The dystrophin superfamily: variability and complexity.
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Amino Acid Sequence↗
Biomedical subjects
F Pons
Publications and source records attributed to F Pons.
Comparison of the foetal development of fibre types in four bovine muscles.
The pattern of expression of different types of myosin heavy chains and the development of different generations of muscle cells during foetal life were studied in four bovine muscles with widely varying characteristics, the Masseter, Longissimus thoracis, Cutaneus trunci and Diaphragma. Different complementary techniques were performed: immunocytochemistry, electrophoresis, immunoblotting and ELISA. Monoclonal antibodies against different myosin heavy chain isoforms were used. The results confirmed the existence of at least two generations of cells during foetal development in cattle. A first generation, which appeared at a very early stage, gave rise to adult type I fibres. A second generation, made up of different cell populations, gave rise to adult fast type IIA and IIB fibres, and to type IIC. In the slow muscles, it also seemed to give rise to type I fibres. The beginning of myogenesis was characterized in the different cell generations by the expression of transitory myosin forms that are not found in the adult. Type 1 myosin heavy chain was observed from 90 days whereas the fast types, 2a and 2b, were present from 210 to 230 days, at which stage the foetal form disappeared. Muscles that have greatly different contractile characteristics in the adult exhibit also different profiles of differentiation: the Diaphragma was the first to develop, followed by Cutaneus trunci, Longissimus thoracis and Masseter.
Animals↗
Lower extremity stress fractures during intermittent cyclical etidronate treatment for osteoporosis.
During intermittent cyclical etidronate treatment, a lower extremity pain syndrome associated with stress fractures was observed in three osteoporotic patients. This report describes the development of stress fractures during initial cycles of treatment, with recurrence of symptoms in two patients when etidronate therapy was resumed. Further studies are needed to confirm whether stress fractures are associated with cyclic etidronate treatment and if so, the incidence and pathophysiology need to be determined.
Aged↗
Does utrophin expression in muscles of mdx mice during postnatal development functionally compensate for dystrophin deficiency?
We correlated utrophin expression with the physiopathological course in mdx mice. Evolution of the pathology was assessed by monitoring expression of developmental MHC in mdx mice versus control. Utrophin expression is detected by dystrophin/utrophin cross-reacting antibodies and can only be evaluated in mdx mouse muscles (in absence of dystrophin). This protein was expressed at the periphery of all myotubes and myofibers during the first postnatal week. It began declining in fast muscles before the third week and disappeared from the soleus between the 3rd and the 4th week. The decrease was concomitant with a sudden degenerative/regenerative process affecting slow muscle earlier and more massively than fast muscles. The pathological process became stable in all muscle types (except the diaphragm), with greater utrophin expression in the soleus. These results in mdx mice along with observed utrophin expression in severely affected DMD patients suggest that overexpression of utrophin is not enough to explain the stability of regenerated fibers in mdx mice.
Animals↗
Relationship between skin collagen and bone changes during aging.
There is evidence that skin collagen content and bone mass are influenced by estrogen deficiency, both of them declining in the years following menopause. The aim of our study was to analyze the relationship between changes in skin collagen content and bone mass during aging. A total of 76 nulliparous women who had been admitted for surgery of non-malignant processes were studied. All subjects were arranged into five age-groups (from 20 to 60 years). Bone mineral density was measured by dual photon absorptiometry and expressed in g/cm2 as the mean of the second to fourth lumbar vertebrae. Additionally, in all patients skin biopsies were taken from a non-sun exposed site in the lower abdomen (4 cm above the pubic symphysis) and osteocalcin levels were determined. Collagen decreased significantly with age after the 40s (P < 0.001) and after menopause (P < 0.001). Changes in bone mass were closely related to those detected in collagen (r = 0.586; P < 0.0001). In conclusion, our data suggest that bone mass and skin collagen decline in parallel with aging and that the hypoestrogenism developing in postmenopausal years has a significant effect on skin collagen content. Nevertheless, the question of whether osteoporosis is an intrinsic collagen disorder remains to be demonstrated.
Adult↗
Estimation of peripheral dose from two linacs: Mevatron MX6700 and Mevatron KDS.
An empirical calculation method for high-energy beam peripheral dose estimation is described. The peripheral dose has been measured for a Siemens Mevatron MX6700 (6 MV) and a Siemens Mevatron KDS (6 and 18 MV) linear accelerators. The dose distribution is parameterized for each beam energy as a function of depth, distance from the edge of the field, and field size. A simple algorithm has been developed for dose calculation up to 100 cm from the field central axes. Predictions by this algorithm are compared with measurements in an Alderson phantom.
Particle Accelerators↗
Nitric oxide biology: implications for cardiovascular therapeutics.
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Cardiovascular Diseases↗
Prevention of further bone mass loss by nasal calcitonin in patients on long term glucocorticoid therapy for asthma: a two year follow up study.
BACKGROUND: Injectable calcitonin is effective in reducing spinal bone loss in steroid-dependent asthma but side effects are frequent. In contrast, a nasal spray presentation has been shown to be effective and well tolerated in involutional osteoporosis. To test the efficacy of nasal calcitonin a two year prospective trial was conducted in 44 steroid-dependent asthmatic patients. METHODS: All patients received a calcium supplement of 1000 mg and were allocated randomly into two groups treated with either salmon calcitonin nasal spray (200 IU every other day, n = 22) or calcium alone (n = 22) for two years. All patients completed the first year of the study. Five patients in each group dropped out during the second year. In the calcitonin group one patient developed generalised pruritus and four lost steroid dependence, and in the calcium alone group five were no longer dependent on steroids. The efficacy of treatment was evaluated as follows: bone turnover assessed by biochemical markers, bone loss assessed by serial measurement of lumbar spine density, and rates of bone fractures. RESULTS: The bone mass in the calcitonin group increased by 2.7% in the first year while in the group receiving calcium alone it decreased by 2.8%; this difference was significant. Calcitonin prevented more bone loss during the second year while the calcium alone group continued losing bone mass (-7.8%). The difference between means was 0.1077 (95% CI 0.0381 to 0.1773). Three new fractures occurred in both groups. No changes in biochemical parameters were detected in either group. CONCLUSIONS: Calcitonin given intranasally increased spinal bone mass during the first year of treatment and maintained bone mass in a steady state during the second year. These results suggest that calcitonin may be a useful agent to prevent steroid-induced osteoporosis. However, the lack of effect of calcitonin on the rate of vertebral fractures does not permit its recommendation for routine use in preventing steroid-induced osteoporosis.
Administration, Intranasal↗
Utrophin localization in normal and dystrophin-deficient heart.
BACKGROUND: The localization of dystrophin at the sarcolemma of cardiac skeletal fibers and cardiac Purkinje fibers has been described. Dystrophin deficiency produces clinical manifestations of disease in skeletal muscles and hearts of patients with Duchenne and Becker muscular dystrophy. Utrophin (or dystrophin-related protein), a dystrophin homologous protein, was found to be expressed in fetal muscles and reexpressed in dystrophin-deficient skeletal muscle fibers. We therefore examined utrophin expression in normal and in dystrophin-deficient hearts. METHODS AND RESULTS: The expression and subcellular distribution of utrophin was examined in cardiac muscle by immunoblot and immunofluorescence analysis in normal bovine heart compared with dystrophin. Utrophin expression was also examined in normal and dystrophin-deficient hearts of MDX mice. Three monoclonal antibodies reacting with dystrophin and utrophin solely or reacting with both proteins along with two polyclonal antibodies reacting with either utrophin or dystrophin and utrophin were tested. In normal bovine heart, utrophin was not expressed at the periphery of fibers but was strongly expressed in intercalated disks and in the cytoplasm of cardiac Purkinje fibers. In cardiocytes, utrophin was colocalized along transverse T tubules with dystrophin. Dystrophin was present at the periphery of cardiocytes and cardiac Purkinje fibers as well as in transverse T tubules but was absent or faintly expressed in intercalated disks. The results with monoclonal and polyclonal antibodies were identical. Western blot analysis revealed that the detected molecules corresponded only to a 400-kD protein band and not to possible shorter transcripts of utrophin or dystrophin (apo-utrophin or apo-dystrophin). In dystrophin-deficient hearts of MDX mice, utrophin alone was abundant but not organized in the same networklike distribution. CONCLUSIONS: This first localization of utrophin in normal heart (in Purkinje fibers, transverse tubules, and intercalated disks) showed a distinct subcellular localization of this protein with dystrophin, suggesting an important function of this protein in intercellular communication. In dystrophin-deficient hearts of MDX mice, utrophin alone is overexpressed as in skeletal muscle sarcolemma, an area normally occupied by dystrophin but not organized in the same networklike distribution.
Animals↗
Bone mineral density of the lumbar spine in white Mediterranean Spanish children and adolescents: changes related to age, sex, and puberty.
Bone mineral content was measured by dual-energy x-ray absorptiometry in the lumbar spine at the L2-L4 level with a Lunar DPX densitometer model in 471 healthy white Mediterranean Spanish children and adolescents (256 boys and 215 girls) randomly selected from the urban area of Barcelona. Ages ranged from 3 mo to 21 y. Weight, height, and pubertal development were in the normal age distribution. Bone mineral content values were corrected by the vertebral surface area scanned and expressed as bone mineral density (BMD) values. BMD increased progressively from infancy to adulthood, and values were similar in both sexes, with the only differences related to the earlier onset of puberty in girls. A statistically significant correlation (p < 0.001) was found between BMD values and age, height, and weight. BMD values increased annually, but the periods of higher increase were observed during the first 3 y of life and late puberty. A significant (p < 0.001) increase in BMD was observed between Tanner pubertal stages III and IV and between Tanner stage IV and adult values. Lumbar BMD values peaked in a similar way to growth height velocity during pubertal development. However, the BMD peak seemed to occur somewhat later than height velocity peak, particularly in girls. In conclusion, we report normative data for BMD values at the lumbar level in our normally growing pediatric population and show that the first 3 y of life and adolescence are critical periods for bone mineralization. These data provide a tool for the investigation and follow-up of pediatric populations at risk for low bone mineralization.
Absorptiometry, Photon↗
[Rwanda and Zaire: a surgical outpost during Operation Turquoise].
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Child↗
[Video-assisted thoracoscopic surgery].
Since the team at the Laennec hospital first performed an extra-pleural thoracoscopy in 1990, a certain number of thoracic surgery units have started using this new technique. Video-assisted thoracoscopy is an absolutely revolutionary technique allowing an intrapleural approach to the mediastinum and to the pulmonary parenchyma without a thoracotomy. It requires a sophisticated technical set up including a video camera, direct or angular optics, and a video screen. The patient is placed in the same position as for a thoracotomy. For the pneumothorax and dystropic bullae, Video assisted thoracoscopic surgery has been largely shown to be the superior technique. The pleura is treated by avivement or sometimes by pleurectomy. Pulmonary biopsies are often taken. Preoperative computed tomography with methylene blue injection is often required for the exeresis of peripheral parenchymatous sub-pleural nodules and sometimes a small fishhook has to be placed within the tumour. Inversely, segmentectomies or lobectomies are rarely performed. There is a certain amount of risk involved in closed chest vascular dissections, and the question of carcinologic rigour has to be raised. Tumours of the mediastinum, both cystic and solid tumours, are relatively easy to approach by dissection using video assisted thoracoscopy. Finally, this technique offers new possibilities for staging bronchial cancers, the treatment of broncho-pleural fistulas, and more recently for non operated chest trauma. This new technique is of great importance for the thoracic surgeon, although an evaluation of long-term results are still required.
Biopsy↗
[Place of arteriography in the assessment of pulmonary sequestrations].
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Angiography↗
[Lung cancer associated with histiocytosis X. A new case].
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Adenocarcinoma↗
Nitric oxide, but not interleukin-1, mediates the local blood flow response to lipopolysaccharide in rabbit skin.
Lipopolysaccharide can mimic many aspects of the inflammatory response to gram-negative bacteria. In rabbit and rat skin, lipopolysaccharide induces neutrophil accumulation and an increase in blood flow. Interleukin-1, tumor necrosis factor-alpha and the vasodilator, nitric oxide (NO) have been implicated in the biological responses to lipopolysaccharide and gram-negative bacteria. In the present study, we characterized the local vascular response to E. coli lipopolysaccharide in rabbit skin and investigated its dependence on de novo protein synthesis, NO, interleukin-1 and neutrophils. The local vascular response to the intradermal injection of lipopolysaccharide was determined by measuring changes in local blood flow with a laser-Doppler flowmeter. Injections of lipopolysaccharide (3, 10 and 30 micrograms/site) induced a dose-related increase in blood flow, with a maximum at 2 h. The response to 10 micrograms/site lipopolysaccharide was abolished by co-injection of actinomycin D (4 x 10(-9) mol/site), reduced by 60% by NG-nitro-L-arginine methyl ester (10(-7) mol/site) and suppressed by 82% in rabbits pretreated with dexamethasone (2 mg/kg, i.v.). However, the lipopolysaccharide-induced increase in blood flow was not affected by co-injection of recombinant human interleukin-1 receptor antagonist (7.0 x 10(-11) mol/site) or by systemic neutrophil depletion. These results demonstrate that lipopolysaccharide causes delayed vasodilatation of the rabbit cutaneous microvasculature which depends on protein synthesis and involves in part the release of NO. However, this response does not depend on interleukin-1 or neutrophils. The vasodilator effect of lipopolysaccharide may involve the expression of the inducible form of NO synthase in the vessel wall, through a mechanism independent of interleukin-1.
Animals↗
Probing functional regions in cardiac isomyosins with monoclonal antibodies.
Seven Mabs prepared against subfragment 1 (S1) of either bovine cardiac beta-specific or rabbit fast skeletal muscle myosin were used to identify functional regions in cardiac isomyosin heavy chains. This approach was designed to improve the understanding of structure-function relationships within the myosin molecule and between alpha and beta myosin heavy chains (MHCs). We used bacterial expression of human beta myosin fragments and determined that the seven antibodies were localized within four different MHC subdomains: amino acid residues 33-37 (one beta-specific antibody), 67-84 (one alpha/beta-specific antibody), 85-106 (four alpha/beta-specific antibodies) and 215-248 (one alpha/beta-specific antibody). All epitopes were accessible on myosin and actomyosin with the same affinities. Therefore, none of these MHC epitopes were located on the interfaces between the myosin head and actin. Three antibodies reacting at three out of the four investigated epitopes enhanced acto-S1 ATPase activities but not myosin, S1, or actomyosin activities. One antibody, which was strictly beta-specific and bound to five amino acid residues near the most N-terminal MHC end, substantially inhibited all myosin or S1 ATPase activities measured with or without actin. The epitope of this antibody coincides with one difference cluster observed between both cardiac MHC isoforms [McNally et al (1989) J. Mol. Biol. 210, 665-671], suggesting that this small variable MHC area could be one of the structural bases to explain observed functional differences in cardiac alpha and beta myosin isoforms.
Amino Acid Sequence↗
Triiodothyronine influences quail myoblast proliferation and differentiation.
The influence of triiodothyronine (T3) on avian myoblast proliferation and differentiation was studied in secondary cultures using plating densities of 2,500 and 7,000 cells/cm2. Culture media were depleted of T3 (control myoblasts) and increasing amounts were then added to concentrations of 0.6, 3 and 15 nM T3 (treated myoblasts). Independent of the cell density, T3 induced a dose-related decrease in myoblast proliferation measured by cell number, doubling time and 3H-thymidine incorporation. However, with the lower plating density, this influence was delayed, occurring only after the third day of culture for 0.6 nM T3-treated myoblasts and simultaneous with the onset of myosin heavy chain accumulation. Moreover, when myoblasts were exposed to BrdU for 48 h, the T3 growth inhibitory effect disappeared, thus showing that this effect was clearly linked to differentiation. In addition, we have shown that T3 induced an early fusion of myoblasts: 65% of the maximal value of the fusion index was reached on day 3 in the T3-treated cells in comparison to 25% in the control myoblasts. This hormone also enhanced accumulation of muscle-specific proteins (connectin, acetylcholine receptors, myosin heavy chain), tested by cytoimmunofluorescence, ELISA, binding experiments and Western blot. All these results show that T3 increased myoblast differentiation through a pathway including myoblast withdrawal from the cell cycle. The influence of T3 could partly explain its previously reported positive effect on the number of muscle fibers.
Animals↗
Bone mineral density in surgically postmenopausal women receiving hormonal replacement therapy as assessed by dual photon absorptiometry.
A total of 118 postmenopausal women who had undergone hysterectomy and bilateral oophorectomy were invited to participate in this study. Patients were randomly allocated to one of four study groups which received, respectively, conjugated equine oestrogens (CEE) 0.625 mg/day over a 25-day cycle each month (n = 28); transdermal 17 beta-oestradiol 50 micrograms/day over a 24-day cycle each month (n = 28), CEE 0.625 mg/day every day of the month (n = 32) and no treatment the control group (n = 30). All the treated patients also received 2.5 mg/day medroxyprogesterone acetate sequentially for the last 12 days of each cycle. Dual photon absorptiometry was performed before therapy commenced and repeated after 1 year in all four groups. The three therapeutic regimens induced increases in bone mass, whereas a significant decrease was observed in the control group (P < 0.05).
Absorptiometry, Photon↗