A second timeless gene in Drosophila shares greater sequence similarity with mammalian tim.
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Amino Acid Sequence↗
Biomedical subjects
R Costa
Publications and source records attributed to R Costa.
Hydrops fetalis associated with erythrocyte pyruvate kinase deficiency.
UNLABELLED: The authors report a case of hydrops fetalis due to severe pyruvate kinase deficiency, the most unusual clinical manifestation of this disease. CONCLUSION: Pyruvate kinase deficiency, as other erythrocyte enzymopathies, must be considered in the differential diagnosis of non-immune hydrops fetalis. This has important implications for clinical investigations, therapy and genetic counselling.
Anemia, Hemolytic, Congenital Nonspherocytic↗
Comparison of representative ranges based on U.S. patient population and literature reference intervals for urinary trace elements.
Reference intervals for trace elements are very hard to obtain because of the difficulty of defining a nonexposed reference population. However, representative ranges for trace elements obtained from a general patient population can provide useful information in interpreting laboratory results. We have used urine specimens submitted for trace metal analysis from patients residing in the United States to calculate representative ranges for 25 urinary trace elements, and to compare them to reference values taken from the literature. All urine analytes were measured by inductively-coupled plasma-mass spectrometry except chromium, which was measured by graphite furnace atomic absorption spectroscopy. For representative range calculation two approaches were used. In the non-parametric calculation first, the top 10% of results were discarded assuming that those specimens came from individuals with unusually high trace element exposures. Next the central 95% of the remaining data was taken as the reference interval. In the parametric calculation the specimens from exposed or not healthy individuals were assumed to appear as outliers and were discarded. The mean and S.D. were calculated, and used to determine representative ranges. The two approaches yielded very similar results, and worked remarkably well for 14 analytes. There were minor discrepancies for 7 analytes, and major for 4 analytes. All analyses of urinary trace elements included a urine creatinine value, which was used to express urinary trace element concentrations in terms of creatinine ratio. This corrects for differences in urine concentration that affects the results for random specimens.
Aging↗
Effect of long-term losartan administration on renal haemodynamics and function in hypertensive patients.
In this study the efficacy and safety of long-term losartan administration on renal haemodynamics were evaluated in mild to moderate hypertension. After a run-in period with placebo, 18 hypertensives without renal or cardiovascular disease were allocated to losartan (50 mg/die for one year) treatment. Renal haemodynamic measurements included renal plasma flow (ERPF) and glomerular filtration rate (GFR) by standardized radioisotope study. Effective renal blood flow (ERBF), filtration fraction (FF), and renal vascular resistance (RVR) were also calculated. Blood pressure was evaluated monthly, whereas renal haemodynamics and function were detected at baseline and after 6 and 12 months of losartan administration. Losartan induced a significant (p < 0.001) decrease in SBP, DBP, and MBP versus baseline values both at 6 months and at 12 months. In addition a significant decrease in RVR (p < 0.001) and in FF (p < 0.05) was also seen. In addition RVR values at 1 year of treatment were higher than their values at 6 months, but this difference was not significant. Our data indicated that long-term control in blood pressure induced by losartan administration was associated with a maintained renal function after 6 months of treatment, but these favourable effects were attenuated after 1 year of treatment.
Antihypertensive Agents↗
Circadian clocks: what makes them tick?
In the not too distant past, it was common belief that rhythms in the physical environment were the driving force, to which organisms responded passively, for the observed daily rhythms in measurable physiological and behavioral variables. The demonstration that this was not the case, but that both plants and animals possess accurate endogenous time-measuring machinery (i.e., circadian clocks) contributed to heightening interest in the study of circadian biological rhythms. In the last few decades, flourishing studies have demonstrated that most organisms have at least one internal circadian timekeeping device that oscillates with a period close to that of the astronomical day (i.e., 24h). To date, many of the physiological mechanisms underlying the control of circadian rhythmicity have been described, while the improvement of molecular biology techniques has permitted extraordinary advancements in our knowledge of the molecular components involved in the machinery underlying the functioning of circadian clocks in many different organisms, man included. In this review, we attempt to summarize our current understanding of the genetic and molecular biology of circadian clocks in cyanobacteria, fungi, insects, and mammals.
Animals↗
The clock gene period of the housefly, Musca domestica, rescues behavioral rhythmicity in Drosophila melanogaster. Evidence for intermolecular coevolution?
In Drosophila, the clock gene period (per), is an integral component of the circadian clock and acts via a negative autoregulatory feedback loop. Comparative analyses of per genes in insects and mammals have revealed that they may function in similar ways. However in the giant silkmoth, Antheraea pernyi, per expression and that of the partner gene, tim, is not consistent with the negative feedback role. As an initial step in developing an alternative dipteran model to Drosophila, we have identified the per orthologue in the housefly, Musca domestica. The Musca per sequence highlights a pattern of conservation and divergence similar to other insect per genes. The PAS dimerization domain shows an unexpected phylogenetic relationship in comparison with the corresponding region of other Drosophila species, and this appears to correlate with a functional assay of the Musca per transgene in Drosophila melanogaster per-mutant hosts. A simple hypothesis based on the coevolution of the PERIOD and TIMELESS proteins with respect to the PER PAS domain can explain the behavioral data gathered from transformants.
Amino Acid Sequence↗
Phase II study of combined immunotherapy, chemotherapy, and radiotherapy in the postoperative treatment of advanced non-small-cell lung cancer.
The association of adoptive immunotherapy (AI) and radiotherapy has been shown to be effective in the control of residual intrathoracic disease, while having no systemic advantages, in patients operated on for locally advanced non-small-cell lung cancer (NSCLC). The potential synergy of coupling immunotherapy and chemotherapy has been emphasized in several tumors including NSCLC. The aim of this work was to determine the feasibility and activity of a combined therapeutic program, including AI, chemotherapy, and radiotherapy in patients who had undergone incomplete resections for NSCLC. In a phase II trial, 13 patients received the combined treatment. AI was given from week 4 after surgery until week 8. Concurrent chemo-(cisplatin and etoposide)-radiotherapy (60 Gy) was given from week 9 to week 14. Twenty eligible patients received chemoradiotherapy only and were used as a non-randomized concomitant group for merely descriptive purposes. At 9-month follow-up, 10 of the 13 patients had progression of disease and the study was stopped. Progression-free survival and survival were similar to those of the chemoradiotherapy group. The present study showed that the sequence of immunotherapy followed by chemotherapy is not effective as adjuvant treatment in patients operated on for stage III NSCLC, at least when used according to the adopted schedule.
Adult↗
Neurohumoral behavior in recipients of cardiac pacemakers controlled by a closed-loop autonomic nervous system-driven sensor.
The purpose of a sensor-driven pacing system is to physiologically correct chronotropic incompetence (CI). The aim of this study was to evaluate the changes in heart rate provided by a sympathetically driven pacemaker (PM) compared with normal sinus function (NSF). Nine men and six women (age 37-80 years) with AV block and a PM controlled by a closed-loop system were studied. Group I included eight patients with CI, and group II included seven patients with NSF. All patients underwent Valsalva maneuver and tilt table testing with measurements of plasma catecholamines and renin activity. Pacing was initially programmed in the DDDC mode at a lower rate (60 ppm) and upper rate limit (0.85 x [220 - age]), then in DDDR in group I and VVIR in group II. The second phase of the study consisted of nitroglycerin and phenylephrine infusions, and the third phase of physiological provocative maneuvers. The second and third phases were performed in three patients from each group with sensor activity On and Off. In group I, heart rate changed during tilt only in the DDDR mode. In group II, heart rate changes were comparable in both modes. Catecholamine levels in group I were higher during DDDC than during DDDR pacing (P < 0.05). In group I, heart rate did not change during phases II and IV of the Valsalva maneuver in the DDDC mode, but behaved nearly physiologically after sensor activation. A late and a paradoxical response to nitroglycerin was observed in groups I and II and to phenylephrine in group I. During physiological maneuvers, significantly greater variations in heart rate were observed during DDDR than during DDDC pacing. Sympathetic SDP provides physiological modulations of the heart rate were provided by a sympathetically driven pacing system in patients with AV block and CI.
Adult↗
Probability of occurrence of life-threatening ventricular arrhythmias in Chagas' disease versus non-Chagas' disease.
The implantable cardioverter defibrillator (ICD) is highly effective in the treatment of ventricular arrhythmias (VA) responsible for sudden cardiac death. However, the probability of occurrence of these arrhythmic events in presence of cardiomyopathy remains uncertain. The aim of this study was to compare the probability of nonoccurrence of life-threatening VA in ICD recipients with Chagas' versus non-Chagas' heart disease. Over a mean follow-up of 10.5 months, 53 ICD recipients (mean age = 50.1 years, 48 male) were evaluated. Eleven patients had Chagas' heart disease, 19 had idiopathic dilated cardiomyopathy and 23 had ischemic cardiomyopathy. Ventricular tachyarrhythmias with a cycle length < 315 ms were considered life-threatening. The cumulative probability of nonoccurrence of life-threatening VA was examined by Kaplan-Meyer method and the outcomes were submitted to the log rank test. At 2 years, the cumulative probability of life-threatening VA nonoccurrence was 0 in the Chagas' heart disease group versus 40% up to 55 months of follow-up in the non-Chagas' disease group (P = 0.0097). Among patients with cardiomyopathies of different etiologies, those with Chagas' heart disease had the lowest cumulative probability of nonoccurrence of life-threatening VA, confirming its unfavorable prognosis and the importance of preventive measures against sudden death in this disease.
Adult↗
Molecular and behavioral analysis of sex-linked courtship song variation in a natural population of Drosophila melanogaster.
Genes controlling the "lovesong" in Drosophila are particularly interesting under a evolutionary point of view as they could be involved in the reproductive isolation between closely related species and, as a consequence, in the speciation process. We carried out a survey of sex-linked molecular and behavioral courtship song variation in 27 lines derived from a natural population of Drosophila melanogaster in Italy. We sequenced a 983 bp fragment of cacophony(cac), a calcium channel gene controlling aspects of the courtship song. The same region was also sequenced in a D. simulans strain. Only 5 non-coding sites were polymorphic among the D. melanogaster lines, and no amino acid substitutions were found between the two species. Statistical tests applied to the data did not reveal any significant deviations from a neutral model. Using the same lines we also carried out an analysis of three different song parameters which are known to be affected by the cac(S) song mutation: interpulse-interval (IPI), pulse amplitude (PA) and cycles per pulse (CPP). We found significant differences among the lines in IPI and PA, and for the latter a significant association with one of the polymorphic sites of cac.
Analysis of Variance↗
Permanent and temporary pacemaker implantation after orthotopic heart transplantation.
PURPOSE:To determine the indication for and incidence and evolution of temporary and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A retrospective review of 114 patients who underwent orthotopic heart transplantation InCor (Heart Institute USP BR) between March 1985 and May 1993. We studied the incidence of and indication for temporary pacing, the relationship between pacing and rejection, the need for pemanent pacing and the clinical follow-up. RESULTS: Fourteen of 114 (12%)heart transplant recipients required temporary pacing and 4 of 114 (3.5%) patients required permanent pacing. The indication for temporary pacing was sinus node dysfunction in 11 patients (78.5%) and atrioventricular (AV) block in 3 patients (21.4%). The indication for permanent pacemaker implantation was sinus node dysfunction in 3 patients (75%) and atrioventricular (AV) block in 1 patient (25%). We observed rejection in 3 patients (21.4%) who required temporary pacing and in 2 patients (50%) who required permanent pacing. The previous use of amiodarone was observed in 10 patients (71.4%) with temporary pacing. Seven of the 14 patients (50%) died during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication for temporary and permanent pacemaker implantation in cardiac transplant recipients. The need for pacing was related to worse prognosis after cardiac transplantation.
Journal Article↗
Permanent and temporary pacemaker implantation after orthotopic heart transplantation
PURPOSE: To determine the indication for and incidence and evolution of temporary and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A retrospective review of 114 patients who underwent orthotopic heart transplantation InCor (Heart Institute USP BR) between March 1985 and May 1993. We studied the incidence of and indication for temporary pacing, the relationship between pacing and rejection, the need for pemanent pacing and the clinical follow-up. RESULTS: Fourteen of 114 (12%) heart transplant recipients required temporary pacing and 4 of 114 (3.5%) patients required permanent pacing. The indication for temporary pacing was sinus node dysfunction in 11 patients (78.5%) and atrioventricular (AV) block in 3 patients (21.4%). The indication for permanent pacemaker implantation was sinus node dysfunction in 3 patients (75%) and atrioventricular (AV) block in 1 patient (25%). We observed rejection in 3 patients (21.4%) who required temporary pacing and in 2 patients (50%) who required permanent pacing. The previous use of amiodarone was observed in 10 patients (71.4%) with temporary pacing. Seven of the 14 patients (50%) died during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication for temporary and permanent pacemaker implantation in cardiac transplant recipients. The need for pacing was related to worse prognosis after cardiac transplantation.
Journal Article↗
Permanent and temporary pacemaker implantation after orthotopic heart transplantation.
PURPOSE: To determine the indication for and incidence and evolution of temporary and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A retrospective review of 114 patients who underwent orthotopic heart transplantation InCor (Heart Institute USP BR) between March 1985 and May 1993. We studied the incidence of and indication for temporary pacing, the relationship between pacing and rejection, the need for permanent pacing and the clinical follow-up. RESULTS: Fourteen of 114 (12%) heart transplant recipients required temporary pacing and 4 of 114 (3.5%) patients required permanent pacing. The indication for temporary pacing was sinus node dysfunction in 11 patients (78.5%) and atrioventricular (AV) block in 3 patients (21.4%). The indication for permanent pacemaker implantation was sinus node dysfunction in 3 patients (75%) and atrioventricular (AV) block in 1 patient (25%). We observed rejection in 3 patients (21.4%) who required temporary pacing and in 2 patients (50%) who required permanent pacing. The previous use of amiodarone was observed in 10 patients (71.4%) with temporary pacing. Seven of the 14 patients (50%) died during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication for temporary and permanent pacemaker implantation in cardiac transplant recipients. The need for pacing was related to worse prognosis after cardiac transplantation.
Adolescent↗
[Guidelines for permanent cardiac pacemaker implantation].
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Arrhythmias, Cardiac↗
[Guidelines for cardioverter defibrillator implantation].
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Defibrillators, Implantable↗
Different period gene repeats take 'turns' at fine-tuning the circadian clock.
The repetitive region of the circadian clock gene period in Drosophila pseudoobscura consists predominantly of a pentapeptide sequence whose consensus is NSGAD. In D. melanogaster, this region is replaced by a dipeptide Thr-Gly repeat, which plays a role in the thermal stability of the circadian phenotype. The Thr-Gly repeat has been shown to form a type II or III beta-turn, whose conformational monomer is (Thr-Gly)3. Here we report, using conformational analyses, that both an NSGAD pentapeptide, and a polymer of the same sequence, form type II beta-turns. Thus two peptide sequences, whose amino-acid composition is very different, nevertheless form the same secondary structure. The implications of these structures for clock function are discussed.
Animals↗
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↗
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↗