Search PubMed⌕ Search

Biomedical subjects

A Legrand

Publications and source records attributed to A Legrand.

At least 73 records · Page 4Linked to original sources
PubMed1998

Mechanical advantage of the human parasternal intercostal and triangularis sterni muscles.

1. Previous studies in dogs have demonstrated that the maximum change in airway pressure (DeltaPao) produced by a particular respiratory muscle is the product of three factors, namely the mass of the muscle, the maximal active muscle tension per unit cross-sectional area ( approximately 3.0 kg cm-2), and the fractional change in muscle length per unit volume increase of the relaxed chest wall (i.e. the muscle's mechanical advantage). In the present studies, we have used this principle to infer the DeltaPao values generated by the parasternal intercostal and triangularis sterni muscles in man. 2. The mass of the muscles and the direction of the muscle fibres relative to the sternum were first assessed in six cadavers. Seven healthy individuals were then placed in a computed tomographic scanner to determine the orientation of the costal cartilages relative to the sternum and their rotation during passive inflation to total lung capacity. The fractional changes in length of the muscles during inflation, their mechanical advantages, and their DeltaPao values were then calculated. 3. Passive inflation induced shortening of the parasternal intercostals in all interspaces and lengthening of the triangularis sterni. The fractional shortening of the parasternal intercostals decreased gradually from 7.7 % in the second interspace to 2.0 % in the fifth, whereas the fractional lengthening of the triangularis sterni increased progressively from 5.9 to 13.8 %. These rostrocaudal gradients were well accounted for by the more caudal orientation of the cartilages of the lower ribs. 4. Since these fractional changes in length corresponded to a maximal inflation, the inspiratory mechanical advantage of the parasternal intercostals was only 2.2-0. 6 % l-1, and the expiratory mechanical advantage of the triangularis sterni was only 1.6-3.8 % l-1. In addition, whatever the interspace, parasternal and triangularis muscle mass was 3-5 and 1-3 g, respectively. As a result, the magnitude of the DeltaPao values generated by a maximal contraction of the parasternal intercostals or triangularis sterni in all interspaces would be only 1-3 cmH2O. 5. These studies therefore confirm that the parasternal intercostals in man have an inspiratory action on the lung whereas the triangularis sterni has an expiratory action. However, these studies also establish the important fact that the pressure-generating ability of both muscles is substantially smaller than in the dog.

Adult↗
PubMed1998

A chromosome 4 satellite I DNA isolated from SV40-transformed human cells.

Analysis of cellular DNA insert isolated from a free replicative plasmid rescued from human cells transformed with an SV40 vector plasmid revealed the presence of two arrays of repetitive DNA arranged in tandem. One sequence was homologous to the consensus sequence of the human alpha satellite DNA and the adjoining sequence was a satellite DNA sequence which consisted of repetitive units of 42 base pairs (bp) and was designated HR42. The degree of homology between repetitive units was about 92%. By Southern analysis the HR42 sequence was detected in HHW416, a somatic cell hybrid containing human chromosome 4, but not in HDm-5, the somatic cell hybrid which has human chromosome 14. By fluorescence in situ hybridization this repetitive DNA was assigned uniquely to the centromeric region of human chromosome 4. These results show that HR42 belongs to a subfamily of satellite I DNA specific for human chromosome 4.

Base Sequence↗
PubMed1998

Pregnenolone reverses the age-dependent accumulation of glial fibrillary acidic protein within astrocytes of specific regions of the rat brain.

Although aged-related modifications of astrocytes have been frequently described, little is known so far about the signals responsible for these modifications. Since it is well demonstrated that astrocytes are highly responsive to a variety of steroids, we hypothesized that modifications of cerebral astrocytes may result from the age-related decrease of circulating steroids. In the present study, we investigated the effects of the chronic administration of pregnenolone (PREG), the precursor of all steroid hormones, on the age-related extension of astrocytic processes in various brain regions. In adult (2-3 month-old) and aged (22-24 month-old) rats, quantitative image analysis was used to estimate, within each region, the number of astrocyte cell bodies immunostained (IS) for S100, and the surface occupied by astrocytic cell bodies and processes IS for glial fibrillary acidic protein (GFAP). In all regions, the surface occupied by GFAP-IS structures was increased in the aged vs. the adult rats, whereas no significant modifications were observed in the number of S100-IS cell bodies. Chronic administration of PREG to aged rats induced a marked decrease in the surface occupied by GFAP-IS structures in the cortex, amygdala and thalamus, without any significant effect on the number of S100-IS cell bodies present in these regions. By contrast, PREG had no significant effect when administered to adult animals. These data suggest that decreased levels of circulating steroid hormones may be responsible for the age-dependent modifications of the astrocytes present in various brain regions, and that these modifications can be at least partly corrected by the administration of PREG.

Aging↗
PubMed1998

Galectin-3 gene (LGALS3) expression in experimental atherosclerosis and cultured smooth muscle cells.

The galectin-3 gene (LGALS3) encodes a beta-galactose binding lectin. LGALS3 expression is associated with neoplastic transformation and with differentiation of monocytes to macrophages. Factors involved in migration, proliferation, adhesion and differentiation of vascular smooth muscle cells (SMC) play a major role during atherosclerosis development. Expression of the galectin-3 gene was not detected in quiescent SMC but was activated in aortas of hypercholesterolemic rabbits, in aortas of rats after balloon injury and in cultured SMC. These results suggest that galectin-3 production is involved in the developmental process of atherogenesis.

Animals↗
PubMed1998

Circulating cardiac troponin I in trauma patients without cardiac contusion.

OBJECTIVES: To describe the evolution and the diagnostic value of cardiac troponin I (cTnI) and to relate its concentrations with the indicators of injury in trauma patients. DESIGN: Prospective, observational study of 17 young, previously healthy, mechanically-ventilated patients during the early post-traumatic period in the Surgical ICU of a University Hospital. METHODS: Serial measurements of serum cTnI, total creatine kinase activity (CKtot) and its isoenzyme MB (CK-MB) (on admission, 12 h later, then daily for 7 days), clinical data and repeated electrocardiographic (ECG) and transesophageal echocardiographic (TEE) recordings. RESULTS: Rhabdomyolysis was observed in all the patients with a significant relationship between CK-MB and CKtot. Despite the fact that no patient demonstrated ECG or TEE signs of myocardial contusion, elevated serum levels of cTnI were observed in six patients (35%) without obvious dilutional interference. As compared with the others, these patients exhibited a more frequent arterial hypotension (83% vs 18%, p = 0.035), required greater volume expansion on day 1 (22,000 vs 8,500 ml, p = 0.027) and usually demonstrated early (83% vs 9%, p = 0.005) and late (66% vs 9%, p = 0.028) multiple organ dysfunction syndrome. CONCLUSIONS: Taking into account the high reported sensitivity and specificity of cTnI dosage, the present results suggest cTnI can play a role in the evaluation of indirect myocardial injury following traumatic shock.

Adult↗
PubMed1998

Mechanical advantage of the canine triangularis sterni.

Recent studies on the canine parasternal intercostal, sternomastoid, and scalene muscles have shown that the maximal changes in airway opening pressure (delta Pao) obtained per unit muscle mass (delta Pao/m) during isolated contraction are closely related to the fractional changes in muscle length per unit volume increase of the relaxed chest wall. In the present study, we have examined the validity of this relationship for the triangularis sterni, an important expiratory muscle of the rib cage in dogs. Passive inflation above functional residual capacity (FRC) induced a virtually linear increase in muscle length, such that, with a 1.0-liter inflation, the muscle lengthened by 17.9 +/- 1.6 (SE) % of its FRC length. When the muscle in one interspace was maximally stimulated at FRC, Pao increased by 0.84 +/- 0.11 cmH2O. However, in agreement with the length-tension characteristics of the muscle, when lung volume was increased by 1.0 liter before stimulation, the rise in Pao amounted to 1.75 +/- 0.12 cmH2O. At the higher volume, delta Pao/m therefore averaged +.053 +/- 0.05 cmH2O/g, such that the coefficient of proportionality between the change in triangularis sterni length during passive inflation and delta Pao/m was the same as that previously obtained for the parasternal intercostal and neck inspiratory muscles. These observations, therefore, confirm that there is a unique relationship between the fractional changes in length of the respiratory muscles, both inspiratory and expiratory, during passive inflation and their delta Pao/m. Consequently, the maximal effect of a particular muscle on the lung can be predicted on the basis of its change in length during passive inflation and its mass. A geometric analysis of the rib cage also established that the lengthening of the canine triangularis sterni during passive inflation is much greater than the shortening of the parasternal intercostals because, in dogs, the costal cartilages slope downward from the sternum.

Anesthesia↗
PubMed1998

Rib cage muscle interaction in airway pressure generation.

We have previously demonstrated in dogs that the change in airway opening pressure (DeltaPao) produced by isolated maximum activation of the parasternal intercostal or triangularis sterni muscle in a single interspace, the sternomastoids, and the scalenes is proportional to the product of muscle mass and the fractional change in muscle length per unit volume increase of the relaxed chest wall. In the present study, we have assessed the interactions between these muscles by comparing the DeltaPao obtained during simultaneous activation of a pair of muscles (measured DeltaPao) to the sum of the DeltaPao values obtained during their separate activation (predicted DeltaPao). Measured and predicted DeltaPao values were compared for the following pairs of muscles: the parasternal intercostals in two interspaces, the parasternal intercostals in one interspace and either the sternomastoids or the scalenes, two segments of the triangularis sterni, and the interosseous intercostals in two contiguous interspaces. For all these pairs, the measured DeltaPao was within approximately 10% of the predicted value. We therefore conclude that 1) the pressure changes generated by the rib cage muscles are essentially additive; and 2) measurements of the mass of a particular muscle and of its fractional change in length during passive inflation can be used to estimate the potential pressure-generating ability of the muscle during coordinated activity as well as during isolated activation.

Air Pressure↗
PubMed1998

[Macroaspartate aminotransferase. Study of 5 cases and review of the literature].

Aspartate aminotransferase can exist as a macroenzyme, which has a higher molecular mass than the corresponding enzyme normally found in serum under physiologic or pathological conditions. This macroenzyme is often an immunoglobulin complexed-enzyme and induces persistently increased serum aspartate aminotransferase activity without any corresponding liver or muscle damage. We report 5 patients with isolated and persistent increased serum aspartate aminotransferase activity in whom a macroenzyme has been detected. Of these 5 cases, four were apparently healthy subjects and the last had chronic active hepatitis. Electrophoresis of aspartate aminotransferase isoenzymes of the subjects' serum showed an abnormal band migrating between mitochondrial and cytosolic aspartate aminotransferase. In 3 cases, the macrocomplex consisted of aspartate aminotransferase and immunoglobulin G, as shown by the immunoprecipitation method. In the patient with chronic active hepatitis, the macroenzyme disappeared after liver transplantation. As macroaspartate aminotransferase and others macroenzymes, may persist for months or even years, it is important for clinicians to be aware of their existence to avoid unnecessary invasive or costly procedures.

Adult↗
PubMed1997

Modulation of platelet-activating-factor production by incorporation of naturally occurring 1-O-alkylglycerols in phospholipids of human leukemic monocyte-like THP-1 cells.

1-O-Alkylglycerols (alkyl-Gro), naturally occurring compounds abundant in shark liver oil, protect patients from radiotherapy side-effects. However, the protection mechanism is not well understood. It might be mediated by alkyl-Gro incorporation into pools of platelet-activating factor (PAF) precursor and subsequent modification of PAF biosynthesis. Using a 3H-labelled or unlabelled natural alkyl-Gro mixture, in which prominent alkyl chains were C18:1(9) (54-65%), C16:1(7) (5-15.5%), and C16:0 (5-10%), we investigated the incorporation of alkyl-Gro into phospholipids of human leukemic monocyte-like THP-1 cells. Incubation of cells for 24 h with [3H]alkyl-Gro (10 microM) resulted in their incorporation into 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (1097+/-25.1 pmol/2x10(6) cells) and into 1-alkyl-2-acyl-sn-glycero-3-phosphoethanolamine (640.4+/-12.5 pmol/2x10(6) cells) with a total yield of 6.5%. Such incorporation induced production of 1-O-[3H]alkyl-2-acetyl-sn-glycero-3-phosphocholine ([3H]PAF), which was increased after stimulation by the calcium ionophore A23187. HPLC analysis of the [3H]PAF molecular species indicated that the three major [3H]alkyl-Gro were used for [3H]PAF synthesis in ratios similar to that of the mixture. Total production of biologically active PAF, as measured by the platelet-aggregation bioassay, was also increased by alkyl-Gro incorporation in resting (+20%) and in A23187-stimulated (+59%) THP-1 cells. HPLC analysis of the [3H]PAF produced in the presence of [3H]acetate, confirmed that levels of PAF, but not of its 1-acyl analog, were increased by alkyl-Gro incorporation in resting and stimulated cells. However, the rise in [3H]acetyl-PAF, which resulted mainly from C16:0 PAF, was reduced by about 50% in the presence of the PAF-receptor antagonist SR 27417, providing evidence that stimulation of total PAF synthesis was caused by the increase in the precursor pool and autocrine amplification of PAF-induced PAF production. Thus, the supplementation of THP-1 cells in culture with naturally occurring alkyl-Gro led to the incorporation of alkyl-Gro into ether-containing phospholipids, which were subsequently used for PAF synthesis. Furthermore, alkyl-Gro incorporation resulted in a significant rise in PAF production by THP-1 cells under resting and stimulated conditions. These results may be of importance for modulating PAF production in several pathophysiological conditions, such as peroxysome deficiencies, that are associated with a lack of ether lipid synthesis.

Glycerol↗
PubMed1997

PSA-NCAM and B-50/GAP-43 are coexpressed by specific neuronal systems of the adult rat mediobasal hypothalamus that exhibit remarkable capacities for morphological plasticity.

The present study was designed to determine whether the mediobasal hypothalamus of adult rats contains neurons that continue to coexpress the highly polysialylated neural cell adhesion molecule (PSA-NCAM) and B-50/GAP-43, two proteins coexpressed by virtually all of the neurons of the fetal and neonatal rat central nervous system. Confocal laser scanning microscopy combined with double- or triple-fluorescence immunostaining was used to identify the hypothalamic neurons that express high levels of both PSA-NCAM and B-50/GAP-43 and to study the possible modifications of their morphological organization following a surgical lesion through the mediobasal hypothalamus. In intact animals, PSA-NCAM and B-50/GAP-43 were found to be colocalized within numerous fibers projecting throughout the external layer of the median eminence that were immunoreactive for either gamma-aminobutyric acid (GABA) or tyrosine hydroxylase (TH). Three to 30 days after a lesion through this region, numerous regenerating axonal sprouts, triple-immunostained for PSA-NCAM, B-50/GAP-43, and either GABA or TH, were detected along the ventricular surface of, and throughout the perivascular layer of, the median eminence. Surprisingly, high levels of PSA-NCAM and B-50/GAP-43 were also associated with numerous supraependymal neurons that exhibited long ramified processes and were immunoreactive for GABA but TH-negative. The use of the proliferation marker, 3H-thymidine, further indicated that the emergence of such supraependymal neurons after median eminence lesion was not related to the proliferation of preexisting quiescent cells. These data indicate that the mediobasal hypothalamus of the adult rat contains two neuronal systems, in which the continued coexpression of PSA-NCAM and B-50/GAP-43 is related to remarkable capacities for postlesional, morphological plasticity.

Animals↗
PubMed1997

alpha-tocopherol enrichment of high-density lipoproteins: stabilization of hydroperoxides produced during copper oxidation.

In the aim to study the effect of an in vitro enrichment of high-density lipoprotein (HDL) with alpha-tocopherol in alcoholic solution on a copper-induced peroxidation, we monitored several markers of lipid peroxidation (alpha-tocopherol consumption, formation of conjugated dienes and of fatty acid hydroperoxides, production of thiobarbituric acid-reactive substances) and the integrity of apolipoprotein A-I. High-density lipoproteins (1.063 < d < 1.21) with a mean of 0.58 alpha-tocopherol molecules per HDL particle were enriched with alpha-tocopherol in alcoholic solution to obtain an average of 3.7 and 21 alpha-tocopherol molecules per HDL particle. HDL oxidation with 5 microM CuSO4 at 37 degrees C resulted in the total disappearance of endogenous alpha-tocopherol after 2 h, but after 24 h about 19% of alpha-tocopherol remained in the most enriched HDL. In agreement with the tocopherol-mediated peroxidation, the formation of conjugated dienes and of fatty acid hydroperoxides was very fast and increased with alpha-tocopherol concentration, whereas TBARS production decreased. These results showed that alpha-tocopherol enrichment stabilized the production of hydroperoxides in HDL and decreased the formation of secondary oxidation products. These latter products are known for deleterious effects towards apolipoproteins. This could explain why we observed that the apolipoprotein A-I of the most enriched HDL was only slightly altered after incubation with CuSO4.

Antioxidants↗
PubMed1997

Interleukin-1 beta and interleukin-6 stimulate 2-methylaminoisobutyric acid uptake in HepG2 cells.

The metabolic response to inflammation involves an increased uptake of amino acids in the liver. It has been suggested that cytokines, such as interleukin-1 beta and interleukin-6, could be involved in this increased amino acid uptake. We investigated the role of these two inflammatory cytokines in regulating hepatic amino acid transport systems in the human hepatoma cell line, HepG2. Uptake of methylaminoisobutyric acid, the most specific known substrate of system A, and of glutamine, both transported by other sodium-dependent transport systems ASC and N, was assayed after incubation of the cells for various times with cytokines, using the cluster-tray method. Interleukin-1 beta and interleukin-6 (1000 U/ml) stimulated methylaminoisobutyric acid uptake by 36 +/- 6 and 41 +/- 4%, respectively (per cent +/- SD, n > or = 6). Under our experimental conditions, these cytokines had no effect on glutamine uptake. The stimulatory effect on methylaminoisobutyric acid uptake was not increased by combining the cytokines or by the presence of dexamethasone. The cytokine effect was abolished by cycloheximide, suggesting the involvement of de novo protein synthesis in this activation of transport system A. These data demonstrate that, in our culture conditions, interleukin-1 beta and interleukin-6 indirectly exert a stimulatory effect on methylaminoisobutyric acid transport in HepG2 cells.

Biological Transport↗
PubMed1997

Modulation of the expression of the rabbit galectin-3 gene by p53 and c-Ha-ras proteins and PMA.

Galectin-3 is a galactose-binding lectin that has been found in several mammalian tissues. Galectin-3 gene is expressed in a wide range of normal and tumoral cells. In the case of myeloid cells, its expression correlates with the differentiation of monocytes to macrophages. In the case of cancer cell lines, its expression correlates with tumorigenicity and metastatic potential. The regulation of the expression of this gene is still largely unknown. The rabbit galectin-3 gene has been isolated and characterized. Its structure revealed an organization similar to that of the murine galectin-3 gene. The genomic sequences located upstream from its 5' end, upon insertion upstream from a promoter-free reporter gene, exhibited a strong promoter activity. This activity was upregulated upon treatment of transfected smooth muscle cells with phorbol 12-myristate 13-acetate (PMA) as well as upon transfection with a EJ/ras encoding plasmid. Conversely, it was downmodulated upon transfection with wild-type p53 but not with mutated p53. The regulatory sequences involved in the positive regulation of the gene were located upon serial deletion experiments.

Animals↗
PubMed1997

Mechanical advantage of sternomastoid and scalene muscles in dogs.

Theoretical studies have led to the prediction that the maximal effect of a given respiratory muscle on airway opening pressure (Pao) is the product of muscle mass, the maximal active muscle tension per unit cross-sectional area, and the fractional change in muscle length per unit volume increase of the relaxed chest wall. It has previously been shown that the parasternal intercostals behave in agreement with this prediction (A. De Troyer, A. Legrand, and T. A. Wilson. J. Physiol. (Lond) 495: 239-246, 1996; A. Legrand, T. A. Wilson, and A. De Troyer. J. Appl. Physiol. 80: 2097-2101, 1996). In the present study, we have tested the prediction further by measuring the response to passive inflation and the pressure-generating ability of the sternomastoid and scalene muscles in eight anesthetized dogs. With 1-liter passive inflation, the sternomastoids and scalenes shortened by 2.03 +/- 0.17 and 5.98 +/- 0.43%, respectively, of their relaxation length (P < 0.001). During maximal stimulation, the two muscles caused similar falls in Pao. However, the sternomastoids had greater mass such that the change in Pao (delta Pao) per unit muscle mass was -0.19 +/- 0.02 cmH2O/g for the scalenes and only -0.07 +/- 0.01 cmH2O/g for the sternomastoids (P < 0.001). After extension of the neck, there was a reduction in both the muscle shortening during passive inflation and the fall in Pao during stimulation. The delta Pao per unit muscle mass was thus closely related to the change in length; the slope of the relationship was 3.1. These observations further support the concept that the fractional changes in length of the respiratory muscles during passive inflation can be used to predict their pressure-generating ability.

Animals↗
PubMed1997

Transformation of rabbit vascular smooth muscle cells by human cytomegalovirus morphological transforming region I.

The association of human cytomegalovirus with atherosclerosis and the monoclonal hypothesis of atherogenesis suggested that transformation of vascular smooth muscle cells may be an outcome of the virus-host cell interaction. To test this hypothesis, rabbit aorta smooth muscle cells were transfected with the morphological transforming region I (mtrI) of human cytomegalovirus (HCMV) linked to the neomycin resistance gene. Foci of neomycin-resistant and morphologically transformed cells were isolated and expanded into fourteen RCMV strains. Eight of these strains acquired immortalization, but only one strain (RCMV-21) retained recombined viral sequences integrated in the cellular DNA. RCMV strains were heterogeneous in their morphology, expression of smooth muscle alpha-actin, growth, and mitogenic response to serum and fibroblast growth factor (FGF)-2 and -4. All RCMV strains assayed except RCMV-3 showed DNA synthesis in low serum medium and, with the exception of RCMV-1 cells, all showed a significant mitogenic response to FGF-2 and FGF-4, Maintenance of the transformed phenotype appeared independent of the retention of the transforming viral sequences, which was suggestive of a "hit-and-run" mechanism. These results suggested that morphological transformation by HCMV DNA sequences could enhance the mitogenic response of vascular smooth muscle cells to fibroblast growth factors.

Animals↗