Biomedical subjects
C Lebreton
Publications and source records attributed to C Lebreton.
A high-density genetic map of hexaploid wheat (Triticum aestivum L.) from the cross Chinese Spring x SQ1 and its use to compare QTLs for grain yield across a range of environments.
A population of 96 doubled haploid lines (DHLs) was prepared from F1 plants of the hexaploid wheat cross Chinese Spring x SQ1 (a high abscisic acid-expressing breeding line) and was mapped with 567 RFLP, AFLP, SSR, morphological and biochemical markers covering all 21 chromosomes, with a total map length of 3,522 cM. Although the map lengths for each genome were very similar, the D genome had only half the markers of the other two genomes. The map was used to identify quantitative trait loci (QTLs) for yield and yield components from a combination of 24 site x treatment x year combinations, including nutrient stress, drought stress and salt stress treatments. Although yield QTLs were widely distributed around the genome, 17 clusters of yield QTLs from five or more trials were identified: two on group 1 chromosomes, one each on group 2 and group 3, five on group 4, four on group 5, one on group 6 and three on group 7. The strongest yield QTL effects were on chromosomes 7AL and 7BL, due mainly to variation in grain numbers per ear. Three of the yield QTL clusters were largely site-specific, while four clusters were largely associated with one or other of the stress treatments. Three of the yield QTL clusters were coincident with the dwarfing gene Rht-B1 on 4BS and with the vernalisation genes Vrn-A1 on 5AL and Vrn-D1 on 5DL. Yields of each DHL were calculated for trial mean yields of 6 g plant(-1) and 2 g plant(-1) (equivalent to about 8 t ha(-1) and 2.5 t ha(-1), respectively), representing optimum and moderately stressed conditions. Analyses of these yield estimates using interval mapping confirmed the group-7 effects on yield and, at 2 g plant(-1), identified two additional major yield QTLs on chromosomes 1D and 5A. Many of the yield QTL clusters corresponded with QTLs already reported in wheat and, on the basis of comparative genetics, also in rice. The implications of these results for improving wheat yield stability are discussed.
Indium- or Zinc-Mediated One-Pot Synthesis of Homoallylamines, beta-Amino Esters, and beta-Amino Nitriles.
Homoallylamines, beta-amino esters, and beta-amino nitriles were obtained in a one-pot synthesis directly from an aldehyde and a secondary amine such as dibenzylamine or diallylamine. Their condensation with titanium(IV) isopropoxide generates an intermediate aminoalkoxy titanium complex. Further reaction in THF with nucleophilic organometallic species, generated in situ from indium or zinc and a reactive halide (allyl bromide, alkyl bromo- or iodoacetate, iodoacetonitrile), furnished the corresponding amines.
Neuropathic arthropathy: a forgotten diagnosis? Two recent cases involving the hip.
Two cases of neuropathic arthropathy of the hip are reported. One was the first manifestation of tabes dorsalis in a 74-year-old man, whereas the second occurred in a 47-year-old woman with a history of spina bifida and L2-L5 epidural lipoma. Radiographic joint destruction occurred within five and three months, respectively. The main clinical and radiological features of neuropathic arthropathy are reviewed, and diagnostic pitfalls are discussed. There are no specific laboratory tests or histologic findings. This now rare condition should be routinely considered in patients with severe joint destruction contrasting with minimal pain. The reasons for the decision to use trochanteric-iliac coaptation in one of our patients and a wait-and-see approach in the other are explained. The literature is reviewed. Ten cases treated by joint replacement have been reported. However, neither joint replacement nor arthrodesis seem capable of restoring satisfactory hip function.
Non-coherent near infrared radiation protects normal human dermal fibroblasts from solar ultraviolet toxicity.
The sun is the most important and universal source of non-ionizing radiation shed on human populations. Life evolved on Earth bathed by this radiation. Solar UV damages cells, leading to deleterious conditions such as photoaging and carcinogenesis in human skin. During the process of evolution, the cells selected dark- and light-dependent repair mechanisms as a defence against these hazardous effects. This study describes the induction by non-coherent infrared radiation (700-2000 nm), in the absence of rising temperature, of a strong cellular defense against solar UV cytotoxicity as well as induction of cell mitosis. Blocking mitoses with arabinoside-cytosine or protein synthesis with cycloheximide did not abolish the protection, leading to the conclusion that this protection is independent of cell division and of protein neosynthesis. The protection provided by infrared radiation against solar UV radiation is shown to be a long-lasting (at least 24 h) and cumulatif phenomenon. Infrared radiation does not protect the lipids in cellular membranes against UVA induced peroxidation. The protection is not mediated by heat shock proteins. Living organisms on the Earth's surface are bathed by infrared radiation every day, before being submitted to solar UV. Thus, we propose that this as yet undescribed natural process of cell protection against solar UV, acquired and preserved through evolutional selection, plays an important role in life maintenance. Understanding and controlling this mechanism could provide important keys to the prevention of solar UV damage of human skin.
[Intramedullary metastases of bronchogenic carcinoma. Two cases].
Intramedullary metastases are uncommon. We report two cases in patients with small cell bronchogenic cancer. The clinical diagnosis was supported by T1 magnetic resonance imaging after gadolinium injection. A unique medullary metastasis associated with other metastatic localizations was observed in the first patient and multiple intramedullary metastases alone in the second. These secondary intramedullary localizations were highly sensitive to chemotherapy after the first monthly cure in the first patient and after the third in the second patient. We emphasize the importance of chemotherapy in such cases, usually associated with focal radiotherapy.
QTL analysis to study the association between leaf size and abscisic acid accumulation in droughted rice leaves and comparisons across cereals.
Plants accumulate abscisic acid (ABA) under droughted conditions. Genetic variation in the accumulation of ABA in deteched and partially dehydrated leaves of rice has previously been reported, and this was found to be associated with variation in leaf size (smaller leaves made more ABA). Correlation analysis failed to distinguish clearly between a causal relationship between the two traits and close genetic between loci controlling the traits. Here we present a detailed genetic analysis of ABA accumulation in detached and partially dehydrated rice leaves. using a population of F2 plants generated from the lowland x upland cross IR20 (high-ABA) x 63-83 (low-ABA) which was mapped with RFLP and AFLP markers. Several highly significant quantitative trait loci (QTLs) for ABA accumulation and leaf weight were identified. Only one of the minor QTLs for ABA accumulation (accounting for only 4% of the phenotypic variance) was coincident with any QTLs for leaf size such that the high-ABA allele was associated with smaller leaves. This analysis, therefore, showed that the association previously found between ABA accumulation and leaf size was probably largely due to genetic linkage and not to a direct effect of leaf size on ABA accumulation or vice versa. Because of the importance of ABA accumulation in regulating responses of plants to drought stress and the effects of plant size on the rate of development of stress, QTLs for drought-induced ABA accumulation, leaf size and tiller number were compared between rice and wheat. In particular, a possible location in rice was sought for a homoeologue of the major wheat vernalization responsive gene, Vrn1, as this gene is also associated with major effects on leaf size, tiller number and ABA accumulation in wheat. The likelihood of homoeologous loci regulating ABA accumulation, leaf size and tiller number in the two crops is discussed.
Modulation of keratinocyte growth factor (KGF) mRNA expression in human dermal fibroblasts grown in monolayer or within a collagen matrix.
In this study, we analysed the modulation of keratinocyte growth factor (KGF) mRNA expression in human dermal fibroblasts cultured either in monolayer or within a collagen matrix (dermal equivalent). In monolayer cultures, KGF expression by quiescent fibroblasts was stimulated by different growth substances such as serum, epidermal growth factor and basic fibroblast growth factor. Moreover, we demonstrated that the induction of this gene was mediated by at least 2 different signalling pathways involving protein kinase C (PKC) and cAMP. In dermal equivalents, we observed that the collagen matrix negatively modulated KGF mRNA expression. Indeed, among the growth substances used, only the serum slightly stimulated KGF expression. Nevertheless, as in monolayers, this induction involved at least PKC and cAMP signalling pathways. As the collagen matrix can modulate fibroblast growth, we also studied KGF expression in growing fibroblasts from either monolayer cultures or dermal equivalents. We then showed that this collagen matrix negatively influenced KGF expression independently of the proliferative state of fibroblasts. All these results underline the fact that KGF mRNA expression by human dermal fibroblasts is induced by different substances; however this expression can be modulated by fibroblast-matrix interactions.
UVA-induced oxidative damage in fibroblasts cultured in a 3-dimensional collagen matrix.
The exposure of dermal equivalent, i.e., fibroblasts cultured in a 3-dimensional collagen matrix to realistic doses of UVA (< or = 200 kJ/m2), results in a lipid peroxidation process as evidenced by the release of thiobarbituric acid-reactive substances in the supernatant. This peroxidative process is shown to be associated with the presence of fibroblasts and is inhibited by preincubation with vitamin E, the well-known chain-breaking antioxidant. Moreover, the UVA irradiation triggers cytotoxic effects which can also be reversed by preincubation with vitamin E. While the peroxidation extent is similar for fibroblasts cultured in monolayers or in dermal equivalent, the cytotoxic response to UVA is more pronounced in dermal equivalent.
Modulation of epidermal growth factor and keratinocyte growth factor effects on human keratinocyte growth by protein kinase C inhibitor, GF 109203X: comparison to fibroblast growth modulation.
In this study, epidermal growth factor (EGF), 20 ng/ml, and keratinocyte growth factor (KGF), 10 ng/ml, were able to stimulate human keratinocyte growth only in presence of GF 109203X 1 microM, a selective PKC inhibitor. This suggests that PKC negatively controls keratinocyte growth in response to EGF and KGF. On the other hand, EGF and KGF have no significant effect on PKC activity. In contrast, in human fibroblasts, EGF stimulated fibroblast growth in the presence or not of GF 109203X. Thus, EGF seems to stimulate fibroblast growth in a PKC independent manner. Moreover, EGF didn't modify significantly PKC activity in fibroblasts. KGF had no effect on fibroblasts. These results show differences in the interconnections between PKC and EGF transduction pathway in the modulation of human keratinocyte and fibroblast growth. Moreover, they especially demonstrate that PKC would negatively control human keratinocyte growth in response to EGF and also to KGF.
[Spinal sites, polyneuropathy and meningeal intra-spinal involvement disclosing recurrence of sarcoidosis. Diagnostic value of MRI].
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Differential modulation of human fibroblast and keratinocyte growth by the protein kinase C inhibitor GF 109203X.
Protein kinase C (PKC) is known to be involved in cellular proliferation and differentiation. In this work, we have investigated the effects of a novel PKC inhibitor, GF 109203X, on normal human fibroblast and keratinocyte growth. GF 109203X selectively inhibited PKC activity extracted from either fibroblasts (IC50 = 0.01 microM) or keratinocytes (IC50 = 0.4 microM). The inhibitory effects of GF 109203X on total PKC activity and Ca(2+)-independent PKC activity were similar. Nevertheless, in keratinocytes Ca(2+)-independent PKC activity represented 95% of total PKC activity, whereas in fibroblasts it corresponded to only 32% of total PKC activity. GF 109203X also inhibited a cellular function related to PKC activity in living fibroblasts and keratinocytes; it blocked the inhibitory effect of 12-O-tetradecanoylphorbol-13-acetate on 125I-epidermal growth factor binding. GF 109203X inhibited fibroblast growth, in terms of tritiated thymidine incorporation and cell counts, in a dose-dependent manner. We also observed that GF 109203X at 1 microM inhibited serum stimulation of expression of mRNA for c-fos and c-jun, which are usually involved in cellular proliferation. These results suggest that PKC stimulates fibroblast growth. In contrast, GF 109203X stimulated keratinocyte growth. We also observed that GF 109203X inhibited c-fos and c-jun mRNA expression in these cells. In fact, in keratinocytes these proto-oncogenes would be involved in the cellular differentiation process rather than in cellular proliferation. This suggests that the inhibition of PKC favors keratinocyte proliferation probably by inhibiting their differentiation. Thus, using GF 109203X, we show that PKC is involved differently in human fibroblast and keratinocyte growth.
[Focal myositis of the leg in a woman with multiple sclerosis].
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[Longitudinal fatigue fracture of the tibia].
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[Cutaneo-muscular bacillary angiomatosis in a patient with AIDS. Therapeutic problems].
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[Magnetic resonance imaging of fluorosis and stress fractures due to fluoride].
Osteocondensation of the spine and stress fractures of the appendicular bones are observed under treatment with sodium fluoride or after long-term drinking of Vichy Saint-Yorre spring water. Five patients with a mean total dose of fluoride intake of 24.7 g (9-66) were studied with MR imaging. Two of them had a diffuse osteocondensation; MRI showed a low signal intensity in the vertebrae on T1 and T2-weighted images. MRI was performed in an asymptomatic patient who was being treated with sodium fluoride for 16 months; it revealed a heterogenous low signal intensity in the pelvis and femoral metaphysis. Two patients experienced stress fractures; MRI demonstrated a linear area of very low signal intensity surrounded by an area of decreased signal intensity on T1-weighted images and high signal intensity on T2-weighted images. MRI of fluorosis shows a non specific low signal intensity linked to a densifying image on the standard radiograph or an area of high technetium-99m intake on bone scan.
[An unusual cause of intrathoracic round opacity].
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Human dermal fibroblasts modulate the effects of retinoids on epidermal growth.
We report the pharmacologic effects of retinoids in a human skin-equivalent model. This sophisticated culture system is composed, as in vivo, of a dermis and epidermis, and provides a unique in vitro system for studying dermal-epidermal interactions and thus, whether normal dermal fibroblasts influence the effects of retinoids on epidermal growth. Epidermalization was initiated on collagen substrates in which fibroblasts were either viable or lysed by osmotic shock. Retinoic acid, isotretinoin, and acitretin at 10(-6) M or 10(-7) M were added to the cultures just after epidermalization, then every two days. Epidermal growth was determined after 2 weeks in terms of the surface area, DNA content, and tritiated thymidine incorporation during the last 24 h of culture. In the absence of viable fibroblasts, retinoic acid and isotretinoin increased epidermal growth, whereas etretin inhibited it. In contrast, in the presence of viable fibroblasts, retinoic acid and isotretinoin inhibited epidermal growth, whereas etretin had no effect. Thus, retinoic acid and isotretinoin had a similar effect on keratinocyte proliferation that contrasted with that of etretin. Taken as a whole, these results show that fibroblasts, present within a collagen substrate, can modulate the pharmacologic effects of retinoids on epidermal growth.