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Biomedical subjects

C Costa

Publications and source records attributed to C Costa.

At least 55 records · Page 3Linked to original sources
PubMed2002

The Italian multi-centre project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk.

This report presents the preliminary results of the first phase (21 months) of a multi-centre, non-randomised, prospective study, aimed at evaluating the effectiveness of contrast-enhanced magnetic resonance imaging (MRI), X-ray mammography (XM) and ultrasound (US) in early diagnosis of breast cancer (BC) in subjects at high genetic risk. This Italian national trial (coordinated by the Istituto Superiore di Sanità, Rome) so far recruited 105 women (mean age 46.0 years; median age 51.0; age range 25-77 years), who were either proven BRCA1 or BRCA2 mutation carriers or had a 1 in 2 probability of being carriers (40/105 with a previous personal history of BC). Eight cases of breast carcinomas were detected in the trial (mean age 55.3 years, median age 52.5; age range 35-70 years; five with previous personal history of BC). All trial-detected BC cases (8/8) were identified by MRI, while XM and US correctly classified only one. MRI had one false positive case, XM and US none. Seven "MRI-only" detected cancers (4 invasive, 3 in situ) occurred in both pre- (n = 2) and post-menopausal (n = 5) women. With respect to the current XM screening programmes addressed to women in the age range 50-69 years, the global incidence of BC in the trial (7.6%) was over ten-fold higher. The cost per "MRI-only" detected cancer in this particular category of subjects at high genetic risk was substantially lower than that of an XM-detected cancer in the general women population. These preliminary results confirmed that MRI is a very useful tool to screen subjects at high genetic risk for breast carcinoma, not only in pre-, but also in post-menopausal age, with a low probability of false positive cases.

Adult↗
PubMed2002

BMRI in early detection of breast cancer in patients with increased genetic risk: our preliminary results.

Because of the higher risk of developing breast cancer and the early onset of the disease in women proved or suspected to be carriers of a breast cancer susceptibility gene, a dedicated screening should be offered as a less invasive approach with respect to the otherwise suggested prophylactic mastectomy. This should be optimized in order to overcome the limitations of conventional breast imaging with the application of new technologies such as Breast Magnetic Resonance Imaging (BMRI). A diagnostic protocol for routine control in patients with high risk for developing breast cancer has been prepared. Within a 7 months period, 23 patients suspected or proved to carry a breast cancer susceptibility gene underwent BMRI. Four breast cancers were identified with BMRI. In these cases mammography was negative because of the density of the parenchyma or for its fibroglandular pattern. US was negative in two cases, not specific for malignancy in one case and considered as only possibly malignant but with biopsy recommendation on the basis of MR findings in the last one. Clinic analysis was positive for mass in two cases. The accuracy of BMRI is known to be higher than that of conventional imaging in the study of breast parenchyma. High spatial resolution and no breast density influence can give more detailed information about smaller lesions and the right extent of the disease.

Adult↗
PubMed2001

Shape changes and growth trajectories in the early stages of three species of the genus Diplodus (Perciformes, Sparidae).

The larvae of three species of the genus Diplodus (Diplodus vulgaris, D. sargus, and D. puntazzo) colonize shallow waters along the Mediterranean coasts and, after a short period spent in the water column, they settle. For all three species this habitat transition is characterized by important shape changes mostly related to swimming capacity and feeding behavior. In this study, geometric morphometrics are used to characterize shape changes during the early juvenile life of specimens collected in a single locality in order to compare growth curves and allometric relationships. Size-related shape changes proved to be similar for all three species and are consistent with the ecological transition. A nonparametric smoothing technique (Loess) was used to fit the scatter of shape on size. The graphical representation (of most size-related shape variability) of this fitting technique shows how major shape changes are rapid for small sizes and slow down successively. The approach allows for the visualization of allometry and the fitting technique might help in defining the allometric growth pattern, thus contributing to the study of the autoecology of the species and in establishing terms for comparison with other ecologically or phylogenetically related species.

Animals↗
PubMed2001

Cloned pigs generated from cultured skin fibroblasts derived from a H-transferase transgenic boar.

Cloned pigs were produced from cultured skin fibroblasts derived from a H-transferase transgenic boar. One 90 day fetus and two healthy piglets resulted from nuclear transfer by fusion of cultured fibroblasts with enucleated oocytes. The cells used in these studies were subjected to an extensive culture time, freezing and thawing, and clonal expansion from single cells prior to nuclear transfer. PCR and FACS analysis determined that the cloned offspring contained and expressed the H-transferase transgene. Microsatellite analysis confirmed that the clones were genetically identical to the boar. The cell culture and nuclear transfer procedures described here will be useful for applications requiring multiple genetic manipulations in the same animal.

Animals↗
PubMed2001

Development of two real-time quantitative TaqMan PCR assays to detect circulating Aspergillus fumigatus DNA in serum.

Several PCR assays have been developed for detecting Aspergillus fumigatus DNA in blood of patients with invasive aspergillosis. However, the best blood fraction to be assayed has not been defined and the multicopy genes used as the DNA targets for amplification not characterized. Firstly, we developed a real-time PCR assays based on the TaqMan technology targeted to a single copy gene. To compare serum, white cell pellet, and plasma for effectiveness as blood assay fractions, we spiked whole blood with A. fumigatus DNA and processed these fractions similarly. The difference between white cell pellet and serum was not significant. In contrast, the yield from plasma was 10 times lower than from serum. Then, we compared serum processed immediately or after 24 h at room temperature and observed a lower yield after 24 h. Secondly, a real-time PCR assay targeted to a mitochondrial gene was also developed. The copy number was estimated between 9 and 10 mitochondrial genes per single copy gene. Therefore, we recommend serum, stored and frozen as soon as possible, to be used for detecting circulating A. fumigatus DNA for diagnosis. Moreover, the mitochondrial multicopy gene was characterized in order to compare results from different patients.

Aspergillosis↗
PubMed2001

Reduced sun exposure and tanning in children after 2 years of a school-based intervention (Australia).

OBJECTIVE: This paper presents the results of the evaluation of measured suntan and parent-reported sun exposure in participating children after 2 years of the Kidskin study, a 5-year school-based sun protection intervention undertaken in Perth, Western Australia (1995-1999). METHODS: The study involves three groups: a control, a "moderate", and a "high" intervention group. Participants were 5 or 6 years of age at the beginning of the study. Control schools received the standard Health Education curriculum, while intervention schools received a multicomponent intervention including a specially designed curriculum. Children in the high intervention group also received program materials over the summer vacation and were offered sun-protective swimwear at low cost. At the end of the second summer, suntan was measured and parents completed a questionnaire about their child's sun-related behavior. RESULTS: Children in the intervention groups--especially the high group--were less tanned at the end of the summer; this effect was greater for the back than for the forearms. These children were also reported to have received less sun exposure and made greater use of sun protection measures. CONCLUSION: Intensive school-based interventions can reduce tanning and reported sun exposure in children.

Child↗
PubMed2001

Impaired recruitment of bone-marrow-derived endothelial and hematopoietic precursor cells blocks tumor angiogenesis and growth.

The role of bone marrow (BM)-derived precursor cells in tumor angiogenesis is not known. We demonstrate here that tumor angiogenesis is associated with recruitment of hematopoietic and circulating endothelial precursor cells (CEPs). We used the angiogenic defective, tumor resistant Id-mutant mice to show that transplantation of wild-type BM or vascular endothelial growth factor (VEGF)-mobilized stem cells restore tumor angiogenesis and growth. We detected donor-derived CEPs throughout the neovessels of tumors and Matrigel-plugs in an Id1+/-Id3-/- host, which were associated with VEGF-receptor-1-positive (VEGFR1+) myeloid cells. The angiogenic defect in Id-mutant mice was due to impaired VEGF-driven mobilization of VEGFR2+ CEPs and impaired proliferation and incorporation of VEGFR1+ cells. Although targeting of either VEGFR1 or VEGFR2 alone partially blocks the growth of tumors, inhibition of both VEGFR1 and VEGFR2 was necessary to completely ablate tumor growth. These data demonstrate that recruitment of VEGF-responsive BM-derived precursors is necessary and sufficient for tumor angiogenesis and suggest new clinical strategies to block tumor growth.

Animals↗
PubMed2001

The effect of oxygen on methanol oxidation by an obligate methanotrophic bacterium studied by in vivo (13)C nuclear magnetic resonance spectroscopy.

13C NMR was used to study the effect of oxygen on methanol oxidation by a type II methanotrophic bacterium isolated from a bioreactor in which methane was used as electron donor for denitrification. Under high (35-25%) oxygen conditions the first step of methanol oxidation to formaldehyde was much faster than the following conversions to formate and carbon dioxide. Due to this the accumulation of formaldehyde led to a poisoning of the cells. A more balanced conversion of (13)C-labelled methanol to carbon dioxide was observed at low (1-5%) oxygen concentrations. In this case, formaldehyde was slowly converted to formate and carbon dioxide. Formaldehyde did not accumulate to inhibitory levels. The oxygen-dependent formation of formaldehyde and formate from methanol is discussed kinetically and thermodynamically.

Journal Article↗
PubMed2001

Neuronal migration defects in the Dreher (Lmx1a) mutant mouse: role of disorders of the glial limiting membrane.

Dreher (dr(J)) is an autosomal recessive mutation in the newly identified LIM homeobox gene, Lmx1a. The homozygous mutant phenotype includes misplaced neurons (heterotopia) in the cerebral cortex, cerebellum and hippocampus, which mimic the mild end of the spectrum of neuronal migration disorders in humans. Heterotopic neurons are found mainly in the normally cell-sparse layer I within the cerebral hemispheres of dr(J) homozygotes. Neu-N immunostaining confirms the neuronal nature of these heterotopic cells, while bromodeoxyuridine-birthdating shows that the misplaced neurons are generated predominantly during the late stages of corticogenesis (E15-E17), suggesting an over-migration of neurons destined for layer II. Immunohistochemistry for laminin, and staining of reticulin fibres, reveals disruption of the glial limiting membrane specifically overlying the areas of heterotopic neurons. Factor VIII (von Willebrand factor) staining shows an abnormal vascular network in layer I, associated with the fragmented glial limiting membrane. Layer I astrocytes, recognized by immunostaining for glial fibrillary acidic protein, exhibit attachment of their end feet to the fragmented glial limiting membrane. We suggest that disruption of the glial limiting membrane is central to the pathogenesis of heterotopic neurons in dreher, perhaps via defective radial glial-guided neuronal migration.

Animals↗
PubMed2001

Quantitative phalangeal bone ultrasound is normal after long-term gluten-free diet in young coeliac patients.

BACKGROUND AND AIMS: To determine bone mass using quantitative phalangeal bone ultrasound in young coeliac patients after a long-term gluten-free diet. SUBJECTS: A total of 99 patients with coeliac disease (CD) (52 girls, mean age 15.5 +/- 9.7 years; 47 boys, mean age 14.4 +/- 8.4 years) and 44 healthy subjects matched for age, weight and height (26 girls, mean age 18.4 +/- 9.9 years; 18 boys, mean age 16.3 +/- 11.2 years) were included in the study. METHODS: Bone status was assessed using an ultrasound device that measures amplitude-dependent speed of sound (Ad-SoS) in metres per second. Measurements were made on the phalanges (II-V) of the non-dominant hand, and an average value was computed. Nutrient intake was assessed using a 7-day record. RESULTS: Analysis of variance (ANOVA) and the unpaired t-test showed that the intake of phosphates (P < 0.05), proteins, fat and carbohydrates (P < 0.005 in all) was higher in patients than in controls. No significant difference in Ad-SoS was found between patients and controls (95% CI -10.9 to 60.6) in the overall group, in girls or boys, or in patients following a gluten-free diet strictly or partially. In the patients, only age (beta 4.01, 95% CI 1.84-6.16, P < 0.0005) and weight (beta 2.62, 95% CI 1.53-3.70, P < 0.0001) showed a significant positive relation with Ad-SoS. CONCLUSIONS: In patients with CD, gluten-free diet and increased nutritional intake were accompanied by normal bone mass values as determined by ultrasound on phalanges.

Adolescent↗
PubMed2001

Analysis of microsatellite markers of Candida albicans used for rapid typing.

To obtain a rapid genotyping method of Candida albicans, three polymorphic microsatellite markers were investigated by multiplex PCR. The three loci, called CDC3, EF3, and HIS3, were chosen because they are on different chromosomes so as to improve the chances of finding polymorphisms. One set of primers was designed for each locus, and one primer of each set was dye-labeled to read PCR signals by using an automatic sequencer. Amplifications were performed directly from the colonies harvested on the agar plate without a sophisticated DNA extraction step. At total of 27 reference strains and 73 clinical independent isolates were tested. The numbers of allelic associations were 10, 22, and 25 for the loci CDC3, EF3, and HIS3, respectively. The combined discriminatory power of the three microsatellites markers was 0.97. The markers were stable after 25 subcultures, and the amplifications were specific for C. albicans. An initial study of 17 clinical isolate pairs, including blood culture and peripheral sites, showed a similar genotype for 15 of them, confirming that candidemia usually originates from the colonizing isolate. Therefore, microsatellite marker analysis with multiplex PCR and automated procedures has a high throughput and should be suitable for large epidemiologic studies of C. albicans.

Candida albicans↗
PubMed2001

Centrifugal pump and reduction of neurological risk in adult cardiac surgery.

This study was performed to assess if the kind of pump used for CPB (roller vs. centrifugal) can influence neurological outcomes of adult cardiac surgery patients. Between 1994 and 1998, 3438 patients underwent coronary and/or valve surgery at our hospital; of these, 1805 (52.5%) underwent surgery with the use of a centrifugal pump, and 1633 (47.5%) were operated with a roller pump. The effect of the type of the pump and of common preoperative and intraoperative risk factors for five different neurological outcomes (permanent neurological deficit, coma, delirium, transient neurological deficit, overall neurological complications) were assessed with univariate and multivariate analyses in the whole patients population, in patients > or = 75 years old and in patients with histories of previous neurological events. Centrifugal pump use was the only protective factor for perioperative permanent neurological deficit in multivariable models developed for the whole patient population and for patients > or = 75 years old. In addition, it resulted as the only protective factor for perioperative coma occurrence in multivariable models developed for patients > or = 75 years old, and for patients with histories of previous neurological events. The use of the centrifugal pump provided a risk reduction for the considered events ranging from 23 to 84%. Centrifugal pump use can be helpful in reducing the occurrence of some of the most feared neurological complications of adult cardiac surgery patients.

Aged↗
PubMed2000

Characteristics of L-glutamine transport during Caco-2 cell differentiation.

Glutamine is the main fuel of intestinal epithelial cells, as well as a precursor for the intense nucleotide biosynthesis which arises with the rapid turnover of enterocytes. In order to determine whether glutamine uptake may vary as a function of metabolic demand, glutamine transport across the brush-border membrane of differentiating Caco-2 cells has been investigated. The uptake of L-[(3)H]glutamine was measured between day 7 and day 21 post-seeding. Kinetic analysis with glutamine concentrations ranging from 6.25 microM to 12.8 mM revealed the involvement of high affinity Na(+)-dependent (K(t)=110 microM) and low affinity Na(+)-independent (K(t)=900 microM) transport components at day 7. Both components were partially inhibited by L-lysine in a competitive fashion, suggesting that four different systems were responsible for glutamine uptake: B(0), B(0,+), b(0,+) and L. All four systems were present during the differentiation process, with systems L and B(0) being responsible for up to 80% of glutamine uptake. Caco-2 cell differentiation was associated with a marked decrease in L-glutamine uptake, which affected both the Na(+)-dependent and the Na(+)-independent components. In contrast to glucose uptake, the development of L-glutamine uptake across the brush-border membrane of Caco-2 cells may reflect an adjustment to cell metabolic demand rather than the progressive appearance of a vectorial transport process.

Binding, Competitive↗
PubMed2000

Significant role for Fas in the pathogenesis of autoimmune diabetes.

Programmed cell death represents an important pathogenic mechanism in various autoimmune diseases. Type I diabetes mellitus (IDDM) is a T cell-dependent autoimmune disease resulting in selective destruction of the beta cells of the islets of Langerhans. beta cell apoptosis has been associated with IDDM onset in both animal models and newly diagnosed diabetic patients. Several apoptotic pathways have been implicated in beta cell destruction, including Fas, perforin, and TNF-alpha. Evidence for Fas-mediated lysis of beta cells in the pathogenesis of IDDM in nonobese diabetic (NOD) mice includes: 1) Fas-deficient NOD mice bearing the lpr mutation (NOD-lpr/lpr) fail to develop IDDM; 2) transgenic expression of Fas ligand (FasL) on beta cells in NOD mice may result in accelerated IDDM; and 3) irradiated NOD-lpr/lpr mice are resistant to adoptive transfer of diabetes by cells from NOD mice. However, the interpretation of these results is complicated by the abnormal immune phenotype of NOD-lpr/lpr mice. Here we present novel evidence for the role of Fas/FasL interactions in the progression of NOD diabetes using two newly derived mouse strains. We show that NOD mice heterozygous for the FasL mutation gld, which have reduced functional FasL expression on T cells but no lymphadenopathy, fail to develop IDDM. Further, we show that NOD-lpr/lpr mice bearing the scid mutation (NOD-lpr/lpr-scid/scid), which eliminates the enhanced FasL-mediated lytic activity induced by Fas deficiency, still have delayed onset and reduced incidence of IDDM after adoptive transfer of diabetogenic NOD spleen cells. These results provide evidence that Fas/FasL-mediated programmed cell death plays a significant role in the pathogenesis of autoimmune diabetes.

Adoptive Transfer↗
PubMed2000

Denitrification with methane as electron donor in oxygen-limited bioreactors.

The microbial population from a reactor using methane as electron donor for denitrification under microaerophilic conditions was analyzed. High numbers of aerobic methanotrophic bacteria (3 10(7) cells/ml) and high numbers of acetate-utilizing denitrifying bacteria (2 10(7) cells/ml) were detected, but only very low numbers of methanol-degrading denitrifying bacteria (4 10(4) cells/ml) were counted. Two abundant acetate-degrading denitrifiers were isolated which, based on 16S rRNA analysis, were closely related to Mesorhizobium plurifarium (98.4% sequence similarity) and a Stenotrophomonas sp. (99.1% sequence similarity). A methanol-degrading denitrifying bacterium isolated from the bioreactor morphologically resembled Hyphomicrobium sp. and was moderately related to H. vulgare (93.5% sequence similarity). The initial characterization of the most abundant methanotrophic bacterium indicated that it belongs to class II of the methanotrophs. "In vivo" 13C-NMR with concentrated cell suspensions showed that this methanotroph produced acetate under oxygen limitation. The microbial composition of reactor material together with the NMR experiments suggest that in the reactor methanotrophs excrete acetate, which serves as the direct electron donor for denitrification.

Anaerobiosis↗
PubMed2000

Crystallization and preliminary X-ray analysis of a membrane-bound nitrite reductase from Desulfovibrio desulfuricans ATCC 27774.

Nitrite reductase from the sulfate-reducing bacterium Desulfovibrio desulfuricans ATCC 27774 is a multihaem (type c) membrane-bound enzyme that catalyzes the dissimilatory conversion of nitrite to ammonia. Crystals of the oxidized form of this enzyme were obtained using PEG and CaCl(2) as precipitants in the presence of 3--(decylmethylammonium)propane-1-sulfonate and belong to the space group P2(1)2(1)2(1), with unit-cell parameters a = 78.94, b = 104.59, c = 143.18 A. A complete data set to 2.30 A resolution was collected using synchrotron radiation at the ESRF. However, the crystals may diffract to beyond 1.7 A and high-resolution data will be collected in the near future.

Bacterial Proteins↗
PubMed2000

Improved sun protection behaviour in children after two years of the Kidskin intervention.

OBJECTIVE: To evaluate a school-based intervention in terms of reducing children's sun exposure and improving their use of sun protection measures. METHODS: 'Kidskin' is a five-year, school-based intervention study in Perth, Western Australia, of a cohort of children who were five or six years old in 1995. The study involves three groups: control, 'moderate' and 'high' intervention. Children in the control schools received the standard health curriculum; those in the intervention schools received a multicomponent intervention, including a specially designed curriculum. Children in the high intervention group also received program materials over the summer holidays and were offered sun-protective swimwear at a low cost. After two years, parents completed a questionnaire about their child's sun-related behavior. RESULTS: Children in the intervention groups--especially the 'high' group--were reported to have had less sun exposure. This involved covering the back more often, spending more time in the shade when outdoors and wearing a style of swimsuit that covered the trunk. There was also evidence that children in the intervention groups spent less time outdoors in the middle of the day. There was little difference between groups in the wearing of hats or sunscreen. CONCLUSIONS: Our school-based intervention improved children's sun protection, but had little effect on specific behaviours that have already been vigorously promoted. IMPLICATIONS: School-based prevention campaigns would benefit from focusing on sun protection using clothing and shade, and reducing sun exposure in the middle of the day. There may be little potential to improve hat and sunscreen use.

Child↗