubiquitous and/or erythroid specific nuclear proteins correlate in location with the positions of point mutations responsible for HPFH. The analysis of the effects of one of these mutations (-175 T greater than C) on in vitro binding of nuclear proteins and on the activity of the mutated promoter in transfection assays indicates that altered binding of the erythroid-specific protein NFE-1 may be responsible for increased activity of the mutated promoter. Other HPFH mutations close to the distal CCAAT box (-117 G greater than A and 13 nucleotide deletions, -114 to -102) have complex effects on in vitro binding of nuclear proteins; their only common effect is the loss of binding of the erythroid-specific factor NFE3. If mechanisms generating the HPFH phenotype are homogeneous, NFE3 might be a negatively acting factor; alternatively, heterogeneous mechanisms might operate and HPFH might additionally be related to loss of binding to the distal CCAAT box region of either NFE1 (-117 HPFH) or of the ubiquitous CCAAT displacement protein-CDP (13 nucleotides deletion). Finally, it is also proposed that increased activity of the HPFH promoters may secondarily cause decreased expression of the delta- and beta-globin genes in cis possibly by competition between gamma- and beta-globin promoters for interaction with common regulatory elements.

Base Sequence↗
PubMed1988

The effects of HPFH mutations in the human gamma-globin promoter on binding of ubiquitous and erythroid specific nuclear factors.

Genetic evidence indicates that single point mutations in the gamma-globin promoter may be the cause of high expression of the mutated gene in the adult period (Hereditary Persistence of Fetal Hemoglobin, HPFH). Here we show that one of these mutations characterized by a T----C substitution at position -175 in a conserved octamer (ATGCAAAT) sequence, abolishes the ability of a ubiquitous octamer binding nuclear protein to bind a gamma-globin promoter fragment containing the mutated sequence; however, the ability of two erythroid specific proteins to bind the same fragment is increased three to five fold. DMS interference and binding experiments with mutated fragments indicate that the ubiquitous protein recognizes the octamer sequence, while the erythroid specific proteins B2, B3 recognize flanking nucleotides. Competition experiments indicate that protein B2 corresponds to an erythroid-specific protein known to bind to a consensus GATAG sequence present at several locations in alpha, beta and gamma-globin genes. Although the distal CCAAT box region of the gamma-globin gene shows a related sequence, an oligonucleotide including this sequence does not show any ability to bind the above mentioned erythroid protein; instead, it binds a different erythroid specific protein, in addition to a ubiquitous protein. The -117 G----A mutation also known to cause HPFH, and mapping two nucleotides upstream from the CCAAT box, greatly decreases the binding of the erythroid-specific, but not that of the ubiquitous protein, to the CCAAT box region fragment.

Base Sequence↗
PubMed1988

[Preanalytical factors in chromium analysis of blood samples].

The problems connected with the collection of blood samples for chromium determination are shown with particular reference to the risk of chromium contamination which characterizes venous and capillary blood sampling. The use of various types of blood taking equipment (syringes with steel needles, platinum/ruthenium needles, intravenous catheters and lancets in steel of quarz) have been compared and analyzed (with references to the potential sources of chromium contamination during the collection and conservation of blood samples). By the use of the use of ETA-AAS "Zeema" procedure the references values of chromium in serum, read cells and whole blood in normal unexposed subjects living in a region of Northern Italy (Lombardy) have been determined.

Blood Specimen Collection↗
PubMedDate not supplied

Distributions of smokers by stage: international comparison and association with smoking prevalence.

OBJECTIVES: The goals of this study were to describe the distribution of smokers by stage of change in Geneva, Switzerland; to compare this result with distributions observed in other countries; and to assess whether, across samples from different countries, the stage distribution of current smokers was associated with the prevalence of smoking. METHODS: Two mailed surveys were conducted in Geneva in 1995-1996, in a representative sample of residents (n = 742) and in a representative sample of university members (n = 2,270). A literature review produced seven studies describing the stage distribution in representative samples. RESULTS: In the Geneva population, 74% of smokers were in the precontemplation stage, 22% in contemplation, and 4% in preparation. In the university sample, the corresponding figures were 72, 20, and 8%. Our results were similar to other European samples, but less favorable than in American samples, where these distributions were typically 40, 40, and 20%, respectively. Across all samples, a low prevalence of smoking was associated with a more favorable stage distribution (r = 0.88, P = 0.002). CONCLUSIONS: Interventions in Europe need to take into account the large proportion of precontemplators repeatedly observed among smokers. A shift to the right of the distribution of current smokers across stages may help increase quit rates and thereby reduce smoking prevalence. This hypothesis should be tested in prospective intervention studies.

Adolescent↗
PubMedDate not supplied

Selenium administration does not cause thyroid insufficiency in subjects with mild iodine deficiency and sufficient selenium intake.

Selenium is a trace element essential for the activity of type I 5'-deiodinase which converts thyroxine (T4) to 3,5,3'-triiodothyronine (T3). In iodine deficient hypothyroid children at low selenium dietary intake the supplementation of selenium induced a significant decrement of serum FT4 and T4 concentrations and an increase of serum TSH concentrations. Since in western countries selenium tablets begin to be largely consumed as a diet integrator, we have administered 100 micrograms/day of selenium as selenium methionine to 8 euthyroid female subjects with a positive iodine-perchlorate discharge test who had a previous episode of subacute or postpartum thyroiditis. We have studied subjects with positive iodine-perchlorate discharge test since the test indicates the existence of a subtle defect of thyroid hormone synthesis and therefore these subjects are prone to develop thyroid dysfunction. In contrast to previous findings in hypothyroid children at low iodine and selenium dietary intake, the supplementation of selenium did not decompensate thyroid hormone synthesis of euthyroid subjects with reduced thyroid iodine organification. The lack of any effect of selenium on thyroid hormone synthesis even in subjects with subtle thyroid hormone synthesis defect may be due to the fact that these subjects had a sufficient selenium dietary intake before selenium supplementation and an only marginally reduced dietary iodine intake.

Adult↗
PubMedDate not supplied

Boron-loaded liposomes in the treatment of hepatic metastases: preliminary investigation by autoradiography analysis.

Boronophenylalanine (BPA)-loaded conventional and stabilized liposomes were prepared by the reversed phase evaporation method to treat liver metastases by boron neutron capture therapy. Conventional vesicles were composed of phosphatidylcholine and cholesterol, molar ratio 1:1. To obtain stealth liposomes, GM1 or PEG were included in the lipidic bilayer at a concentration of 6.67 or 5 mol%, respectively. Large unilamellar vesicles were formulated encapsulating BPA in the liposome aqueous compartment as a complex with fructose; BPA free base also was embedded into the lipidic bilayer. In vivo experiments were carried out after intravenous injection of liposome suspensions in BD-IX strain rats in which liver metastases had been induced. Alpha particle spectroscopy associated with histological analysis was performed to visualize boron spatial distribution in liver. Simultaneously, tissue boron concentrations were determined using inductively coupled plasma-mass spectroscopy. Results showed that PEG-modified liposomes accumulated boron in therapeutic concentrations (> 30 micrograms boron/g tissue) in metastatic tissue. The PEG-liposomes could be further explored in enhancing boron delivery to tumor cells.

Animals↗
PubMedDate not supplied

CEA levels in gastric juice in precancerous conditions and cancer.

First described in 1965 as a specific antigen for cancer of the colon, CEA is now considered to be an antigen associated with many types of malignant neoplasia, although the CEA-Test's role in clinical routine has yet to be clearly defined. In the present study CEA levels in gastric juice were measured in subjects with gastric carcinoma (n = 25) and with benign gastric lesions (n = 171). CEA was significantly (p less than 0.05) higher in patients with gastric carcinoma (GC) than in subjects with benign gastric lesions, other than chronic atrophic gastritis (CAG) associated with intestinal metaplasia (IM). In this latter condition CEA levels were similar to those in patients with GC. These results suggest that the assay of CEA in gastric juice could be included in the diagnostic program for gastric cancer and its precursors with the aim of assessing its utility as risk indicator in the management of precancerous conditions and lesion.

Adolescent↗
PubMedDate not supplied

[Reference values of urinary mercury in the Italian population].

This paper shows the results of a polycentric study performed to assess the reference values of urinary mercury (U-Hg) in Italian population. 374 subjects from four Italian cities (Bari, Brescia, Genova e Siena) have been examined. A questionnaire on life style, dietary habits, occupational or environmental exposure to Hg and clinical history has been administered to every participant and number and surface of dental amalgams have been verified for all subjects. The determination of U-Hg has been performed on urinary extemporary samples by hydride generation atomic absorption method (HG-AAS); urinary creatinine has been determinated to reduce the intraindividual variability. U-Hg reference values were: 0.21-3.20 micrograms/g creat (5 degrees and 95 degrees percentile) and 0.12-6.04 micrograms/g creat (range). Moreover study results have shown that number and surface of dental amalgams, dietary fish intake and body mass index (BMI) influenced significatively U-Hg excretion. U-Hg reference values from this polycentric study resulted comparable to those assessed in other European countries, whereas the mean U-Hg observed in the referent Italian population was lower.

Adolescent↗
PubMedDate not supplied

[Distribution of blood lead level in a general population].

The goal of this study was to evaluate the distribution of blood lead level (B.L.L.) in a general adult population aged between 20 and 79 years non professionally exposed to lead, and to verify the influence on B.L.L. of demographic variables (i.e. sex and age), behavioural habits (i.e. alcohol consumption and cigarette smoking), and anthropometric variables (i.e. body mass index--BMI). We studied the distribution of B.L.L. by explorative analysis method (E.D.A.), which showed that data did not follow a Gaussian distribution. Distribution fit to normality was determined by Shapiro-Wilk test, that identified the natural logarithm of B.L.L. as the best transformation in order to normalize the parameter. According to literature data, sex appears one of the most important variable in determining B.L.L. In both sexes we found a direct relation between B.L.L. and age. Alcohol consumption emerged as the third most important variable that influences B.L.L. BMI and cigarette smoking do not influence data distribution.

Adult↗