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Biomedical subjects

R Costa

Publications and source records attributed to R Costa.

At least 19 recordsLinked to original sources
PubMed1999

Hospitalization and Alzheimer's disease: results from a community-based study.

BACKGROUND: Prior studies offer conflicting findings on whether Alzheimer's disease (AD) is associated with an increased risk of hospitalization. METHODS: We investigated AD and hospitalization in the Washington Heights-Inwood Columbia Aging Project (WHICAP), a community-based study of 2,334 elders in New York City. In 1996, an electronic medical records system was established that allows an e-mail alert to be sent to the research team whenever WHICAP subjects are admitted to Columbia-Presbyterian Medical Center (CPMC), the site of hospital care for the majority of subjects. RESULTS: Of the WHICAP cohort, 13.1% was admitted to CPMC in 21 months of follow-up; 17.5% of AD patients and 11.9% of unaffected subjects were admitted (p<.01). Multivariate logistic regression models showed that more advanced AD (Clinical Dementia Rating scale 3+) was a significant risk factor for hospitalization independently of age, gender, education, comorbid medical conditions, and death in the follow-up period (OR 2.3; 95% CI: 1.1, 4.6); subjects with mild or moderate AD did not show a significantly elevated risk. The prevalence of psychiatric symptoms did not differ between AD subjects who were hospitalized in the reporting period and AD subjects who were not hospitalized. Infectious disease was a more common discharge diagnosis for subjects with AD (p<.05). CONCLUSIONS: In this community-based cohort, subjects with severe AD were more likely to be hospitalized than unaffected subjects. The increased use of hospital care by these AD patients appears to be specific to AD but is not a result of psychiatric morbidity or end-of-life care. Rather, a greater risk of medical complications that require hospital care, especially infections, appears to be characteristic of severe AD.

Age Factors↗
PubMed1999

Functional reduction and associated cellular rearrangement in SHRSP rat basilar arteries are affected by salt load and calcium antagonist treatment.

The stroke-prone spontaneously hypertensive rat (SHRSP) is a strain with high incidence of cerebrovascular accidents increased by salt-rich diet and decreased by calcium-antagonist treatment. In the SHRSP rat basilar artery the authors have previously shown reduced contractility and altered structure including regions of smooth muscle cell (SMC) disorganization. The aims of this study have been to analyze (1) the morphology of these abnormal regions, (2) the structural modifications responsible for the reduced function, and (3) the effect of salt and calcium-antagonist treatment on vascular structure and function. Wistar Kyoto and SHRSP rats, untreated or treated from week 8 through 14 with 1% NaCl or 1% NaCl + 1 mg x kg(-1) x d(-1) lacidipine, were used. Function was studied with wire myography. Structure was analyzed in fixed intact arteries with confocal microscopy. Basilar arteries from SHRSP rat showed (1) reduced contractility, (2) discrete foci of SMC disarray with altered proportion of adventitia to SMC, and (3) decreased SMC and increased adventitial cell number. Arteries from salt-loaded SHRSP rats showed a higher degree of SMC disarray and further reduction in contractility. Lacidipine treatment of salt-loaded rats significantly improved structure and function. These data suggest that vascular remodeling can provide an explanation for the observed reduction in vascular contractility of SHRSP rat basilar arteries and might show light on the effects of salt load and calcium-channel blockers in life span and the incidence of cerebrovascular accidents in SHRSP rats.

Animals↗
PubMed1998

Molecular coevolution within a Drosophila clock gene.

The period (per) gene in Drosophila melanogaster provides an integral component of biological rhythmicity and encodes a protein that includes a repetitive threonine-glycine (Thr-Gly) tract. Similar repeats are found in the frq and wc2 clock genes of Neurospora crassa and in the mammalian per homologues, but their circadian functions are unknown. In Drosophilids, the length of the Thr-Gly repeat varies widely between species, and sequence comparisons have suggested that the repeat length coevolves with the immediately flanking amino acids. A functional test of the coevolution hypothesis was performed by generating several hybrid per transgenes between Drosophila pseudoobscura and D. melanogaster, whose repetitive regions differ in length by about 150 amino acids. The positions of the chimeric junctions were slightly altered in each transgene. Transformants carrying per constructs in which the repeat of one species was juxtaposed next to the flanking region of the other were almost arrhythmic or showed a striking temperature sensitivity of the circadian period. In contrast, transgenes in which the repeat and flanking regions were conspecific gave wild-type levels of circadian rescue. These results support the coevolutionary interpretation of the interspecific sequence changes in this region of the PER molecule and reveal a functional dimension to this process related to the clock's temperature compensation.

Amino Acid Sequence↗
PubMed1998

Effect of pharmacologically induced changes in milk ejection on suckling in Bos taurus.

This experiment was to test the hypothesis that suckling behavior in Bos taurus is related to milk ejection. Intra-gland milk transport was manipulated by applying four different treatments to four cow-calf pairs: T1, injection of oxytocin during the post-stimulation period; T2, injection of oxytocin before a meal; T3, injection of saline solution at the same times as oxytocin was applied (control) in T1 and T2; T4, injection of an oxytocin antagonist in a similar way as T1. Drugs were applied i.v. and by remote control in order to prevent the animals from noticing the injection. All non-control treatments resulted in significant changes in the time calves spent performing uninterrupted suckling at a specific teat.

Animals↗
PubMed1998

Functional and evolutionary implications of natural variation in clock genes.

Nearly all studies of natural variation within clock genes involve the period (per) locus, which was originally isolated in the fruit-fly. Intra- and interspecific work on per has focused mostly on a region of Thr-Gly or Ser-Gly repeats, which show rapid length and sequence evolution. The functional implications of nucleotide variation in this repetitive array have been characterised using behavioural, molecular, ecological, structural and statistical analyses. A population genetics approach to variation in per has also been useful in defining species histories within Drosophilids and, in some cases, in implicating selective processes in the evolution of the per gene. Interspecific analysis of per expression patterns reveals evolutionary alterations in this clock gene's regulation.

Animals↗
PubMed1998

Ventricular arrhythmias in normotensive subjects and in mild hypertensive patients.

Twenty-five normotensive subjects (14 men, 11 women) aged from 25 to 60 years (mean 36) and 30 untreated patients with mild hypertension (stages 1 and 2, JNC V) without target organ damage (16 men, 14 women), aged 26-59 years (mean 35.8) underwent continuous 24-hour ECG Holter monitoring with a Fukuda Denshi SM-40 ambulatory recorder and SCM-400 ECG analyzer. During 24-hour ambulatory ECG recording, mean heart rate was slightly but not significantly higher in hypertensive patients (73.3 +/- 10 beats per minute [bpm]) in comparison with normotensive subjects (71.2 +/- 12 bpm). The prevalence of premature atrial contractions was similar in the two groups. Total ventricular arrhythmias were more prevalent in the group of mild hypertensive patients (P < 0.05), who also had a higher prevalence in complex forms of ectopy (r = 0.81 for bigeminy; r = 0.83 for trigeminy; r = 0.83 for couplets). Holter recordings did not show abnormalities of ST-T wave or episodes of silent ischemia.

Adult↗
PubMed1998

[Catheterization of the subclavian vein through the cannulation of the external jugular vein. Our experience].

UNLABELLED: The cannulation technique of the subclavian vein by the external jugular vein is described. OBJECTIVE: To point out this simple and safe method without complications deriving from the direct needle-prick of the subclavian vein. METHODS: Experimental plan. The comparative study includes 30 patients in the resuscitation department during the second half-year in 1996. Place. Resuscitation Department of the University Polyclinic in Palermo. Patients. 30% of these patients were male and 70% were female; coagulative serious disorders were present in some patients, in others the coagulative picture was unknown. Interventions and observations. The modified Seldinger technique has ben used, introducing a J wire through the needle cannula put in the external jugular vein, taking care not to exceed the length of the latter with the J wire. Less rigid and small catheters have been used which can fluctuate in the running blood and be carried in the superior vein cava. Once the subclavian vein has been cannulated, a Rx graph control of the thorax was made, showing the excellent position of the catheter. RESULTS: Only one failure, but this technique has not showed complications. CONCLUSIONS: This technique finds applications in all situations of extreme emergency, in which on the one hand it needs a central blood vessel, on the other there are hemorrhagic problems or there isn't any possibility to do a coagulative screening in short time.

Aged↗
PubMed1997

Natural variation in a Drosophila clock gene and temperature compensation.

The threonine-glycine (Thr-Gly) encoding repeat within the clock gene period of Drosophila melanogaster is polymorphic in length. The two major variants (Thr-Gly)17 and (Thr-Gly)20 are distributed as a highly significant latitudinal cline in Europe and North Africa. Thr-Gly length variation from both wild-caught and transgenic individuals is related to the flies' ability to maintain a circadian period at different temperatures. This phenomenon provides a selective explanation for the geographical distribution of Thr-Gly lengths and gives a rare glimpse of the interplay between molecular polymorphism, behavior, population biology, and natural selection.

Alleles↗
PubMed1997

The bacteriophage T7 binary system activates transient transgene expression in zebrafish (Danio rerio) embryos.

The bacteriophage T7 binary expression system is widely used in vitro for high level selective expression of cloned genes but its application to in vivo models has not yet been investigated. In the present work, we show that coinjection into fertilized zebrafish eggs of pE1T7R, an expression plasmid bearing the T7 RNA polymerase gene driven by the cytomegalovirus (CMV) promoter, together with reporter vectors containing the Escherichia coli lacZ gene driven by the T7 promoter, resulted in the efficient expression of the reporter gene in 24-h mosaic transgenic embryos. Conversely, embryos receiving an unrelated CMV-expression plasmid, instead of pE1T7R, lacked significant reporter gene activity, indicating the strict requirement of T7 polymerase to activate the T7 promoter in these embryos. The present study demonstrates the possibility of applying efficiently the bacteriophage T7 binary system in vivo to a vertebrate model.

Animals↗
PubMed1997

Conceptual translation of timeless reveals alternative initiating methionines in Drosophila.

We have sequenced genomic fragments which encode the N-terminus of the TIMELESS (TIM) clock protein in Drosophila simulans and D. yakuba. We observe that in these two species, the initiating methionine appears to lie downstream of the one proposed to encode the translational start inD.melanogaster, thereby truncating the N-terminus by 23 amino acids. We then sequenced the corresponding 5'fragment in a number of D. melanogaster individuals from different strains. We observed a polymorphism which strongly suggests that the originally proposed start site cannot be utilised in some individuals, and that these flies will initiate translation of TIM at the downstream ATG. Given the current interest in TIM regulation in D. melanogaster, it is important to correctly define the N-terminus in this species.

Alternative Splicing↗
PubMed1997

Linkage disequilibrium, mutational analysis and natural selection in the repetitive region of the clock gene, period, in Drosophila melanogaster.

We have used the method of disequilibrium pattern analysis to examine associations between the threonine-glycine (Thr-Gly) encoding repeat region of the clock gene period (per) of Drosophila melanogaster, and polymorphic sites both upstream and downstream of the repeat, in a number of European fly populations. The results are consistent with the view that selection may be operating on various haplotypes which share the Thr-Gly length alleles encoding 17, 20 and 23 dipeptide pairs, and that the repeat itself may be the focus for selection. These conclusions lend support to a number of other population and behavioural investigations which have provided evidence that selection is acting on the Thr-Gly region. The linkage analysis was also used to infer an approximate mutation rate (mu) for the repeat, of 10(-5) < mu < 4 x 10(-5) per gamete per generation. Direct measurements of the mutation rate using the polymerase chain reaction in a pedigree analysis of tens of thousands of individuals do not contradict this value. Consequently, the Thr-Gly repeat does not have a mutation rate that is as high as some of the non-coding minisatellites, but it is several orders of magnitude higher than the nucleotide substitution rate. The implications of this elevated mutation rate for linkage disequilibria and selection are discussed.

Alleles↗
PubMed1997

Minimizing interferences in the quantitative multielement analysis of trace elements in biological fluids by inductively coupled plasma mass spectrometry.

The determination of trace and ultratrace elements in biological fluids, including urine and serum, by inductively coupled plasma mass spectrometry (ICP-MS) is discussed. Nonspectral interferences and their corrections by external calibration and calibrator addition are discussed in detail. External calibration with internal calibration and dilution is mostly sufficient to correct for encountered biological matrix effects. For some elements, such as Cs and Zn, the use of calibrator addition provides more accurate results. The importance of spectral interferences and their elimination by isotope selection was also studied. Two examples, Cu and Zn, demonstrate the prime importance of selecting an isotope with minimal polyatomic interferences for analysis. By using 65Cu and 68Zn, accurate results for urine and serum can be obtained without excessive pretreatment of samples. Two reference materials, Bio-Rad Lyphochek urine and Kaulson Contox sera, were analyzed. Accuracy was evaluated by comparison with target values, and precision was estimated by the CV within 95% confidence.

Calibration↗
PubMed1996

Genesis, a winged helix transcriptional repressor with expression restricted to embryonic stem cells.

A novel member of the winged helix (formerly HNF-3/Forkhead) transcriptional regulatory family, termed Genesis, was isolated and characterized. Putative translation of the complete cDNA revealed the winged helix DNA binding domain to be centrally located within the protein, with regions on either side that contain known transcriptional regulatory motifs. Extensive Northern analysis of Genesis found that the message was exclusively expressed in embryonic stem cells or their malignant equivalent, embryonal carcinoma cells. The Genesis transcript was down-regulated when these cells were stimulated to differentiate. DNA sequences that Genesis protein would interact with were characterized and were found to contain a consensus similar to that found in an embryonic stem cell enhancer sequence. Co-transfection experiments revealed that Genesis is a transcriptional repressor. Genesis mapped to mouse chromosome 4 in a region syntenic with human chromosome 1p31, a site of nonrandom abnormalities in germ cell neoplasia, neuroblastoma, and acute lymphoblastic leukemia. Genesis is a candidate for regulating the phenotype of normal or malignant embryonic stem cells.

Amino Acid Sequence↗
PubMed1996

Control of apolipoprotein AI gene expression through synergistic interactions between hepatocyte nuclear factors 3 and 4.

Apolipoprotein AI (apoAI) gene expression in liver depends on synergistic interactions between transcription factors bound to three distinct sites (A, B, and C) within a hepatocyte-specific enhancer in the 5'-flanking region of the gene. In this study, we showed that a segment spanning sites A and B retains substantial levels of enhancer activity in hepatoblastoma HepG2 cells and that sites A and B are occupied by the liver-enriched hepatocyte nuclear factors (HNFs) 4 and 3, respectively, in these cells. In non-hepatic CV-1 cells, HNF-4 and HNF-3beta activated this minimal enhancer synergistically. This synergy was dependent upon simultaneous binding of these factors to their cognate sites, but it was not due to cooperativity in DNA binding. Separation of these sites by varying helical turns of DNA did not affect simultaneous binding of HNF-3beta and HNF-4 nor did it influence their functional synergy. The synergy was, however, dependent upon the cell type used for functional analysis. In addition, this synergy was further potentiated by estrogen treatment of cells cotransfected with the estrogen receptor. These data indicate that a cell type-restricted intermediary factor jointly recruited by HNF-4 and HNF-3 participates in activation of the apoAI enhancer in liver cells and suggest that the activity of this factor is regulated by estrogen.

Animals↗
PubMed1996

Mutational mechanisms, phylogeny, and evolution of a repetitive region within a clock gene of Drosophila melanogaster.

The D. melanogaster clock gene period (per) is an internally repetitive gene encoding a tandem array of Thr-Gly codons that are highly polymorphic in length in European natural populations. The two major length variants, (Thr-Gly)20 and (Thr-Gly)17, show a highly significant latitudinal cline. In this study we present the complete sequence of the Thr-Gly region of 91 individuals from 6 natural populations of D. melanogaster, 5 from Europe and 1 from North Africa. We further characterized these 91 individuals for polymorphic sites in two other regions, one upstream and one downstream of the Thr-Gly repeat. We used the haplotypic combinations of Thr-Gly allele with flanking markers in an attempt to identify the mechanisms involved in the evolution of the D. melanogaster Thr-Gly region and to infer the phylogenetic relationship existing among the Thr-Gly alleles. We observe evidence for both intra- and interallelic mutational mechanisms, including replication slippage, unequal crossing-over, and gene conversion.

Africa, Northern↗
PubMed1996

[Effects of Sjögren's syndrome on pulmonary function impairment in patients with rheumatoid arthritis].

The influence of Sjögren syndrome (SS) on pulmonary function impairment in rheumatoid arthritis (RA) patients has been few studied. The aim of this study was to analyse the pulmonary function impairment in RA patients, and to establish differences between patients associated or not to SS. Pulmonary function of 57 patients, non smokers and without another pulmonary disease, diagnosed of RA were studied. Fourteen (24.6%) were associated to SS, and 43 (75.4%) to RA without SS. Age and time of evolution of disease were similar. Eight patients with associated SS (57.2%), and in 20 (46.5%) without SS showed pulmonary function disorder. Airflow obstruction and DLCO diminution were the most common types of impairment, respectively. The comparison between the types of impairment and the mean values of FEVI, FVC, FEVI/FVC %, FEF 25-75 and DLCO were not statistical different. This results suggest a poor influence on pulmonary function impairment in RA patients with SS.

Aged↗
PubMed1996

[Usefulness of DR, PGRS, and spoligotyping in the typing of Mycobacterium tuberculosis. Comparison with IS6110].

BACKGROUND: To evaluate 4 markers (IS6110, DR, PGRS and spoligotyping) to differentiate the strains of Mycobacterium tuberculosis isolated in our surroundings, most specially in those which contain a reduced number of IS6110 copies. In addition, to confirm the identity of the strains that share the same IS6110 restriction-hybridization pattern. METHODS: We selected 37 strains from a previous study: 25 had a unique IS6110 pattern and 12 grouped in 3 clusters (8 strains with 11 bands, 2 with 17 bands and 2 which shared the same six-band pattern). The PGRS and DR-RFLPs were obtained by AluI restriction and synthetic oligonucleotides specific to these sequences. The polymorphism of the DR region spacers was analyzed by spoloigotyping. For the amplification of the spacers we used the DRa and DRb primers. Detection was done hybridizing the PCR products on a membrane in which 43 specific spacers had been previously immobilized. RESULTS: Twenty-three different PGRS patterns and 18 spolygotyping patterns were obtained from 25 strains with unique IS6110 pattern. Eight patterns resulted from the 10 strains studied by DR. The 8 strains which shared an 11-band pattern, as well as the 2 strains which shared a 17-band pattern, resulted identical by the other markers. However, 2 strains which shared a 6-band pattern were different by both PGRS and DR or spoligotyping. CONCLUSIONS: 1) IS6110 resulted the most discriminative marker of all. 2) The clonality of clusters with a low number of bands has to be confirmed with alternative markers.

Bacterial Typing Techniques↗