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Biomedical subjects

A Westphal

Publications and source records attributed to A Westphal.

At least 19 recordsLinked to original sources
PubMed2004

Effect of glucocorticoïd receptor ligands on myosin heavy chains expression in rat skeletal muscles during controllable stress.

The influence of agonist (dexamethasone) and antagonist (mifepristone) of glucocorticoïd receptor during controllable painless stress was evaluated on myosin heavy chains expression in three masticatory and two nape rat muscles: anterior digastric (AD), anterior temporalis (AT), masseter superficialis (MS), longissimus capitis (L) and rectus capitis dorsalis major (R). The relative amounts of myosin heavy chain (MHC) protein isoform contained were significantly affected in four muscles studied by dexamethasone and in three muscles studied under mifepristone, versus control during the stress procedure, after only 1 week of treatment. The control group AT muscles contained respectively 18.2% of MHC 2A, 34.5% of MHC 2X and 47.4% of MHC 2B. The effects of dexamethasone and mifepristone were opposite in this muscle: under dexamethasone, the relative proportions of the three isoforms were 14.2, 31.0 and 54.8%: consequently, MHC 2A and 2X decreased with the profit of 2B. Under mifepristone, the relative proportions were 21.1, 36.6 and 42.3% (MHC 2A and 2X increased to the detriment of 2B). The L muscle was not affected by the two treatments and MS muscle was only affected by dexamethasone. Dexamethasone increased MHC 2B to the detriment of MHC 2A in MS, AD and R. Mifepristone and dexamethasone induced the same changes in AD. The mifepristone treatment decreased the MHC 2X profile in R. Under dexamethasone, four muscles exhibited a significantly higher proportion of the more rapid isoforms than under mifepristone. A previous work showed that controllable stress induced a marked increase in the relative expression of MHC 2B in the same skeletal muscles (Martrette et al. , 1998). Our results confirm then a significant participation of glucocorticoïd in MHC isoform expression during controllable stress.

Animals↗
PubMed2001

Influence of the Lurcher mutation on myosin heavy chain expression in skeletal and cardiac muscles.

This study evaluated the influence of Lurcher mutation, characterized by degeneration of cerebellar Purkinje cells, granule cells, and inferior olive neurons, on cardiac and skeletal muscles: one respiratory (diaphragm, Dia), three masticatory (anterior temporalis, AT; masseter superficialis, MS and anterior digastric, AD), one hind limb (soleus, S), entire tongue (T), and one cardiac (ventricle, V) muscles. Body and muscle weight, muscle protein content, and myosin heavy chain (MHC) isoforms relative expression were then compared in Lurcher mutant mice vs. normal, according to sex. Male body weight was always greater than female one, but there was no specific muscle difference in females, except for T relative weight which was greater in normal females. Muscle protein concentration was greater in normal males except for AD and T in which it was lower. Lurcher mutant mice showed a reduced whole body growth but no specific muscle atrophy (except in male AT), and a global decrease in muscle protein content which made muscles more fragile (except in female Dia and male T, in which it was greater). Lurcher mutation induced a global reduction of muscle protein concentration whereas a general influence of sex could not be disclosed. Concerning MHC relative composition, all the muscles were fast-twitch: Dia, AT, MS, AD, S, and T predominantly expressed the fast type 2 MHC isoforms, except female S, whereas V contained only MHC alpha, also a fast MHC. Female muscles were slower than male ones and classification of muscles in terms of shortening velocity was comparable in normal male and female. In other respects, male Lurcher mutant muscles were slower and consequently more fatigue resistant than normal, except T which became faster and less fatigue resistant. On the contrary, in female mutants, only the Dia was slower than normal one, MS and AD were comparable to normal ones and finally, AT, S, and T were faster than normal ones. It should be noted that a developmental MHC (neonatal) was present in Lurcher AD. Motor control, which influences muscle structure, is altered in Lurcher mutant and could be one of the causal factor of the fast-to-slow MHC switches observed in some mutant muscles. It seems therefore that cerebellar Purkinje cells, granule cells, and inferior olive neurons are very important in maintaining the structural integrity of both cardiac and skeletal muscle, and their degeneration is accompanied by important muscles modifications. J. Cell. Biochem. Suppl. 36: 222-231, 2001.

Animals↗
PubMed2001

Impact of vascular branching sites on focal progression of allograft vasculopathy in transplanted hearts.

BACKGROUND: Cardiac allograft vascular disease (CAVD) represents one of the most accelerated progressing coronary syndromes in the human heart. A variety of risk factors have been identified over recent years; however, little is known about the influence of physical forces. As a model for differences in focal blood flow dynamics, we analyzed progression of intimal hyperplasia at vascular bifurcational sites using intravascular ultrasound (IVUS). METHODS: The most diseased vascular sites ("worst sites") in 59 coronary arteries were assessed (30 MHz, motorized pull back) in 25 consecutive heart transplant recipients at baseline (52.8+/-15.3 days postoperatively) and after 1 year of follow up (360.5+/-24.9 days). Progression of intimal hyperplasia was compared between branching and non-branching lesions as well as in focal relation to the position of the flow divider. RESULTS: A total of 41 (69.5%) worst sites were identified at branching locations. Progression of intimal hyperplasia was found to be significantly more severe at bifurcational sites with an increase in plaque area by 1.5+/-1.8 mm(2) in branching versus 0.4+/-0.6 mm(2) in non-branching lesions (P=0.015). The highest rate in focal progression was found at the opposite site of the flow divider with an increase in maximal intimal thickness by 0.3+/-0.23 mm (180 degrees ) as compared to 0.11+/-0.15 mm (90 degrees, P<0.001) and 0.15+/-0.15 mm (P=0.014) at 270 degrees. CONCLUSIONS: Using serial intravascular ultrasound examinations, vascular branching sites could be identified to be predisposing locations not only for a donor related arteriosclerosis, but also for progression of intimal hyperplasia within transplanted hearts. The highest regional increase in intimal thickness was found at the outer wall of the flow divider, suggesting focal shear or wall stress to be involved in pathogenesis.

Coronary Disease↗
PubMed2000

Progression of cardiac allograft vascular disease as assessed by serial intravascular ultrasound: correlation to immunological and non-immunological risk factors.

OBJECTIVE: To characterise the severity and progression of cardiac allograft vascular disease (CAVD) in a large patient cohort, and to evaluate possible immunological and non-immunological risk factors for progression. DESIGN: A prospective observational study using intravascular ultrasound. SETTING: Two university hospitals. PATIENTS AND MAIN OUTCOME MEASURES: Changes in focal plaque, lumen, and total vessel area (worst site method) were assessed at baseline and after 12.1 (2.8) months (mean (SD)) of follow up in a cohort of 96 patients (79 male, 17 female; mean age 48.7 (9.6) years; time post-transplant 26.0 (32.4) months). RESULTS: Overall, the mean (SD) intimal index of worst sites increased by 6.7 (8.8)%. The increase in the first 12 months was 7.5 (9.4)%, v 5.9 (8.0)% after the first year (NS). Analysing immunological and non-immunological risk factors (age, underlying disease, sex, donor age, immunosuppression, cytomegalovirus, rejection episodes, cholesterol), low density lipoprotein (LDL) cholesterol was found to be the most important predictor of severe progression (as defined by an increase in intimal index of >/= 15% (p = 0.01). CONCLUSIONS: Progression of CAVD is characterised by a continuing increase in intimal hyperplasia, especially within the first year after heart transplantation. LDL cholesterol is an important predictor of major progression.

Adult↗
PubMed1999

Dystonia musculorum mutation and myosin heavy chain expression in skeletal and cardiac muscles.

This study evaluated the influence of dystonia musculorum (dt) mutation, characterized by spinocerebellar fibers degeneration, on cardiac and skeletal muscles: one respiratory (diaphragm, Dia), three masticatory (anterior temporalis, AT; masseter superficialis, MS; and anterior digastric, AD), one hindlimb (soleus, S), tongue (T), and one cardiac (ventricle, V). Body and muscle weight, muscle protein content, and myosin heavy chain (MHC) isoforms relative expression were then compared in dt mutant mice and in normal mice, according to sex. Male body and muscle weight was always greater than that of females, but there was no specific muscle difference in females. dt mutant mice showed a reduced whole body growth but no specific muscle atrophy, as well as a global decrease in muscle protein content that made muscles more fragile. dt mutation induced a global reduction of muscle protein concentration, whereas a general influence of sex could not be disclosed. Concerning MHC relative composition, all the muscles were fast-twitch: Dia, AT, MS, AD, S, and T expressed predominantly the fast type 2 MHC isoforms, whereas V contained only MHC alpha, also a fast MHC. Female muscles were slower than male muscles, except for S, which was faster. However, classification of muscles in terms of shortening velocity was very different in normal males and females. In other respects, dt mutant muscles were slower and consequently more fatigue resistant than normal, except for S, which became faster and less fatigue resistant. dt mutation exhibits then a specific effect on this continually active postural muscle. In the other muscles, global increased fatigue resistance could constitute an adaptive response to work requirements modifications linked to the muscle damage. It should be noted that a developmental MHC (neonatal) was present in female dt AD. Innervation, which influences muscle structure, is altered in dt mutant and could be another causal factor of the fast-to-slow MHC switches. It appears that dystonin, the dt gene product, is very important in maintaining the structural integrity of both cardiac and skeletal muscle and in its absence, the muscle becomes more fragile and is damaged by modified activity.

Animals↗
PubMed1999

Effects of controllable stress on masticatory behaviour and muscle structure: partial protective effect of clomipramine.

The influence of controllable painless stress and clomipramine treatment was evaluated on masticatory behaviour and myosin heavy chain expression in masticatory rat muscles: anterior digastric, anterior temporalis and masseter superficialis. The adult fast isoforms of myosin heavy chains detected were myosin heavy chains 2A, 2X and 2B. The myosin heavy chains composition of anterior temporalis muscle was unchanged by stress or by treatment. In anterior digastric and masseter superficialis muscles, stress induced an increase in 2B and a decrease in 2X and 2A. Under stress, whereas the myosin heavy chains composition of anterior temporalis and anterior digastric muscles was unaffected by clomipramine, this drug modified significantly the myosin heavy chains composition of masseter superficialis muscle which became comparable to that of control muscle. Stress-induced myosin heavy chains transformations led to an increased velocity of anterior digastric and masseter superficialis muscles but not anterior temporalis muscle. Gnawing and mastication were increased by stress and incisor grinding was reduced. Stress shortened the duration of gnawing and increased the fatigability of anterior digastric and masseter superficialis muscles, whereas clomipramine increased the duration of mastication and reduced the fatigability of masseter superficialis muscle. Stress produces selective changes in masticatory muscles and behaviour. This study demonstrates the muscle type-specific protective effect of clomipramine against stress-induced structural transformations of masseter superficialis muscle and the specific concomitant behavioural modifications.

Animals↗
PubMed1998

Effects of pre- and perinatal exposure to hypergravity on muscular structure development in rat.

This study evaluated the influence of precocious exposure to hypergravity on the expression of myosin heavy chain (MHC) protein isoforms in nape, masticatory and respiratory developmental rat muscles. Pregnant females were maintained at 1.8 g from the 11th day of gestation to the 7th day after birth. The 7-day-old rats were used for muscle sampling. Hypergravity induced a marked decrease in the weight and protein content of all six muscles. Three MHC isoforms were detected in the young rats' muscles: embryonic (E), perinatal (P) and slow type 1 MHC. In centrifuged nape and masticatory muscles, there was a decrease in MHC E and an increase in P without reduction (indeed, even an increase) in MHC 1, whereas in the respiratory muscle MHC E was increased and MHC 1 decreased. These results indicate that hypergravity produces important changes in the contractile properties not only of antigravity muscles but also masticatory and respiratory muscles. MHC P has a higher shortening velocity than MHC E, which has a higher one than MHC 1. The hypergravity-induced transformations of MHC isoforms would thus lead to increased velocity of all muscles studied. In spite of the observation of a hypergravity-induced muscle hypotrophy, the results of this study reflect the adaptational properties of developing muscles to increased gravitational forces.

Animals↗
PubMed1998

Effect of controllable stress on myosin heavy chain expression and muscle-specific protection by clomipramine.

This study evaluated the influence of a controllable and painless stress, conditioned bright-light active-avoidance, on the expression of myosin heavy chain (MHC) protein isoforms in two nape and three masticatory rat muscles: longissimus capitis (L), rectus capitis dorsalis major (R), anterior digastric (AD), anterior temporalis (AT) and masseter superficialis (MS). The effects of a concomitant antidepressant treatment with clomipramine (CMI) on the muscle structure were also investigated. The three adult fast MHC isoforms were detected in all muscles studied: MHC 2A, 2X and 2B. The AT structure was not significantly modified by stress either under saline or under CMI treatment. In the other muscles studied, the stress situation induced a marked increase in the relative expression of MHC 2B and a decrease in MHCs 2X and 2A, except in L in which the MHC 2A decrease did not reach a statistically significant level. Under controllable stress, the CMI treatment led to the same MHC profile in AT, L, R and AD as saline, except in L where the MHC 2X decrease was no longer statistically significant. However, in MS, under controllable stress and CMI treatment, the MHC distribution was significantly different from the stressed saline-treated group and became comparable to the control again. MHC 2B has a higher shortening velocity than MHC 2X, which has a higher one than MHC 2A. According to total MHC isoform expression, the controllable stress-induced transformations would thus lead to increased velocity of all five muscles studied except in AT. This latter seems, therefore, not very sensitive to environmental requirements. Our results indicate that controllable stress produces important changes in the contractile properties of nape and masticatory muscles. Furthermore, this study demonstrates the protective effect of CMI against muscle structure transformations induced by controllable stress in MS, and that these effects are muscle type-specific.

Animals↗
PubMed1997

Improvement of diffraction quality upon rehydration of dehydrated icosahedral Enterococcus faecalis pyruvate dehydrogenase core crystals.

Members of the family of 2-oxoacid dehydrogenase multienzyme complexes catalyze the oxidative decarboxylation of alpha-keto acids and are among the most remarkable enzymatic machineries in the living cell. These multienzyme complexes combine a highly symmetric (cubic or icosahedral) core with a dynamic and flexible arrangement of numerous subunits and domains surrounding the core. The center of the complex is formed by either 24 or 60 copies of dihydrolipoamide acetyltransferase (E2)-a multidomain enzyme. The hollow icosahedral cores are composed of 60 identical subunits of the catalytic domain of E2 with a molecular weight of about 1.8 million Da. Bipyramidal crystals suitable for X-ray diffraction of the icosahedral core of the pyruvate dehydrogenase multienzyme complex from Enterococcus faecalis were grown up to 0.7 mm in each dimension. The crystals belong to space group R32 with a = b = 244.3 A (hexagonal setting), and have a solvent content of 73%. The asymmetric unit contains one-third of the molecule, i.e., 20 of the 60 subunits. Initial X-ray crystallographic data to 7 A resolution were collected at cryotemperatures at synchrotron facilities. Interestingly, the diffraction was improved significantly upon rehydrating dehydrated crystals and extended to 4.2 A.

Crystallography, X-Ray↗
PubMed1996

A novel type of pyridine nucleotide-disulfide oxidoreductase is essential for NAD+- and NADPH-dependent degradation of epoxyalkanes by Xanthobacter strain Py2.

Epoxide degradation in cell extracts of Xanthobacter strain Py2 has been reported to be dependent on NAD+ and dithiols. This multicomponent system has now been fractionated. A key protein encoded by a DNA fragment complementing a Xanthobacter strain Py2 mutant unable to degrade epoxides was purified and analyzed. This NADP-dependent protein, a novel type of pyridine nucleotide-disulfide oxidoreductase, is essential for epoxide degradation. NADPH, acting as the physiological cofactor, replaced the dithiols in epoxide conversion.

Adenine Nucleotides↗
PubMed1995

Influence of stress and occlusal interference on the EMG activity of some masticatory muscles during a single mastication cycle.

The aim of the study was to investigate the influence of stress on the open-close activity in mastication, using an animal model. For this, we have compared the single-motor activities of three muscles: anterior digastric (AD), anterior temporalis (AT) and the superficial masseter (MS) in different groups of rats classed according to emotional state and dental occlusion. The EMG graphs have been analysed by the method proposed by the Weijs & Dantuma (1975). The results show that a dominant action of the stress on the AD and a combined action of the stress and the occlusal state on AT and MS occur during a single mastication cycle. A suppression of the reflex myotatic inhibition for AT and MS occurred in the presence of an occlusal interference.

Animals↗
PubMed1992

Substitution of Arg214 at the substrate-binding site of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens.

The gene encoding p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens was cloned in Escherichia coli to provide DNA for mutagenesis studies on the protein product. A plasmid containing a 1.65-kbp insert of P. fluorescens chromosomal DNA was obtained and its nucleotide sequence determined. The DNA-derived amino acid sequence agrees completely with the chemically determined amino acid sequence of the isolated protein. The enzyme is strongly expressed under influence of the vector-encoded lac promotor and is purified to homogeneity in a simple three-step procedure. The relation between substrate binding, the effector role of substrate and hydroxylation efficiency was studied by use of site-directed mutagenesis. Arg214, in ion-pair interaction with the carboxy moiety of p-hydroxybenzoate, was replaced with Lys, Gln and Ala, respectively. The affinity of the free enzymes for NADPH is unchanged, whereas the affinity for the aromatic substrate is strongly decreased. For enzymes Arg214-->Ala and Arg214-->Gln, the effector role of substrate is lost. For enzyme Arg214-->Lys, binding of p-hydroxybenzoate highly stimulates the rate of flavin reduction. In the presence of substrate or substrate analogues, the reduced enzyme Arg214-->Lys fails to stabilize the 4 alpha-hydroperoxyflavin intermediate, essential for efficient hydroxylation. Like the wild-type, enzyme Arg214-->Lys is susceptible to substrate inhibition. From spectral and kinetic results it is suggested that secondary binding of the substrate occurs at the re side of the flavin, where the nicotinamide moiety of NADPH is supposed to bind.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1992

A preliminary study of manducatory behaviour influenced by stress and dental occlusion.

Stress and dental occlusion often are incriminated as causes of dysfunction of the manducatory system. How and in what degree these two factors came through has not yet been clearly worked out. Our study is carried out on a group of rats presenting one or both of these two factors and we proposed to examine the duration and frequency of some components of their behaviour--intake of solid food and grooming, to detect some possible perturbations on manducatory behaviour caused by stress and/or occlusal interference. Our study shows that stress induced by emotion or occlusal interference will change the microstructure of behaviour rather than the global component in itself. This implies that we must find a clear definition of the different types of microstructure to find out which ones are changed by the two incriminating factors and which part of the behaviour component will remain stable.

Animals↗
PubMed1992

[Evaluation of a histochemical method specific for myosin ATPase activity in the masticatory muscles of the rat].

A biological study of masticatory muscle behaviour (Divry and Westphal, 1991) suggested the analysis of physiologic correlates (biologic parameters related to a behavioural event) such as histochemical reactions of muscular fibres studied by M-ATPase and SDH activities. For such investigations, routine methods are needed. In the present study, a modification of the original method of Tunell and Hart (1977) was used, in which three features of the original alkaline preincubation method (composition, incubation time and pH) were modified. These allowed a single step differentiation of the various fibre types found in rat masticatory muscles, for which the classical technics gave only a weak contrast, not suitable for image analysis. Acid preincubation was also tested but failed to give new information. By combining this modified technic with SDH staining (Nachlas, 1957) a classification of fibres into 12 theoretical types was proposed.

Alkalies↗