Search PubMed⌕ Search

Biomedical subjects

J Roca

Publications and source records attributed to J Roca.

At least 19 recordsLinked to original sources
PubMed2001

Varying levels of positive and negative supercoiling differently affect the efficiency with which topoisomerase II catenates and decatenates DNA.

Type II DNA topoisomerases catalyze the transport of one DNA double helix through another. Here, by using a non-hydrolyzable analog of ATP, I examined the single-step DNA transport preferences of the yeast type II topoisomerase bound to positively and negatively supercoiled DNA rings. I found that negative supercoiling favors decatenation of DNA rings more than positive supercoiling. Conversely, positive supercoiling favors the catenation and knotting of DNA rings more than negative supercoiling. This vectorial effect of DNA supercoiling handedness supports a model in which type II topoisomerases can recognize three DNA segments, and highlights a novel influence of DNA supercoiling in global DNA topology.

Blotting, Southern↗
PubMed2001

New 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives with dual action at 5-HT1A serotonin receptors and serotonin transporter as a new class of antidepressants.

A series of new 3-[4-(aryl)piperazin-1-yl]-1-(benzo[b]thiophen-3-yl)propane derivatives were synthesized in an attempt to find a new class of antidepressant drugs with dual activity at 5-HT1A serotonin receptors and serotonin transporter. Title compounds were evaluated for in vitro activity on 5-HT1A receptor and 5-HT transporter. They show high nanomolar affinity for both activities, and in particular, compounds 1-(5-chlorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (7) and 1-(5-fluorobenzo[b]thiophen-3-yl)-3-[4-(2-methoxyphenyl)piperazin-1-yl]propan-1-ol (8) show values (nM) of K(i)=30 and 2.3 for 5-HT1A receptors and K(i)=30 and 12 for serotonin transporters, respectively. In GTPgammaS binding assays, compound 8 revealed antagonist properties to 5-HT1A receptors. Such a pharmacological profile could lead to potent antidepressant agents with new dual mechanism of action.

Animals↗
PubMed2001

Impaired muscle oxygen transfer in patients with chronic renal failure.

We hypothesized that impaired O2 transport plays a role in limiting exercise in patients with chronic renal failure (CRF). Six CRF patients (25 +/- 6 yr) and six controls (24 +/- 6 yr) were examined twice during incremental single-leg isolated quadriceps exercise. Leg O2 delivery (QO2(leg)) and leg O2 uptake (VO2(leg)) were obtained when subjects breathed gas of three inspired O2 fractions (FI(O2)) (0.13, 0.21, and 1.0). On a different day, myoglobin O2 saturation and muscle bioenergetics were measured by proton and phosphorus magnetic resonance spectroscopy. CRF patients, but not controls, showed O2 supply dependency of peak VO2 (VO2(peak)) by a proportional relationship between peak VO2(leg) at each inspired O2 fraction (0.59 +/- 0.20, 0.47 +/- 0.10, 0.43 +/- 0.10 l/min, respectively) and 1) work rate (933 +/- 372, 733 +/- 163, 667 +/- 207 g), 2) QO(2leg) (0.80 +/- 0.20, 0.64 +/- 0.10, 0.59 +/- 0.10 l/min), and 3) cell PO2 (6.3 +/- 5.4, 1.7 +/- 1.3, 1.2 +/- 0.7 mmHg). CRF patients breathing 100% O2 and controls breathing 21% O2 had similar peak QO2(leg) (0.80 +/- 0.20 vs. 0.79 +/- 0.10 l/min) and similar peak VO2(leg) (0.59 +/- 0.20 vs. 0.57 +/- 0.10 l/min). However, mean capillary PO2 (47.9 +/- 4.0 vs. 38.2 +/- 4.6 mmHg) and the capillary-to-myocite gradient (40.7 +/- 6.2 vs. 34.4 +/- 4.0 mmHg) were both higher in CRF patients than in controls (P < 0.03 each). We conclude that low muscle O2 conductance, but not limited mitochondrial oxidative capacity, plays a role in limiting exercise tolerance in these patients.

Adult↗
PubMed2000

Viability and fertility of rabbit spermatozoa diluted in Tris-buffer extenders and stored at 15 degrees C.

Artificial insemination (AI) in rabbits is not extensive in the breeding programs of the rabbit meat industry. A limiting factor is related to the semen preservation. In order to improve the use of AI, two experiments have been conducted to evaluate sperm viability and fertility of rabbit semen chilled and stored at 15 degrees C after dilution in Tris-based extenders. In Experiment 1, pooled semen samples were diluted 1:10 (semen/extender) in four different Tris-based extenders (Tris-citric-glucose (TCG), TES-Tris-glucose (TTG), Tris-citric-fructose (TCF) and TES-Tris-fructose (TTF)) and stored at 15 degrees C. Sperm viability was evaluated at 0, 24, 48, 72 and 96 h following dilution for total sperm motility (TSM), forward progressive motility (FPM), plasma membrane integrity (PMI) and acrosome integrity (NAR). Viability of spermatozoa declined with time of storage (P<0.05), irrespective of the extender used. There were interactions between extender and time of storage (P<0.05) in all viability parameters evaluated. After 96 h of storage, TCG provided the highest sperm viability (P<0.05) and TTG the lowest (P>0.05). In Experiment 2, a field trial was conducted at a commercial farm to evaluate the conception and farrowing rates of rabbit spermatozoa extended in TCG. After synchronization of oestrous and induction of ovulation, 3713 does with different physiological conditions (nulliparous, primiparous, lactating and re-breeding) were inseminated one time (15x10(6) sperm per doses) with semen stored at 0 (n: 1275), 24 (n: 1503) and 48 h (n: 935) at 15 degrees C. Overall conception and farrowing rates were 77.1+/-0.7 and 70.4+/-0.7, respectively, and the mean litter size was 7.6+/-0.1. Fertility results were unaffected by the time of semen storage (P>0.05). Regardless of time of semen storage, fertility results were affected by the physiological conditions of does (P<0.05). Nulliparous and lactating does showed the highest fertility and primiparous the lowest. In summary, these results indicate that Tris-buffer extenders are effective for preserving viability and fertilizing capability of rabbit spermatozoa stored at 15 degrees C.

Acrosome Reaction↗
PubMed2000

Circular minichromosomes become highly recombinogenic in topoisomerase-deficient yeast cells.

In topoisomerase-deficient yeast cells, we have found that circular minichromosomes are present as broad distributions of multimeric forms, which consist of tandemly repeated copies of their monomeric sequences. This phenomenon selectively occurs in Deltatop1 cells, and is highly magnified in double mutant Deltatop1 top2-4 cells. No multimers are observed in single mutant top2-4 or Deltatop3 cells, or in Deltatop1 cells that express a plasmid-borne TOP1 gene. Interconversion among multimeric forms takes place rapidly in double mutant Deltatop1 top2-4 cells, and the multimeric distributions are readily reverted to the monomeric form when a plasmid-borne TOP1 gene is expressed from an inducible promoter. These observations are a new example of the interplay between DNA topology and genome stability, and suggest that the cell capacity to modulate DNA supercoiling is limited when DNA is organized in small topological domains. Yeast minichromosome multimerization provides an appropriate system in which to study mechanistic aspects of DNA recombination.

Base Sequence↗
PubMed2000

Mortality of HIV-positive and HIV-negative heroin abusers as a function of duration of injecting drug use.

OBJECTIVE: To determine the incidence of mortality of injecting drug users as a function of the duration of injecting drugs and HIV status, and to assess how these effects vary according to age at initiation and calendar period (before and after 1992). METHODS AND DESIGN: Cohort of 376 intravenous heroin users admitted to detoxification between February 1987 and January 1990. SETTING: Patients referred from outpatient clinics of metropolitan Barcelona. Duration and characteristics of drug use were determined by interviews. Blood samples were collected during admission and analyzed for HIV, CD4+ cell count and different biologic parameters. Assessment of vital status and causes of death were obtained by hospital charts, death certificates, and autopsies. RESULTS: The study population consisted of 299 men and 77 women, whose mean age at entry was 26 years, mean duration of injecting drug use before admission 6.1 years; HIV seroprevalence at entry 70.2%. By the end of the follow-up (median 5.6 years), 21.8% of individuals had died (26.6% in HIV-positive, and 10.7% in HIV-negative injecting users). Based on Kaplan-Meier estimates, 10%, 20%, and 30% of HIV negative patients died by 8.7, 11.3 and 14.3 years, respectively, after initiating injecting drugs. The corresponding survival times for the seropositives were substantially lower: 6.6, 8.5, and 11.6 years, respectively. Overall, the survival time was significantly (p < .05) decreased by 22% in HIV-positive injecting drug users. Older age at initiation of injecting drug use was significantly (p < .05) associated with mortality in HIV-positive heroin users but it showed the opposite direction among HIV-negative people. Death rates in HIV-positive patients of the same duration of drug use were similar in periods before and after 1992 (relative hazard (RH) = 0.97; 95% confidence interval: 0.58-1.61). Although not statistically significant, the hazard of death in HIV-negative injecting drug users was substantially lower after 1992 (RH = 0.59). CONCLUSIONS: Before introduction of potent antiretroviral therapies, HIV infection further increased rates of mortality that had already been heightened by injecting drug use. Furthermore, HIV infection modifies the effect of age at initiation and eliminates the seemingly downward trend of mortality in HIV-negative people.

Adolescent↗
PubMed2000

Predictive factors and long-term evolution of early endothelial dysfunction after cardiac transplantation.

BACKGROUND: Abnormal coronary vasomotion appears to be a common finding after heart transplantation (HTx). However, the pathophysiology and outcome of this functional disturbance remains poorly understood. Aims of the study were to determine the prevalence, predictive factors and long-term evolution of endothelial dysfunction after cardiac transplantation. METHODS: The endothelium-dependent coronary vasomotion of 50 patients, who showed angiographically normal coronary arteries, were studied early (at 3 +/- 1 months) and at follow-up (16 +/- 5 months) after HTx. Endothelial function was studied by selective infusion of serial doses of acetylcholine (ACh) (10(-8), 10(-7)and 10(-6) mol/l) in the left anterior descending coronary artery. Changes in mean luminal diameter after the infusion of each dose were evaluated by quantitative coronary angiography (QCA). RESULTS: At early study, 17 patients (34%) showed a vasoconstriction after maximal dose of ACh (-13.3 +/- 13%) indicative of endothelial dysfunction. Logistic regression analysis identified the following variables as independent predictors of early endothelial dysfunction: donor inotropic support (p = 0.004), female donor (p = 0.04) and rejection at the time of the study (p = 0.01). Forty-one patients were re-studied at follow-up. Nine of them (22%) presented endothelial dysfunction. Early endothelial dysfunction was restored in 6 patients (43%) at follow-up. The number of episodes of rejection was the only variable associated to late endothelial dysfunction. CONCLUSIONS: Endothelial dysfunction is a common finding after cardiac transplantation. The pathogenesis of this functional disturbance appears to be donor-related and immune-mediated. The reversibility of this phenomenon observed at follow-up suggests the episodic nature of the immunologic injury.

Acetylcholine↗
PubMed2000

Association study of proposed candidate genes/regions in a population of Spanish asthmatics.

A number of genes/regions have recently been reported to be linked to asthma or its related phenotypes (i.e. atopy and bronchial hyperresponsiveness), by genetic linkage and allele-sharing methods. We have performed a case-control study comparing the allelic distribution of nine microsatellite markers and two genetic variants in a group of patients attended at emergency room departments because of an acute attack of asthma with respect to an external healthy population of controls. A total of 146 asthmatic subjects and 50 population controls from Barcelona, Spain, were genotyped for nine microsatellite markers from some asthma/atopy candidate genes/regions: the beta-subunit of the high-affinity IgE receptor (Fc epsilonRI-beta) located on chromosome 11; the 5q31-32 candidate region; the T-cell receptor genes, TCR-alpha on chromosome 14 and TCR-beta on chromosome 7. Two genetic variants of the beta-subunit of the high-affinity IgE receptor (Fc epsilonRI-beta) gene were also analyzed. None of the asthmatic or control individuals carried the Ile181Leu variant. There were no significant differences between asthmatic and control subjects neither for the polymorphic markers nor for the other variant of the beta-subunit of the high-affinity IgE receptor (Fc epsilonRI-beta) gene. No association could be observed in this sample of Spanish asthmatics with the genes/regions studied.

Adult↗
PubMed2000

Noninvasive assessment of respiratory resistance in severe chronic respiratory patients with nasal CPAP.

Noninvasive measurement of respiratory resistance during nasal ventilatory support could be useful to assess the mechanical status of the patient and to optimize the ventilator settings. The aim was to investigate whether the forced oscillation technique (FOT) applied through a nasal mask allows reliable noninvasive estimation of respiratory resistance (Rrs) in patients with severe chronic respiratory disease. FOT Rrs (5 Hz) and lung resistance (R(L)) measured simultaneously from spontaneous breathing signals by an oesophageal balloon were compared in eight patients with chronic obstructive pulmonary disease and in six patients with a restrictive ventilatory defect due to chest wall disease. Measurements were performed in sitting and supine postures during application of nasal continuous positive airway pressure (CPAP): 4, 8 and 12 cmH2O in obstructive patients and 4 cmH2O in restrictive patients. In the restrictive patients Rrs and R(L) (in cmH2O x s x L(-1)) were virtually coincident: mean+/-SD, 12.6+/-6.1 and 11.6+/-6.6 (r=0.96) in sitting and 9.7+/-3.1 and 10.2+/-3.3 (r=0.92) in supine posture, respectively. In the obstructive patients (CPAP = 4 cmH2O), Rrs slightly underestimated R(L): mean+/-SD, 11.5+/-5.9 and 14.4+/-16.8 (r=0.92) in sitting and 15.0+/-9.8 and 21.1+/-12.6 (r=0.96) in supine posture, respectively. Similar results were found at CPAP = 8 and 12 cmH2O. The results obtained in patients with resistance values in the range typically found in nasal ventilatory support suggest that forced oscillation technique could be valuable to noninvasively estimate a patient's respiratory mechanical resistance.

Aged↗
PubMed2000

Evaluation of a method for assessing respiratory mechanics during noninvasive ventilation.

Noninvasive assessment of respiratory resistance (Rrs) and elastance (Ers), which is not easy with conventional methods, could be useful in the optimization of pressure support ventilation. The aim of this study was to evaluate a simple noninvasive method (Delta-inst) of measuring Rrs during nasal pressure support ventilation. Rrs and Ers (Delta-inst) were computed from inspiratory mask pressure, flow and volume recorded during pressure support ventilation. The Delta-inst method was compared with the forced oscillation technique (FOT) in seven patients with chronic obstructive pulmonary disease (COPD) and in eight healthy subjects without and with added resistance (3.1 cmH2O x s x L(-1)). Rrs measured by Delta-inst (5.2+/-1.7, 7.2+/-0.5 and 6.9+/-1.2 cmH2O x s x L(-1)) and by FOT (5.0+/-0.7, 7.6+/-0.9 and 8.1+/-2.7 cmH2O x s x L(-1)) in healthy subjects without and with added resistance and COPD, respectively, were not significantly different (p>0.05). Rrs measured by both techniques showed a significant coefficient of linear correlation (r=0.70 s) (p<0.01). In the COPD patients, the variability of Delta-inst Rrs (30%) was greater than that of FOT Rrs (21%). The agreement between Ers obtained by Delta-inst and by FOT was less than that found for Rrs. Delta-inst is a noninvasive and simple method for reliably assessing resistance. Therefore, it is useful for monitoring airway obstruction and is potentially helpful in adapting the settings for pressure support ventilation in accordance with patient mechanics.

Adult↗
PubMed2000

Pulmonary gas exchange response to oxygen breathing in acute lung injury.

The mechanisms and time course of the pulmonary gas exchange response to 100% O(2) breathing in acute respiratory failure needing mechanical ventilation were studied in eight patients with acute lung injury (ALI) (48 +/- 18 yr [mean +/- SD]) and in four patients (66 +/- 2 yr) with chronic obstructive pulmonary disease (COPD). We postulated that, in patients with ALI while breathing 100% O(2), the primary mechanism of hypoxemia, i.e., increased intrapulmonary shunt, would further worsen (increase) as a result of reabsorption atelectasis. Respiratory and inert gases, and systemic and pulmonary hemodynamics were measured at maintenance fraction of inspired oxygen (FI(O(2))-m), at 30 and 60 min while breathing 100% O(2), and then at 30 min of resuming FI(O(2))-m. During 100% O(2) breathing, in patients with ALI, Pa(O(2)) (by 207 and 204 mm Hg; p < 0.01 each), Pa(CO(2)) (by 4 mm Hg each) (p < 0.05 each), and intrapulmonary shunt (from 16 +/- 10% to 22 +/- 11% and 23 +/- 11%) (p < 0.05 each) increased respectively. By contrast, in patients with COPD, Pa(O(2)) (by 387 and 393 mm Hg; p < 0.001 each), Pa(CO(2)) (by 4 and 5 mm Hg) and the dispersion of pulmonary blood flow (log SDQ) (from 1.33 +/- 0.10 to 1.60 +/- 0.20 and 1.80 +/- 0.30 [p < 0.05]) increased, respectively. In patients with ALI, the breathing of 100% O(2) deteriorates intrapulmonary shunt owing to collapse of unstable alveolar units with very low ventilation-perfusion (V A/Q) ratios, as opposed to patients with COPD, in whom only the dispersion of the blood flow distribution is disturbed, suggesting release of hypoxic pulmonary vasoconstriction.

Aged↗
PubMed1999

Age-related changes in the hamster epididymis.

Reproductive ability is decreased in aged animals and in men. Little is known about the changes taking place in the epididymis, and the possible influence on the loss of sperm quality. We studied the age-related alterations in the epididymis and in epididymal spermatozoa of hamsters. Adult (6-month-old), middle-aged (18-month-old), and aged (24-month-old) hamsters were used. Serum samples were obtained to determine testosterone levels. Testes and epididymides were removed and studied by light and electron microscopy. Epididymal sperm was also obtained and the motility, position of cytoplasmic droplet, and concentration were evaluated. Measurements of the height of the epithelium, length of stereocilia, external tubular diameter, and thickness of the muscular wall were performed. The proliferative activity was also studied. An ANOVA analysis was used to compare quantitative differences between epididymal zones and age groups. Aged hamsters presented involutive changes in the epididymis. A decrease in tubular diameter was found in cauda; principal cell ultrastructure showed changes including the appearance of damaged mitochondria, bundles of filaments, and the accumulation of lipofuscin. Some clear cells showed an unusual morphology by the presence of large electrondense vacuoles. A reduction in sperm quality was also observed, including a decrease in sperm motility and concentration, and alterations in the migration of sperm cytoplasmic droplet. Testosterone levels and cellular proliferative activity did not change. Aging causes a morphological alteration of hamster epididymis (mainly in the cauda), and a decrease in sperm quality.

Aging↗
PubMed1999

One-stage decompression and posterolateral and interbody fusion for severe spondylolisthesis. An analysis of 14 patients.

STUDY DESIGN: A retrospective study of 14 patients with high-grade L5-S1 spondylolisthesis surgically treated with one-stage decompression and posterolateral and interbody fusion (technique of Bohlman and Cook). OBJECTIVE: To determine the efficacy of this technique in managing severe lumbosacral spondylolisthesis. SUMMARY OF BACKGROUND DATA: Controversy exists over the most appropriate method for managing high-grade spondylolisthesis. Circumferential in situ fusion from a single-stage posterior approach was described in 1982, but to the current authors' knowledge, there are not many reports on clinical results in the literature. The current authors studied 14 patients (mean age, 21 years) with severe L5-S1 spondylolisthesis. The percentage of slipping averaged 77%; slip angle averaged 36 degrees. The average follow-up period was 30 months. All patients had severe back or radicular symptoms. Two patients had foot drop, and four had minor neurologic dysfunction. Four patients had extremely tight hamstrings. METHODS: Pre- and postoperative radiographic films and computed tomography scans were reviewed. Magnetic resonance imaging was carried out in 11 patients before surgery and at follow-up examination. Patients were evaluated for fusion rate, clinical outcome, and complications. RESULTS: All six patients with motor deficit of the nerve roots showed complete strength recovery at follow-up examination. None of the patients had tightness of hamstrings. Twelve patients demonstrated incorporation of the graft with solid fusion, one patient had a fracture of the fibular graft, and one had graft resorption. All patients but one rated the surgical result as excellent. One patient was not satisfied with the cosmetic result. Transient paresthesias in the leg of the donor graft were documented in two patients. CONCLUSIONS: Posterior decompression of the spinal canal combined with anterior and posterior arthrodesis performed at one stage through a posterior approach is a safe and effective technique for managing severe spondylolisthesis.

Adolescent↗
PubMed1999

[The polymerase chain reaction as a marker of cytomegalovirus infection in heart transplant recipients].

BACKGROUND: To evaluate the usefulness of PCR in peripheral blood leukocytes for the diagnosis of CMV infection and for prognosis of CMV disease in patients with heart transplantation. PATIENTS AND METHODS: A total of 54 heart transplant recipients included in a protocolized virological follow-up with blood samples (total samples: 594). Mean time of follow-up: 14.8 months (range 1-34 months). We compared a qualitative nested PCR with tube culture (CC), shell vial culture (SV) and pp65 quantitative antigenemia test (AGC). RESULTS: PCR was the most sensitive test (89.9%) followed by AGC (68.1%), SV (42.6%) and CC (33.4%). Specificity: 80 samples were positive only by PCR, 77 of which form patients with virologically documented CMV active infection, so they were considered as true positives. Three samples were from 2 patients in which the unique positive marker was PCR. If we considered these results as false positive, the calculated specificity was 99.0%. PCR was the first positive marker in 44 out of 45 patients with active CMV infection. In 9 of these patients no other viral marker was positive in the first positive sample, except for PCR. A total of 16 episodes of CMV disease were observed along the study, and a positive PCR result was detected in 15 of them. The remaining patient did not show amplification with the set of primers used in this study, but it gave a positive PCR by amplifying with a different primer pair. Positive predictive value of PCR for CMV disease was low (33.3%). Thus, a positive PCR result did not allow to distinguish between asymptomatic infection and CMV disease. CONCLUSIONS: In heart transplantation recipients CMV-PCR is a highly sensitive, specific and early marker of CMV infection but its positive predictive value for CMV disease seems unsatisfactory.

Biomarkers↗