Cystic fibrosis patients with the 3272-26A>G splicing mutation have milder disease than F508del homozygotes: a large European study.
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Alleles↗
Biomedical subjects
J Dapena
Publications and source records attributed to J Dapena.
Absence of Pneumocystis carinii carriers among patients with cystic fibrosis.
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Adolescent↗
Comparison of the kinematics of the full-instep and pass kicks in soccer.
PURPOSE: The goal of this study was to gain a better understanding of the mechanics of the inside-of-the-foot passing shot used in soccer ("pass kick"). METHODS: The motions of the pass kick were compared with those of the full-instep kick ("full kick"). The study followed an inverse dynamics approach, using three-dimensional cinematographic techniques. RESULTS: At impact, the pelvis and the thigh-shank plane pointed more toward the right in the pass kick; the shank-foot plane also pointed further outward relative to the thigh-shank plane. Knee extension accounted for most of the speed of the foot in both kicks (86% in the full kick; 67% in the pass kick). In the pass kick, pelvis tilt toward the right and hip adduction contributed to a medial component of foot velocity (8.4 m.s-1) normal to the thigh-shank plane, which made the resultant foot velocity vector more oblique to the plane than in the full kick. This facilitated ball impact with the medial aspect of the foot. The slower ball speed in the pass kick was because of a slower foot speed (18.3 m.s-1 vs 21.6 m.s-1). Limitations in the maximum medial velocity that can be generated may force players to restrain the within-plane (and therefore also the resultant) velocity of the foot to be able to impact the ball squarely with the medial aspect of the foot. CONCLUSIONS: To impact the ball with the medial aspect of the foot in the pass kick, the player orients the pelvis, the right leg, and the foot more toward the right and introduces a medial component of foot velocity. However, most of the speed of the foot is still generated through knee extension.
Adult↗
Missense mutation R1066C in the second transmembrane domain of CFTR causes a severe cystic fibrosis phenotype: study of 19 heterozygous and 2 homozygous patients.
We report the clinical features of 21 unrelated cystic fibrosis (CF) patients from Portugal and Spain, who carry the mutation R1066C in the CFTR gene. The current age of the patients was higher in the R1066C/any mutation group (P < 0.01), as compared to the deltaF508/deltaF508 group. Poor values for lung radiological involvement (Chrispin-Norman) and general status (Shwachman-Kulcycki) were observed in the R1066C/any mutation group (P < 0.005 and P < 0.0004). A slightly, but not significantly worse lung function was found in the R1066C/any mutation group when compared with the deltaF508/deltaF508 patients. No significant differences were detected regarding the age at diagnosis, sweat Cl-values, or percentiles of height and weight between the two groups. Neither were significant differences observed regarding sex, meconium ileus (4.7% vs. 11.1%), dehydration (10.5% vs. 14.7%), or pancreatic insufficiency (PI) (100% vs. 97.8%). The proportion of patients with lung colonization by bacterial pathogens was slightly, but not significantly higher in the R1066C/any mutation group (70.0%), as compared with the deltaF508/deltaF508 group (57.5%). Other clinical complications were significantly more frequent in the R1066C/any mutation patients(P < 0.02) than in the deltaF508/deltaF508 group. The two homozygous R1066C/R1066C patients died at the ages of 3 months and 7 years. The data presented in this study clearly demonstrate that the R1066C mutation is responsible for a severe phenotype similar to that observed in homozygous deltaF508 patients. The poor clinical scores and complications of patients with the R1066C mutation are probably related to their slightly longer survival.
Adolescent↗
Genotype-phenotype relationship in 12 patients carrying cystic fibrosis mutation R334W.
We present a phenotype-genotype correlation analysis in 12 patients with cystic fibrosis (CF) carrying the mutation R334W in the CFTR gene. The clinical data obtained for this group were compared with the clinical data of deltaF508/deltaF508 patients. Current age and age at diagnosis were significantly higher in the R334W mutation group (p=0.028 and p=0.0001). We found a lower rate of Pseudomonas aeruginosa colonisation in patients carrying the R334W mutation, although the difference was not found to be statistically significant. However, we found a statistically significant higher age of onset of Pseudomonas aeruginosa colonisation (p=0.0036) in the group of patients with the R334W mutation. Thirty three percent of R334W patients were pancreatic insufficient, significantly lower than the deltaF508/deltaF508 patients (p=0.004). We also found that the weight expressed as a percentage of ideal weight for height was significantly higher in patients with the R334W mutation (p=0.0028).
Adolescent↗
Thirteen cystic fibrosis patients, 12 compound heterozygous and one homozygous for the missense mutation G85E: a pancreatic sufficiency/insufficiency mutation with variable clinical presentation.
To study the severity of mutation G85E, located in the first membrane spanning domain of the CFTR gene, we studied the clinical features of 13 Spanish patients with cystic fibrosis (CF) carrying this mutation. G85E accounts for about 1% of Spanish CF alleles. One patient was homozygous G85E/G85E and the rest were compound heterozygotes for G85E and other mutations (delta F508 nine patients, delta I507 two patients, and 712-1G > T one patient). The characteristics of the pooled G85E/any mutation group were compared with those of 30 delta F508 homozygotes. Mean age at diagnosis and percentage of ideal height for age were higher in the G85E/any mutation group (4.2 (SD 4.7) v 2.4 (SD 2.3), p < 0.05, and 102.8 (SD 4.7) v 97.8 (SD 4.1), p < 0.01), both probably related to the greater prevalence of pancreatic sufficiency (70% v 0%, p < 0.01). The G85E homozygote was pancreatic sufficient. Sweat sodium levels were slightly higher, and salt loss related problems more frequent, in the G85E/any group. Two of the G85E patients died of respiratory failure aged 6 and 14 years. Striking discordance in the phenotype was observed in two pairs of sibs, one of them dizygotic twins, suggesting that factors, genetic and environmental, other than CFTR genotype are important in determining CF phenotype.
Child↗
Clinical characteristics of 16 cystic fibrosis patients with the missense mutation R334W, a pancreatic insufficiency mutation with variable age of onset and interfamilial clinical differences.
We present the genotype/phenotype correlation analysis for 16 cystic fibrosis (CF) patients who carry mutation R334W. Current age and age of diagnosis was significantly higher in the R334W/any-mutation group (P < 0.05 and P < 0.01), compared with the delta F508/delta F508 group. A slightly, but not significantly, worse lung function was found in the R334W/any-mutation group, when compared with the delta F508/delta F508 patients. The proportion of patients with lung colonization with bacterial pathogens was slightly, but not significantly, higher in the R334W/any-mutation group (71.4%), compared with the delta F508/delta F508 or R334W/delta F508 groups (55.5%). None of the R334W patients had meconium ileus but 60% were pancreatic insufficient (PI), a significantly lower proportion (P << 0.001) than delta F508/delta F508 patients. Two R334W/N1303K compound heterozygous sisters of three sibs with genotype R334W/delta F508 showed interfamilial discordant clinical data for lung and pancreatic function. The data provided here for mutation R334W demonstrate that this mutation is responsible for a less severe form of CF than delta F508. Interfamilial differences for PI and lung function suggest that other factors, viz. genetic, environmental and medical, contribute to the wide spectrum of clinical differences observed in CF patients with the same CF transmembrane conductance regulator genotypes.
Age of Onset↗
Molecular and clinical analyses of cystic fibrosis in the south of Spain.
We report molecular and clinical analyses in 71 unrelated patients with cystic fibrosis (CF) from Andalusia (South of Spain). Direct mutation analysis of six mutations of the CFTR gene (delta F508, G542X, R1162X, N1303K, W1182X and 1949de184) was performed. The proportion of CF chromosomes with the above-mentioned mutations was 58.5%. Haplotype analysis was performed with the marker/enzyme pairs XV2C/TaqI and KM19/PstI. A particular haplotype has been found associated with each of the studied mutations, while the pooled data for the unknown mutations are not associated with any particular haplotype. This lack of association indicates that there will not be a single predominant mutation amongst the other CF chromosomes. To assess the relationship between genotype and phenotype in these patients, we correlated the pancreatic status and the occurrence of chronic Pseudomona aeruginosa infection with the observed genotype. Pancreatic insufficiency was present in all patients in whom the analyzed mutations were found to be homozygous or compound heterozygous. We also found a higher rate of Pseudomonas colonization in the group of patients in whom the genotype was homozygous or compound heterozygous for the analysed mutations when compared with the group of patients with a different genotype, but the difference was not statistically significant.
Chi-Square Distribution↗
Uniparental inheritance of microsatellite alleles of the cystic fibrosis gene (CFTR): identification of a 50 kilobase deletion.
More than 250 mutations have been detected in the cystic fibrosis (CF) transmembrane regulator (CFTR) gene, most of which are single point mutations or small deletions or insertions of a few nucleotides. Here we report the first large deletion identified in the CFTR gene, which involves 50 kb in two stretches of DNA: one of 10 kb from exon 4 to exon 7, and another of 40 kb, spanning exons 11 to 18. The deletion has been detected via uniparental inheritance of CFTR microsatellite alleles (IVS17BTA and IVS17BCA) in 3 independent CF families. Clinical status of the 3 CF patients, of which two have the delta F508 mutation as the other CF allele, suggests that this mutation is responsible for a severe clinical phenotype, indistinguishable from homozygous delta F508 patients. The deletion detected here suggests that other large, but less complex molecular defects could also exist in the CFTR gene.
Adult↗
[Other therapeutic aspects of pulmonary disease in cystic fibrosis].
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Child↗
Linear kinematics of the men's 110-m and women's 100-m hurdles races.
Twenty-three male and nine female hurdlers were filmed using three-dimensional methods during competition at the 1988 United States Olympic Trials. An entire four-step cycle was analyzed, including the clearances of the men's fifth hurdle and the women's fourth hurdle. The results showed an increase in vertical velocity and a decrease in forward horizontal velocity during the takeoff of the hurdle step. The forward velocity was recovered mainly in the second support phase after the hurdle. The downward motion of the center of mass (c.m.) was not stopped until the second support phase after the hurdle clearance. The peak of the c.m. parabola was almost directly over the hurdle in the men, and 0.30 m before the hurdle in the women. It was shown that the women used a parabola with a larger margin over the top of the hurdle than the men: A lower parabola would shorten the hurdle step, and would require the lengthening of the three interhurdle steps. It would also make the duration of the airborne phase too short, which would not give the legs enough time to prepare for landing after the execution of their motions over the hurdle. Therefore, women should not be coached to imitate the men's hurdle clearance technique.
Biomechanical Phenomena↗
Angular momentum in the men's 110-m and women's 100-m hurdles races.
Twenty-three male and nine female hurdlers were filmed using three-dimensional methods at the 1988 United States Olympic Trials. With respect to the athletes, the X, Y, and Z axes pointed to the right, forward, and upward, respectively. During hurdle clearance, the X component of angular momentum was negative (clockwise rotation in a view from the right). Early in the airborne phase, it was associated with the motion of the trail leg. The downward motion of the lead leg was produced mainly by transfer of angular momentum from the trail leg, rather than by the lifting of the head-trunk. The Y component of angular momentum was negative (counterclockwise in a back view of a hurdler taking off from the right foot). It was necessary for the abduction of the trail leg. When this abduction slowed down, the angular momentum was taken up by the lowering (and slight adduction) of the left leg and elevation of the right elbow. The hurdle clearance required a positive Z component of angular momentum (counterclockwise in an overhead view): The clockwise angular momentum of the right arm as it swept backward was not enough to compensate for the larger counterclockwise angular momentum required for the forward motion of the trail leg. Our improved understanding of the rotations involved in hurdling will be useful for the correction of technique defects in individual athletes.
Biomechanical Phenomena↗
Influence of the direction of the cable force and of the radius of the hammer path on speed fluctuations during hammer throwing.
Hammer speed increases gradually during a throw, but this general increasing trend has one fluctuation superimposed in each turn. In some throwers, gravity and the forward translation of the system produce most of the fluctuation; in others, a marked fluctuation remains after the effects of gravity and of the forward translation of the system have been subtracted out. The remaining fluctuation could be produced through two mechanisms: (a) pulling on the hammer cable in a direction alternately ahead and behind the position of the centroid of the hammer path and (b) alternately shortening and lengthening the distance between the hammer head and the centroid of its path. Three-dimensional film analysis of eight highly-skilled throwers showed that the portion of the hammer speed fluctuation not due to gravity nor to the forward motion is produced mainly by pulling alternately ahead and behind the position of the centroid of the hammer path.
Biomechanical Phenomena↗
A three-dimensional analysis of angular momentum in the hammer throw.
Eight hammer throwers were studied using three-dimensional cinematography. The local term of angular momentum of each thrower (HTL) followed a wide conical path, while the remote term (HTR) and the hammer angular momentum (HH) followed much narrower conical paths. HT, the sum of HTL and HTR, followed a conical path similar to that of HTL, although with smaller amplitude. HH was half of a cycle out of phase with HT. It was also larger but followed a narrower conical path. As a result, the conical paths of HH and HT counteracted each other, and HS, the total angular momentum vector of the thrower-hammer system, had little conical motion. The paths of the angular momentum vectors, the trunk tilt, and the height of the hammer plane relative to the system center of mass were interrelated. Some throwers kept the hammer plane high and the trunk tilting back in all the turns; other throwers kept the hammer plane low and the trunk tilting forward in the early turns, but the hammer plane rose in their late turns and the trunk tilted back. Two theories were proposed to explain why the athletes who had forward trunk tilt in the early turns tilted backward in the final part of the throw.
Biomechanical Phenomena↗
Vertical and radial motions of the body during the take-off phase of high jumping.
By placing the muscles of the take-off leg in faster eccentric or slower concentric conditions, a high jumper can increase the ground reaction force and the height of the jump. Film analysis of seven high jumpers showed that the radial velocity of the center of mass with respect to the supporting foot was more negative or less positive than the vertical velocity throughout the take-off phase. This favored faster eccentric or slower concentric conditions of the leg muscles. The radial distance from the hip of the take-off leg to the center of mass (RG/H) first decreased by 0.030 m, due to negative radial motions of the arms and swinging leg. This contributed to a smaller negative radial velocity of the hip (VRH), and thus to slower eccentric conditions of the muscles of the take-off leg. Therefore, it may have helped to cushion the initial impact with the ground. Subsequently, RG/H increased by 0.120 m, due to positive radial velocities of the arms, the swinging leg, and the head and trunk. This contributed first to larger negative (and later to smaller positive) VRH values, and thus to faster eccentric and slower concentric conditions of the muscles of the take-off leg.
Biomechanical Phenomena↗
A kinematic study of center of mass motions in the hammer throw.
Eight highly-skilled hammer throwers were studied using film analysis procedures. The location and velocity of the center of mass (c.m.) of each thrower, hammer and thrower-hammer system were calculated. The vertical component of motion of all three c.m.s followed cyclic patterns with one fluctuation per turn. The fluctuation of the c.m. of the thrower was ahead of that of the hammer by approximately a third of a cycle, and this made the periods of upward vertical acceleration of the system c.m. coincide approximately with the double-support phases. In the horizontal direction, the c.m.s of the thrower and of the hammer followed roughly trochoid patterns as a result of the combination of rotation with forward displacement across the throwing circle. Their rotations were out of synchrony by approximate synchrony with the hammer, or an essentially straight trajectory. The results of this study suggest that the investigation of the hammer throw might be facilitated by the use of a quasi-inertial non-rotating reference frame that follows the general motion of the system c.m. while ignoring its fluctuations within each turn.
Humans↗
Correction for 'three-dimensional cinematography with control object of unknown shape.
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Biomechanical Phenomena↗
The pattern of hammer speed during a hammer throw and influence of gravity on its fluctuations.
Hammer speed at release is one of the most important factors contributing to the distance of a hammer throw. Hammer speed follows a generally increasing trend during the throw, with one fluctuation per turn. The purpose of the present paper was to quantify the influence of gravity on the speed fluctuations. Eight experienced hammer throwers were studied with three-dimensional filming methods. Instantaneous values of hammer velocity and speed were calculated from the film data. The rate of change of hammer speed due to the tangential component of gravity was computed, and integrated to calculate the accumulated contribution of gravity to hammer speed at all instants of the throw. These values were subtracted from the corresponding values of hammer speed. The amplitude of the fluctuations was reduced in the corrected speed functions, indicating a contribution of gravity to the original fluctuations. However, the fluctuations were still clearly present in the corrected speed functions, indicating the existence of other causal factors.
Acceleration↗