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Biomedical subjects

M Baldini

Publications and source records attributed to M Baldini.

At least 19 recordsLinked to original sources
PubMed2003

Evaluation of the CD14 C-159 T polymorphism in the German Multicenter Allergy Study cohort.

BACKGROUND: Multiple genetic studies have shown linkage of atopy-related phenotypes to chromosome 5q31. In this region several candidate genes for atopy are localized such as the Th2 cytokines IL-4, IL-5 and IL-13, but also CD14, a receptor for LPS. Recently, a functional CD14 promoter polymorphism was related to total and specific IgE responsiveness. OBJECTIVE: The aim of our study was to evaluate the role of this single nucleotide polymorphism (SNP) in a large German birth cohort. METHODS: Atopy-related phenotypes were longitudinally carefully evaluated in over 800 children from birth to the age of 10 years. Yearly visits included standardized interviews, physical examinations and determination of total and specific IgE antibodies. Pulmonary function tests and histamine provocations were performed at the age of seven. Eight-hundred and seventy-two children of the Multicenter Allergy Study (MAS) cohort were genotyped using melting curve and restriction digest analyses. RESULTS: CD14-159 allele frequencies were consistent with previous reports, however, no association of the SNP with asthma, atopic dermatitis, allergic rhinitis, total or specific IgE levels could be observed. CONCLUSION: The CD14-159 SNP might not play a major role in the development of atopy in German children.

Follow-Up Studies↗
PubMed2002

Benefits of immunotherapy with a standardized Dermatophagoides pteronyssinus extract in asthmatic children: a three-year prospective study.

BACKGROUND: Although widely practiced for over 80 years, the role of specific immunotherapy (SIT) in pediatric asthma treatment is still controversial. We assessed the effects of a 3-year period of subcutaneous administration of a standardized preparation of Dermatophagoides pteronyssinus (D pt) on the respiratory health in a group of asthmatic children monosensitized to house dust mite (HDM). METHODS: A randomized clinical trial was performed after 1-year run-in period. Fifteen children receiving SIT for HDM and 14 controls (four drop-outs), matched for age, allergen sensitization, asthma severity, lung function, and non-specific bronchial reactivity (BHR), were studied during the 3-year treatment period. During the whole trial, respiratory symptoms, pharmacological and respiratory function parameters were regularly evaluated. Skin prick tests and methacholine challenge were performed at the beginning and end of the study. RESULTS: In the SIT group significant improvement in asthmatic symptoms and marked reduction in drug intake was observed. The SIT group also showed a significant decrease in non-specific bronchial BHR. No new sensitivity occurred during the study period in the SIT group only. No major local or systemic side-effects were reported during the study. CONCLUSIONS: Our results confirm that SIT is effective in asthmatic children sensitive to mites. It is associated with a decrease in BHR and it may prevent the development of new sensitizations in monosensitized subjects.

Adolescent↗
PubMed2002

Treatment of benign nodular goitre with mildly suppressive doses of L-thyroxine: effects on bone mineral density and on nodule size.

OBJECTIVES: To evaluate (i) the demineralizing effect of L-thyroxine (LT4) therapy at doses mildly inhibiting serum thyroid stimulating hormone (TSH) in patients with benign nodular goitre; (ii) the efficacy of treatment on nodule size. DESIGN: Cross-sectional study comparing euthyroid women with nodular goitre treated with LT4 for > or = 2 years (52 +/- 32 months, range 24-138, median 42) and a matched group with untreated goitre. SUBJECTS: A total of 89 female outpatients (53.3 +/- 9 years; 36 pre- and 53 postmenopausal), 43 treated and 46 untreated. MAIN OUTCOME MEASURES: Bone mineralization was measured with total body and regional mineralometry [dual energy X-ray absorptiometry (DEXA)], and indirectly evaluated with biochemical parameters (alkaline phosphatase, osteocalcin). Efficacy of LT4 therapy was assessed by measuring the nodule size during ultrasonography. The adequacy of the treatment was evaluated on the basis of serum TSH levels. RESULTS: No significant differences were found at DEXA for total body and regional mineralization (P > 0.05 for all comparisons) in treated and untreated patients, both in pre- and postmenopausal states. Evaluation of the nodule size during the ultrasound scan showed a reduction of > or = 30% in 11 of 43 treated patients (26%) versus none of the untreated, an unchanged size in 29 treated patients (67%) versus 18 untreated, an increase of nodules and/or new nodule development in three treated patients (7%) versus 28 untreated (61%). CONCLUSIONS: L-thyroxine (LT4) treatment at doses slightly suppressing TSH does not significantly affect bone mineralization, nor does it represent a risk factor for osteoporosis, even in postmenopausal patients. The efficacy of this therapeutic schedule on goitre size is comparable with the effects previously reported with suppressive doses.

Adult↗
PubMed2001

Differences in proliferation of the hematopoietic cell line TF-1 and cytokine production by peripheral blood leukocytes induced by 2 naturally occurring forms of human IL-3.

BACKGROUND: A naturally occurring polymorphism in the coding region of the human IL3 gene leads to a change in amino acid residue 8 from proline to serine. OBJECTIVE: We sought to determine whether the 2 different forms of IL-3 varied in function. These different forms are available as recombinant proteins (recombinant human IL-3/proline 8 [rhIL-3/P8] and recombinant human IL-3/serine 8 [rhIL-3/S8]). METHODS: The erythroleukemic cell line TF-1 was incubated with varying concentrations of rhIL-3/P8 or rhIL-3/S8 to determine the capacity of each type of IL-3 to induce proliferation. Human leukocytes were primed with rhIL-3/P8 or rhIL-3/S8 for up to 24 hours and then stimulated with anti-IgE and assessed for leukotrienes (LTs), IL-4, and TNF-alpha. RESULTS: Proliferation of TF-1 cells was induced by both forms of IL-3 at 48 and 72 hours but to a greater degree by rhIL-3/P8. In contrast, the mean fold increase over control values of LT and IL-4 production was higher after priming the cells with rhIL-3/S8 versus rhIL-3/P8. Additionally, TNF-alpha production was greater (and reached significance only) for rhIL-3/S8. This activity was independent of IgE and thus directly stimulated by IL-3. Studies with basophil-enriched and basophil-depleted cell preparations revealed that LT production was evident only from the former and TNF-alpha only from the latter. CONCLUSION: We conclude that the 2 naturally occurring forms of human IL-3 have similar spectra of activities on cells with IL-3 receptors, but the 2 forms have reversed relative efficacies for promoting proliferation (rhIL-3/P8 > rhIL-3/S8) compared with priming or inducing mediator secretion (rhIL-3/S8 > rhIL-3/P8).

Cell Line↗
PubMed2001

Factor analysis of asthma and atopy traits shows 2 major components, one of which is linked to markers on chromosome 5q.

BACKGROUND: A variety of definitions of asthma and atopy traits have been used in genetic studies. The variables used may be correlated, increasing the likelihood of type I error. OBJECTIVE: We sought to clarify and quantify phenotypes that may be characterized by related traits. Principal components and factor analysis were applied to the correlation matrix of asthma and atopy traits before linkage analysis. METHODS: Factor analysis was performed on 468 Hispanic and non-Hispanic white children enrolled in the Tucson Children's Respiratory Study, with complete information on 24 items, including skin test response to 7 allergens, total serum IgE levels, presence or absence of asthma attacks, wheezing episodes, hay fever, and cough. Factor score coefficients were then applied to all siblings (n = 877), and quantitative factor scores were derived. Single-point and multipoint nonparametric sib-pair analyses were performed to assess linkage to markers on chromosome 5q31-33. Analyses were also performed for individual items. RESULTS: Two main factors were identified: Factor I had high loadings on atopic items, including skin test responses, IgE, and hay fever, and Factor II had high loadings that included asthma diagnosis, wheezing, cough, and Alternaria species skin test response. Factors I and II were correlated at an r value of 0.19. For the quantitative factor scores, significant single-point linkage (P < .0001) was demonstrated only for atopic Factor I, and a peak multipoint LOD score of 2.7 was seen for marker D5S479. Multipoint LOD scores for individual items were 1.1 or less. CONCLUSION: These analyses suggest evidence for a locus or loci mapping to chromosome 5q31-33 associated with this composite atopic phenotype.

Asthma↗
PubMed2001

Influence of laboratory homogenization procedures on trace element content of food samples: an ICP-MS study on soft and durum wheat.

Sample contamination as a consequence of abrasion of grinding tools during the homogenization of food materials to be analysed for trace elements was addressed. The possible release of 15 trace elements (Al, As, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb, Se, Sn, V, Zn) from six different grinding and milling devices, operating either continuously or discontinuously, was evaluated. All the devices were commercially available and were representative of models usually employed in food and agricultural laboratories. Wheat grains belonging to one soft and one durum cultivar were used as test material. The determination of the analyte concentrations in subsamples submitted to the different preparation treatments was performed by quadrupole inductively coupled plasma mass spectrometry (Q-ICP-MS). Accordingly, a suitable digestion method was developed and the ArC+ interference affecting Cr determination was evaluated and corrected. Statistical differences with respect to the control were detected for 10 elements (Al, Cd, Co, Cr, Cu, Fe, Mn, Mo, Ni, Pb) and in most cases contamination of the samples was traced back to the composition of the grinding equipment. None of the investigated devices was contamination-free with respect to all of the quantified elements. Abrasion of the grinding tools was higher with durum wheat than with soft wheat as a consequence of their different hardiness.

Analysis of Variance↗
PubMed2001

CD14: a bridge between innate immunity and adaptive IgE responses.

Total IgE levels are known to be under genetic control. Linkage studies have indicated that one or more loci on chromosome 5q may control total IgE, as well as asthma and bronchial hyperresponsiveness to non-specific stimuli. Our group has undertaken a systematic analysis of chromosome 5q, and has recently characterized five single nucleotide polymorphisms at position -1619, -1359, -1145, -809, and -159 in the promoter of the gene encoding CD14, the myeloid pattern recognition receptor that is critical for efficient innate immune responses to lipopolysaccharide and bacterial ligands. Individuals homozygous for the three major CD14 haplotypes found in the Children Respiratory Study population (n = 390) were analyzed for serum levels of total IgE and soluble CD14. A strong inverse correlation was found between these two parameters, i.e. carriers of the -1359T/-1145A/-159C haplotype had the highest levels of IgE, and the lowest levels of sCD14. Conversely, carriers of the -1359G/-1145G/-159T haplotype had the highest levels of sCD14 and the lowest IgE values. Our results suggest that genetic variation in CD14, a key gene of innate immunity, may modulate the effects that exposure to bacterial ligands has on the development of Th2 responses.

Child↗
PubMed2000

CT-guided radiolabelled aerosol studies for assessing pulmonary impairment in children with bronchiectasis.

OBJECTIVE: To determine whether CT-guided mucociliary clearance studies allow differentiation between bronchiectasis associated with primary ciliary dyskinesia (PCD) and those unrelated to congenital or genetically transmitted defects. MATERIALS AND METHODS: Fifteen children aged 4-18 years with a CT diagnosis of bronchiectasis were included in the study. Six had PCD, while in nine cases no congenital disorder was demonstrated. RESULTS: CT showed bronchiectasis in 26 (29%) of 90 lung regions. Radiolabelled aerosol studies were conducted globally for each lung and on the regions affected by bronchiectasis. Global half-time of activity (t 1/2) values of patients with PCD were significantly higher (P < 0.001) than those with bronchiectasis unrelated to congenital disorders. Among the 26 lung regions in which CT demonstrated bronchiectasis, regional clearance was abnormal in 24 cases. Patients with PCD showed no statistically significant difference between regional and global t 1/2 values. Patients with bronchiectasis unrelated to congenital disorders showed significantly higher regional t 1/2 values in the affected regions with respect to the corresponding global pulmonary t 1/2 (P < 0.06). CONCLUSIONS: The combination of morphological CT information with functional data concerning the clearance of radiolabelled aerosol adds to our understanding of pulmonary impairment in children with bronchiectasis. In particular, regional studies allow the recognition of different mucociliary clearance patterns in bronchiectasis associated with PCD and those unrelated to congenital or genetically transmitted defects.

Adolescent↗
PubMed2000

A cluster of seven tightly linked polymorphisms in the IL-13 gene is associated with total serum IgE levels in three populations of white children.

BACKGROUND: Increased levels of total serum IgE are a strong risk factor for the development of asthma. IgE is also involved in host defenses against parasites and fungi. Linkage of total serum IgE with markers located close to the 3 Mb cluster of cytokine genes in chromosome 5q31 has been reported. IL-4 or IL-13 are regarded as essential for IgE synthesis. OBJECTIVE: We tested whether polymorphisms in the IL-13 gene might explain the linkage between chromosome 5q31 and total serum IgE levels. METHODS: We used denaturing HPLC to detect polymorphisms in overlapping PCR fragments of the IL-13 gene including promoter and 3' untranslated regions. After sequencing was performed to identify the locations of the polymorphisms, PCR and primer-induced restriction site assays were used to genotype subjects in 3 unselected populations. RESULTS: We report here 7 polymorphisms (6 novel) in IL-13. Four of these polymorphisms are tightly linked to a variant in the terminal portion of the coding region of the gene that results in a predicted amino acid change in residue 130 (Arg130Gln). The Gln form is strongly associated (P =.000002) with increased serum IgE levels in 3 different populations comprising a total of 1399 children. Two additional polymorphisms in the promoter region of IL-13 are more loosely linked to Arg130Gln and are also less significantly associated with total serum IgE levels. CONCLUSION: These data suggest that the Arg130Gln polymorphism in IL-13, or others in close linkage with it, is associated with the development of the elevated serum IgE phenotype.

Asthma↗
PubMed2000

Dietary intake exposure to sulphites in Italy--analytical determination of sulphite-containing foods and their combination into standard meals for adults and children.

The theoretical risk of exceeding the Acceptable Daily Intake (ADI) for sulphites has mostly been examined on the basis of a worst-case scenario. In order to examine the real situation the determination of residue sulphite levels in ready-to-consume foods is required. The aim of this paper is to assess the actual sulphite content of diets obtained from a combination of realistic meals high in sulphite-containing foods. Food products available in Italy containing added sulphites were identified. Overall, 211 samples of foods and beverages (including 85 samples of wine) were collected. The determination of sulphite residues was carried out on the foods which were prepared according to normal domestic practice. It was shown that the diets obtained from these foods would lead to an intake of 23 mg/day in children and 50 mg/day in adults (both slightly above the ADI for respectively a 30 kg child and a 60 kg adult). Among all sulphite-containing foods, the highest contributors to the intake were dried fruit and wine, both ingested without further treatment. The analysis of specific consumption data confirmed the existence of a risk of exceeding the ADI related to sulphite residue levels in wine.

Adult↗
PubMed2000

Estimation of lead intake from crystalware under conditions of consumer use.

The purpose of this study was to estimate the lead intake from crystalware resulting from short-term contacts with beverages, under conditions that are likely to occur to a consumer. The extraction ability of different kinds of beverages was estimated by comparison with 4% acetic acid under conditions of continuous contact for 3 h. It was found that lead release increased in the following order: cola drink > HAc > whisky > white wine. Under conditions of repeated use under different scenarios, lead release showed a steep decrease with increasing number of contacts, for both wine and cola drink. The maximum lead intake resulted from the cola drink, corresponding to an ingestion of 14.5 micrograms Pb for consumption of 350 ml beverage. Assuming a fixed contribution from the diet of 71 micrograms/day, in the six scenarios taken into consideration, total daily lead intake levels ranged from a minimum of about 76 micrograms up to a maximum of 86 micrograms lead. As these values, converted on a weekly basis, would correspond to 35% and 40% PTWI respectively, significant health risks resulting from the ingestion of beverages in contact with crystalware can be excluded. Finally it was found that the use of a dishwater did not affect significantly the release of lead into wine, while release into cola drink was slightly but significantly increased after the third cycle.

Alcoholic Beverages↗
PubMed2000

Cadmium in organs and tissues of horses slaughtered in Italy.

The cadmium content of muscle, liver, kidney and blood samples from 62 horses slaughtered in Italy was investigated. Cadmium was determined by graphite furnace atomic absorption spectrometry (GFAAS) after wet digestion of the samples. The mean and median contents of all samples were (on a fresh weight basis) 75 and 41 micrograms kg-1 for muscle, 2.46 and 2.10 mg kg-1 for liver, 20.0 and 13.5 mg kg-1 for kidney. The cadmium level in blood samples was always below 6 micrograms l-1. The cadmium concentrations in muscle, liver and kidney were found to be related to the life span of the specimens and increased with age. Females exhibited higher levels than males, but this difference was significant only in the case of muscle tissue. The geographical origin was recognized as the main factor influencing the cadmium content of the equine specimens analysed. The differences between horses coming from the three main breeding countries considered in this study (Poland, Lithuania, Hungary) were marked and statistically significant. The average intake of cadmium from equine meat was estimated for the general population and for population groups resident in areas with high consumption of this food item. While the cadmium intake from equine meat for the average consumer accounts for about 1% of the total cadmium intake estimated for Italy, in the latter case the enhanced consumption of equine muscle is often accompanied with the consumption of substantial quantities of equine liver and this may lead to high cadmium intakes.

Age Factors↗
PubMed2000

[Not Available].

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Communicable Diseases↗
PubMed2000

[Not Available].

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History, Ancient↗
PubMed1999

A Polymorphism* in the 5' flanking region of the CD14 gene is associated with circulating soluble CD14 levels and with total serum immunoglobulin E.

Total serum immunoglobulin (Ig)E levels are genetically regulated, but the mechanism of inheritance is not well understood. Cytokines produced by T-helper (Th)1 and Th2 lymphocytes control IgE synthesis. Bacterial antigens may favor the development of Th1 cells from naive CD4-positive T cells through a CD14-dependent pathway. CD14 is constitutively expressed on the surface of monocytes and macrophages, and is also present in serum in a soluble form (sCD14). The CD14 gene maps to chromosome 5q31.1, a candidate region for loci regulating total serum IgE. We hypothesized that genetic variants in the CD14 gene could influence Th-cell differentiation and thus total serum IgE. We identified a C-to-T transition at base pair -159 from the major transcription start site (CD14/-159). Among 481 children recruited from a general population sample, frequency of allele C was 51.4%. TT homozygotes had significantly higher sCD14 levels than did carriers of both the CC and CT genotypes (P = 0.01). TT homozygotes also had significantly lower levels of IgE than did carriers of the other two genotypes, but differences were significant only among children who were skin test-positive to local aeroallergens (P = 0.004). There was no association between CD14/-159 and either interleukin (IL)-4 or interferon (IFN)-gamma responses by peripheral blood mononuclear cells. However, IFN-gamma and IL-4 responses were positively and negatively correlated, respectively, with serum sCD14 levels. We conclude that CD14/-159 plays a significant role in regulating serum sCD14 levels and total serum IgE levels.

Base Sequence↗