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Biomedical subjects

D Duprez

Publications and source records attributed to D Duprez.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sonic hedgehog (SHH) specifies muscle pattern at tissue and cellular chick level, in the chick limb bud.

Development of the musculature in chick limbs involves tissue and cellular patterning. Patterning at the tissue level leads to the precise arrangement of specific muscles; at the cellular level patterning gives rise to the fibre type diversity in muscles. Although the data suggests that the information controlling muscle patterning is localised within the limb mesenchyme and not in the somitic myogenic precursor cells themselves, the mechanisms underlying muscle organisation have still to be elucidated. The anterior-posterior axis of the limb is specified by a group of cells in the posterior region of the limb mesenchyme, called the zone of polarizing activity (ZPA). When polarizing-region cells are grafted to the anterior margin of the bud, they cause mirror-image digit duplications to be produced. The effect of ZPA grafts can be reproduced by application of retinoic acid (RA) beads and by grafting sonic hedgehog (SHH)-expressing cells to the anterior margin of the limb. Although most previous studies have looked at changes of the skeletal patterning, ZPA and RA also affect muscle patterning. In this report, we investigated the role of SHH in tissue and cellular patterning of forearm wing muscles. Ectopic application of a localised source of SHH to the anterior margin of the wing, leading to complete digit duplication, is able to transform anterior forearm muscles into muscles with a posterior identity. Moreover, the ectopic source of SHH induces a mirror image duplication of the normal posterior muscles fibre types in the new posterior muscles. The reorganisation of the slow fibres can be detected before muscle mass cleavage has started; suggesting that the appropriate fibre type arrangement is in place before the splitting process can be observed.

Animals↗
PubMed1999

Expression of Frzb-1 during chick development.

We cloned the chick homolog of Xenopus and mouse Frzb-1, a secreted Wnt antagonist and performed in situ hybridizations to determine the pattern of cFrzb-1 expression in the developing chick embryo. At early stages, cFrzb-1 transcripts are located exclusively in the ectodermal layer corresponding to the neural plate. The labelling continues in the neural tube, but is always excluded from the floor plate. cFrzb-1 mRNA is expressed by migrating cephalic and truncal neural crest cells. Later, cFrzb-1 transcripts are found in a subset of neural crest derivatives such as cephalic cartilage, nerves and spinal ganglia. In addition to ectodermal derivatives, cFrzb-1 transcripts were also observed in mesodermal derivatives such as vertebral and limb cartilage, the adrenal cortex, the gonads, and a subpopulation of blood cells.

Animals↗
PubMed1999

Relationship between left ventricular mass index and 24-h urinary free cortisol and cortisone in essential arterial hypertension.

OBJECTIVE: Besides arterial blood pressure, nonhemodynamic factors are known to induce cardiac hypertrophy. In Cushing's syndrome, severe ventricular hypertrophy has been linked not only to increased aortic pressure, but also to elevated plasma cortisol. The aim of this study was to examine the relationship between the cortisol/cortisone levels and left ventricular mass index (LVMI) in essential arterial hypertension with and without echocardiographic left ventricular hypertrophy (LVH). DESIGN: Eighteen untreated Caucasian patients (nine men, nine women, mean age 48+/-6 years) with essential hypertension (163+/-26/100+/-14 mm Hg) were enrolled. An age-matched control group of 13 subjects (seven men, six women) with normotension (121+/-9/79+/-7 mm Hg) were enrolled also. Left ventricular dimensions were echocardiographically assessed and cortisol production evaluated by 24-h urinary free cortisol and cortisone concentrations. RESULTS: LVMI averaged 115+/-31 g/m2 and 24-h urinary free cortisol and cortisone were 23+/-14 microg per 24 h and 31+/-18 microg per 24 h. Prevalence of echocardiographic LVH was 56%. LVMI correlated significantly with 24-h urinary free cortisol (r = 0.61, P = 0.007) and cortisone (r = 0.60, P = 0.009). Patients with echocardiographic LVH were characterized by higher daytime ambulatory blood pressure, LVMI (particularly the posterior wall), and 24-h urinary cortisol, while office blood pressure, septal: posterior wall ratio and 24-h urinary cortisone were comparable in all patients. In control individuals, LVMI averaged 91+/-18 g/m2 and 24-h urinary free cortisol and cortisone, respectively, were 34.7+/-6.6 microg per 24 h and 64.3+/-10.8 microg per 24 h (P<0.05 versus patients). Neither LVMI nor the contributing ventricular dimensions showed significant correlation with 24-h urinary free cortisol or cortisone in the control group. CONCLUSIONS: Our data provide evidence for a significant relationship between LVMI and cortisol production independently of arterial blood pressure in untreated mild to moderate hypertension.

Adult↗
PubMed1999

Why is training effective in the treatment of patients with intermittent claudication?

Patients with peripheral arterial obstructive disease (PAOD) often have complaints of intermittent claudication. This causes a great limitation in the quality of life because of reduction in walking ability. PAOD is associated with increased morbidity and mortality. Beside other therapies, training has been shown to be an effective treatment option for patients with intermittent claudication. Exercise training significantly increases walking distance and consequently the functional behaviour of the patient. Several authors have identified different mechanisms involved in this beneficial effect. The most important are discussed in this review, namely adaptation or redistribution of the peripheral blood flow, inhibition of the progression of the atherosclerotic disease, changes in blood rheology, metabolic changes, changes in skeletal muscle morphology, economisation of walking, a change in pain perception and an effect on the cardiovascular system. It is concluded that training works through a combination of mechanisms. Further research is needed to clarify the precise mechanisms.

Exercise Therapy↗
PubMed1998

HB-GAM/pleiotrophin but not RIHB/midkine enhances chondrogenesis in micromass culture.

The heparin-binding growth-associated molecule HB-GAM (also named pleiotrophin) and the retinoic acid-induced heparin-binding protein RIHB (chicken midkine) are developmentally regulated proteins forming a new family of heparin-binding molecules with putative functions during cell growth and differentiation. A direct involvement of these molecules during chondrogenesis in vivo was suggested by their patterns of expression. The putative chondrogenic activity of these molecules was investigated in vitro using micromass cultures from chicken limb bud mesenchymal cells. Exogenous HB-GAM, not RIHB, was found to enhance chondrogenesis in this system. These results provide a strong incentive for considering and further investigating the role of this protein in the control of limb cartilage differentiation.

Animals↗
PubMed1998

BMP-2 induces ectopic expression of cardiac lineage markers and interferes with somite formation in chicken embryos.

In Drosophila induction of the homeobox gene tinman and subsequent heart formation are dependent on dpp signaling from overlying ectoderm. In order to define vertebrate heart-inducing signals we screened for dpp-homologues expressed in HH stage 4 chicken embryos. The majority of transcripts were found to be BMP-2 among several other members of the BMP family. From embryonic HH stage 4 onwards cardiogenic mesoderm appeared to be in close contact to BMP-2 expressing cells which initially were present in lateral mesoderm and subsequently after headfold formation in the pharyngeal endoderm. In order to assess the role of BMP-2 for heart formation, gastrulating chick embryos in New culture were implanted with BMP-2 producing cells. BMP-2 implantation resulted in ectopic cardiac mesoderm specification. BMP-2 was able to induce Nkx2-5 expression ectopically within the anterior head domain, while GATA-4 was also induced more caudally. Cardiogenic induction by BMP-2, however remained incomplete, since neither Nkx2-8 nor the cardiac-restricted structural gene VMHC-1 became ectopically induced. BMP-2 expressing cells implanted adjacent to paraxial mesoderm resulted in impaired somite formation and blocked the expression of marker genes, such as paraxis, Pax-3, and the forkhead gene cFKH-1. These results suggest that BMP-2 is part of the complex of cardiogenic signals and is involved in the patterning of early mesoderm similar to the role of dpp in Drosophila.

Animals↗
PubMed1998

Sonic hedgehog is required for survival of both myogenic and chondrogenic somitic lineages.

In vertebrates, the medial moieties of the somites give rise to the vertebrae and epaxial muscles, which develop in close relationship with the axial organs, neural tube and notochord. The lateral moieties contribute to the ribs and to limb and body wall muscles (hypaxial muscles) after a phase of lateral and ventral migration. Surgical ablation of the neural tube and notochord in the chick embryo during segmentation and early differentiation of the somites (day 2 of incubation) does not affect primary development of the hypaxial muscles, but leads to a complete absence of epaxial muscles, vertebrae and ribs, due to cell death in the somites. Here we demonstrate that cell death, which occurs within 24 hours of excision of the axial organs, affects both myogenic and chondrogenic cell lineages defined, respectively, by the expression of MyoD and Pax-1 genes. In contrast, Pax-3 transcripts, normally present in cells giving rise to hypaxial muscles, are preserved in the excised embryos. Backgrafting either the ventral neural tube or the notochord allows survival of MyoD- and Pax-1-expressing cells. Similarly, Sonic hedgehog-producing cells grafted in place of axial organs also rescue MyoD- and Pax-1-expressing cells from death and allow epaxial muscles, ribs and vertebrae to undergo organogenesis. These results demonstrate that the ventral neural tube and the notochord promote the survival of both myogenic and chondrogenic cell lineages in the somites and that this action is mediated by Sonic hedgehog.

Animals↗
PubMed1998

Two domains in vertebral development: antagonistic regulation by SHH and BMP4 proteins.

It has previously been shown that the notochord grafted laterally to the neural tube enhances the differentiation of the vertebral cartilage at the expense of the derivatives of the dermomyotome. In contrast, the dorsomedial graft of a notochord inhibits cartilage differentiation of the dorsal part of the vertebra carrying the spinous process. Cartilage differentiation is preceded by the expression of transcription factors of the Pax family (Pax1/Pax9) in the ventrolateral domain and of the Msx family in the dorsal domain. The proliferation and differentiation of Msx-expressing cells in the dorsal precartilaginous domain of the vertebra are stimulated by BMP4, which acts upstream of Msx genes. It has previously been shown that the SHH protein arising from the notochord (and floor plate) is necessary for the survival and further development of Pax1/Pax9-expressing sclerotomal cells. We show here that SHH acts antagonistically to BMP4. SHH-producing cells grafted dorsally to the neural tube at E2 inhibit expression of Bmp4 and Msx genes and also inhibits the differentiation of the spinous process. We present a model that accounts for cartilage differentiation in the vertebra.

Animals↗
PubMed1998

Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5.

Activation of myogenesis in newly formed somites is dependent upon signals derived from neighboring tissues, namely axial structures (neural tube and notochord) and dorsal ectoderm. In explants of paraxial mesoderm from mouse embryos, axial structures preferentially activate myogenesis through a Myf5-dependent pathway and dorsal ectoderm preferentially through a MyoD-dependent pathway. Here we report that cells expressing Wnt1 will preferentially activate Myf5 while cells expressing Wnt7a will preferentially activate MyoD. Wnt1 is expressed in the dorsal neural tube and Wnt7a in dorsal ectoderm in the early embryo, therefore both can potentially act in vivo to activate Myf5 and MyoD, respectively. Wnt4, Wnt5a and Wnt6 exert an intermediate effect activating both Myf5 and MyoD equivalently in paraxial mesoderm. Sonic Hedgehog synergises with both Wnt1 and Wnt7a in explants from E8.5 paraxial mesoderm but not in explants from E9.5 embryos. Signaling through different myogenic pathways may explain the rescue of muscle formation in Myf5 null embryos, which do not form an early myotome but later develop both epaxial and hypaxial musculature. Explants of unsegmented paraxial mesoderm contain myogenic precursors capable of expressing MyoD in response to signaling from a neural tube isolated from E10.5 embryos, the developmental stage when MyoD is present throughout the embryo. Myogenic cells cannot activate MyoD in response to signaling from a less mature neural tube. Together these data suggest that different Wnt molecules can activate myogenesis through different pathways such that commitment of myogenic precursors is precisely regulated in space and time to achieve the correct pattern of skeletal muscle development.

Animals↗
PubMed1998

Sonic Hedgehog induces proliferation of committed skeletal muscle cells in the chick limb.

Myogenic Regulatory Factors (MRFs) are a family of transcription factors whose expression in a cell reflects the commitment of this cell to a myogenic fate before any cytological sign of muscle differentiation is detectable. Myogenic cells in limb skeletal muscles originate from the lateral half of the somites. Cells that migrate away from the lateral part of the somites to the limb bud do not initially express any member of the MRF family. Expression of MRFs in the muscle precursor cells starts after the migration process is completed. The extracellular signals involved in activating the myogenic programme in muscle precursor cells in the limb in vivo are not known. We wished to investigate whether Sonic Hedgehog (SHH) expressed in the posterior part of the limb bud could be involved in differentiation of the muscle precursor cells in the limb. We found that retrovirally overexpressed SHH in the limb bud induced the extension of the expression domain of the Pax-3 gene, then that of the MyoD gene and finally that of the myosin protein. This led to an hypertrophy of the muscles in vivo. Addition of SHH to primary cultures of myoblasts resulted in an increase in the proportion of myoblasts that incorporate bromodeoxyuridine, resulting in an increase of myotube number. These data show that SHH is able to activate myogenesis in vivo and in vitro in already committed myoblasts and suggest that the stimulation of the myogenic programme by SHH involves activation of cell proliferation.

Animals↗
PubMed1998

Mild to moderate hyperhomocysteinaemia in cardiovascular disease.

Elevated serum levels of homocysteine, a sulphur-containing amino acid, are increasingly recognized as an independent risk factor for atherosclerotic and thrombotic vascular disease. Presence of a thermolabile variant of methylenetetrahydrofolatereductase and an inadequate folate status are the most common causes of hyperhomocysteinaemia. Homocysteine damages the vessel wall mainly through generation of oxygen radicals and creates a prothrombotic environment. In the majority of cases, normalization of homocysteine levels can be achieved with administration of vitamins of the B-group. The effect of this treatment on cardiovascular outcome, however, remains undefined.

Arteriosclerosis↗
PubMed1998

HB-GAM/pleiotrophin: localization of mRNA and protein in the chicken developing leg.

The heparin-binding growth-associated molecule HB-GAM (also named pleiotrophin) is a developmentally-regulated protein that belongs to a new family of heparin-binding molecules with putative functions during cell growth and differentiation. In order to study the localization of HB-GAM during chicken embryogenesis, we produced specific monoclonal antibodies to this factor. HB-GAM protein is first observed at stage 23 in the developing nervous system and later in the forming cartilage. We present an investigation of the HB-GAM mRNA expression and HB-GAM protein distribution in the developing leg by in situ hybridization and immunocytochemical studies. We focused our attention on the development of the tibia, where the HB-GAM protein appears at stage 27-28, i.e., just after the condensation of the mesodermal precursor cells of the chondrocytes. The protein then progressively accumulates in the central part of the embryonic cartilage (diaphysis). It persists until stage 42-44 in the regions where hypertrophic cartilage is being replaced by bone marrow. In contrast to the protein, the transcript is first detected at stage 26-27 and later expressed essentially in the epiphysis until stage 37. Therefore the localization of the mRNA does not parallel that of the protein and our data suggest a long half-life of the protein in the hypertrophic cartilage. In addition, the layer of stacked cells surrounding the cartilage core (usually considered as the osteoprogenitor cells) clearly expresses the HB-GAM message between stages 30-37 whereas differentiated osteoblasts do not. Furthermore, the distribution of HB-GAM protein in the osteoblast/osteoid layer suggests an involvement of this protein in early steps of osteogenesis. HB-GAM is absent from the newly formed bone.

Animals↗
PubMed1998

How to study sympatho-vagal balance in arterial hypertension and the effect of antihypertensive drugs?

Blood pressure homeostasis and variability are the resultant of many complicated neurohumoral interactions. The autonomic nervous system plays a key role in the process. Since arterial hypertension is characterized by an increased sympathetic tone, the determination of the sympatho-vagal balance can give more insight in the autonomic nervous function in this pathology. The assessment of sympatho-vagal balance has been derived from reflex manoeuvres as the study of the baroreceptor function by phenylephrine or nitroglycerin test, by the application of negative or positive pressure around the neck or at the lower limbs or by tilting. Other reflex manoeuvres are hand-grip, cold pressure test, Valsalva manoeuvre, mental arithmetics and microneurography, providing information about the sympathetic reflex activity, and deep breathing about vagal reflex activity. These reflex tests have several limitations, because they request cooperation of the patient. Power spectral analysis of beat-to-beat blood pressure and RR-interval recordings permit to evaluate autonomic activity at baseline conditions and to separate the different components of variability which seem to reflect specific regulatory mechanisms. For the RR-interval, the high frequency component (HF) is a marker of vagal activity, while the low frequency component (LF) is a marker of sympathetic and vagal activity. The LF/HF ratio can be considered as a marker of sympatho-vagal balance. The significance of the LF and HF components of arterial blood pressure variability is less clear. Spectral analysis can be used to study the effect of antihypertensive drugs on sympatho-vagal balance.

Antihypertensive Agents↗
PubMed1997

Prognostic value of thoracic recurrent nerve nodal involvement in esophageal squamous cell carcinoma.

BACKGROUND: The determination of a simple and reliable prognostic factor that allows identification of patients at high risk of early cancer recurrence and subsequent death after resection of esophageal carcinoma should contribute to more accurate management of patients suffering from this disease. STUDY DESIGN: The aim of this study was to assess the prognostic value of thoracic recurrent nerve nodal involvement after curative resection of esophageal squamous cell carcinoma. The prognostic importance of gender, age, tumor penetration, and extent of lymph node involvement was evaluated in 55 patients after curative resection of esophageal squamous cell carcinoma. RESULTS: Thirty-four of 55 patients (62%) had nodal metastases and 10 of 55 (18%) had thoracic recurrent nerve nodes involved. The median overall survival was 28 months. By univariate analysis, survival was higher in association with the absence of adventitial invasion (p = 0.04), of nodal involvement (p = 0.03), and of thoracic recurrent nerve nodal involvement (p = 0.0001). In a Cox proportional hazards regression model, thoracic recurrent nerve nodal involvement appeared the strongest predictive factor (adjusted hazard ratio 8.4 (3.0-23.7)). CONCLUSIONS: Assessment of thoracic recurrent nerve nodes is appropriate to identify patients who are at high risk of disease-related death after surgical resection.

Adult↗