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Biomedical subjects

C Fabre

Publications and source records attributed to C Fabre.

At least 19 recordsLinked to original sources

Quantum limits on optical resolution

We discuss the ultimate limit imposed by quantum fluctuations of light for resolution of fine details in optical images. For this purpose, we extend in the quantum domain the classical analysis of the object reconstruction, or superresolution, in terms of prolate spheroidal function basis. We derive the expression for ultimate resolution limit in the reconstructed object using an illumination of the full object plane by a multimode squeezed vacuum. We show that the gain in resolution using multimode squeezed light is maximum when the Shannon number of the imaging system is close to unity.

Journal Article↗

Crystal structure of the arcelin-1 dimer from Phaseolus vulgaris at 1.9-A resolution.

Arcelin-1 is a glycoprotein from kidney beans (Phaseolus vulgaris) which displays insecticidal properties and protects the seeds from predation by larvae of various bruchids. This lectin-like protein is devoid of monosaccharide binding properties and belongs to the phytohemagglutinin protein family. The x-ray structure determination at 1.9-A resolution of native arcelin-1 dimers, which correspond to the functional state of the protein in solution, was solved using multiple isomorphous replacement and refined to a crystallographic R factor of 0.208. The three glycosylation sites on each monomer are all covalently modified. One of these oligosaccharide chains provides interactions with protein atoms at the dimer interface, and another one may act by preventing the formation of higher oligomeric species in the arcelin variants. The dimeric structure and the severe alteration of the monosaccharide binding site in arcelin-1 correlate with the hemagglutinating properties of the protein, which are unaffected by simple sugars and sugar derivatives. Sequence analysis and structure comparisons of arcelin-1 with the other insecticidal proteins from kidney beans, arcelin-5, and alpha-amylase inhibitor and with legume lectins, yield insights into the molecular basis of the different biological functions of these proteins.

Amino Acid Sequence↗

Characterization and sugar-binding properties of arcelin-1, an insecticidal lectin-like protein isolated from kidney bean (Phaseolus vulgaris L. cv. RAZ-2) seeds.

Arcelin-1 is a lectin-like protein found in the seeds of wild varieties of the kidney bean (Phaseolus vulgaris). This protein displays insecticidal properties, but the mechanism of action is as yet unknown. In the present study we investigated the biochemical and biophysical properties of arcelin-1 from Phaseolus vulgaris cv. RAZ-2. Native arcelin-1 is a dimeric glycoprotein of 60 kDa, built from the non-covalent association of two identical monomers. This dimer resists dissociation by chaotropic agents and is highly resistant to proteolytic enzymes. Each subunit contains 10% (w/w) neutral sugars which belong to the high-mannose and complex-type glycans attached to three glycosylation sites. No interaction of the protein with simple sugars could be detected, but arcelin-1 displays an intrinsic specificity in binding complex glycans. Arcelin-1 therefore differs from the closely related phytohaemagglutinin lectins and alpha-amylase inhibitor in several respects: oligomerization states, sugar-binding affinities and the type and number of glycan chains. These features may be related to the toxicity of arcelin-1.

Amino Acid Sequence↗

Small-angle X-ray scattering and crystallographic studies of arcelin-1: an insecticidal lectin-like glycoprotein from Phaseolus vulgaris L.

Arcelin-1 and alpha-amylase inhibitor are two lectin-like glycoproteins expressed in the seeds of the kidney bean (Phaseolus vulgaris). They display insecticidal activities and protect the seeds from predation by larvae of various bruchids through different biological actions. Solution-state investigations by small-angle X-ray scattering (SAXS) show the dimeric structure of arcelin-1, a requirement for its hemagglutinating properties. Anions were found to have specific properties in their effectiveness to disrupt protein aggregates, affect solubility, and improve crystallizability. The SAXS results were used to improve crystallization conditions, and single crystals diffracting beyond 1.9 A resolution were obtained. X-ray diffraction data analysis shows that noncrystallographic symmetry-related arcelin-1 molecules form a lectin-like dimer and reveals the presence of a solvent-exposed anion binding site on the protein, at a crystal-packing interface. The solution state properties of arcelin-1 and crystal twinning may be explained by the anion specificity of this binding site.

Amino Acid Sequence↗

Effectiveness of individualized aerobic training at the ventilatory threshold in the elderly.

This study was designed to specify whether an individualized training program at the ventilatory threshold in elderly subjects produces greater training adaptations than a standardized training program performed at 50% of heart rate reserve. Sixteen subjects participated in the study. Maximal exercise tests were performed on a treadmill before and after the training program. Eight subjects trained at the ventilatory threshold (ITG) and eight trained at 50% of heart rate reserve (STG). The mean training heart rate was 129 +/- 14.2 bpm and 115 +/- 7.9 bpm in the individualized training group (ITG) and the standardized training group (STG), respectively. The maximal O2 uptake (VO2max) was improved significantly by 20% in ITG (within group p < .05), whereas no significant improvement was noted in STG. The improvement in ITG compared to the nonsignificant change in STG was significant (p < .05). In addition, submaximal ventilation and heart rate were more decreased in ITG than STG. We conclude that for elderly people an individualized training program at the level of the ventilatory threshold is significantly more effective in terms of VO2max and submaximal cardiorespiratory adaptations.

Adaptation, Physiological↗

Comparison of two training programmes in chronic airway limitation patients: standardized versus individualized protocols.

This study tested the effect of two methods of training, one individualized at the heart rate corresponding to the gas exchange threshold (GET) and the other at the heart rate corresponding to 50% of maximal heart rate reserve, on maximal and submaximal cardiorespiratory response in 24 patients with chronic airway limitation (CAL). The patients were randomly assigned to either the individualized training group (IT; n = 12) or the standardized training group (ST; n = 12). The training programme consisted of 4 weeks of stationary bicycle exercise, 5 days.week-1. Before reconditioning began, the target level based on heart rate was not significantly different between groups (109 +/- 4 versus 110 +/- 3 beats.min-1, in IT and ST, respectively). Post-training, a significant increase in symptom-limited oxygen uptake (V'O2.sl) and maximal O2 pulse was found in IT, whereas ST exhibited no significant change. In each group, GET was statistically increased in much the same way as V'O2,sl, with a higher increase in IT (p < 0.01) than ST (p < 0.05). Nevertheless, IT exhibited a concomitant and gradual decrease in minute ventilation (V'E), carbon dioxide production (V'CO2), and venous lactate concentration ([La]), whereas ST presented no significant change in these parameters (intergroup p < 0.01). Breathing pattern was also altered after IT, at the same metabolic level and at the same ventilation level (intergroup p < 0.05). Cardiac responses were modified in the two groups. At the same metabolic level, a significantly lower cardiac frequency was found both for IT and ST (intragroup p < 0.05 after training). In contrast, the increase in O2 pulse was only significantly higher in It after training. These data show the greater efficiency of an individualized training protocol based on determination of gas exchange threshold as compared to a standardized protocol, in improving exercise performance, when applied to a patient group. Despite an apparently similar target training level, the individualized method clearly optimized the physiological training effects in patients with chronic airway limitation and, more particularly, decreased their ventilatory requirement.

Bicycling↗

Mutagenesis of N-glycosylation sites in the human vasoactive intestinal peptide 1 receptor. Evidence that asparagine 58 or 69 is crucial for correct delivery of the receptor to plasma membrane.

The functional role of N-linked carbohydrates in the human vasoactive intestinal peptide (VIP) 1 receptor was investigated by site-directed mutagenesis (Asn-->Thr) of the four consensus N-glycosylation sites on Asn58, Asn69, Asn100 (N-terminal extracellular domain) and Asn293 (second extracellular loop). Mutated receptors were investigated after transient expression in Cos-7 cells, by ligand binding assay, affinity cross-linking, western blotting, and confocal laser microscopy of epitope-tagged receptor proteins. Mutations of each consensus site revealed that Asn58, Asn69, and Asn100 were occupied by a 9-kDa N-linked carbohydrate whereas Asn293 was not used for glycosylation. Each mutated receptor was expressed (western blot) and delivered at the plasma membrane (confocal microscopy) of Cos-7 cells. They displayed a dissociation constant similar to that of the wild-type receptor, i.e., 0.5-1 nM. In contrast, no VIP binding to Cos-7 cells could be observed with the mutant devoid of consensus N-glycosylation sites due to a strict sequestration of this mutant in the perinuclear endoplasmic reticulum. However, when solubilized with a zwitterionic detergent, this mutant bound [125I]VIP specifically, indicating that it retained intrinsic binding activity. The construction of other mutants in which three out of four N-glycosylation sites were altered, demonstrated that N-glycosylation at either Asn58 or Asn69 is necessary and sufficient to ensure correct delivery of the receptor to the plasma membrane. Further pharmacological studies involving incubation of Cos-7 cells with castanospermine or deoxymannojirimycin immediately after transfection of mutated cDNAs encoding receptors with a single glycosylation site at Asn58 or Asn69 suggested that carbohydrate at Asn58 was involved in a calnexin-dependent folding process of the receptor whereas carbohydrate at Asn69 was not. These studies highlight the functional importance of the N-glycosylation of the human VIP 1 receptor which belongs to a new subfamily of seven membrane-spanning receptors.

Amino Acid Sequence↗

Pulmonary gas exchange capacity is reduced during normovolaemic haemodilution in healthy human subjects.

PURPOSE: To test the hypothesis that a physiological compensatory mechanism maintains respiratory gas exchange during normovolaemic haemodilution. METHODS: Pulmonary gas exchange capacity was evaluated in seven healthy subjects by measuring the lung diffusion of carbon monoxide (DLCO). During the measurement, various breath-holding times, inspiratory volumes, and sitting or supine positions, were randomly selected in an attempt to alter pulmonary capillary perfusion. KCO was calculated as the percentage of theoretical values of the ratio of DLCO by alveolar volume and normalized by sex, age, and height. Normovolaemic haemodilution (NH) was performed by bleeding an average blood volume of 1 L with simultaneous Dextran 60 replacement to obtain an haematocrit below 35%. RESULTS: After NH, haemoblogin concentration [Hb] decreased from 14.94 +/- 0.96 to 12.5 +/- 0.98 g.dl-1 (P < 0.001). KCO decreased (P < 0.02) but remained closely correlated to [Hb] at every lung volume (P < 0.02). Breathholding time and body position had no effect. CONCLUSION: Moderate NH impairs pulmonary gas exchange capacity in awake, resting healthy subjects. There is no evidence of any compensatory mechanism since the KCO vs [Hb] relationship is unchanged.

Adult↗

Adjuvant radiotherapy versus combined sequential chemotherapy followed by radiotherapy in the treatment of resected nonsmall cell lung carcinoma. A randomized trial of 267 patients. GETCB (Groupe d'Etude et de Traitement des Cancers Bronchiques).

BACKGROUND: The effect of adjuvant chemotherapy after resection of nonsmall cell lung cancer (NSCLC) remains an unresolved question. METHODS: From October, 1982, to November, 1986, 267 patients with resected NSCLC were included in a randomized trial. The adjuvant allocated treatments were either postoperative radiotherapy, 60 Gy in 6 weeks (radiotherapy group = 129 patients), or three courses of postoperative COPAC (cyclophosphamide, doxorubicin, cisplatin, vincristine, lomustine) chemotherapy followed by a similar radiotherapy schedule (chemotherapy/radiotherapy group = 138 patients). RESULTS: The sex ratio (M:F) was 19/1; mean age was 57 +/- 9 years. According to postoperative staging, 8 patients were Stage I, 70 were Stage II, and 189 were Stage III. The histologic type was squamous cell carcinoma in 175 patients, adenocarcinoma in 57, and large cell carcinoma in 35. The minimum follow-up was 6 years. Four patients were lost to follow-up. Death was recorded in 233 patients. No significant difference was observed in terms of disease free interval (P = 0.47, log-rank test), or overall survival (P = 0.68, log-rank test). With respect to the first site of relapse, distant metastasis occurred more frequently in the radiotherapy group (P = 0.09, log-rank test) whereas local relapse occurred similarly in both groups (P = 0.27). An interaction was observed between lymph node involvement and treatment in terms of overall survival. CONCLUSIONS: The COPAC chemotherapy as postoperative treatment failed to improve overall survival in patients with resected NSCLC receiving postoperative radiotherapy but decreased the pattern of metastatic progression, mainly in the N2 patients.

Antineoplastic Combined Chemotherapy Protocols↗

Pulmonary gas exchange and ventilatory responses to brief intense intermittent exercise in young trained and untrained adults.

To investigate pulmonary gas exchange and ventilatory responses to brief intense intermittent exercise and to study the effects of physical fitness on these responses, nine trained and nine untrained healthy male subjects aged 18-33 years performed the force-velocity (F-v) exercise test. This test consisted of 6-s sprints against increasing braking forces (F) separated by 5-min recovery periods. Oxygen uptake (VO2), carbon dioxide output (VCO2), and ventilation (VE) were continuously measured during the test and the magnitudes of their responses to the sprints were then calculated. For all subjects VO2 increased rapidly after beginning the sprints, and the peaks of the responses (F = 13.4; P < 0.001), end of recovery values (F = 6.5; P < 0.01), and VO2 magnitudes of response (F = 12.4; P < 0.001) rose significantly with the repetition of the sprints. The VO2 magnitudes of response correlated with the corresponding sprint power outputs (r = 0.55; P < 0.001) and with the sprint repetitions (r = 0.51, P < 0.001). The VCO2 (F = 7.1; P < 0.01) and VE (F = 5.0; P < 0.01) peaks of response increased with the initial load incrementation, then stabilized when the subjects attained peak power output. End of recovery VCO2 (F = 18.0; P < 0.001) and VE (F = 14.1; P < 0.001) values rose with increasing F. The F-v peak VO2, VCO2, VE, tidal volume and respiratory frequency responses attained 53%, 40%, 44%, 66%, and 82% of the peak values measured at exhaustion of maximal graded exercise, respectively. (ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Anaerobic and aerobic peak power output and the force-velocity relationship in endurance-trained athletes: effects of aging.

The aim of this investigation was to test the hypothesis that the anaerobic peak power output (Pan, peak) declines more than the peak aerobic power (Paer, peak) with increasing age. In addition, the force-velocity (F-v) relationship was studied to determine which of these two factors is primarily responsible for the expected alterations in anaerobic power. The Pan, peak, the maximal F when v is equal to zero (F0) and the maximal v when F is equal to zero (v0) were assessed by F-v test i.e. a brief intense intermittent exercise test using incremental braking forces. The Paer, peak was measured by a maximal increment exercise test. A group of 12 young athletes (YA) and 12 master athletes (MA) mean age 24.8 (SEM 1.3) and 65.1 (SEM 1.2) years, respectively, participated in this study. The YA and MA had similar body masses, heights and endurance training schedules. The results showed that Pan, peak was 42.7% lower in the older subjects, corresponding to mean values of 1089 (SEM 40) compared to 624 (SEM 33) W (t = 8.9, P < 0.001) for YA compared to MA, respectively. The F0 and V0 indices showed values that were lower by 30.3% and 15.2%, respectively. The Paer, peak was 35% lower with mean values of 323 (SEM 12) W for YA compared to 210 (SEM 6) W for MA (t = 8.3, P < 0.001). The mean maximal oxygen uptake was 34.7% lower with 4240 (SEM 160) ml.min-1 for YA compared to 2770 (SEM 120) ml.min-1 for MA (t = 7.2, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

[Anosognosic graphomimia: an uncommon variety of hypergraphia in right sylvian infarction].

Following a massive infarction in the territory of the right sylvian artery, a right-handed patient with a left hemiplegia and anosognosia, developed a peculiar hypergraphia. It consisted of an inappropriate and permanent writing behaviour, disappearing only during sleep. Space-constructional components of writing were severely disturbed. Graphemes were poorly formed. The graphic disturbances were different from hypergraphia previously described in stroke patients who produced linguistically correct but semantically loose writing. They were also different from graphomania reported in a case of fronto-callosal glioma. Our case of anosognosic hypergraphia suggests a sudden loss of inhibition of writing activity of the left hemisphere. The term graphomimia is proposed to distinguish this writing behaviour from the cases of hypergraphia previously reported and from graphomania.

Aged↗

A receptor for VIP-related peptides with an unusual selectivity profile on the melanoma cell line IGR37.

A receptor capable of recognizing VIP-related peptides with unusual functional characteristics and selectivity profile was characterized on human IGR37 melanoma cells. When using either [125I]VIP or [125I]N-AcPACAP27 as a tracer, PACAP38 had the highest affinity, while PACAP27, VIP, helodermin, GRF and the VIP fragment VIP10-28 showed the same low affinity. Moreover, this receptor did not recognize PHM, PHV, helospectin, secretin, GIP, glucagon and glucagon-like peptide-1(7-36). Surprisingly, none of the peptides significantly stimulated the cAMP production. By covalent crosslinking, the receptor was shown to have a M(r) = 60,500.

Binding, Competitive↗