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Biomedical subjects

C Alexandre

Publications and source records attributed to C Alexandre.

At least 73 records · Page 4Linked to original sources
PubMed1997

Impact on bone of thyroid hormone therapy.

Results of recent cross-sectional and longitudinal studies of the effects on bone of thyroid hormone therapy are reviewed. Substantial discrepancies exist, perhaps because bone density is influenced by many factors, including the underlying disease, dietary factors and hormonal status. No effect on bone mineral density of the dose of thyroid hormones given as replacement or suppressive therapy was found. However, prospective studies demonstrated increased bone remodeling with transient bone loss early during treatment. Whether antiosteoclastic agents may prevent bone loss associated with thyroid hormone therapy is discussed.

Animals↗
PubMed1996

Transcriptional activation of hedgehog target genes in Drosophila is mediated directly by the cubitus interruptus protein, a member of the GLI family of zinc finger DNA-binding proteins.

Members of the Hedgehog (Hh) family of secreted proteins have been identified recently as key signaling molecules that regulate a variety of inductive interactions central to the development of both Drosophila and vertebrates. Despite their widespread importance, the way in which Hh signals are transduced inside the cell remains poorly understood. The best candidate for a transcription factor that mediates Hh signaling in Drosophila is the product of the cubitus interruptus (ci) gene, a zinc finger protein that exhibits significant homology to protein products of the vertebrate GLI gene family. Here, we show that elevated levels of Ci are sufficient to activate patched (ptc) and other hh target genes, even in the absence of hh activity. We also show that Ci can function as a transcriptional activator in yeast and demonstrate that the zinc finger domain of the protein is sufficient for its target specificity. Finally, we identify sequences in the promoter region of the ptc gene, a primary target of Hh signaling, that are identical to the consensus-binding sequence of the GLI protein and are required for reporter gene expression in response to Hh activity. Taken together, our results strongly support the role for Ci as the transcriptional activator that mediates hh signaling.

Animals↗
PubMed1996

Architectural modifications and cellular response during disuse-related bone loss in calcaneus of the sheep.

The results of simple biomechanical unloading in models of acute-disuse osteoporosis are influenced by systemic and regional effects of the method used to generate the bone loss. A model in which strain-gauge measurements confirmed that the os calcis was unloaded in healthy ewes during ambulation was assessed by histomorphometry. Twelve nonovariectomized adult female Welsh mountain sheep were submitted to hock joint immobilization by an external fixation procedure from the tibia to the metatarsus for a period of 12 wk. Histomorphometric analysis showed that this model was able to produce pure local bone loss, as transiliac bone biopsies failed to reveal any difference between the initial and final results. Immobilized and nonimmobilized calcanei were both removed postmortem. After the 12 wk of the study, osteoclastic activity was increased in accordance with the usual disuse process. An unexpected increase of osteoblastic activity was also observed, possibly related to recovery after the initial dramatic bone loss, but an artifact of the surgical procedure such as a regional acceleration phenomenon cannot be definitively excluded. However, the increased osteoblastic activity was not sufficient to prevent accentuation of the negative bone balance, resulting in a 29% decrease of trabecular bone volume in immobilized calcanei compared with nonimmobilized calcanei. This reduction was due to thinning of trabeculae (72.4 +/- 12.1 vs. 98.9 +/- 15.9 microns; P < 0.05) without any change in trabecular number (2.74 +/- 0.72 vs. 2.79 +/- 0.40/mm2; not significant). In conclusion, this model only locally increased both osteoclastic and osteoblastic activities leading to bone loss and architectural modifications. The decreased bone formation usually observed in other models of disuse osteoporosis may therefore not constitute a local phenomenon generated by unloading.

Animals↗
PubMed1996

Are somatosensory evoked potential recording and magnetic resonance imaging useful for evaluating the risk of neurologic compromise in rheumatoid arthritis patients with atlantoaxial subluxation?

The objective of this study was to determine whether early somatosensory evoked potential recording and/or magnetic resonance imaging are helpful for evaluating and monitoring the risk of neurologic compromise in rheumatoid arthritis patients. Thirty-seven patients with definite rheumatoid arthritis were studied, including 18 with atlantoaxial subluxation. A physical examination, roentgenograms of the cervical spine, early somatosensory evoked potential recording at all four limbs and magnetic resonance imaging of the cervical spine were done in each case. Alterations in somatosensory evoked potentials and magnetic resonance imaging evidence of compression of the medulla oblongata or spinal cord were found in similar proportions of patients with and without atlantoaxial subluxation. These results support the view that physical findings and changes on plain films of the cervical spine are the most reliable data for evaluating and monitoring the risk of neurologic damage in patients with atlantoaxial subluxation. Somatosensory evoked potential studies and magnetic resonance imaging should be reserved for those cases in which physical and roentgenographic data cannot be collected in a satisfactory manner and for patients who are included in study protocols that require accurate evaluation of lesions.

Adolescent↗
PubMed1995

Secretion of the amino-terminal fragment of the hedgehog protein is necessary and sufficient for hedgehog signalling in Drosophila.

BACKGROUND: The Drosophila segment polarity gene hedgehog encodes a member of a family of secreted proteins that are involved in a variety of patterning processes, in both vertebrates and invertebrates. Some of these processes depend upon short-range or contact-dependent interactions, whereas others seem to involve long-range signalling. Two different models have been proposed to account for the execution of these contrasting processes by the same proteins: one postulates that Hedgehog acts exclusively over short distances, its long-range influences being effected through regulation of other signalling factors; the second postulates that different aspects of Hedgehog activity are mediated by distinct forms of the protein that are generated by autoproteolysis. RESULTS: We have investigated these models by mutating the hedgehog coding region such that only the amino-terminal or carboxy-terminal half of the protein is secreted. Deletion of the carboxy-terminal portion has little effect on the signalling activity of the protein, whereas abolishing the secretion of the amino-terminal half leads to a complete loss of signalling. In addition, we find that increases in the level of expression within the normal hedgehog transcriptional domain of either the wild-type protein or the carboxy-terminal-deleted form expand the range of activity to a limited extent, but have only minor effects on cell identity. CONCLUSIONS: In Drosophila, all of the signalling activity of Hedgehog resides in the amino-terminal portion of the protein, the secretion of which is essential for its function. The range of Hedgehog is limited by the close association of the amino-terminal peptide with the cell surface but can be extended by elevating the level of its expression.

Amino Acid Sequence↗
PubMed1995

The relations between physical ability and bone mass in women aged over 65 years.

In this cross-sectional study of 55 women (mean age 73.54 +/- 5.87), the magnitude of the relation between different indices of physical ability and confounding factors to bone density were determined. Physical fitness was assessed by direct measurement of maximal oxygen consumption (VO2 max), isokinetic muscle strength, and quadriceps and psoas muscle surfaces and densities using computed tomography. Anthropometry, chronological and gynecological ages, and dietary calcium intake were also recorded. The bone mineral density (BMD) was evaluated at the axial level (lumbar spine and proximal femur) and at the peripheral level (radius and tibia, cancellous and cortical compartments). Parameters related to physical ability proved to be the best predictors of BMD in radial and tibial cancellous compartments, spine, femoral neck, and trochanter, accounting for 15-27.5% of the total variance. The VO2 max was a major determinant of the femoral mineral density and one of the predictors of radial and tibial cancellous compartments. Psoas parameters were strongly related to spine mineral density and also constituted a predictor of radius (cancellous) and tibia mineral densities. The arm muscle strength could predict, though weakly, the BMD of axial skeleton, whereas thigh muscle strength only predicted the BMD of inferior limbs. No correlation was observed between current dietary calcium intake and BMD. Age-postmenopause and fertile life remained predictive of BMD at mostly cancellous sites, whereas anthropometry exerted important effects on radial and tibial cortices. The study suggests distinct sets of relations between physical ability and the BMD variables. Subjects with greater and denser psoas muscles had greater spine BMD, and those with higher VO2 max had greater proximal femur BMD.

Absorptiometry, Photon↗
PubMed1995

Physical exercise during remobilization restores a normal bone trabecular network after tail suspension-induced osteopenia in young rats.

To determine how bone recovers from immobilization-induced bone loss and to specify whether its recovering capacity is improved by physical exercise, 5-week-old male Wistar rats (287.07 g +/- 10.65 SD) were tail suspended for 14 days, then returned to either normal weight-bearing (R) or controlled physical exercise for 28 days (R + E). Bone mineral density (BMD) was measured in three parts of the femur. Using histomorphometric analysis, bone mass and architecture were estimated in the primary (1 degree sp) and secondary spongiosa (2 degrees sp) of the proximal tibial metaphysis. Bone cellular parameters were measured in the 2 degrees sp of the tibia. Tail suspension induced a significant decrease in BMD, 2 degrees sp bone mass, mineral apposition rate, and bone formation rate and marked alterations of the trabecular network. In R rats, BMD was still significantly decreased, except in the distal part of the femur. Long-bone lengthening was significantly altered. The 2 degrees sp bone mass returned to the age-matched control values; however, the trabeculae were still significantly thinner and bone resorption was significantly higher. R + E rats had a normal long bone lengthening and a significant increase in 2 degrees sp bone mass and trabecular thickness when compared with R rats. Bone resorption was significantly depressed, and osteoid surfaces and thickness were significantly increased. Thus, although bone mass returns to normal values in the R group, trabecular alterations persist.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗
PubMed1995

Effect of physical training on bone adaptation in three zones of the rat tibia.

This study as been conducted to examine the effects of physical exercise on the bone trabecular network and the cellular adaptations in three different areas of a single bone, the tibia. Male Wistar rats (9 weeks old) were treadmill-trained for 0, 3, 4, or 5 weeks at 60% of their measured maximal O2 consumption (VO2max). Histomorphometric analysis of the proximal tibia of running and age-matched control groups was performed in the epiphyseal trabecular bone, in the primary spongiosa and in the secondary spongiosa. Dynamic and static bone cell activities and serum calcium and phosphorus levels were measured. VO2max increased significantly by 18.4% after 5 weeks of training. In the epiphysis, a 9% increase in bone volume, associated with more numerous trabeculae (8%) was detected the third week of training. In primary spongiosa a significant increase (6.7%) in newly formed trabeculae was found. In secondary spongiosa bone volume increased significantly by 26.2% the fifth week of exercise and was associated with thicker trabeculae. The number of osteoclast profiles was significantly depressed. Osteoid surfaces and bone formation rate increased significantly in weeks 3 to 5. Serum calcium levels were found to be significantly decreased in weeks 3 and 4. There was no change in osteoid thickness or mineral apposition rate. These results suggest 1) a rapid increase in osteoblastic recruitment without change of the cell activity in response to moderate exercise; 2) a decreased bone resorption associated with a marked increased in bone formation from the third week of training; 3) adaptation of the trabecular network to exercise that seems to be bone-site-dependent, suggesting a cell sensitivity to training-engendered strain distribution within the bone or to strain-related local factors.

Adaptation, Physiological↗
PubMed1995

Ineffectiveness of calcitonin on a local-disuse osteoporosis in the sheep: a histomorphometric study.

Local immobilization is a good model for studying disuse-induced bone loss and to appreciate the effects of drugs, especially preventive action of antiresorptive therapy. In fact, increased osteoclastic activity is the main point of such a bone loss. The effect of salmon calcitonin was investigated on immobilization-induced osteoporosis in the sheep. Twenty-four nonovariectomized, adult, female, Welsh mountain sheep were submitted, by an external fixator procedure, to hock joint immobilization from the tibia to the the metatarsus for 12 weeks. The sheep were randomized into two groups receiving either an injection of placebo or salmon calcitonin (100 IU) three times per week, for 12 weeks. Histomorphometric analysis was performed on pre- and posttherapeutic transiliac bone biopsies, and on immobilized (left) and nonimmobilized calcanei removed after sacrifice. Results showed a 29% significant decrease of cancellous bone volume in the placebo group due to a significant reduced trabecular thickness when we compared immobilized versus nonimmobilized calcaneus. This structural adaptation appeared to be the consequence of an overall increased bone turnover. In the calcitonin group, same changes were observed, with a 23% reduction of bone mass in the immobilized calcaneus. By comparing calcitonin with placebo groups in both left and right calcanei, no difference was found. On the other hand, a significant increase of mineralization parameters in the iliac crest was only observed in the calcitonin group. In conclusion, salmon calcitonin, at a dose of 100 IU/day three times a week, was ineffective in preventing local disuse osteoporosis in this sheep model.

Animals↗
PubMed1995

Cross-sectional study of muscle strength and bone mineral density in a population of 106 women between the ages of 44 and 87 years: relationship with age and menopause.

This study examined the correlations between isokinetic muscle strength of knee and elbow flexors and extensors with vertebral and femoral bone mineral density in a population of 106 women between the ages of 44 and 87 years. The absolute value of muscle strength correlated significantly with bone mineral density; muscle strength of the upper limb appeared to be more closely correlated with bone mass, while muscle strength in the lower limb was more specific for femoral mineral bone density. The most important finding that these results demonstrated was a concomitant decline in muscle strength of the upper limb and bone mineral density between the 5th and 6th decades. In contrast, they also showed a decline in muscle strength of the lower limbs after the 6th decade, occurring before the decline in bone mineral density observed between the 7th and 8th decades. From these results it would appear that other studies are required to examine the relationship between the essentially hormonal role in postmenopausal decline in muscle strength and the decline in physical activity during the senile period. These elements are important because they must be taken into account in physical exercise programmes designed to prevent osteoporosis.

Adult↗
PubMed1995

Diagnosis and treatment of osteoporosis.

A new definition of osteoporosis has been proposed by an expert panel of the World Health Organization, in which cutoff diagnostic and therapeutic values are derived from bone mass measurements, leading to the practical idea of densitometric osteoporosis with or without fractures. At the individual level, risk factors of bone fragility are not accurate enough to allow definition of an "at risk" population. Thus, bone densitometry remains the major parameter to be analyzed. In terms of therapy, all protocols refer to the more academic definition of osteoporosis, so that no true innovation appeared in the literature over the past year. The roles of calcium, exercise, hormone replacement therapy, calcitonin, fluoride, and bisphosphonates are more accurately defined in established osteoporosis. However, new studies are needed in the investigation of densitometric osteoporosis.

Aged↗
PubMed1995

Bone changes in 6-mo-old rats after head-down suspension and a reambulation period.

In mature rats experiencing 14-day head-down suspension or 14-day head-down suspension followed by 28-day reambulation, the hindlimb long bones, humerus, and skull were removed for the determination of morphometry and bone mineral content (BMC) and density (BMD) with dual-energy X-ray absorptiometry, dry and ash weights, and calcium content. The bones of the animals in the control groups (killed at days 0, 14, and 42) had their own maturation rate. The body weights of suspended animals were lower than those of the control animals. Suspension does not appear to impair the long-bone elongation rate. However, the tibia of suspended rats exhibited a lower calcium content, ash weight, BMC, and BMD. Similar trends were observed in the femur. In the humerus, no significant change was observed. In the skull, the values of the suspended rats were similar to those of the control rats. At the end of the reambulation period, the body weights showed no difference between the control and experimental animals. The bone alterations were not completely reversible compared with their respective controls. In the tibia, BMC and BMD were always decreased. In the femur, trends toward low values were still visible. The skull showed a decrease in BMC and ash and dry weights. This unexpected finding suggested that importance of a rapid decrease in cephalad fluid shift at the time of desuspension. Finally, we showed that dual-energy X-ray absorptiometry measurement is sufficiently accurate to detect intergroup differences.

Absorptiometry, Photon↗
PubMed1995

Shape changes of osteoblastic cells under gravitational variations during parabolic flight--relationship with PGE2 synthesis.

The relationship existing between cell morphology and cell metabolism, and the role of mechanical load in bone remodelling are well-known. In osteoblasts, PGE2 mediates part of the response to mechanical stress and induce cell shape changes. We studied the influence of gravity variations on osteoblast morphology and its relationship with PGE2 synthesis during a parabolic flight. ROS 17/2.8 osteosarcoma cells flew 15 or 30 parabolae. We measured cell area and shape factor after fluorescein staining with a semi-automatic image analyser and PGE2 levels by RIA. Significant flight-induced shape changes consisted in a decrease in cell area and an increase in shape factor (cell irregularity), in some cells, as compared to ground controls. This heterogeneity in cell response might be explained by a cell-cycle sensitivity to mechanical stress. A 45 min pretreatment with indomethacin inhibited the flight-induced increase in cell irregularity whereas cell area remained decreased. PGE2 levels were higher in flight than in ground controls. Linear regression analysis showed a significant negative relationship between cell area and PGE2 synthesis. We concluded that ROS 17/2.8 are highly sensitive to gravitational variations and that PGE2 is partly implicated in cell shape changes observed during parabolic flight. However, other mechanisms than PGE2 synthesis condition ROS 17/2.8 morphology in response to mechanical changes.

Animals↗
PubMed1995

Considerations about a unique clinical pattern: flexion block of the shoulder.

Frozen shoulder is a well-defined nosologic entity characterized by retraction of the anterior portion of the glenohumeral joint capsule. When clinical findings are inconclusive, arthrography can differentiate a frozen shoulder from a stiff and painful shoulder. We report three cases of stiffness of the shoulder that we believe was due to a unique pathological process. Flexion was restricted to 120 degrees and a sensation suggestive of mechanical blockage was felt upon passive flexion. Medical rotation was restricted and painful, whereas lateral rotation with the elbow held against the torso was normal. Findings upon arthrography or magnetic resonance imaging were normal, with no evidence of capsulitis or chronic rotator cuff lesions. Our pathogenic hypotheses include a lesion of the proximal portion of the long head of the biceps brachii or a focal ligamentous lesion. Treatment should consist of specific physical therapy and, in refractory forms, gentle mobilization under general anesthesia.

Adult↗