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D Duprez

Publications and source records attributed to D Duprez.

At least 55 records · Page 3Linked to original sources
PubMed1997

Relationship between dose, distance and time in Sonic Hedgehog-mediated regulation of anteroposterior polarity in the chick limb.

Anteroposterior polarity in the vertebrate limb is thought to be regulated in response to signals derived from a specialized region of distal posterior mesenchyme, the zone of polarizing activity. Sonic Hedgehog (Shh) is expressed in the zone of polarizing activity and appears to mediate the action of the zone of polarizing activity. Here we have manipulated Shh signal in the limb to assess whether it acts as a long-range signal to directly pattern all the digits. Firstly, we demonstrate that alterations in digit development are dependent upon the dose of Shh applied. DiI-labeling experiments indicate that cells giving rise to the extra digits lie within a 300 microm radius of a Shh bead and that the most posterior digits come from cells that lie very close to the bead. A response to Shh involves a 12-16 hour period in which no irreversible changes in digit pattern occur. Increasing the time of exposure to Shh leads to specification of additional digits, firstly digit 2, then 3, then 4. Cell marking experiments demonstrate that cells giving rise to posterior digits are first specified as anterior digits and later adopt a more posterior character. To monitor the direct range of Shh signalling, we developed sensitive assays for localizing Shh by attaching alkaline phosphatase to Shh and introducing cells expressing these forms into the limb bud. These experiments demonstrate that long-range diffusion across the anteroposterior axis of the limb is possible. However, despite a dramatic difference in their diffusibility in the limb mesenchyme, the two forms of alkaline phosphatase-tagged Shh proteins share similar polarizing activity. Moreover, Shh-N (aminoterminal peptide of Shh)-coated beads and Shh-expressing cells also exhibit similar patterning activity despite a significant difference in the diffusibility of Shh from these two sources. Finally, we demonstrate that when Shh-N is attached to an integral membrane protein, cells transfected with this anchored signal also induce mirror-image pattern duplications in a dose-dependent fashion similar to the zone of polarizing activity itself. These data suggest that it is unlikely that Shh itself signals digit formation at a distance. Beads soaked in Shh-N do not induce Shh in anterior limb mesenchyme ruling out direct propagation of a Shh signal. However, Shh induces dose-dependent expression of Bmp genes in anterior mesenchyme at the start of the promotion phase. Taken together, these results argue that the dose-dependent effects of Shh in the regulation of anteroposterior pattern in the limb may be mediated by some other signal(s). BMPs are plausible candidates.

Animals↗
PubMed1997

Noggin acts downstream of Wnt and Sonic Hedgehog to antagonize BMP4 in avian somite patterning.

In the vertebrate embryo, the lateral compartment of the somite gives rise to muscles of the limb and body wall and is patterned in response to lateral-plate-derived BMP4. Activation of the myogenic program distinctive to the medial somite, i.e. relatively immediate development of the epaxial muscle lineage, requires neutralization of this lateral signal. We have analyzed the properties of molecules likely to play a role in opposing lateral somite specification by BMP4. We propose that the BMP4 antagonist Noggin plays an important role in promoting medial somite patterning in vivo. We demonstrate that Noggin expression in the somite is under the control of a neural-tube-derived factor, whose effect can be mimicked experimentally by Wnt1. Wnt1 is appropriately expressed in the neural tube. Furthermore, we show that Sonic Hedgehog is able to activate ectopic expression of Noggin resulting in the blocking of BMP4 specification of the lateral somite. Our results are consistent with a model in which Noggin activation lies downstream of the SHH and Wnt signaling pathways.

Animals↗
PubMed1996

Effect of nifedipine on superior mesenteric artery impedance in humans.

OBJECTIVE: In a randomized, double-blind placebo-controlled study the acute effect of sublingual nifedipine (10 mg) on the superior mesenteric artery pulsatility index (p.i.) was studied over 60 min in 12 healthy subjects (Age 43 y). METHODS: p.i. was considered as a parameter of vascular resistance and was calculated as the peak-to-peak amplitude of the waveform divided by the mean amplitude. p.i. measurements were performed with the subject resting and fasting and were made 5, 10, 15, 30, 45 and 60 min for 1 hour after nifedipine (10 mg) or placebo. Arterial blood pressure and heart rate were measured at the same times. RESULTS: Placebo administration failed to change arterial blood pressure, heart rate or p.i. 5 min after 10 mg sublingual nifedipine, p.i. had significantly decreased from 5.0 to 3.8, with a nonsignificant decrease in arterial blood pressure and an increase in heart rate. By 15 min after nifedipine administration p.i. had further decreased to 3.1, and there was a concomitant significant decrease in mean arterial blood pressure and increase in heart rate. Sixty minutes after drug intake p.i. and arterial blood pressure were still below baseline not significant but the heart rate remained significantly increased. CONCLUSION: Our data indicate that in healthy subjects sublingual administration of nifedipine had a vasodilator effect (decrease in p.i.) on the superior mesenteric vascular bed.

Adult↗
PubMed1996

Overexpression of BMP-2 and BMP-4 alters the size and shape of developing skeletal elements in the chick limb.

Bone morphogenetic proteins are members of the transforming growth factor beta (TGF beta) superfamily which are involved in a range of developmental processes including modelling of the skeleton. We show here that Bmp-2 is expressed in mesenchyme surrounding early cartilage condensations in the developing chick limb, and that Bmp-4 is expressed in the perichondrium of developing cartilage elements. To investigate their roles during cartilage development, BMP-2 and BMP-4 were expressed ectopically in developing chick limbs using retroviral vectors. Over-expression of BMP-2 or BMP-4 led to a dramatic increase in the volume of cartilage elements, altered their shapes and led to joint fusions. This increase in volume appeared to result from an increase in the amount of matrix and in the number of chondrocytes. The latter did not appear to be due to increased proliferation of chondrocytes, suggesting that it may result from increased recruitment of precursors. BMP-2 and BMP-4 also delayed hypertrophy of chondrocytes and formation of the osteogenic periosteum. These data provide insights into how BMP-2 and BMP-4 may model and control the growth of skeletal elements during normal embryonic development, suggesting roles for both molecules in recruiting non-chondrogenic precursors to chondrogenic fate.

Animals↗
PubMed1996

Epidural spinal cord stimulation does not improve microvascular blood flow in neuropathic pain.

For many years, spinal cord stimulation (SCS) has been used successfully in various pain syndromes. SCS is also used to treat vascularly-impaired patients since it apparently improves the microcirculation. The exact physiological mechanisms involved are still unclear. There are even some anecdotal reports of a cooling of the legs during SCS. This study investigated the vascular effects of SCS in 15 patients with failed back surgery syndrome, using infrared thermography of the affected foot and capillaroscopy in the nailfold of the big toe. There were no statistically significant differences (Student's t test) in temperature (P = 0.923) or red blood cell velocity (P = 0.819 first day and P = 0.218 second day) in the affected foot with or without stimulation. A physiological difference in relation to neuropathic pain might explain the lack of improvement in skin microcirculation with SCS.

Adult↗
PubMed1996

The role of bone morphogenetic proteins in vertebral development.

This study first shows a striking parallel between the expression patterns of the Bmp4, Msx1 and Msx2 genes in the lateral ridges of the neural plate before neural tube closure and later on, in the dorsal neural tube and superficial midline ectoderm. We have previously shown that the spinous process of the vertebra is formed from Msx1- and 2-expressing mesenchyme and that the dorsal neural tube can induce the differentiation of subcutaneous cartilage from the somitic mesenchyme. We show here that mouse BMP4- or human BMP2-producing cells grafted dorsally to the neural tube at E2 or E3 increase considerably the amount of Msx-expressing mesenchymal cells which are normally recruited from the somite to form the spinous process of the vertebra. Later on, the dorsal part of the vertebra is enlarged, resulting in vertebral fusion and, in some cases (e.g. grafts made at E3), in the formation of a 'giant' spinous process-like structure dorsally. In strong contrast, BMP-producing cells grafted laterally to the neural tube at E2 exerted a negative effect on the expression of Pax1 and Pax3 genes in the somitic mesenchyme, which then turned on Msx genes. Moreover, sclerotomal cell growth and differentiation into cartilage were then inhibited. Dorsalization of the neural tube, manifested by expression of Msx and Pax3 genes in the basal plate contacting the BMP-producing cells, was also observed. In conclusion, this study demonstrates that differentiation of the ventrolateral and dorsal parts of the vertebral cartilage is controlled by different molecular mechanisms. The former develops under the influence of signals arising from the floor plate-notochord complex. These signals inhibit the development of dorsal subcutaneous cartilage forming the spinous process, which requires the influence of BMP4 to differentiate.

Animals↗
PubMed1996

Why do we need to perform ambulatory blood pressure monitoring?. Conversation with the patient.

Ambulatory blood pressure monitoring (ABPM) has become one of the major clinical tools used to investigate the hypertensive patient. The technique is still cumbersome and embarassing for the patient, both during daily activities and during nightly rest. Nonetheless, the information to be obtained can be very useful for diagnosis and eventually for treatment of the patient. Therefore, it is important to convince the patient to give his permission for the recording to be performed. The recording should be performed under the best possible conditions. In the following, some of the arguments used in the hypertensive clinics will be outlined.

Journal Article↗
PubMed1996

Blood pressure pattern in the recovery period after coronary artery bypass grafting.

BACKGROUND: Data on ambulatory blood pressure profiles after coronary artery bypass grafting (CABG) are largely lacking in the literature. OBJECTIVE: To examine the ambulatory blood pressure profile and its short- and long-term variability (daytime, night-time and 24 h) 1, 6 and 14 weeks after CABG in 15 patients (14 men, one woman) who remained uncomplicated postoperatively and during the 14 weeks' follow-up. Therapy remained unchanged over the study period. METHODS: Short-term blood pressure and heart rate variability were assessed by power spectral analysis of a sample length of 256 beats of these parameters obtained with subjects supine and having stood for 30 min, using the Finapres device 1, 6 and 14 weeks after CABG. The low-frequency (0.04-0.15 Hz): high-frequency (0.15-0.40 Hz) ratio of the R-R interval variability was considered a study parameter for the autonomic balance. RESULTS: During the rehabilitation period office and mean ambulatory blood pressure parameters were within the normotensive range. There was a progressive increase in 24 h and daytime systolic and diastolic blood pressures from 1 (121+/- 11/72+/-9 and 124+/-11/74+/-9 mmHg, respectively) to 14 weeks (129+/- 11/79+/-10 and 134+/-11/82+/- 11 mmHg, respectively) after CABG. The nocturnal blood pressure dip was restored progressively but incompletely 14 weeks after CABG. In parallel there was a progressive but also incomplete restoration of the sympathicovagal balance. CONCLUSION: Our results indicate an incomplete recovery of the autonomic nervous system and 24 h blood pressure variation 14 weeks after CABG. Further studies are required to examine whether incomplete restoration of the nocturnal blood pressure dip and sympathicovagal balance have independent prognostic implications for the CABG patient.

Journal Article↗
PubMed1995

Influence and interference of isosorbide dinitrate and food intake on superior mesenteric artery impedance in humans.

The influence of isosorbide dinitrate (ISDN) and food ingestion on superior mesenteric artery impedance was investigated in 24 healthy volunteers (age 40 +/- 2.7 years). Superior mesenteric artery circulation was assessed by duplex ultrasound. Pulsatility index (PI) was considered as a parameter of vascular resistance and was calculated as the peak-to-peak amplitude of the waveform divided by the mean amplitude. The subjects were randomly allocated to four groups (ISDN, meal, ISDN + meal, meal + ISDN). PI measurements were performed in resting and fasting conditions and serially for 1 h after sublingual 5 mg ISDN, ingestion of a 300-kcal, 300-ml mixed liquid meal; sublingual 5 mg ISDN followed 10 min later by the test meal; and ingestion of the test meal followed 5 min later by sublingual 5 mg ISDN. Five minutes after 5 mg sublingual ISDN, PI had increased from 6.8 to 12.4, while after intake of a meal PI had decreased from 7.6 to 4.9. Separate effects of 5 mg ISDN and meal intake lasted for at least 1 h. The reflex vasoconstrictive effect of 5 mg ISDN on the superior mesenteric artery circulation was counterbalanced by ingestion of a meal in healthy volunteers.

Adult↗
PubMed1995

Influence of central command and ergoreceptors on the splanchnic circulation during isometric exercise.

The splanchnic circulation can make a major contribution to blood flow changes. However, the role of the splanchnic circulation in the reflex adjustments to the blood pressure increased during isometric exercise is not well documented. The central command and the muscle chemoreflex are the two major mechanisms involved in the blood pressure response to isometric exercise. This study aimed to examine the behaviour of the superior mesenteric artery during isometric handgrip (IHG) at 30% maximal voluntary contraction (MVC). The pulsatility index (PI) of the blood velocity waveform of the superior mesenteric artery was taken as the study parameter. A total of ten healthy subjects [mean age, 21.1 (SEM 0.3) years] performed an IHG at 30% MVC for 90 s. At 5 s prior to the end of the exercise, muscle circulation was arrested for 90 s to study the effect of the muscle chemoreflex (post exercise arterial occlusion, PEAO). The IHG at 30% MVC caused a decrease in superior mesenteric artery PI, from 4.84 (SEM 1.57) at control level to 3.90 (SEM 1.07) (P = 0.015). The PI further decreased to 3.17 (SEM 0.70) (P = 0.01) during PEAO. Our results indicated that ergoreceptors may be involved in the superior mesenteric artery vasodilatation during isometric exercise.

Adult↗
PubMed1995

Renin-angiotensin-aldosterone system, RR-interval and blood pressure variability during postural changes after myocardial infarction.

Low frequency (LF, 0.04-0.15 Hz) and high frequency (HF, 0.15-0.40 Hz) components of heart rate variability have been used to evaluate the autonomic nervous system. The sympathico-vagal balance as well as the renin-angiotensin-aldosterone (RAA) axis are disturbed in the post-acute phase of acute myocardial infarction (AMI). This study examined the relationship between the RAA-axis and spectral indices of the RR-interval and blood pressure (BP) variabilities during postural manoeuvres in the post-AMI period. Power spectral analysis of the RR-interval and BP variability was computed from non-invasive beat-to-beat BP measurements 10-12 days post-AMI, using Fast-Fourier transforms. Concomitantly, hormonal changes of the RAA-axis were determined and data were further correlated with the left ventricular ejection fraction. When the patient moved from the lying to the supine position all RAA-axis parameters significantly increased. Both LF and HF components of total RR-interval variability decreased upon standing, while the LF component of systolic and diastolic BP variability increased and HF components remained constant. In the upright position, plasma renin activity (P<0.01) and angiotensin II (borderline) were inversely related with the LF component of systolic BP. The aldosterone level was dissociated from plasma renin activity and angiotensin II. The left ventricular ejection fraction was inversely correlated (P<0.05) with systolic and diastolic BP variabilities and their LF and HF powers. These results suggest that the renin-angiotensin II system in the post-acute phase of AMI patients treated with aspirin and beta-blocking agents is correlated with cardiovascular autoregulation during postural manoeuvres.

Autonomic Nervous System↗
PubMed1995

MN blood group, a genetic marker for essential arterial hypertension in young adults.

The MN blood group has been linked with blood pressure levels and sodium-lithium counter-transport in red blood cells of normotensives. The aim of the study was to compare the distribution of MN phenotypes according to age at diagnosis of essential hypertension and to investigate the relationship between MN phenotypes, severity of complications and therapeutic needs. MN blood group polymorphism was studied in 386 Caucasians with established essential arterial hypertension, treated for at least one year. In 285 healthy normotensive blood donors, blood pressure was measured and MN blood group was typed. MN blood groups were typed with polyclonal antisera and confirmed with monoclonal antisera. MN blood group phenotype frequencies in hypertensives were 0.207 (MM), 0.601 (MN), and 0.192 (NN), which differs (P < 0.000002) from the distribution in the controls: 0.270 (MM), 0.540 (MN) and 0.189 (NN). The relative MN phenotype frequency was strongly over-represented (P < 0.05). Age at detection of hypertension was significantly lower for MN patients (P < 0.0005). With increasing age of detection, the relative frequency of MN phenotype gradually decreases from 0.73 in those detected before age 40 to 0.50 for patients detected after 60. This observation holds true for both male and female hypertensive. Furthermore, hypertensives with a MM blood group had a lower (P < 0.05) prevalence of cerebrovascular accidents. In controls, blood pressure was comparable for the three MN phenotypes. The present study suggests that the MN phenotype is a genetic factor associated with early detection of essential hypertension.

Adolescent↗
PubMed1995

Gene expression, polarising activity and skeletal patterning in reaggregated hind limb mesenchyme.

The developing chick limb has two major signalling centres; the apical ectodermal ridge maintains expression of several important genes and outgrowth of the limb, and the polarising region specifies the pattern of skeletal elements along the anteroposterior axis. We have used reaggregated leg grafts (mesenchyme dissociated into single cells, placed in an ectodermal jacket and grafted to a host) to study patterning in a system where the developmental axes are severely disrupted. Reaggregates from different regions of leg mesenchyme developed correspondingly different digits, giving a system in which skeletal phenotype could be compared with the expression of genes thought to be important in patterning. We found that posterior third and whole leg reaggregates gave rise to different digits, yet expressed the same combination of HoxD, Bmp-2 and shh genes throughout their development. Anterior thirds initially only express the 3' end of the HoxD cluster but activate the more 5' members of the cluster sequentially over a period of 48 hours, a period during which Bmp-2 is activated but no shh or Fgf-4 expression could be detected. Our results suggest that there are two independent mechanisms for activating the HoxD complex, one polarising region-dependent and one independent, and that shh expression may not be necessary to maintain outgrowth and patterning once a ridge has been established.

Animals↗
PubMed1994

Comparison of athletes with life-threatening ventricular arrhythmias with two groups of healthy athletes and a group of normal control subjects.

Sudden cardiac death in well-trained athletes is most often superimposed on the presence of structural heart disease. However, some athletes die suddenly in the absence of overt heart disease. To improve identification of athletes at high risk for ventricular tachycardia (VT), ventricular repolarization, the signal-averaged electrocardiogram (ECG), and the echocardiogram from 13 male athletes with symptomatic VT and without evidence of manifest cardiac disease were compared with data obtained in 3 matched control groups (15 apparently healthy professional road cyclists, 10 professional basketball players, and 15 normal control subjects without any sports activity). All patients had apparently normal QRS duration on the routine ECG, and none were taking antiarrhythmic drugs. Echocardiography and signal-averaged electrocardiography were useful in distinguishing the group of athletes with tachyarrhythmias from the group of normal nonsporting controls, but not from both groups of normal athletes. The QT interval (V4) and the QT interval corrected with the cubic root were shorter for the nonsporting controls. Three parameters for QT dispersion showed significant differences (p < 0.003) between athletes with disease and all other groups. It is concluded that although significant differences were detected between normal subjects and the 3 groups of athletes by routine ECG, the signal-averaged ECG, and echocardiography, only an increased QT dispersion from the 12-lead ECG was helpful in distinguishing athletes with VT from other athletes.

Adult↗
PubMed1994

Organisation and promoter activity of the retinoic-acid-induced-heparin-binding (RIHB) gene.

The heparin-binding protein, RIHB, is encoded by a gene that is expressed temporarily during the early period of chicken embryogenesis. We have now isolated genomic clones of the chicken RIHB gene, determined its transcription initiation sites, characterized its promoter region and established the functional activity of the RIHB gene promoter. The 5' flanking region and the beginning of the first exon revealed a structural organisation characteristic of housekeeping and growth-control-related genes. It lacked canonical TATA or CAAT boxes but contained several GC boxes. The structure of the RIHB gene is compared with those of the human and mouse midgestation kidney (MK) genes. In the coding exons, the similarities between the three genes are striking. In contrast, the structure and location of the first non-coding exon is different. Analysis of the promoter activity suggests an indirect regulation of transcription by retinoic acid and demonstrates a high degree of complexity of the regulation of the RIHB gene.

Amino Acid Sequence↗
PubMed1994

Cardiovascular responses elicited by different simulated diving manoeuvres.

It has been documented that placing an ice-bag on the forehead causes similar cardiac and vascular responses as face immersion. There has been disagreement concerning the contribution of separate cold stimulation on the face and breathholding in the diving response. This study set out to unravel the extent to which these two factors contribute individually to the observed cardiovascular changes during the combined manoeuvre. It further aimed to reveal whether peripheral vascular responses to these stimuli are different in forearm and calf. We observed a significant rapid increase in the RR-interval, which was maintained until the end of the 25-s observation period and a homogeneous vasoconstriction in forearm and calf, despite minor changes in arterial blood pressure, during breathholding, placing the icebag on the forehead and the combined stimuli. Cardiac and peripheral vascular responses to the combined manoeuvre did not differ significantly from the responses elicited by the two stimuli separately. This test is another example that illustrates the heterogeneous cardiovascular response involving both parasympathetic and sympathetic activation. Moreover, since the icebag on the forehead test is technically easy to perform and does not require the active co-operation of the patient, it may be a valid method to replace a full face immersion test accompanied by breathholding.

Adult↗