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Biomedical subjects

J Cortés

Publications and source records attributed to J Cortés.

At least 19 recordsLinked to original sources

Synthetic peptides from Plasmodium falciparum apical membrane antigen 1 (AMA-1) specifically interacting with human hepatocytes.

Plasmodium falciparum apical membrane antigen 1 (AMA-1) is expressed during both the sporozoite and merozoite stage of the parasite's life cycle. The role placed by AMA-1 during sporozoite invasion of hepatocytes has not been made sufficiently clear to date. Identifying the sequences involved in binding to hepatocytes is an important step towards understanding the structural basis for sporozoite-hepatocyte interaction. Binding assays between P. falciparum AMA-1 peptides and HepG2 cell were performed in this study to identify possible AMA-1 functional regions. Four AMA-1 high activity binding peptides (HABPs) bound specifically to hepatocytes: 4310 ((74)QHAYPIDHEGAEPAPQEQNL(93)), 4316 ((194)TLDEMRHFYKDNKYVKNLDE(213)), 4321 ((294)VVDNWEKVCPRKNLQNAKFGY(313)) and 4332 ((514)AEVTSNNEVVVKEEYKDEYA(533)). Their binding to these cells became saturable and resistant to treatment with neuraminidase. Most of these peptides were located in AMA-1 domains I and III, these being target regions for protective antibody responses. These peptides interacted with 36 and 58 kDa proteins on the erythrocyte surface. Some of the peptides were found in exposed regions of the AMA-1 protein, thereby facilitating their interaction with host cells. It is thus probable that AMA-1 regions defined by the four peptides mentioned above are involved in sporozoite-hepatocyte interaction.

Amino Acid Sequence↗

[Characteristic craniofacial features in a group of unilateral cleft lip and palate patients in Chile].

INTRODUCTION: Craniofacial growth in cleft lip and palate patients is controversial. Structural alterations of the face in these patients could be due to the surgical treatment combined with the primary variations of the cranial base morphology. Our objective was to ana-lyze the morphology of the craniofacial skeleton in a group of unilateral cleft lip and palate Chilean patients. MATERIAL AND METHOD: We studied 43 non syndromic operated unilateral complete cleft lip and palate patients. Ages ranged from 10 to 18 years for both genders. This cohort was compared with a control group of 40 non cleft patients, matched for age and sex, using Delaire's structural and architectural craniofacial analysis on lateral radiographs and performed by the same operator. RESULTS: Cleft patients presented with significantly different configurations of the craniofacial skeleton, specifically a flatter basi-cranium, a reduced posterior maxillary height, a retrusive maxilla deficient in length with an associated crossbite.

Adolescent↗

[Techniques to block the sciatic nerve by a lateral approach through the popliteal fossa].

Lateral approaches to the sciatic nerve through the popliteal fossa have recently been described as useful for providing adequate anesthesia and postoperative analgesia for foot and ankle surgery. Numerous publications have appeared on the approach in recent years, proposing new anatomical landmarks to facilitate location of the nerve, reduce the rate of complications, and increase the rate of success. When the lateral popliteal approach has been compared to other approaches to the sciatic nerve, similar success rates have been observed. However, when this technique is used certain factors must be borne in mind because they can influence both latency time and success. This review describes the lateral popliteal approach, its main variations, the factors that can affect latency time or success, and the possibility of providing continuous analgesia. We also sought to compare this approach to other techniques for blocking the sciatic nerve.

Humans↗

A path planning approach for computing large-amplitude motions of flexible molecules.

MOTIVATION: Motion is inherent in molecular interactions. Molecular flexibility must be taken into account in order to develop accurate computational techniques for predicting interactions. Energy-based methods currently used in molecular modeling (i.e. molecular dynamics, Monte Carlo algorithms) are, in practice, only able to compute local motions while accounting for molecular flexibility. However, large-amplitude motions often occur in biological processes. We investigate the application of geometric path planning algorithms to compute such large motions in flexible molecular models. Our purpose is to exploit the efficacy of a geometric conformational search as a filtering stage before subsequent energy refinements. RESULTS: In this paper two kinds of large-amplitude motion are treated: protein loop conformational changes (involving protein backbone flexibility) and ligand trajectories to deep active sites in proteins (involving ligand and protein side-chain flexibility). First studies performed using our two-stage approach (geometric search followed by energy refinements) show that, compared to classical molecular modeling methods, quite similar results can be obtained with a performance gain of several orders of magnitude. Furthermore, our results also indicate that the geometric stage can provide highly valuable information to biologists. AVAILABILITY: The algorithms have been implemented in the general-purpose motion planning software Move3D, developed at LAAS-CNRS. We are currently working on an optimized stand-alone library that will be available to the scientific community.

Algorithms↗

Geometric algorithms for the conformational analysis of long protein loops.

The efficient filtering of unfeasible conformations would considerably benefit the exploration of the conformational space when searching for minimum energy structures or during molecular simulation. The most important conditions for filtering are the maintenance of molecular chain integrity and the avoidance of steric clashes. These conditions can be seen as geometric constraints on a molecular model. In this article, we discuss how techniques issued from recent research in robotics can be applied to this filtering. Two complementary techniques are presented: one for conformational sampling and another for computing conformational changes satisfying such geometric constraints. The main interest of the proposed techniques is their application to the structural analysis of long protein loops. First experimental results demonstrate the efficacy of the approach for studying the mobility of loop 7 in amylosucrase from Neisseria polysaccharea. The supposed motions of this 17-residue loop would play an important role in the activity of this enzyme.

Algorithms↗

Is a double-injection technique superior to a single injection in posterior subgluteal sciatic nerve block?

BACKGROUND AND OBJECTIVES: Currently, no information is available on the effects of a double-injection technique on onset time and efficacy following subgluteal sciatic nerve blockade. We hypothesized that the success rate and time to onset of subgluteal nerve block following a double-injection technique would be superior to that after a single injection. METHODS: Fifty ASA I or II patients undergoing foot or ankle surgery randomly received a single or double injection subgluteal sciatic nerve block. Group S (n=25) received a single injection of 30 ml of 0.75% ropivacaine to the sciatic nerve. In Group D (n = 25), 15 ml of the same solution was injected to each sciatic nerve component. Completion of sensory and motor blockade, and patient acceptance, was evaluated by a blinded anesthesiologist. RESULTS: Complete sensory and motor blockade of the foot was achieved faster with the double injection (7.4 [5.9-8.8] min and 12.3 [10.4-14.2] min, respectively) than with the single-injection technique (12.5 [10.7-14.3] min and 18.8 [16.7-21.0] min, respectively) (P<0.001 and P<0.001, respectively). Success rate and acceptance were similar in both groups. Severe or moderate discomfort during the procedure was less frequent after a single injection (P = 0.013). CONCLUSIONS: Both the single- and double-injection technique for subgluteal sciatic nerve blockade resulted in acceptable anesthesia in most patients. The double injection generated a faster onset of anesthesia than the single injection. However, the double-injection technique caused more patient discomfort during establishment of the nerve block.

Amides↗

[Comparison of 4 techniques for internal saphenous nerve block].

OBJECTIVE: To assess the efficacy of 4 techniques for internal saphenous nerve block with 10 mL of 1.5% mepivacaine. METHODS: Eighty ASA I-II patients scheduled for foot (hallux valgus) surgery with combined sciatic and saphenous nerve blocks were randomized to receive the saphenous nerve block by one of the following techniques: a paravenous approach (n = 20), a transsartorial approach (n = 20), a femoral nerve approach in the inguinal region using a nerve stimulator (n = 20), and by subcutaneous infiltration between the tibial tuberosity and the internal gastrocnemius muscle (n = 20). A pressure cuff was placed 10 cm below the knee of all patients. Success was assessed by pin prick inside the ankle 30 minutes after initiation of the block. Tolerance of the pressure cuff and discomfort during performance of the technique were also assessed. RESULTS: The 4 groups were similar as to distribution of males and females and mean weight, age, and height. Blocking the saphenous nerve by way of the femoral nerve in the inguinal region was the most effective approach (success in 95% of patients), significantly better than the other 3 techniques (P < 0.05). The paravenous approach was successful in 60% of cases, the transsartorial approach in 50%, and the subcutaneous infiltration technique in 45%. The pressure cuff was well tolerated by all patients (100%) in whom the femoral nerve approach was used. The cuff was tolerated by 70% in the paravenous approach group, by 65% in the transsartorial approach group, and by 60% in the subcutaneous infiltration group. Patients reported more discomfort during initiation of the blockade in the paravenous approach and subcutaneous infiltration groups than in the femoral nerve or transsartorial approach groups (P < 0.05). CONCLUSION: The femoral nerve approach in the inguinal region, with nerve stimulator, to block the internal saphenous nerve led to a larger number of successful blocks than did the paravenous or transsartorial approaches, or the technique of subcutaneous infiltration between the tibial tuberosity and internal gastrocnemius muscle.

Aged↗

Contribution of the initial features of systemic lupus erythematosus to the clinical evolution and survival of a cohort of Mediterranean patients.

BACKGROUND: Systemic lupus erythematosus has a wide spectrum of immunological and clinical manifestations. Its course is characterised by exacerbations which may result in mortality or morbidity to vital organs/systems. OBJECTIVE: To determine clear and early prognostic markers to avoid further complications. METHODS: 245 adult patients diagnosed between January 1978 and March 2001 were studied. Clinical manifestations and laboratory findings both at onset and during the clinical course were collected. The number, type, and severity of the flares were also noted. Statistical analyses between disease features at onset, subsequent flares, and mortality were performed. RESULTS: 239 patients entered the study. Their mean age at onset was 30 years. The mean time between onset and diagnosis was 36 months and the mean evolution time was 114 months. 205 patients developed 915 flares; 205 (22.4%) of these flares were major flares, and affected 110 patients. Cardiac, neurological, or renal affection at onset were associated with a higher probability of developing cardiac (p=0.022), neurological (p<0.001), and renal (p<0.001) exacerbations, respectively, during the evolution. Lupus anticoagulant (LA) and anticardiolipin antibodies (aCL) were predictors of stroke (aCL, p=0.000; LA, p=0.001). Age at diagnosis (p=0.003) and valvular disease at onset (p=0.008) were independent predictors of low survival. CONCLUSIONS: Renal, cardiac, or neurological involvement and the presence of LA or aCL positivity at onset were predictors of renal, cardiac, or neurological flares, respectively. Age and valvular involvement at onset were found to be independent adverse outcome predictors for low survival.

Adult↗

[Peripheral nerve block for surgical anesthesia and postoperative analgesia of the legs].

Even though peripheral nerve blocks (PNB) on the lower limb offer advantages over neuroaxial blockades and general anesthesia, their use has not been fully established. The infrequency with which PNBs are used may be due to inadequate learning, the need to make several injections, the time until onset of block, or anesthesiologists' and surgeons' lack of familiarity with the benefits of regional blocks. Interest seems to have increased in recent years, as numerous publications have focused on lower limb PNBs for surgery and postoperative analgesia. Our aim was to review the main approaches used and the indications for each.

Analgesia↗

Effect of uterine horn ligation on bone mass: an experimental study in rats.

OBJECTIVE: After tubal ligation, normal bone mass in the presence of gonadal deficit has been reported. These incongruent results motivated us to examine the topic. STUDY DESIGN: Bone mass was assessed by densitometry and ultrasonography 60 days after surgery on 100-day-old female Wistar rats. Fifteen Wistar rats with uterine horn ligation (TL) were compared with 15 unoperated, 15 with a sham uterine horn ligation (Sham-TL), and 15 ovariectomized (OVX), using ANOVA and a correlation test to determine the relations between results. RESULTS: Femoral and vertebral bone mass were significantly lower in the OVX y TL groups than in unoperated and controls groups (P<0.0001). CONCLUSIONS: Our study revealed significantly lower axial and peripheral bone mass in rats with uterine horn ligation.

Animals↗

Remarkably high antibody levels and protection against P. falciparum malaria in Aotus monkeys after a single immunisation of SPf66 encapsulated in PLGA microspheres.

Single dose immunisation is a major goal in vaccine design. The purpose of this study was the development of a single dose delivery system for the SPf66 malaria vaccine, based on this antigen's microencapsulation in PLGA microspheres by double emulsion method. Results indicate that a single immunisation in mice and monkeys with the SPf66 malaria vaccine, encapsulated in a mixture of two formulations of PLGA microspheres, induced a remarkably high and long-lasting immune response as assessed by ELISA and Western Blott. This immune response was associated with a good protective capacity in Aotus monkeys, after experimental challenge, indicating that antigen integrity lasted following the microencapsulation process. PLGA biodegradable microspheres thus serve as an effective delivery system for the design of a single dose immunisation vaccine, such as the SPf66 synthetic malaria vaccine.

Alum Compounds↗

Fixed higher dose schedule of suramin plus hydrocortisone in patients with hormone refractory prostate carcinoma a multicenter Phase II study.

BACKGROUND: Using a fixed higher-dose schedule, the efficacy and toxicity of suramin plus hydrocortisone were assessed in patients with metastatic hormone-refractory prostate carcinoma (HRPC). METHODS: Fifty consecutive patients with HRPC (including those in whom hormonotherapy was withdrawn) and an Eastern Cooperative Oncology Group performance status of 0-2 were recruited. Treatment was comprised of a bolus intravenous infusion of 200 mg of suramin followed by suramin (500 mg/m(2) intravenously [i.v.] over 24 hours) given daily over 5 days as a loading course, followed by suramin (350 mg/m(2) i.v. over 2 hours) administered weekly for 12 weeks. This 12-week course was repeated at 6-month intervals. All patients received concomitant hydrocortisone. RESULTS: Five hundred fifty weekly doses of therapy were delivered over the course of the entire study. A partial response, based on a > 50% decrease in the prostate specific antigen (PSA) level, was achieved in 27 patients (54%; 95% confidence interval [95% CI], 44.7-65.0%), 16 of whom (32%; 95%CI, 23.9-43.2%) had a > 75% decrease in their PSA levels. The measurable disease objective response rate was 18% (95% CI, 2.3-51.8%). Of the 37 patients with bone pain requiring analgesia, 27 patients (73%; 95% CI, 55.9-86.2%) reduced their medication consumption to a lower level on the World Health Organization analgesic ladder. The median duration of response was 15.5 weeks (range, 6-70 weeks), the median time to disease progression was 13 weeks, and the median overall survival time was 11 months. Treatment generally was well tolerated. Fatigue and severe lymphopenia were the most commonly reported significant toxicities. In addition, there was 1 septic toxic death reported, and 10% of the patients were found to have NCI Grade 3-4 neurotoxicity. CONCLUSIONS: The results of the current study demonstrated that the fixed-dose suramin regimen administered herein showed high, although short-lived, activity and a good tolerance profile in HRPC patients.

Aged↗

Engineering of complex polyketide biosynthesis--insights from sequencing of the monensin biosynthetic gene cluster.

The biosynthesis of complex reduced polyketides is catalysed in actinomycetes by large multifunctional enzymes, the modular Type I polyketide synthases (PKSs). Most of our current knowledge of such systems stems from the study of a restricted number of macrolide-synthesising enzymes. The sequencing of the genes for the biosynthesis of monensin A, a typical polyether ionophore polyketide, provided the first genetic evidence for the mechanism of oxidative cyclisation through which polyethers such as monensin are formed from the uncyclised products of the PKS. Two intriguing genes associated with the monensin PKS cluster code for proteins, which show strong homology with enzymes that trigger double bond migrations in steroid biosynthesis by generation of an extended enolate of an unsaturated ketone residue. A similar mechanism operating at the stage of an enoyl ester intermediate during chain extension on a PKS could allow isomerisation of an E double bond to the Z isomer. This process, together with epoxidations and cyclisations, form the basis of a revised proposal for monensin formation. The monensin PKS has also provided fresh insight into general features of catalysis by modular PKSs, in particular into the mechanism of chain initiation.

Biotechnology↗

Conditions for single-strand conformation polymorphism (SSCP) analysis of BRCA1 gene using an automated electrophoresis unit.

The single-strand conformation polymorphism procedure has been applied in routine testing for hereditary diseases and cancer. However, temperature, running time, gel composition, fragment length, etc. can influence its sensitivity. Mutation detection in the clinical setting depends on the development of automated technology, especially for large genes such as the breast cancer gene BRCA1. We analysed DNA samples with BRCA1 mutations in an automated system (GenePhor System; Amersham-Pharmacia Biotech, Uppsala, Sweden). The concentrations of DNA template and PCR primers, the effect of chilling after denaturation, and the temperature and time of the electrophoresis were investigated. All band-shifts were detected by electrophoresis at 5 degrees C for 2 h 15 min. Concentrations of DNA and samples used in the PCR did not affect the SSCP pattern, but chilling the PCR product in ice after denaturation was required. The type and position of mutation in the fragments did not influence the probability of a mobility shift, although SSCP analysis was more sensitive for fragments shorter than 350 bp. This automated SSCP method meets the requirements of fast turnaround and sensitivity and can be readily adapted to the screening of large genes such as BRCA1.

BRCA1 Protein↗

[Conjugal violence in the city Temuco. Prevalence studies and associated factors].

BACKGROUND: Violence against women is a recognized public health problem in developed countries. There is increasing awareness on family violence in Chile, but there is scant information about its prevalence. AIM: To determine the prevalence of family violence against women in a population sample in Temuco, Chile. MATERIAL AND METHODS: A standardized questionnaire about family violence was applied to a sample of 422 women at their homes. The questionnaire had six sections that included a list of violent behaviors from husbands or partners, a standardized instrument to assess mental health and alcohol consumption by the couple, history of child abuse, community support, type of employment and years of school education. RESULTS: Forty nine percent of women reported psychological aggression, 13% reported physical violence and 5.5%, sexual violence. The presence of anxiety or depressive symptoms, being witness of violence between parents during childhood, a lower educational level, being a housewife, alcohol abuse and lack of community support were risk factors for violence among women. Among men, the history of child abuse, a lower education level, and alcohol abuse were identified as risk factors for violent behaviors. CONCLUSIONS: Conjugal violence is a significant mental health problem in Temuco, Chile.

Adolescent↗

[Child abuse in in the city Temuco. Prevalence study and associated factors].

BACKGROUND: Child maltreatment is recognised as a significant health problem in developed countries. There is increasing awareness on family violence in Chile, becoming a health priority in the last five years, but there is scant information about its prevalence. AIM: Determine prevalence of child abuse, and associated factors in a population sample from Temuco, Chile. MATERIAL AND METHODS: A standardised questionnaire was applied to a sample of 422 women at their homes. Instrument had questions about disciplinary practices by caretakers, a standardised questionnaire to assess mental health, as measures of risk and protective factors for violence RESULTS: The prevalence of psychological aggression delivered by mothers or fathers was 17.5% and 6.8% respectively. The figures for corporal punishment delivered by mother or fathers were 42.3% and 17% respectively. Three percent of mothers and 1.2% of fathers recognised severe physical abuse. Associated factors were mother impaired mental health, antecedents of child abuse in both parents, parents alcohol abuse and child emotional/behavioral problem. CONCLUSION: Child abuse is a extended significant problem in Temuco that requires multidisciplinary intervention programs.

Adolescent↗