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Biomedical subjects

C Alexandre

Publications and source records attributed to C Alexandre.

At least 19 recordsLinked to original sources

Human and Drosophila homeodomain proteins that enhance the DNA-binding activity of serum response factor.

Cells with distinct developmental histories can respond differentially to identical signals, suggesting that signals are interpreted in a fashion that reflects a cell's identity. How this might occur is suggested by the observation that proteins of the homeodomain family, including a newly identified human protein, enhance the DNA-binding activity of serum response factor, a protein required for the induction of genes by growth and differentiation factors. Interaction with proteins of the serum response factor family may allow homeodomain proteins to specify the transcriptional response to inductive signals. Moreover, because the ability to enhance the binding of serum response factor to DNA residues within the homeodomain but is independent of homeodomain DNA-binding activity, this additional activity of the homeodomain may account for some of specificity of action of homeodomain proteins in development.

Amino Acid Sequence

Microgravity and bone adaptation at the tissue level.

Our knowledge of the adaptation of human bone microgravity remains poor despite long-term Russian spaceflights and the recent use of accurate techniques for bone mass measurements. The extent of bone deficits in the adaptation of the whole skeleton is not clear. At the tissue level, bone resorption and formation activities have been studied only in bones from rats after spaceflights lasting a few days to 3 weeks. In these animals, architectural features consistent with osteoporosis have been found in the proximal tibia. In pregnant animals the osteoclast population is increased at other skeletal sites. In areas of weight-bearing bones that are not protected by muscular insertions, bone resorption is not markedly altered after 7 days of spaceflight and bone formation is reduced. In areas of weight-bearing bones with muscular insertions and in non-weight-bearing bones, similar changes in bone cell activity are delayed. The severity of the response seems to vary with the location of the bone in the skeleton and its initial level of bone turnover. After 12.5 days the acute bone changes are less and no additional changes are observed after 21 days in space. We conclude that generalized bone deficits do not appear to be a consequence of microgravity but occur in localized areas according to the level of modeling and remodeling and of the support function of each bone at 1 g.

Adaptation, Physiological

Bone mass and bone cellular variations after five months of physical training in rhesus monkeys: histomorphometric study.

Five Rhesus Monkeys (Macaca mulatta), a suitable nonhuman model, performed 5 months of rope-climbing exercise. Duration of the training sessions was progressively increased to reach 1 hour/day after 1 month of training and was maintained until the end of the experiment. Bone mass parameters, bone resorption, and bone formation activity were measured by histomorphometric analysis on iliac crest bone biopsies before and after the experiment. Mineral apposition rate was measured in cortices and trabecular bone after double calcein labeling. Five months of rope-climbing exercise had determined a significant decrease of bone volume with a slight decrease of the number and thickness of trabeculae. This might induce an alteration of biomechanical properties of bone. These architectural modifications were associated with a nonsignificant decrease of bone resorption activity. But the main effect of training was an important decrease of bone formation activity without change of the mineral apposition rate. Endurance exercise at low intensity has determined a decreased bone turnover with osteoblastic depression. This animal experiment points out that exercise modalities might be important in the bone response to training and should be carefully defined for preventive use in humans.

Animals

Effect of a five-week swimming program on rat bone: a histomorphometric study.

To specify the exercise-induced changes on different skeletal sites, the effect of a 5-week endurance swim training was studied in rats. Eighteen Lyon strain (Sprague-Dawley) 5-week old female rats were divided into nine sedentary and nine swimming rats. Each swim training session was increased by 15 minutes from 2-6 hours per day. A histomorphometric study was performed at the primary and secondary spongiosa of the distal femur and at the secondary spongiosa of lumbar and thoracic vertebral bodies. After training, bone loss was observed in the secondary spongiosa of lumbar vertebral bodies (24.7%) and in the primary spongiosa of distal femur (15.2%). A tendency to bone loss was also detected in the secondary spongiosa of distal femur (10.8%), whereas no change was detected in thoracic vertebral bodies. In secondary spongiosa, bone loss was accompanied with a thinning of trabeculae. Total eroded surfaces and osteoid surfaces were significantly decreased in the three studied skeletal sites, suggesting a decreased bone turnover. The decreased thickness of osteoid seams in both lumbar vertebrae and distal femur could mean that the osteoblastic activity has also been altered at the cell level, leading to thinning of trabeculae. Five-week swim training with such duration and intensity of exercise appears unable to increase bone volume in rats and, therefore, causes adverse effects. The three studied bones seemed to adapt differently to experimental conditions. The lack of ground reaction forces induced by water immersion might have contributed to the observed bone loss. "Normal" gravity would be an important cofactor in the osteogenic effects of exercise.

Adaptation, Physiological

Bone tissue response to four-month antiorthostatic bedrest: a bone histomorphometric study.

A histomorphometric analysis were made on iliac crest biopsies from eight healthy male volunteers submitted to a 4-month antiorthostatic bedrest. Bone mass and bone cell parameters, reflecting resorption and formation activities, were measured before and after the bedrest period. Trabecular bone volume and mean cortical thickness were not modified despite a decreased number of trabeculae and nonsignificant increase of the trabecular thickness; total and active resorption surfaces and the number of osteoclast per mm2 of trabecular surfaces do not vary significantly. Osteoid thickness does not vary but we found a reduced osteoid surface and a nonsignificant decreased osteoid volume. Our results suggest that bone architecture may be more affected by the reduction of mechanical forces than the bone mass. These modifications were supposed to be the result of an accelerated bone turnover in the early stage of immobilization. In this study, we failed to find disuse osteoporosis; however, we must point out that the new organization of the trabeculae could affect the bone mechanical properties.

Adult

Contributions of chronological age, age at menarche and menopause and of anthropometric parameters to axial and peripheral bone densities.

Bone mineral density (BMD) was measured in 128 normal postmenopausal women at different skeletal sites: lumbar spine and proximal femur, using dual-energy X-ray absorptiometry (DXA), and the cancellous and cortical envelopes of the distal third of radius and tibia, using precise low-dose quantitative computed tomography (QCT). Multivariate analysis included chronological age, ages related to menstrual history (menopause and menarche) and anthropometric factors, e.g. height and weight, as independent predictive variables. Weight is a much-studied predictor of bone density. At sites of high bone turnover, i.e. cancellous envelope, the effect of weight appeared overshadowed by estrogen-related parameters: age-past-menopause was the first predictor of BMD in the cancellous compartment of radius and in Ward's triangle, and the number of reproductive years was the strongest predictor of BMD in the cancellous compartment of tibia and in the spine (L2-4). This suggests that in addition to menopause, the length of menstrual life should be considered as an explanation for the variations in current bone mass in postmenopausal women. At the cortical level of radius, the effect of chronological age was predominant. At the cortical level of tibia, height and weight were the best predictors of BMD. We conclude that the influence of parameters related to menstrual history is predominant in sites with mainly cancellous tissue and that anthropometric factors constitute the best predictors of BMD in the cortical sites of weight-bearing bones.

Absorptiometry, Photon

Bacterial pyomyositis in a patient with a multiple myeloma.

Pyomyositis is relatively rare in regions with a temperate climate. The most common aetiologic agent is staphylococcus aureus. Most patients with pyomyositis from temperate regions involve immunocompromised states. Because of the rarity, it is often initially misdiagnosed. Computed tomography scan is considered the most helpful tool for the diagnosis of pyomyositis. We present a case in a patient with multiple myeloma.

Female

[Bone histomorphometric study in involuted fractured osteoporosis treated with 1-ethane-1-hydroxybiphosphonate (etidronate) during one year].

The efficacy of the biphosphonate etidronate has recently been demonstrated versus the vertebral fracture rate in fractured involuted osteoporosis in the literature. However, it would appear that the increase in bone mass (measured from the calcium density) may alone account for these results. The authors undertook a histomorphometrie study in 20 patients with a group mean age of 55 years presenting recent vertebral fracture in the context of osteoporosis, in order to assess the cell changes which may affect bone quality. This factor remains the only one which can account for the reduced number of fractures. The patients received treatment with phosphorus (1,500 mg/d) for 3 days followed by etidronate (400 mg/d) for 14 days every 90 days. A permanent daily intake of 50 mg of calcium and 400 IU of vitamin D was also administered. Each patient underwent bone biopsy of the iliac wing before and after one year of treatment (4 cycles). No change in the bone mass or architectural parameters was observed. However, general slowing of the bone remodeling was found, affecting the natality and activity of the osteoforming and osteoresorbing cells. However, this remodeling which is traditionally uncoupled in osteoporosis was once more coupled. This results in a slowing of bone loss, ageing of the bone present and no change in the architecture. Thus, the diphosphonates appear to have a beneficial effect on the quality of bone rather than on its quantity. This represents a novel approach to the treatment of osteoporosis.

Aged

[In vitro identification of a mononuclear precursor of osteoclast].

Osteoclast is derived from mononuclear hematopoietic stem cells, most likely within the granulocyte-macrophage lineage. The exact differentiation process of osteoclasts precurssors has only been partially uncovered. The authors isolated in vitro, from the medullary bone of hens a mononuclear precursor of the osteoclast. This cell expressed several characteristics of mature and multinucleated osteoclast including the capacity to resorb the extracellular bone matrix.

Animals

Cortical osteoclasts are less sensitive to etidronate than trabecular osteoclasts.

Acute osteoporosis after spinal cord injury is related to an early increase in osteoclastic resorption. Healthy subjects subjected to bed rest similarly increase their osteoclast number in trabecular bone. Bisphosphonates possess a highly antiosteoclastic activity. The effects of a 120 day bed rest period, with or without etidronate therapy on cortical bone were measured in 15 subjects. Cortical thickness and cortical porosity were measured on transiliac bone biopsies taken before and after the bed rest period. Osteoclasts were detected histochemically and were counted with a semiautomatic image analyzer. Cortical thickness, cortical porosity, and cortical osteoclast number were not significantly modified in subjects submitted to bed rest alone. In the etidronate-treated patients, cortical bone mass parameters were also found to be unaffected, but the most striking feature was that the osteoclast number was unchanged. Trabecular osteoclasts, on the contrary, were increased in the untreated subjects (+95.2%) but decreased in the treated subjects (-78%). Bone cells may have heterogeneous responses according to their trabecular or cortical location. Cortical osteoclasts seem to be unaffected by etidronate therapy.

Adult

Hyperparathyroidism in proximal femur fractures biological and histomorphometric study in 21 patients over 75 years old.

Proximal femur fractures in elderly people are more and more frequent. Falls and senile bone disorders are the risk factors of this fracture. In order to understand the mechanisms of these bone disorders, we studied 21 consecutive patients with this fracture using bone histomorphometry. Measurements of serum intact parathormone (PTH), 25-(OH)-vitamin D, 1,25-(OH) 2-vitamin D and osteocalcin have been performed in these 21 patients, included in a larger series. We excluded patients with renal failure (serum creatinine greater than 140 mumols/l), cancer, or previous metabolic bone disease. There were 19 female and 2 male patients, ranging from 75 to 96 years, (mean 84.9). We found a low frequency of cortical (2/21) and trabecular (3/21) osteoporosis. There was no case of clearcut osteomalacia. Following histomorphometric bone study, two patients showed a typical pattern of hyperparathyroidism, and in a third one, this condition seemed very likely. In these three patients who were among the oldest, and who had high levels of serum PTH, chronic renal failure and primary hyperparathyroidism could be excluded. High bone remodeling was frequent in our patients, as reflected by the enhancement of eroded surfaces (13 cases) and of osteoid thickness (7 cases). Intact PTH level was elevated in our series compared to normal values in adults (in accordance to the PTH elevation in the case control study in a larger series). These findings suggest a major role of a secondary hyperparathyroidism in senile bone disorders favoring proximal femur fractures. This hyperparathyroidism is probably secondary to mild calcium and vitamin D deficiency. It may lead to architectural bone changes favoring this fracture.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Osteoclast cytomorphometry demonstrates an abnormal population in B cell malignancies but not in multiple myeloma.

Increased bone resorption in the vicinity of myeloma cells is mediated by local stimulating factors. Other malignancies of the B cell lineage are also able to produce resorbing factors responsible for increased bone resorption. We have studied three groups of subjects: 10 patients with overt multiple myeloma, 10 patients with a B cell malignancy, and 10 healthy human subjects as controls. Patients were studied at the time of diagnosis and had a transiliac bone biopsy. Osteoclasts were evident on histological sections by their acid phosphatase activity. A software was developed on an automatic image analyzer (Leitz TAS+) for measuring the maximal Feret's diameter (Oc.Le) of each osteoclast (corresponding to the osteoclast length). The histogram of Oc.Le frequency distribution was supplied in each group. In myeloma patients, the Oc.Le frequency distribution was similar to that in normal subjects and showed the histogram to be asymetric with a positive skew (maximum peak at 20-25 microns). With a graphical analysis, this distribution was shown to follow a lognormal distribution corresponding to a homogeneous osteoclast population. In other B cell malignancies, Oc.Le displayed a bimodal distribution with a peak at 20-25 microns and a lower peak at 10-15 microns. The graphical analysis showed that small (mononucleated?) osteoclasts are present in B cell malignancies with normal osteoclasts. This might reflect the secretion of different soluble factors by malignant cells of the B lymphocyte lineage.

Acid Phosphatase

Bone physiology.

Marked improvement in the knowledge of bone physiology has occurred during the last few years. In particular, the development of immunology of bone leads to better understanding of bone cell origin and lineage. At the same time, development of biochemical markers of bone formation and resorption activities allows for better analysis of several pathologic conditions.

Arthritis, Rheumatoid

Relationships between bone and skin atrophies during aging.

Bone mineral density (BMD) was measured in 133 female subjects (age: 61.7 +/- 16.3 years) by dual energy X-ray absorptiometry (DEXA). Vertebral bone mineral density (BMD; L1-L4) and BMD of the whole upper femoral extremity were taken into account. In addition, skinfold thickness was measured with a callipers on the dorsum of the nondominant hand. A significant negative correlation was found between skinfold thickness and age (r = -0.623, p less than 0.0001). Both vertebral and femoral BMD decreased with age and the slopes were similar to those observed by other authors. Skinfold thickness was significantly correlated with vertebral (r = 0.364, p less than 0.0001) and femoral BMD (r = 0.486, p less than 0.0001). Skin and bone are connective tissues whose extracellular matrix mainly contains type I collagen. It is postulated that age-related skin atrophy and bone atrophy have a common genetic mechanism. Skinfold thickness measurement may help in defining the women at risk for osteoporotic bone fractures who should be referred for a DEXA examination.

Absorptiometry, Photon