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Biomedical subjects

C Fabre

Publications and source records attributed to C Fabre.

At least 19 recordsLinked to original sources

Immunotherapy with an aluminum hydroxide-adsorbed Juniperus ashei foreign pollen extract in seasonal indigenous cypress pollen rhinoconjunctivitis. A double-blind, placebo-controlled study.

BACKGROUND: The efficacy of standardized Juniperus ashei extract was assessed in patients with allergic rhinoconjunctivitis due to European cypress pollens. METHODS: Forty adults with European cypress-allergic rhinoconjunctivitis were randomized to receive immunotherapy or a matched placebo. Specific immunotherapy was performed with a standardized, aluminum hydroxide-adsorbed J. ashei extract with a potency of 100 IR (arbitrary index of reactivity) containing 54 microg of Jun a 1/ml (Alustal, Stallergenes, France). Subcutaneous injections started in October 2000. The maintenance dose was 0.30 ml of the 100-IR concentration per month. Rhinitis and conjunctivitis symptoms were rated according to a 4-point score. RESULTS: Seventeen patients from the treated group and 15 patients from the placebo group completed year 2001; 14 in each group completed year 2002. A statistically significant improvement (41%, p < 0.02) in the conjunctivitis symptom score was observed in actively treated patients compared to the placebo group at the peak of the 2001 pollen season. Improvement in rhinitis (17%) was not significant. This significant improvement was greater at the peak of the 2002 pollen season (63%, p < 0.01). CONCLUSIONS: This study therefore indirectly validates the concept of treatment by major allergen because J. ashei is absent from the region in which this study was conducted.

Adsorption↗

NF-kappaB inhibition sensitizes to starvation-induced cell death in high-risk myelodysplastic syndrome and acute myeloid leukemia.

CD34(+) bone marrow blasts from high-risk myelodysplastic syndrome (MDS) patients as well as MDS patient-derived cell lines (P39 and MOLM13) constitutively activate the nuclear factor-kappaB (NF-kappaB) pathway and undergo apoptosis when NF-kappaB is inhibited. Here, we show that the combination of conventional chemotherapeutic agents (daunorubicin, mitoxantrone, 5-azacytidine or camptothecin) with the NF-kappaB inhibitor BAY11-7082 did not yield a synergistic cytotoxicity. In contrast, BAY11-7082 (which targets the NF-kappaB-activating I-kappaB kinase (IKK) complex) or knockdown of essential components of the NF-kappaB system (such as the IKK1 and IKK2 subunits of the IKK complex and the p65 subunit of NF-kappaB), by small interfering RNAs sensitized MDS cell lines to starvation-induced apoptosis. The combination of BAY11-7082 and nutrient depletion synergistically killed the acute myeloid leukemia (AML) cell line U937 as well as primary CD34(+) bone marrow blasts from AML and high-risk MDS patients. The synergistic killing by BAY11-7082, combined with nutrient depletion, led to cell death accompanied by all hallmarks of apoptosis, including an early loss of the mitochondrial transmembrane potential, the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, activation of caspase-3, phosphatidylserine exposure on the plasma membrane surface and nuclear chromatin condensation. Transmission electron microscopy revealed the presence of numerous autophagic vacuoles in the cytoplasm before cells underwent nuclear apoptosis. Nonetheless, cell death was neither inhibited by the pan-caspase inhibitor z-VAD-fmk nor by knockdown of AIF or of essential components of the autophagy pathway (ATG5, ATG6/Beclin-1, ATG10, ATG12). In contrast, external supply of glucose, insulin or insulin-like growth factor-I could retard the cell death induced by BAY11-7082 combined with starvation. These results suggest that in MDS cells, NF-kappaB inhibition can precipitate a bioenergetic crisis that leads to an autophagic stress response followed by apoptotic cell death.

Acute Disease↗

Inhibition of NEMO, the regulatory subunit of the IKK complex, induces apoptosis in high-risk myelodysplastic syndrome and acute myeloid leukemia.

In high-risk myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), blasts constitutively activate the antiapoptotic transcription factor nuclear factor-kappaB (NF-kappaB). Here, we show that this NF-kappaB activation relies on the constitutive activation of the IkappaB kinase (IKK) complex, which is formed by the IKKalpha, IKKbeta and IKKgamma/NF-kappaB essential modulator (NEMO) subunits. A cell-permeable peptide that mimics the leucine zipper subdomain of IKKgamma, thus preventing its oligomerization, inhibited the constitutive NF-kappaB activation and induced apoptotic cell death in a panel of human MDS and AML cell lines (P39, MOLM13, THP1 and MV4-11). Small interfering RNA-mediated knockdown of the p65 NF-kappaB subunit or the three IKK subunits including IKKgamma/NEMO also induced apoptotic cell death in P39 cells. Cell death induced by the IKKgamma/NEMO-antagonistic peptide involved the caspase-independent loss of the mitochondrial transmembrane potential as well as signs of outer mitochondrial membrane permeabilization with the consequent release of cytochrome c, apoptosis-inducing factor and endonuclease G. Primary bone marrow CD34(+) cells from high-risk MDS and AML patients also succumbed to the IKKgamma/NEMO-antagonistic peptide, but not to a mutated control peptide. Altogether, these data indicate that malignant cells in high-risk MDS and AML cells critically depend on IKKgamma/NEMO to survive. Moreover, our data delineate a novel procedure for their therapeutic removal, through inhibition of IKKgamma/NEMO oligomerization.

Acute Disease↗

Direct production of tripartite pump-signal-idler entanglement in the above-threshold optical parametric oscillator.

We calculate the quantum correlations existing among the three output fields (pump, signal, and idler) of a triply resonant nondegenerate optical parametric oscillator operating above threshold. By applying the standard criteria [P. van Loock and A. Furusawa, Phys. Rev. A 67, 052315 (2003)], we show that strong tripartite continuous-variable entanglement is present in this well-known and simple system. Furthermore, since the entanglement is generated directly from a nonlinear process, the three entangled fields can have very different frequencies, opening the way for multicolored quantum information networks.

Journal Article↗

Targeting NF-kappaB in hematologic malignancies.

The transcription factor nuclear factor kappa B (NF-kappaB) can intervene in oncogenesis by virtue of its capacity to regulate the expression of a plethora of genes that modulate apoptosis, and cell survival as well as proliferation, inflammation, tumor metastasis and angiogenesis. Different reports demonstrate the intrinsic activation of NF-kappaB in lymphoid and myeloid malignancies, including preneoplastic conditions such as myelodysplastic syndromes, underscoring its implication in malignant transformation. Targeting intrinsic NF-kappaB activation, as well as its upstream and downstream regulators, may hence constitute an additional approach to the oncologist's armamentarium. Several small inhibitors of the NF-kappaB-activatory kinase IkappaB kinase, of the proteasome, or of the DNA binding of NF-kappaB subunits are under intensive investigation. Currently used cytotoxic agents can induce NF-kappaB activation as an unwarranted side effect, which confers apoptosis suppression and hence resistance to these drugs. Thus, NF-kappaB inhibitory molecules may be clinically useful, either as single therapeutic agents or in combination with classical chemotherapeutic agents, for the treatment of hematological malignancies.

Hematologic Neoplasms↗

Identification of healthy elderly fallers and non-fallers by gait analysis under dual-task conditions.

OBJECTIVE: We compared falling and non-falling healthy elderly subjects to identify balance disorders associated with falling. Gait parameters were determined when carrying out single and dual tasks. DESIGN: Case comparison study. SETTING: Subjects were studied in the gait laboratory at Hôpital Roger Salengro, Lille, France. SUBJECTS: A group of 40 healthy elderly women were assigned to one of two groups according to their falling history: 21 fallers aged 70.4 +/- 6.4 years and 19 non-fallers aged 67.0 +/- 4.8 years. All subjects performed first a single leg balance test with two conditions (eyes open/closed). Then, gait parameters were analysed under single-task and dual motor-task conditions (walking with a glass of water in the hand). MAIN MEASURES: Falls, number of times suspended foot touched the floor during the single leg balance test, cadence, speed, stride time, step time, single-support time, stride length and step length during walking under single- and dual-task conditions. RESULTS: During the single leg balance test, fallers placed their feet on the floor three times more often than non-fallers under eyes open conditions (P < 0.05) and twice as often under eyes closed conditions (P < 0.05). In the single-task condition, no significant difference in gait parameters was reported between fallers and non-fallers. There was a significant difference (P < 0.05) in the gait parameters (cadence, speed, stride and step time, single-support time) between fallers and non-fallers under dual-task conditions. CONCLUSIONS: Dual tasks perturb walking in fallers, who exhibit deteriorated static balance. Consequently, walking under dual-task conditions plus a single leg balance test could be helpful in detecting walking disorders and planning physiotherapy to prevent falls.

Accidental Falls↗

Recrudescence of imported falciparum malaria after quinine therapy: potential drug interaction with phenytoin.

Quinine remains a reliable treatment for falciparum malaria in most parts of the world. We report recrudescence of imported Plasmodium falciparum malaria following quinine treatment in the context of concurrent phenytoin use. Supported by a subtherapeutic quinine level, we hypothesise that a drug interaction with phenytoin may compromise the efficacy of quinine in the treatment of malaria.

Anticonvulsants↗

[Effects of training on static and dynamic balance in elderly subjects who have had a fall or not].

OBJECTIVE: To evaluate the effects of a physical training program on static and dynamic balance during single and dual task conditions in elderly subjects who have had a fall or not. PATIENTS: Two groups, comprising a total of 33 elderly subjects, were trained: 16 who had a fall were 69.2 +/- 5.0 years old and 17 who had not had a fall were 67.3 +/- 3.8 years. METHODS: All subjects underwent an unipedal test with eyes open and eyes closed, followed by gait assessment during single and dual motor task conditions, before and after a physical training program. RESULTS: All subjects showed a significant decrease, by six times for subjects who had fallen and four times by those who had not, in the number of touch-downs in the unipedal test with eyes open (P < 0.05), and by 2.5 and 2 times, respectively, with eyes closed (P < 0.05) after the training program. All subjects showed a significant increase in speed (P < 0.05), cadence (P < 0.05) and stride length (P < 0.05) and a significant decrease in the single support time (P < 0.05) and stride time (P < 0.05) in gait assessment during single and dual task conditions after the training program. During the training program, no subjects fell. CONCLUSION: The physical training program improved static balance and quality of gait in elderly subjects who had had a fall and those who had not, which could contribute to minimizing and/or retarding the effects of aging and maintaining physical independence.

Accidental Falls↗

Evidence of exercise-induced O2 arterial desaturation in non-elite sportsmen and sportswomen following high-intensity interval-training.

The aim of this study was to investigate the development of exercise-induced hypoxemia (EIH defined as an exercise decrease > 4 % in oxygen arterial saturation, i. e. SaO (2) measured with a portable pulse oximeter) in twelve sportsmen and ten sportswomen (18.5 +/- 0.5 years) who were non-elite and not initially engaged in endurance sport or training. They followed a high-intensity interval-training program to improve V.O (2)max for eight weeks. The training running speeds were set at approximately 140 % V.O (2)max running speed up to 100 % 20-m maximal running speed. Pre- and post-training pulmonary gas exchanges and SaO (2) were measured during an incremental running field-test. After the training period, men and women increased their V.O (2)max (p < 0.001) by 10.0 % and 7.8 %, respectively. Nine subjects (seven men and two women) developed EIH. This phenomenon appeared even in sportsmen with low V.O (2)max from 45 ml x min (-1) x kg (-1) and seemed to be associated with inadequate hyperventilation induced by training: because only this hypoxemic group showed 1) a decrease in maximal ventilatory equivalent in O (2) (V.E/V.O (2), p < 0.01) although maximal ventilation increased (p < 0.01) with training, i. e. in EIH-subjects the ventilatory response increased less than the metabolic demand after the training program; 2) a significant relationship between SaO (2) at maximal workload and the matched V.E/V.O (2) (p < 0.05, r = 0.67) which strengthened a relative hypoventilation implication in EIH. In conclusion, in this field investigation the significant decrease in the minimum SaO (2) inducing the development of EIH after high-intensity interval-training indicates that changes in training conditions could be accompanied in approximately 40 % non-endurance sportive subjects by alterations in the degree of arterial oxyhemoglobin desaturation developing during exercise.

Adolescent↗

[Ragweed pollinosis in the Gard and the Vaucluse: myth or reality? For the Associated Group of Independent Allergologues and Hospital Staff of Nimes].

Thirteen allergists reviewed 18 patients living and working in Vaucluse and Gard who suffered from ragweed from August 15 to October 15 2004. This preliminary study showed how difficult it is to realise a clinical data collection about pollinosis. It is entirely necessary to work together to build the protocol, with a clear and valid definition of inclusion and exclusion criteria.

Adolescent↗

Conditional preparation of a quantum state in the continuous variable regime: generation of a sub-Poissonian state from twin beams.

We report the first experimental demonstration of conditional preparation of a nonclassical state of light in the continuous variable regime. Starting from a nondegenerate optical parametric oscillator which generates above threshold quantum intensity correlated signal and idler "twin beams," we keep the recorded values of the signal intensity only when the idler intensity falls inside a band narrower than its standard deviation. By this very simple technique, we generate a sub-Poissonian state 4.4 dB (64%) below shot noise from twin beams exhibiting 7.5 dB (82%) of noise reduction in the intensity difference.

Journal Article↗

Surpassing the standard quantum limit for optical imaging using nonclassical multimode light.

Using continuous wave superposition of spatial modes, we demonstrate experimentally displacement measurement of a light beam below the standard quantum limit. Multimode squeezed light is obtained by mixing a vacuum squeezed beam and a coherent beam that are spatially orthogonal. Although the resultant beam is not squeezed, it is shown to have strong internal spatial correlations. We show that the position of such a light beam can be measured using a split detector with an increased precision compared to a classical beam. This method can be used to improve the sensitivity of small displacement measurements.

Journal Article↗

Improvement of cognitive function by mental and/or individualized aerobic training in healthy elderly subjects.

The aim of this study was to compare the effects of aerobic and mental training on cognitive function and to determine if the association of the two techniques shows better results. Thirty-two healthy elderly subjects (60 - 76 years) were assigned to one of four groups: aerobic training, mental training, combined aerobic and mental training and a control group. All subjects took two cognitive tests and an incremental exercise test before and after the training period. The intensity of exercise was individualized at the heart rate corresponding to the ventilatory threshold of each subject. After two months, the control group showed no alteration in physiological and cognitive variables. After the training period, the results showed a significant improvement in VO(2)max (F = 4.45, DF = 1, p < 0.05) of 12 % and 11 % in aerobic training and combined aerobic and mental training groups, respectively. Logical memory (F = 4.31, DF = 1, p < 0.05), as well as paired associates learning scores (F = 5.47, DF = 1, p < 0.05) and memory quotient (F = 6.52, DF = 1, p < 0.01) were significantly improved in the three trained groups. The mean difference in memory quotient between pre and post training was significantly higher in the combined aerobic and mental training group compared to aerobic training or mental training groups (F = 11.60, DF = 3, p < 0.001). We conclude that the specific aerobic training and mental training used in this study could induce the same degree of improvement in cognitive function and that combined training seemed to lead to greater effects than either technique alone.

Aged↗

Effects of high intensity intermittent training on peak VO(2) in prepubertal children.

This study was designed to examine peak VO(2) responses of prepubescent children following a 7-week aerobic training. Twenty-three boys and thirty girls (9.7 +/- 0.8 years) were divided into a high intensity experimental group (HIEG: 20 girls and 13 boys) and a control group (CG: 10 girls and 10 boys). A graded 20-m shuttle run with measurement of gas exchange values was performed prior to and after the 7-week training program. The test consisted of a 3-min run at 7 km x h(-1) to determine energy cost of running, immediately followed by a 20-meter shuttle run test. HIEG had two 30 min-sessions of short intermittent aerobic training per week at velocities ranging from 100 up to 130 % of the maximal aerobic speed. For HIEG, absolute peak VO(2)(9.1 %) and relative to body mass peak VO(2)(8.2 %) increased significantly (p < 0.001); it was unchanged in the CG. Similarly, maximal shuttle run improved significantly in HIEG (5.1 %, p < 0.001). In contrast, there was no significant change for CG. For both groups energy cost of running remained unchanged. These findings show that prepubescent children could significantly increase their peak VO(2) and maximal shuttle velocity with high intensity short intermittent aerobic exercises.

Age Factors↗

[Cupressaceae hay fever].

Cypress allergy or rather Cupressaceae allergy is an extraordinary observation subject and study model. Annual R.N.S.A. meeting is a good opportunity to share the analysts and sentinel doctors' point of view on this subject. For the medicine sentinel of the Nîmes's pollen site, the development of these Cupressaceae sensitivities is becoming a true public health priority. This feeling is shared by the southern sector responsible of the French network. It is absolutely necessary to develop actions.

France↗

[The allergic pregnant woman].

Drugs administrated to pregnant women must be carefully monitored. Prevention of dietary sensitization in foetus via the mother is still discussed. However, it must not induce any dietary deficiency to both the mother and the foetus. Environmental prevention is also controversial. Asthmatic pregnant women must be treated because under- or non treatment is more dangerous for both the woman and the foetus compared to eventual drug side effect. Asthma must be treated with inhaled glucocorticosteroid in order to be stabilized because giving birth is the only moment which can not be interrupted. Antihistamine-H1 which can be used during pregnancy are dexchlorpheniramine for the first and second third and cetirizine during the last third of the pregnancy.

Abnormalities, Drug-Induced↗

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↗