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Biomedical subjects

F Santamaria

Publications and source records attributed to F Santamaria.

At least 19 recordsLinked to original sources
PubMed2000

A two B-Z junction containing DNA resolves into an all right-handed double-helix.

Natural and artificial oligonucleotides are capable of assuming many different conformations and functions. Here we present results of an NMR restrained molecular modelling study on the conformational preferences of the modified decanucleotide d((m)C1G2(m)C3G4C5(L)G6(L)(m)C7G8(m)C9G10) .d((m)C11G12(m)C13G14C15(L)G (L)16(m)C17-G18(m)C19G20 ) which contains L deoxynucleotides in its centre. This chimeric DNA was expected to form a right-left-right-handed B-type double-helix (BB*B) at low salt concentration. Actually, it matured into a fully right-handed double helix with its central C(L)pG(L) core forming a right-handed Z-DNA helix embedded in a B-DNA matrix (BZ*B). The interplay between base-base and base-sugar stackings within the core and its immediately adjacent residues was found to be critical in ensuring the stabilisation of the right-handed helix. The structure could serve as a model for the design of antisense oligonucleotides resistant to nucleases and capable of hybridising to natural DNAs and RNAs.

Base Sequence↗
PubMed2000

Stereochemical control of DNA biosynthesis.

Stereochemical control of DNA biosynthesis was studied using several DNA-synthesizing complexes containing, in each case, a single substitution of a 2'-deoxy-D-nucleotide residue by an enantiomeric L-nucleotide residue in a DNA chain (either in the primer or in the template) as well as 2'-deoxy-L-ribonucleoside 5'-triphosphates (L-dNTPs) as substrates. Three template-dependent DNA polymerases were tested, Escherichia coli DNA polymerase I Klenow fragment, Thermus aquaticus DNA polymerase and avian myeloblastosis virus reverse transcriptase, as well as template-independent calf-thymus terminal deoxynucleotidyl transferase. Very stringent control of stereoselectivity was demonstrated for template-dependent DNA polymerases, whereas terminal deoxynucleotidyl transferase was less selective. DNA polymerase I and reverse transcriptase catalyzed formation of dinucleoside 5',5'-tetraphosphates when L-dTTP was used as substrate. Comparison between models of template-primer complexes, modified or not by a single L-nucleotide residue, revealed striking differences in their geometry.

Base Sequence↗
PubMed2000

Bronchial hyperresponsiveness in children and adolescents with Crohn's disease.

Pulmonary manifestations have been described in Crohn's disease (CD). Bronchial responsiveness to methacholine (MCh) was evaluated in 14 children with CD with no evidence of airway disease, 10 asthmatics, and 10 healthy subjects. In patients with CD total blood eosinophils and serum IgE were 0.20 x 10(9) x L(-1) (95% CI -1.68 to 2.08) and 138.4 kU x L(-)(1) (95% CI 18.84 to 257.96), respectively. Three patients with CD had positive prick tests. Bronchial hyperresponsiveness (BHR) was demonstrated in 10 patients with CD (71%) and in the asthmatics, but not in control subjects. In patients with CD PD(20) appeared significantly greater than in asthmatics (699 microg [95% CI 238 to 1,115] versus 104 microg [95% CI 37.35 to 293]; p < 0.05), and was not related either to baseline FEV(1) or IgE or eosinophils (r = 0.32; r = -0.5; r = -0.15, p = NS, respectively). Neither activity nor treatment or duration of CD affected BHR. Five nonatopic CD patients underwent a second MCh challenge over a 25-mo period: the PD(20) appeared significantly greater than basal PD(20) (1,941 microg versus 575 microg, p < 0.05, respectively), in the absence of significant changes of disease activity. BHR might be the expression of subclinical airway inflammation, a phenomenon which can be responsible for the development of various pulmonary manifestations in CD.

Adolescent↗
PubMed2000

Regulation of PTHrP and PTH/PTHrP receptor by extracellular Ca2+ concentration and hormones in the breast cancer cell line 8701-BC.

It was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor (PTHrP-R) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulation of PTHrP and PTHrP-R by breast cancer cells has been poorly investigated so far, we have chosen the 8701-BC cell line as a model system to investigate whether alterations in the extracellular Ca2+ concentration ([Ca2+]e) and treatment with some well-known differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, all-trans retinoic acid and transforming growth factor-beta1 might (i) modulate quantitatively the release of iPTHrP, (ii) affect the PTHrP promoter usage and mRNA splicing patterns, and (iii) modify the expression of PTHrP-R. The data obtained indicate that 8701-BC cells are potentially able to utilise different start sites and mRNA splicing patterns for PTHrP transcription, and respond to variations of [Ca2+]e and to the addition of two hormones, hydrocortisone and progesterone, with modifications in the extracellular amount of iPTHrP. Moreover, expression of PTHrP-R is also modulated by changes of [Ca2+]e or treatment with hydrocortisone. This indicates that the 8701 -BC cell line is a suitable in vitro model for further studies on the complex molecular regulation of the PTHrP/PTHrP-R pair in breast cancer.

Breast Neoplasms↗
PubMed1999

Ciliary motility at light microscopy: a screening technique for ciliary defects.

To verify whether or not ciliary motility can be reliably assessed by light microscopy alone, we examined the nasal brushings of 53 patients with suspected ciliary dyskinesia and 10 healthy controls. The results of light microscopy were compared with cilia ultrastructure assessed with electron microscopy. Ciliary motility was significantly related with cilia ultrastructure. However, eight cases of lung disease due to bronchiectasis of unknown origin had immotile cilia on light microscopy, but normal ciliary ultrastructure on electron microscopy. Instances of normal and abnormal ultrastructure were detected in one case with motile cilia. There was an 83% agreement between electron microscopy and light microscopy. Sensitivity and specificity of light microscopy were 92% and 80%, respectively. In conclusion, light microscopy evaluation of ciliary motility does not appear to be a reliable screening test for ciliary dyskinesia because it does not quantify ciliary beat activity, which is a criterion for deranged ciliary motion. A complete evaluation of ciliary ultrastructure together with in vivo, if applicable, or in vitro function test (namely, the analysis of ciliary beat frequencies and/or waveform) is required for a definite diagnosis of ciliary dyskinesia.

Adolescent↗
PubMed1998

Pulmonary manifestations of Gaucher disease: an increased risk for L444P homozygotes?

Pulmonary disease is a complication of Gaucher disease (GD), a lysosomal disorder due to the deficiency of glucocerebrosidase. Lung involvement was investigated through chest radiography, high-resolution computed tomography of the chest, pulmonary function tests (PFT), and oxygen saturation (SaO2) at 21% FI(O2) in 13 Italian GD patients, six homoallelic for the L444P mutation (Group A), seven with various genotypes (Group B). Echocardiography and transcutaneous oxygen tension measurement at room air and after breathing 100% oxygen were performed to exclude pulmonary hypertension and/or intrapulmonary shunts. A score index (SI) including lung involvement evaluated the severity of GD. In three Group A patients with respiratory symptoms and in an asymptomatic male interstitial involvement was demonstrated; one child died of aspiration pneumonia. Group B patients had no signs of lung damage; PFT were normal in all cases but one. SaO2 was normal in both groups. Pulmonary vascular disease was ruled out in three cases with respiratory symptoms. In Groups A and B the median SI were 22 and 13, respectively (p < 0.01). L444P homozygotes appear at major risk for developing pulmonary disease, even at earlier ages. A comprehensive evaluation of lung involvement is recommended primarily in these subjects.

Adolescent↗
PubMed1998

Cystic fibrosis: when should high-resolution computed tomography of the chest Be obtained?

OBJECTIVE: To provide indications for high-resolution computed tomography (HRCT) of the chest in patients with cystic fibrosis (CF). DESIGN: We compared the HRCT and conventional chest radiography (CCR) scores and assessed their correlation with clinical scores and pulmonary function tests. SETTING: Department of Pediatrics, Federico II University, Naples, Italy. SUBJECTS: A total of 30 patients with CF 6.75 to 24 years of age. RESULTS: CCR scores correlated highly with HRCT (r = -0.8) and clinical (r = 0.5) scores, whereas total HRCT scores were not related to clinical scores. Of all the specific HRCT findings, only bronchiectasis appeared related significantly to the clinical score (r = 0.6). Most pulmonary function tests were related to CCR and total HRCT scores, but not to HRCT scoring of specific changes. Forced vital capacity and CCR scores appeared the best predictors of the HRCT score (multiple R = 0.58 and 0.79, respectively). In patients with mild lung disease, HRCT detected bronchiectasis and air trapping in 57% and 71% of the cases, respectively. In patients with more abnormal chest radiographs, bronchiectasis and air trapping were demonstrated on HRCT in all cases. CONCLUSIONS: These findings suggest that HRCT of the chest is most useful in the identification of early lung abnormalities in patients with CF with mild respiratory symptoms, whereas for established disease, CCR is still the first-line imaging technique. The advantage of detecting early changes on CT imaging awaits additional confirmation, at least until early therapeutic interventions affecting significantly the final outcome of the disease are demonstrated. In patients with advanced disease, HRCT may be useful in the evaluation of specific lung changes when more aggressive treatment such as chest surgical interventions is indicated. Given the cost of the procedure and the high radiation dosage compared with CCR, a careful assessment of the cost:benefit ratios of HRCT is strongly recommended in CF.

Adolescent↗
PubMed1996

Physical performance in patients with thalassemia before and after transfusion.

Patients with thalassemia who are on chronic transfusion programs have chronic ventilatory and cardiocirculatory abnormalities. We studied flow-volume curves, blood gas exchange, and cardiorespiratory responses to exercise in 12 patients with thalassemia major (TM) before and 24 hours after transfusions. Cardiorespiratory fitness was assessed with an exercise tolerance test on a cycle-ergometer. Ten healthy controls underwent the same protocol twice, first at baseline and then 24 hours later, without having had transfusions. We identified two subgroups of patients with a questionnaire: 1) those with no history of airway disease; and 2) those with a history of airway obstruction. Patients with no history of airway disease had normal baseline expiratory flows and no posttransfusion changes; those with a history of airway obstruction had lower pretransfusion expiratory flows rates and significantly decreased posttransfusion forced expiratory volume in 1 second (FEV1) and forced expiratory flow at 25-75% of forced vital capacity (FEV25-75%). As a group, TM patients had significantly lower pretransfusion cardiorespiratory function than controls; TM patients' maximum workload was 33% lower, maximum ventilation was 38% lower, maximum oxygen uptake was 25.7% lower, oxygen pulse was 28.6% lower, dyspnea index was 10.6% lower, and ventilatory equivalent for oxygen was 27.1% lower than in control subjects. Although cardiorespiratory responses to exercise improved in both subgroups after transfusion, patients with a history of airways obstruction had a significant posttransfusion increase in their dyspnea index (P = 0.05) and further increased their already abnormally high values of PETCO2 (43 mmHg). These results suggest that the transfusion worsened relative hypoventilation at the maximum workload only in the subgroup with a history of airway obstruction.

Adolescent↗
PubMed1996

Early detection of lung involvement in lysinuric protein intolerance: role of high-resolution computed tomography and radioisotopic methods.

Pulmonary disease of unknown etiology is a potentially fatal complication in patients with lysinuric protein intolerance (LPI), an autosomal recessive disorder caused by the defective transport of cationic amino acids. Lung involvement was investigated in nine Italian LPI patients through pulmonary function tests and lung imaging studies consisting of conventional chest radiography, high-resolution computed tomography (HRCT), and perfusion and ventilation scintigraphy. One 10-yr-old patient died of severe respiratory insufficiency from alveolar proteinosis. All of the remaining patients were asymptomatic at the time of the study, although HRCT scans revealed signs of lung involvement defined by the presence of acinar nodules, inter- and/or intralobular thickening of the interstitial septa, and subpleural cysts in five of the patients. Radioisotope studies showed an uneven distribution of perfusion and ventilation, and confirmed the presence of segmental and/or diffuse pulmonary functional defects. No abnormalities of pulmonary function were evident, and answers to a questionnaire excluded primary coexisting lung disease. In patients with LPI, including those without clinical and functional impairment, HRCT and radioisotopic studies appear to be the most sensitive methods for the early diagnosis of lung disease and correct assessment of its progression.

Adult↗
PubMed1995

Simultaneous prolonged recordings of proximal and distal intraesophageal pH in children with gastroesophageal reflux disease and respiratory symptoms.

OBJECTIVES: To characterize both proximal and distal esophageal acid exposure in children with gastroesophageal reflux-related respiratory disease and to investigate the usefulness of dual-channel intraesophageal pH monitoring in these patients. METHODS: Continuous simultaneous recording of distal and proximal esophageal pH was performed in 40 patients with gastroesophageal reflux disease and respiratory symptoms (wheezing, nocturnal cough, obstructive bronchitis) (age range 3-168 months) (group A), in 20 patients with reflux disease alone (age range 7-156 months) (group B), and in 14 controls (age range 5-108 months) (group C). RESULTS: (expressed as median +/- SD) 1) The two groups of patients did not differ with regard to distal and proximal esophageal acid exposure (percentage of reflux) during both the total recording period [distal, A: 9.2 +/- 4, B: 10.7 +/- 7 (NS), C: 1.9 +/- 1.0; and proximal, A: 4.8 +/- 3.3, B: 4.0 +/- 3.3 (NS), C: 1.0 +/- 0.7] and during nighttime [distal, A: 8.0 +/- 6.2, B: 10.4 +/- 6.1 (NS), C: 0.9 +/- 0.65; and proximal, A: 3.72 +/- 3, B: 3.6 +/- 3.0 (NS), C: 0.75 +/- 0.45]. 2) The two groups did not differ with regard to the ratio between proximal and distal esophageal acid exposure during both total and nocturnal periods of analysis. 3) No significant correlation was found between distal and proximal esophageal acid exposure during total and nocturnal recording periods. 4) In patients with reflux-related respiratory disease, the respiratory symptomatic index was significantly higher during distal esophageal acid exposure alone (47.0 +/- 28.6%) than during simultaneous reflux at the two esophageal levels (26.9 +/- 27%) (p < 0.05). Furthermore, reflux episodes associated with respiratory symptoms reached lower pH values than those in patients without symptoms at the two recording sites. CONCLUSIONS: Gastroesophageal reflux into the proximal esophagus does not discriminate between patients with reflux disease alone and those with reflux disease complicated by respiratory symptoms. Symptoms of asthma in reflux patients appear to be elicited more by a reflex mechanism than by aspiration of gastric refluxate into the airways. Intraesophageal acidification seems to be involved in eliciting respiratory symptoms related to reflux disease, and prolonged intraesophageal two-level pH measurement does not seem to be useful in the approach to patients with reflux disease associated with respiratory symptoms.

Adolescent↗
PubMed1994

The effect of transfusion on pulmonary function in patients with thalassemia major.

Pulmonary involvement has been documented in thalassemia major (TM). We studied 12 patients with TM before and 24 hr after transfusion to evaluate the effect of transfusion on baseline lung function. Personal and family histories of respiratory illnesses were obtained by a questionnaire. Spirometry and carbon monoxide diffusion capacity (KCO) measurements were made. Blood gases (PO2 and SO2) were determined on arterialized samples. Baseline expiratory volumes and flows were within normal range in all patients. Transfusion resulted in a significant reduction of forced expiratory volume in 1 sec (FEV1) and forced expiratory flow between 25 and 75% vital capacity (FEF25-75%). In two subgroups of patients identified by the questionnaire, those with no history of airway disease had normal baseline flows and no posttransfusion changes; those with history of airway obstruction had lower pretransfusion flows and significantly decreased posttransfusion FEV1 and FEF25-75%. The mean pretransfusion KCO value of 80% predicted for the whole group, significantly increased after transfusion (P < 0.05). Blood gases also significantly increased after transfusion (P < 0.05). When tested for the spirometric response to albuterol, patients with a history of asthma had a slightly greater increase in FEV1 and FEF25-75% than those who had never had asthma. We conclude that in our small study group, transfusion resulted in improved gas exchange and lung perfusion. The effect on flow limitation evident in some patients could, in part, be related to a preexisting bronchial hyperreactivity. Accurate evaluation of pulmonary function and of bronchial reactivity is advisable for patients with TM.

Adolescent↗
PubMed1994

Monitoring steatorrhoea in cystic fibrosis.

The aim of the study was the evaluation of the relationship between chemical fat analysis and some more rapid tests proposed to estimate steatorrhoea. Stool collections (72 h) were obtained on 32 occasions in 22 patients with cystic fibrosis and in seven healthy children. A very close relationship was found between faecal fat, as measured by standard chemical methods, and faecal energy (r = 0.95, P < 0.001). We conclude that the determination of faecal energy, easier to measure than faecal fat, can provide reliable information about the extent of steatorrhoea in cystic fibrosis.

Adolescent↗
PubMed1994

[Comparison of nisoldipine and diltiazem in the treatment of effort angina pectoris].

BACKGROUND: In order to evaluate the benefits of a calcium-antagonist medium-term treatment, 20 patients with effort stable angina pectoris were treated with nisoldipine in comparison to diltiazem. METHODS: Twenty patients with stable effort angina completed a double-blind, placebo controlled trial, comparing 10 twice daily nisoldipine per os and diltiazem 120 three times daily per os for 28 days. After wash-out, placebo and drug period, ergometer stress tests were performed. Exercise tolerance, angina frequency, nitrate consumption and side effects were evaluated. RESULTS: Our results showed that both drugs significantly increased exercise tolerance. Exercise duration was 330 +/- 107 sec after placebo, 397 +/- 106 sec after nisoldipine (p < 0.05) and 378 +/- 99 sec after diltiazem (p < 0.05). Effort angina episodes decreased from 20 after placebo to 8 after nisoldipine and diltiazem. Both drugs reduced rate-pressure product at submaximal exercise in comparison to placebo. There were no differences at peak exercise between placebo or drug periods. Both drugs similarly reduced nitrate consumption and weekly effort angina attacks. No patients referred serious side-effects. CONCLUSIONS: nisoldipine, like diltiazem, is an effective drug in the treatment of stable effort angina. Moreover, the therapeutic effects of nisoldipine during medium-term treatment are probably related to decrease in oxygen consumption.

Administration, Oral↗