Search PubMed⌕ Search

Biomedical subjects

A Legrand

Publications and source records attributed to A Legrand.

At least 91 records · Page 5Linked to original sources

Rostrocaudal gradient of mechanical advantage in the parasternal intercostal muscles of the dog.

1. Previous theoretical studies have led to the predictions that, in the dog, the parasternal intercostal muscles in the rostral interspaces shorten more during passive inflation than those in the caudal interspaces and have, therefore, a greater inspiratory mechanical advantage. The present studies were undertaken to test these predictions. 2. The effects of passive inflation on the length of the parasternal intercostals interspaces 1 to 7 were evaluated with markers implanted in the costal cartilages. Although the muscles in all interspaces shortened with passive inflation, the fractional shortening increased from the first to the second and third interspaces and then decreased continuously to the seventh interspace. 3. To understand this peculiar distribution, a geometric model of the parasternal area was then developed and a relation was obtained between muscle shortening and the angles that describe the orientation of the muscle and costal cartilage relative to the sternum. Measurement of these angles indicated that the rostrocaudal gradient of parasternal shortening resulted from the different orientations of the costal cartilages and their different rotations during passive inflation. 4. The changes in airway pressure generated by the parasternal intercostals in interspaces 3, 5 and 7 were finally measured during selective, maximal stimulation. The fall in pressure was invariably greatest during contraction of the third interspace and smallest during contraction of the seventh. 5. These observations indicate that, in the dog, the rostrocaudal gradient in rib rotation induces a rostrocaudal gradient of mechanical advantage in the parasternal intercostals, which has its climax in the second and third interspaces. These observations also support the concept that the respiratory effect of a given respiratory muscle can be computed from its behaviour during passive inflation.

Animals↗

Rostrocaudal gradient of electrical activation in the parasternal intercostal muscles of the dog.

1. Because the inspiratory mechanical advantage of the canine parasternal intercostal muscles is greatest in the third interspace and decreases gradually in the caudal direction, the electromyograms of these muscles in interspaces 3, 5 and 7 have been recorded in anaesthetized, spontaneously breathing dogs. Each activity was expressed as a percentage of the activity measured during tetanic, supramaximal stimulation of the internal intercostal nerve (maximal activity). 2. Parasternal inspiratory activity during resting, room air breathing was invariably greater in the third than in the fifth interspace (62.0 +/- 6.0 vs. 41.3 +/- 4.6% of maximal activity; P < 0.001) and smallest in the seventh interspace (22.8 +/- 2.7% of maximal activity; P < 0.001). This distribution of activity persisted during hyperoxic hypercapnia and during breathing against increased inspiratory airflow resistance. 3. This rostrocaudal distribution of activity also persisted after complete paralysis of the diaphragm as well as after deafferentation of the ribcage. 4. Studies of the distribution of the muscle fibre types indicated that the parasternal intercostals in all interspaces had a higher proportion of slow-twitch oxidative (SO; type I) fibres than fast-twitch oxidative-glycolytic (FOG; type II a) fibres. 5. Thus the topographic distribution of parasternal inspiratory activity along the rostrocaudal axis of the ribcage is precisely matched with the topographic distribution of mechanical advantage. This extraordinarily effective pattern of activation probably results from the unequal distribution of central inputs throughout the parasternal motoneurone pool.

Animals↗

Decreased erythrocyte deformability in glycogen storage disease.

Liver glycogen storage diseases (GSD) are disorders associated with severe dyslipidaemia which can induce cell membrane alterations and possibly reduced cell deformability. Since decreased erythrocyte deformability is known to disturb blood flow in capillaries and may promote ischaemic diseases, this study was designed to investigate erythrocyte deformability using a new filtration system, the Cell Transit Analyser (CTA), and to examine lipid compounds in the blood of 23 patients affected with GSD, aged from 1 to 20 years and 18 controls aged from 1 to 17 years. The patients showed a mixed hyperlipidaemia with predominant hypertriglyceridaemia and an increase in erythrocytes mean transit times (TT) due to the presence of more rigid erythrocytes subpopulations when compared to controls. Thus the erythrocyte rigidity, in addition to the lipid abnormalities must be taken into account for long-term evolution of GSD patients. Moreover this cellular alteration may contribute to shortened erythrocyte survival.

Adolescent↗

Feasibility and Realization of Single-Pulse Laue Diffraction on Macromolecular Crystals at ESRF.

Laue diffraction patterns with an exposure time of ca 60 ps have been acquired at the European Synchrotron Radiation Facility (ESRF) on protein crystals by using the single-bunch mode of the storage ring. A 10 ns laser pulse initiating photodissociation was synchronized with the X-ray pulse. The potential for a quantitative detection of conformational changes in proteins on the nanosecond timescale with this technique is demonstrated using the example of carbonmonoxymyoglobin, from simulations and real data. The instrumental aspects of the experiment (highly intense X-ray beam, fast shutter system, Laue camera, detector, laser apparatus and synchronization technique) are emphasized.

Journal Article↗

Resistance of lipoprotein(a) to lipid peroxidation induced by oxygenated free radicals produced by gamma radiolysis: a comparison with low-density lipoprotein.

Lipid peroxidation of lipoprotein(a) [Lp(a)] by defined oxygen-centred free radicals (O2-/OH, O2-, O2-/HO2) produced by gamma radiolysis was compared with that of paired samples of low-density lipoprotein (LDL). Lp(a) appeared to be more resistant to oxidation than LDL, as indicated by the kinetic study of four markers of lipid peroxidation; decrease in vitamin E, formation of conjugated dienes and aldehydic products, and modification of electrophoretic mobility. In contrast, similar kinetics of lipid peroxidation were obtained for LDL and Lp(a-), which is the lipoparticle issued following the reductive cleavage of apolipoprotein(a) from Lp(a), thus suggesting that the greater resistance of Lp(a) to lipid peroxidation was due to the presence of apolipoprotein(a). Lipid peroxidation of Lp(a) and LDL induced by peroxyl radicals, which were produced by an azo compound [2,2'-azobis-(2-amidinopropane)dihydrochloride], confirmed both the resistance of Lp(a) to lipid peroxidation and the propensity of Lp(a-) to exhibit a greater susceptibility to oxidation than intact Lp(a). Our findings also indicated that the high content of apolipoprotein(a) in N-acetylneuraminic acid residues was only partly responsible for the resistance of Lp(a) to oxidation.

Amidines↗

Alterations in erythrocyte membrane fluidity and fatty acid composition in glycogen storage disease.

Liver glycogen storage diseases (GSD) are disorders associated with severe dyslipidaemia which can induce cell membrane alterations. Reduced erythrocyte membrane fluidity has been associated with ischaemic cardiovascular disease. Our study has been designed to investigate membrane erythrocyte fluidity, and to determine its lipid composition and peroxidation parameters. Membrane erythrocyte fluidity has been studied by electron spin resonance (ESR) with two fatty acid nitroxide probes (5NS and 16NS). Twenty-five GSD cases aged 1-27 years and 15 controls aged 1-28 years were included. The erythrocyte membrane of GSD patients appeared less fluid with the two probes (P < 0.001). The membrane fatty acid pattern explained this reduced fluidity. Patients showed a relative saturated fatty acid (SFA) increase and polyunsaturated fatty acid (PUFA) decrease which induced lower PUFA/SFA ratio than in controls. We have provided evidence that the PUFA decrease was independent of the oxidative process. These findings should be taken into account for the management of the dietary treatment of GSD patients.

Adolescent↗

Isolation of carbohydrate metabolic clones from cultured astrocytes.

Astrocytes are the principal sites of glycogen synthesis in the nervous tissue. Growing evidence shows that there are many types of astrocytes. The aim of the present investigation was to isolate different types of astrocytes that display different carbohydrate anabolism. Astrocytes from newborn rat brain were directly cloned from primary cultures without a previous transformation. Many clones were obtained, and they were termed CP clones. Another series of clones, termed SV clones, were obtained after the transfection of the primary cultures by the SV40 T antigen. The effectiveness of the transfection was verified by the rate of DNA synthesis using flow cytometry and by the presence of plasmid DNA in the genomic DNA of the astrocytes using the Southern blot method. After the transfection, the growth velocity increased greatly. The size and shape of the astrocytes were the same for each cell in a given clone, regardless of the cloning method utilized. However, these sizes and shapes could be different from one clone to another in CP clones, whereas all the astrocytes of all the SV clones looked like each other. All the clones obtained stained positively with anti-glial fibrillary acidic protein antibodies. Glycogen stained in the clones using concanavalin A-horseradish peroxidase. The glycogen content was also measured using biochemical analysis. Concordant results obtained using two methods showed that some clones contained an important quantity of glycogen while other clones contained a small amount, in the CP series as well as in the SV series. This property was the same for the intracellular glucose concentrations. The activity of the gluconeogenic enzyme fructose-1, 6-bisphosphatase was measured in each clone using spectrophotometry. This activity was also significantly different from one clone to another. The clones containing large amounts of glycogen had important fructose-1,6-bisphosphatase activity. The present results show that it is possible to clone astrocytes either directly from primary cultures without immortalization or after their transformation. When analyzing these clones, it appears that carbohydrate anabolism can be significantly different from one astrocyte to another. This difference may also exist in vivo.

Animals↗

Blood lipids and rheological modifications in glycogen storage disease.

OBJECTIVES: Hyperlipidemia is a feature of liver glycogen storage disease (GSD). Recent studies have suggested that rheological mechanisms such as elevated erythrocyte aggregation may be involved in the pathogenesis of ischemic syndromes associated with hyperlipidemia. DESIGN AND METHODS: We investigated erythrocyte aggregation, lipids, and circulatory proteins in the blood of 24 patients affected with GSD, aged from 1 to 23 years (mean = 8) and 26 controls aged from 1 to 28 years (mean = 9). RESULTS: The aggregation results were much higher in patients than controls. The lipid data showed a mixed hyperlipidemia with predominant hypertriglyceridemia, low HDL-C, apoA-I and LpA-I/A-II, and high apoB as compared with controls. However, the LpA-I was not significantly different from controls. CONCLUSIONS: In conclusion, patients with GSD presented hyperlipidemia and elevated erythrocyte aggregation such that they are at long-term risk of ischemic complications.

Adolescent↗

Abnormal lipoprotein pattern in patients with Alagille syndrome depends on Icterus severity.

BACKGROUND & AIMS: Children with Alagille syndrome have lipid abnormalities that differ according to the severity of icteric periods. The lipoprotein profiles of 22 patients with Alagille syndrome were determined and the findings were compared with the severity of jaundice. METHODS: Plasma lipids and apolipoproteins (apos), isolated lipoprotein composition, and lecithin/ cholesterol acyltransferase (LCAT) activity were analyzed in patients. Patients were classified into two groups according to their bilirubin levels; patients in group I had total bilirubin levels of > 100 mumol/L, and patients in group II had total bilirubin levels of < 100 mumol/L. RESULTS: In patients from group II, hypercholesterolemia was associated with increased levels of high-density lipoprotein and high concentrations of apoAI and apoAII; in a few cases, an abnormal lipoprotein with a slow alpha migration was observed. In contrast, in patients from group I, the levels of high-density lipoprotein cholesterol and apoAI and apoAII were very low, and the abnormal lipoprotein X was in many cases responsible for hypercholesterolemia. In group I, the decreased LCAT activity was consistent with the very high level of unesterified cholesterol and the emergence of lipoprotein X. In both groups of patients, the levels of apoE, apoCII, and apoCIII were high, and all the lipoprotein fractions were enriched in phospholipids. CONCLUSIONS: The variations of LCAT activity caused by the degree of jaundice in patients with Alagille syndrome are implicated in the abnormal lipid profiles.

Adolescent↗

alpha-Tocopherol in human spermatozoa and seminal plasma: relationships with motility, antioxidant enzymes and leukocytes.

The chain-breaking antioxidant alpha-tocopherol has not been reported to be present in mammalian spermatozoa, unlike other cell types where it contributes to cell integrity and function. Semen samples obtained from 36 male partners of infertile couples during infertility investigations were analysed for alpha-tocopherol content of seminal plasma and spermatozoa, and the superoxide dismutase and glutathione peroxidase activities of spermatozoa were determined concomitantly with routine semen analysis. A wide range of alpha-tocopherol concentrations was detected in human spermatozoa (85 +/- 51 ng/10(8) spermatozoa, range 10-245). The concentration of alpha-tocopherol in spermatozoa was not found to be significantly related to the concentration or the total amount of alpha-tocopherol in seminal plasma. The percentage of motile spermatozoa was significantly related to sperm alpha-tocopherol content (r = 0.84, P < 0.001). alpha-tocopherol concentration and superoxide dismutase and glutathione peroxidase activities of spermatozoa were significantly elevated when the semen samples contained < 10(6) leukocytes/ml (mean +/- SD, 94 +/- 53 compared with 54 +/- 29 ng/10(8) spermatozoa, P < 0.02, 1.15 +/- 0.41 compared with 0.77 +/- 0.30 IU/10(8) spermatozoa, P < 0.02 and 60 +/- 26 compared with 30 +/- 14 spermatozoa mlU/10(8) spermatozoa, P < 0.005 respectively). From these results, it is suggested that alpha-tocopherol might play a role in association with antioxidant enzymes, for preserving the functional competence of spermatozoa subjected to an oxidative attack.

Adult↗

Anhedonia, depression and the deficit syndrome of schizophrenia.

A total of 29 deficit schizophrenics were compared with 121 non-deficit schizophrenics using the Physical Anhedonia Scale (PAS) and the abridged form of the Beck Depression Inventory (BDI). The results show that the deficit schizophrenics had a higher score on the PAS and lower score on the BDI than the non-deficit schizophrenics.

Adult↗

On the mechanism of the mediolateral gradient of parasternal activation.

Recent studies have shown that in spontaneously breathing dogs the parasternal intercostals are activated according to a mediolateral gradient. To assess the mechanism of this regionalization of activity, we assessed the pattern of activation of these muscles after section of the dorsal roots and examined the topographic distribution of the muscle fiber types from the sternum to the chondrocostal junctions. The pattern of parasternal activity after dorsal rhizotomy was similar in all respects to that previously observed in intact animals. Thus activity in the medial parasternal bundles at the onset of inspiration frequently preceded activity in the middle bundles, and no activity was recorded from the lateral bundles. The amount of medial activity, when expressed as a percentage of the activity recorded during supramaximal tetanic stimulation of the internal intercostal nerve (maximal activity), was also consistently greater than the amount of middle activity (52.6 +/- 4.6 vs. 23.1 +/- 2.6% maximal activity; P < 0.001). Furthermore, the medial, middle, and lateral parasternal bundles had a higher proportion of slow-twitch oxidative fibers than of fast-twitch oxidative-glycolytic fibers; no topographic difference in fiber type distribution was observed. We conclude, therefore, that the mediolateral gradient of parasternal activity is probably due to the unequal distribution of central inputs throughout the pool of alpha-motoneurons.

Animals↗

Mediolateral gradient of mechanical advantage in the canine parasternal intercostals.

Previous theoretical studies have postulated that the potential effect of a given respiratory muscle on lung volume or pleural pressure (i.e., its respiratory effect) is proportional to the change in length of the muscle during inflation of the passive chest wall (T. A. Wilson and A. De Troyer J. Appl. Physiol. 73: 2283-2288, 1992). To test this prediction, we have studied the parasternal intercostals in 18 interspaces in 8 supine anesthetized dogs. In each interspace, we have measured the changes in length of the medial and lateral portions of the parasternal during passive inflation and we have also assessed the changes in airway opening pressure (delta Pao) generated by these portions during isolated bilateral stimulation of the internal intercostal nerve. The results showed that 1) the medial fibers shorten more than the lateral fibers during passive inflation (P < 0.001); 2) when stimulated, the medial portion generated a larger fall in Pao than the lateral portion (P < 0.001); and 3) delta Pao was closely related to change in length (r = 0.81; P < 0.001). These observations thus imply that the medial portion of the parasternal intercostals contributes much more to lung expansion during breathing than the lateral portion. These observations also suggest, in agreement with the theoretical prediction, that measurements of the changes in length of the different respiratory muscles during passive inflation can be used to predict the potential respiratory effect of these muscles and to compare their mechanical advantages.

Animals↗

Complementation analysis of carnitine palmitoyltransferase I and II defects.

Carnitine palmitoyltransferase (CPT) consists of two activities located in the outer (CPT I) and the inner (CPT II) mitochondrial membranes. CPT II deficiency in the adult as well as in the infantile form of the disease has been shown to result from mutations in the CPT II cDNA. Nothing is known regarding the genetic defect in CPT I deficiency. We carried out complementation experiments between CPT I- and infantile CPT II-deficient cell lines. Restoration of 3H2O release from [9,10(n)-3H]-palmitate was chosen as criterion of complementation. As expected, no complementation was observed in heteropolykaryons resulting from fusions between CPT II-deficient cells. Similar results were obtained in fusions between CPT I-deficient cells, suggesting that the enzymatic defect in these cell lines results from mutations in the same gene. Conversely, complementation was observed in fusions between CPT I- and CPT II-deficient cells. These data support that CPT I and CPT II defects result from mutations in distinct genes. Palmitate oxidation by control or CPT I-deficient cell lines was decreased when cocultured with infantile CPT II-deficient cell lines. This effect, not observed in coculture including an adult CPT II-deficient cell line, was carnitine-dependent. The possible mechanism of this effect, suppressed by a high carnitine concentration, is discussed.

Adult↗

Transcriptional expression of mannose receptor gene during differentiation of human macrophages.

Mannose receptor is a differentiation marker of macrophages. Circulating monocytes isolated from plasma are devoid of this receptor; upon culture this receptor is rapidly expressed. Its expression is modulated by a variety of inflammatory and anti-inflammatory agents. In the present study, we investigated its transcription level during the differentiation process. Mannose receptor mRNA was monitored by quantitative RT-PCR on freshly harvested monocytes and on monocytes cultivated up to four days. No transcription was detected in freshly harvested cells, the transcription increased during the first 24 h upon adhesion and then decreased.

Antigens, Differentiation↗