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Biomedical subjects

B Robin

Publications and source records attributed to B Robin.

At least 19 recordsLinked to original sources
PubMed2001

Twelve novel mutations in the tissue-nonspecific alkaline phosphatase gene (ALPL) in patients with various forms of hypophosphatasia.

Hypophosphatasia is a rare inherited disorder characterized by defective bone mineralization and deficiency of serum and tissue liver/bone/kidney tissue alkaline phosphatase (L/B/K ALP) activity. We report here the characterization of tissue-nonspecific alkaline phosphatase (TNSALP) gene mutations in a series of 11 families affected by various forms of hypophosphatasia. Nineteen distinct mutations were found, 7 of which were previously reported. Eleven of the 12 new mutations were missense mutations (Y11C, A34V, R54H, R135H, N194D, G203V, E218G, D277Y, F310G, A382S, V406A), the last one (998-1G>T) was a mutation affecting acceptor splice site.

Adult↗
PubMed2001

A molecular approach to dominance in hypophosphatasia.

Hypophosphatasia is an inherited disorder characterized by defective bone mineralization and a deficiency of tissue-nonspecific alkaline phosphatase (TNSALP) activity. The disease is highly variable in its clinical expression, because of various mutations in the TNSALP gene. In approximately 14% of the patients tested in our laboratory, only one TNSALP gene mutation was found, despite exhaustive sequencing of the gene, suggesting that missing mutations are harbored in intron or regulatory sequences or that the disease is dominantly transmitted. The distinction between these two situations is of importance, especially in terms of genetic counseling, but dominance is sometimes difficult to conclusively determine by using familial analysis since expression of the disease may be highly variable, with parents of even severely affected children showing no or extremely mild symptoms of the disease. We report here the study of eight point mutations (G46 V, A99T, S164L, R167 W, R206 W, G232 V, N461I, I473F) found in patients with no other detectable mutation. Three of these mutations, G46 V, S164L, and I473F, have not previously been described. Pedigree and/or serum alkaline phosphatase data suggested possible dominant transmission in families with A99T, R167 W, and G232 V. By means of site-directed mutagenesis, transfections in COS-1 cells, and three-dimensional (3D) modeling, we evaluated the possible dominant effect of these eight mutations. The results showed that four of these mutations (G46 V, A99T, R167 W, and N461I) exhibited a negative dominant effect by inhibiting the enzymatic activity of the heterodimer, whereas the four others did not show such inhibition. Strong inhibition resulted in severe hypophosphatasia, whereas partial inhibition resulted in milder forms of the disease. Analysis of the 3D model of the enzyme showed that mutations exhibiting a dominant effect were clustered in two regions, viz., the active site and an area probably interacting with a region having a particular biological function such as dimerization, tetramerization, or membrane anchoring.

Adolescent↗
PubMed1994

Phosphorus magnetic resonance spectroscopy: a noninvasive technique for the study of occlusive arterial leg disease and peripheral vasodilator therapy.

Using 31P nuclear magnetic resonance spectroscopy of the calf muscle, the authors studied patients with peripheral arterial occlusive disease. They studied PCr depletion and intracellular pH during aerobic exercise in patients and controls. The phosphocreatine (PCr) index ([PCr]/([PCr] + [Pi])) at rest was correlated with blood flow measured by plethysmography. During aerobic exercise a greater decrease in pH was obtained in patients (p < 0.03). They also studied the work necessary to reach a PCr index = 0.5 during ischemic exercise. This workload was lower in patients than in controls: 32.99 +/- 3.04 J vs 58.89 +/- 8.55 J, p < 0.05. After vasodilator therapy the workload was improved in patients: 32.99 +/- 3.04 J vs 38.85 +/- 3.54 J, p < 0.05. These results suggest that therapy resulted in improved tissue perfusion in patients.

Arterial Occlusive Diseases↗
PubMed1994

[The parasites of animals in Europe and their traditional treatment in the second half of the 18th century].

During the second half of the 18th century, knowledge of parasites of farm animals progressed significantly, due to the work of F.W. Hastfer, Ph.-E. Lafosse, Ph. Chabert and B. Clark. All four scientists provided better description of the parasites and the diseases. Treatments, at that time, were based on the animal or plant kingdoms and minerals. Very accurate antiparasitic molecules and vaccine were only developed during the second half of the 20th century.

Animal Diseases↗
PubMed1991

Reduction of primary posttraumatic adhesion formation with the prostacyclin analog iloprost in a rodent model.

Recent evidence suggests that inhibition of postsurgical adhesion formation may be effected by modulation of the activities of inflammatory cells contributing to mesothelial repair. Iloprost, a stable analog of prostacyclin, has been shown to exert vasodilatory, antiinflammatory, fibrinolytic, and antithrombotic influences. To determine whether these properties of iloprost might protect mesothelial surfaces from perioperative damage and hence prevent adhesion formation, we evaluated the effect of iloprost on peritoneal healing in a hamster model for primary pelvic injury. Perioperative iloprost therapy significantly reduced posttraumatic adhesion formation when compared with that in vehicle-treated controls. Dose-response studies demonstrate adhesion prevention with doses ranging from 0.04 to 4 mg/kg per 8 hours given subcutaneously over the course of 3 days. These data demonstrate that iloprost is a potent positive modulator of peritoneal healing after pelvic trauma. Further studies to characterize the potential application of iloprost as an adjuvant in reproductive surgery are indicated.

Animals↗
PubMed1991

Periovulatory calcium channel blockade enhances reproductive performance in an animal model for endometriosis-associated subfertility.

Current evidence suggests that peritoneal inflammatory cell hyperactivation may be the essential pathologic abnormality in patients with endometriosis-associated subfertility. In these experiments we utilized an animal model to evaluate the use of an immunomodulatory agent as an alternative treatment for endometriosis-associated subfertility. The right uterine horn of 12 golden hamsters was resected and 2 x 2 mm squares were explanted onto the left uterine mesentery. Controls included hamsters undergoing uterine horn resection without endometrial explantation (n = 6) and nonsurgically treated animals (n = 6). Ovulation induction was initiated 6 weeks postoperatively with 40 IU of pregnant mare's serum gonadotropin on day 1 and 40 IU of human chorionic gonadotropin on day 3. Groups of six explant-bearing hamsters and six nonsurgical control hamsters were treated with verapamil (250 micrograms/kg every 8 hours subcutaneously), a calcium channel-blocking agent known to inhibit macrophage activation, from day 1 to 48 hours after administration of human chorionic gonadotropin. Animals were then killed and the number of embryos and oocytes in left tube counted as a reflection of reproductive performance. Fertilization was completely inhibited in animals bearing uterine explants. Treatment with verapamil dramatically reversed this effect. These data suggest that periovulatory treatment with an immunomodulatory agent such as verapamil may be an effective alternative to conventional treatment for endometriosis-associated subfertility.

Animals↗
PubMed1990

[Phosphorus NMR spectroscopy. Its value in the diagnosis of metabolic myopathies. A case of Mac Ardle's disease].

Phosphorus nuclear magnetic resonance spectroscopy is a non-invasive method used to study muscle bioenergetics in vivo. A new case of Mc Ardle's disease (myophosphorylase deficiency) is reported here. In a context of metabolic myopathy this method can provide a diagnosis of glycogenosis. The spectra obtained at exercise and during recovery determine the degree of enzyme deficiency with satisfactory precision.

Adult↗
PubMed1990

Skeletal muscle metabolism in the leg during exercise in patients with congestive heart failure.

1. Using 31P nuclear magnetic resonance, it has previously been demonstrated that patients with congestive heart failure exhibit a greater than normal phosphocreatine (PCr) depletion in the working skeletal muscles of the arm. We have studied the importance of the work necessary to reach a similar PCr depletion ([PCr]/([PCr] + [Pi]) = 0.5) in calf muscle. Our results show significantly lower values for patients with congestive heart failure in both aerobic and ischaemic conditions (respectively: 0.009 +/- 0.007 vs 0.026 +/- 0.013 W/kg body weight, P less than 0.01; 0.29 +/- 0.16 vs 0.90 +/- 0.25 J/kg body weight, P less than 0.01). 2. This original model of skeletal muscle exercise facilitates a comparison of PCr recovery rate due to a similarity in the PCr depletion and intracellular pH in the two series at the start of recovery. However, the PCr recovery rate is similar after both normoxic and ischaemic exercise, i.e. respective percentages of PCr increase in the first 25 s recovery spectrum were: (a) aerobic exercise, congestive heart failure 133 +/- 18%, control series 138 +/- 18%; (b) ischaemic exercise, congestive heart failure 114 +/- 13%, control series 118 +/- 12%. The absence of a difference in PCr recovery rate and the greater PCr depletion by ischaemic work in patients with congestive heart failure suggest modifications that cannot be explained by a reduced blood flow to the muscle. 3. When comparing the two series, intracellular pH evolved similarly in normoxia and ischaemia during both work and recovery. Thus, no increase in anaerobic glycolytic activity appears when equivalent PCr depletion has occurred.

Adult↗
PubMed1990

Effect of early reperfusion on use of triphenyltetrazolium chloride to differentiate viable from non-viable myocardium in area of risk.

STUDY OBJECTIVE - The aim of the study was to assess the value of triphenyltetrazolium chloride (TTC) staining as an indicator of non-viable myocardium after early reperfusion of ischaemic myocardium. DESIGN - Left anterior descending artery occlusion was performed in pigs for various lengths of time and at two different sites (proximal and distal). After 120 min reperfusion, TTC was injected distal to the occlusion while the remainder of the myocardium was stained with Evans Blue. Myocardial enzymes were measured in non-ischaemic zone, regions of risk and in necrotic zones and related to staining characteristics. SUBJECTS - 31 male Hampshire pigs, weight 34-39 kg, were studied. Twelve were excluded because of resistant ventricular fibrillation or poorly defined areas of infarction. In the remaining 19 pigs, proximal occlusion was carried out in 15 and distal in four. Occlusion lasted for 15 min in six animals, for 30 min in eight (four of which were the animals with distal occlusions), and for 45 min in five. MEASUREMENTS and RESULTS - Biopsies from non-ischaemic zones, regions of risk and necrotic zones were analysed for creatine kinase and lactate dehydrogenase. In the 15 min group, myocardial creatine kinase in the region of risk (red stained) was similar to the non-ischaemic (blue) zone, but in the 30 min distal occlusion group it was reduced. After 30 and 45 min of proximal occlusion, creatine kinase activity in the necrotic (white) zone was reduced compared to the red zone in the same group, and in the red zone of both groups it was reduced compared to the non-ischaemic area. CONCLUSIONS - The red zone, as defined by TTC staining, may be associated with significant creatine kinase depletion after relatively brief periods of occlusion and subsequent reperfusion. This suggests that the red region may be a heterogeneous area of dead and viable cells.

Animals↗
PubMed1986

Quantitation of absolute area of a coronary arterial stenosis: experimental validation with a preparation in vivo.

The absolute cross-sectional area of a coronary stenosis measured by quantitative coronary angiography correlates well with its hemodynamic significance. We evaluated a combined approach using edge detection applied to the normal segment and videodensitometry applied to the stenosis to determine the absolute cross-sectional area of the stenosis (videodensity method). The results were then compared with those with the edge detection method applied directly to the stenosis. The area of the stenosis by the edge detection method was calculated by analyzing two orthogonal projections for irregular stenoses and with use of the formula for the area of an ellipse (ellipse method). The accuracy of both these techniques was assessed by analyzing digital angiograms acquired from closed-chest dogs in which 10 plastic cylinders with precisely machined circular and irregular lumina were inserted into the coronary arteries. Angiograms of irregular stenoses were acquired in two orthogonal views. The ellipse method applied to circular stenoses was very accurate, with r = .97, average absolute difference (AAD) = 0.21 mm2, and SEE = 0.30. For the videodensity method r = .97, AAD = 0.84 mm2, and SEE = 0.40. Irregular stenoses were better quantitated by the videodensity method applied in one view (AAD = 0.50 mm2, SEE = 0.47) than by the ellipse method applied in two orthogonal projections (AAD = 1.03 mm2, SEE = 0.87). Overall, the two methods were comparable in accuracy (for videodensity, AAD = 0.65 mm2, SEE = 0.71 vs AAD = 0.54 mm2, SEE = 0.79 for ellipse).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiography↗