Biomedical subjects

R Candau

Publications and source records attributed to R Candau.

50 records · Page 3Linked to original sources

PubMed1995

Transcriptional control by steroid hormones: the role of chromatin.

The mouse mammary tumour virus (MMTV) promoter contains a complex hormone-responsive unit composed of four hormone-responsive elements, a nuclear factor I (NFI) binding site and two octamer motifs. All these sites are required for optimal hormonal induction. Although synergism has been found between hormone receptors and octamer transcription factor 1 (Oct-1/OTF-1), we were unable to detect a positive interaction between receptors and NFI in vitro. In chromatin, the MMTV hormone-responsive unit is contained in a phased nucleosome. The precise positioning of the DNA double helix on the surface of the histone octamer precludes binding of NFI and Oct-1/OTF-1 to their cognate sequences, while still allowing recognition of two hormone-responsive elements by the hormone receptors. Hormone treatment leads to a characteristic change in chromatin structure that makes the centre of the nucleosome more accessible to digestion by DNase I and facilitates binding of receptors, NFI and Oct-1/OTF-1 to the nucleosomally organized promoter. The MMTV promoter functions in yeast in a hormone receptor-dependent and NFI-dependent fashion. Depletion of nucleosomes activates hormone-independent transcription from the MMTV promoter. These results imply that nucleosome positioning not only represses hormone-independent transcription, but also enables binding of a full complement of transcription factors to the hormone-responsive unit after hormone induction.

Animals↗

PubMed1995

Mechanical step variability during treadmill running.

The present study was designed to study intra-individual step variability measured both on vertical displacement of the body (delta Z) and on step time (delta t) parameters by means of a kinematic arm and during treadmill running. A group of 17 subjects ran successively at 60%, 80%, 100% and 140% of their maximal aerobic velocity (Vamax). The total number of steps analysed was 6116. The absolute delta Z step variability (sigma delta Z) ranged between 5 mm and 21 mm while the absolute delta t variability (sigma delta t) ranged between 6 ms and 40 ms. Step variabilities were due to step asymmetry (from 38.5% to 48.5% of the step variability) and to stride variability. For submaximal velocities (60%, 80%, and 100% Vamax) both sigma delta t and sigma delta Z were independent of velocity or body dimensions whereas differences between subjects were significant (P < 0.01) for sigma delta Z. On the other hand, variabilities were significantly increased when velocity was changed from submaximal to the 140% Vamax level. Furthermore, at submaximal levels sigma delta Z was linked to the subject's energy cost of running (P < 0.05). Therefore, the intra-individual step variability should not be neglected in future studies on mechanical efficiency of running and it is suggested that, to obtain a good accuracy (better than 1%, P < 0.05) on mean value and variability of the mechanical parameters, measurements should be performed on at least 32-64 consecutive steps, which corresponds to about 15 to 20s of running.

Adult↗

PubMed1995

Constitutive repression and nuclear factor I-dependent hormone activation of the mouse mammary tumor virus promoter in Saccharomyces cerevisiae.

To study the influence of various transactivators and the role of nucleosomal structure in gene regulation by steroid hormones, we have introduced mouse mammary tumor virus (MMTV) promoter sequences along with expression vectors for the glucocorticoid receptor (GR) and nuclear factor I (NFI) in Saccharomyces cerevisiae, an organism amenable to genetic manipulation. Both in the context of an episomal multicopy vector and in a centromeric single-copy plasmid, the MMTV promoter was virtually silent in the absence of inducer, even in yeast strains expressing GR and NFI. Induction was optimal with deacylcortivazol and required both GR and NFI. The transactivation function AF1 in the N-terminal half of GR is required for ligand-dependent induction and acts constitutively in truncated GR lacking the ligand binding domain. A piece of the MMTV long terminal repeat extending from -236 to +111 is sufficient to position a nucleosome, B, over the regulatory region of the promoter from -45 to -190 and another nucleosome over the transcription start region. The rotational orientation of the DNA on the surface of nucleosome B is the same as that previously found in animal cells and in reconstitution experiments. This orientation is compatible with binding of GR to two sites, while it should preclude binding of NFI and hence be responsible for constitutive repression. Upon ligand induction, there is no major chromatin rearrangement, but the proximal linker DNA, including the TATA box, becomes hypersensitive to nucleases. The transcriptional behavior of the MMTV promoter was unaffected by deletions of the genes for zuotin or SIN1/SPT2, two proteins which have been claimed to assume some of the functions of linker histones. Thus, despite the lack of histone H1, yeast cells could be a suitable system to study the contribution of nucleosomal organization to the regulated expression of the MMTV promoter.

Animals↗

PubMed1994

Fatigue and fitness modelled from the effects of training on performance.

The purpose of this study was to compare two ways of estimating both fatigue and fitness indicators from a systems model of the effects of training on performance. The model was applied to data concerning the training of a hammer thrower. The variations in performance were mathematically related to the successive amounts of training. The model equation was composed of negative (NF) and positive (PF) functions. The NF and PF were associated with the fatigue and fitness estimated in previous studies. Using another method, fatigue and fitness indicators were estimated from a combination of NF and PF. The influence of training on performance was negatively associated with fatigue (NI), and positively to fitness (PI). The changes in performance were well described by the model in the present study (r = 0.96, N = 19, P < 0.001). Significant correlations were observed between PF and PI (r = 0.90, P < 0.001) on the other. The absolute values and the time variations of PI and NI were closer to the change in performance than NF and PF. The NF and PF were accounted for mainly by the accumulation of amounts of training. On the other hand, NI and PI were accounted for rather by the impact of these amounts of training on performance.

Adaptation, Physiological↗

PubMed1992

Effects of training on iron status in cross-country skiers.

Haematological changes were studied in cross-country skiers during a 33-week training season (7 h a week). The daily amounts of training were calculated from the duration and the intensity of the exercise and then used to estimate training responses associated with a first order transfer function. The profile of system training responses (STR) was determined by convolution between the amounts of training and a first-order transfer function. Linear regressions were used to determine correlation coefficients between STR and iron status indices. Among the values for the time constants of decay, the one giving the best fit between STR and iron status indices was chosen. A relationship was noted between on the one hand STR and changes in serum ferritin concentration ([FERR]) and on the other hand STR and change in mean cell volume (MCV). The [FERR] was decreased and MCV was increased by training. It is suggested that a decrease in [FERR] could have been related to a decrease in total body iron stores. However, large and rapid changes in [FERR] could not have been a reflection of changes in total body iron stores. Equilibrium between [FERR] and total body iron stores could have been temporarily altered by the effects of training. Moreover, iron stores did not seem to have been sufficiently depleted to restrict erythropoiesis. The MCV increased slightly in response to intense training suggesting that training enhances the proportion of young erythrocytes.

Adolescent↗

PubMed1992

Regulation of Gibberellin Biosynthesis in Gibberella fujikuroi.

Gibberellin production by Gibberella fujikuroi started only after the nitrogen source was depleted and ceased upon its renewal. Nitrogen repression of gibberellin biosynthesis is not an indirect effect of the growth arrest that follows the depletion of an essential nutrient because gibberellins were not produced upon depletion of phosphate. Mycelia produced gibberellins when suspended in a glucose solution. Production ceased some time after depletion of glucose and resumed upon its readdition. Under certain conditions, the gibberellin production rate was inversely proportional to the glucose concentrations. The specific regulation of gibberellin biosynthesis by the nitrogen source imposes a revision of the concept that gibberellins are secondary metabolites whose production is triggered by imbalance or cessation of growth.

Journal Article↗

PubMed1991

In vivo channeling of substrates in an enzyme aggregate for beta-carotene biosynthesis.

The existence and the mode of operation of certain enzyme aggregates may be established from the concentrations of intermediates measured in the presence of specific inhibitors. beta-Carotene, the most abundant carotenoid pigment in the fungus Phycomyces blakesleeanus, arises from ring formation at both ends of lycopene. The inhibitors nicotine, imidazole, alpha-picoline, and 2-(4-chlorophenylthio)triethylamine lead to the simultaneous accumulation of lycopene, beta-carotene, and the one-ring intermediate gamma-carotene. The quantitative analytical values obey precise mathematical relationships: those expected from the operation of an enzyme aggregate with two cyclases equally sensitive to the inhibitors. The intermediates lycopene and gamma-carotene rejected by chemically inhibited enzymes may be readmitted to other cyclases in the wild type but not in heterokaryons containing a carA mutation. We have calculated the fraction of inhibited cyclase under each condition, the affinity constant of each inhibitor for the cyclase, and the probability that a rejected intermediate molecule will be readmitted and further metabolized. The probabilities for lycopene and gamma-carotene are identical and independent of the inhibitor responsible for the rejection. Our calculations suggest that each rejected intermediate molecule is readmitted to the enzyme aggregates two or three times on the average.

Carotenoids↗

PubMed1991

Gibberellins and Carotenoids in the Wild Type and Mutants of Gibberella fujikuroi.

A new screening procedure was used to isolate 14 gib mutants of Gibberella fujikuroi with modifications in the production of gibberellins. The production of carotenoids and gibberellins was investigated in the gib mutants and in representative car mutants with various modifications of carotenoid biosynthesis. The determinations of gibberellins were carried out with a simplified fluorescence method. One of the mutants lacked both gibberellins and carotenoids. In many mutants the two pathways compensated each other: an increase in the production of one group of compounds was accompanied by a decrease in the production of the other. Under certain conditions the compensation was quantitative when the output of the two pathways was measured in moles of the common precursor, geranylgeranyl pyrophosphate. alpha-Picoline, an inhibitor of lycopene cyclase in G. fujikuroi, inhibits gibberellin biosynthesis. Other agents that affect the accumulation of carotenoids have no noticeable effect on the accumulation of gibberellins; such is the case with diphenylamine and beta-ionone, two inhibitors of phytoene dehydrogenation, and visible light, which stimulates carotenogenesis.

Journal Article↗

PubMedDate not supplied

[Immunological study in patients with severe myoclonic epilepsy in childhood].

OBJECTIVE: Clinical and experimental data support the role of immune mechanisms in the pathogeny of childhood epilepsy. The purpose of this report is to study the immunological aspects in severe myoclonic epilepsy in infancy (SMEI). PATIENTS AND METHODS: 12 patients selected according to the following criteria: no previous personal history of disease, frequent familial history of epilepsy, beginning in the first year of life with seizures usually febriles, onset of afebrile seizures between 18 months and 4 years, normal EEG and psychomotor development are at the onset, seizures resistant to antiepileptic drugs. The following immunological evaluation, has been carried out: granulocytes phagocytic activity, lymphocytics subpopulations, serum immunoglobulins and IgG subclasses, hemolytic capacity of complement, lymphocytic transformation test. RESULTS: In five cases the immunological study was normal; five cases had IgA deficiency, associated in two to high serum IgG1 levels and in two to high IgG1 and low IgG2 levels; one case shows an IgM increase associated to hemolytic capacity of complement deficiency (CH50); four cases have a reduced response to different mitogens. CONCLUSIONS: The value of this results is doubtful. It is possible that genetical and environmental factors are involved in SMEI and that the immunological abnormalities found favor the hyperergic reactions in given circumstances.

Adolescent↗

PubMedDate not supplied

[Severe myoclonic epilepsy in childhood. Epidemiologic analytical study].

INTRODUCTION AND OBJECTIVE: Severe myoclonic epilepsy in infancy (SMEI) is a relatively rare disorder which etiology is unknown. The descriptive epidemiologic study tries to find the exposure agents or other circumstances present in affected children. Were have studied this agents and circumstances in 28 children with SMEI. PATIENTS AND METHODS: The study included 28 children, 17 girls and 11 boys, diagnosed of SMEI. Patients were selected according to the criteria established by Dravet et al in 1984. For each patient, the following features were studied: sex, parents age, prenatal antecedents, perinatal antecedents, new born stage, psychomotor development until the first convulsion, country/urban social class, family history of epilepsy and for febrile seizures, and cause of the first seizure. RESULTS: All parents are young adults, between 25 and 40 years at the birth of the child. The number of the fratry is between the first and the fourth. There is no pre and perinatal antecedents. The birth's weight is between 1,800 g and 4,600 g (X: 3,580 g). In 16 children (57.15%), the first seizure appeared after any dose DTP vaccination, frequently the second. Familial antecedents existed for epilepsy in nine cases and for febrile convulsions in six cases. CONCLUSIONS: The more interesting findings are the high percentage of cases that have the first convulsions after any dose of vaccination DTP and the high percentage of cases with family history of epilepsy and/or febrile seizures. It suggests that in pathogenesis of the SMEI there is a constitutional factor or predisposition genetically conditioned in relation to immunological disorders or to a multifocal cortical microdysgenesis, possibly triggered by toxic-allergic factors.

Brain↗

PubMedDate not supplied

[Anhidrosis and hyperthermia associated with treatment with topiramate].

INTRODUCTION: It has been observed that if topiramate (TPM) is given together with other antiepileptic drugs when the temperature of the environment is high, a disorder involving sweating and thermo regulation may be seen as a side effect. PATIENTS AND METHODS: We describe ten patients, of an average age of 7 years and 8 months, with refractory epileptic seizures. All were treated with topiramate, associated with the antiepileptic drugs they had been taking previously. During the summer months, when the environmental temperature was over 37 C, they had slight hyperthermia, hypohydrosis or more usually anhydrosis, red faces and tiredness which was markedly worse on effort. In one case there was also retention of urine and four others had known side effects. In seven patients the symptoms disappeared when the dose of TPM was reduced or the environment became cooler. In the other three cases TPM was withdrawn, due to the severe adverse effects seen in two cases and for being ineffective as treatment in the other cases. CONCLUSIONS: It is considered that in predisposed children, TPM causes autonomic dysfunction, probably of central origin, which is seen as a disorder of sweating and thermoregulation. Although the mechanism of this disorder is not known, since it occurs when the temperature is over 37 C, it would seem that it is due to a reduction in carbonic anhydrase isoenzymes II and IV. We suggest that it would be useful to establish a method to predict the patients at risk in summer, in hot regions, at the first sign of fatigability.

Adolescent↗

PubMedDate not supplied

[Semiologic value of tonic-axial crises in children (author's transl)].

The tonic-axial crises described clinically and by electroencephalo-grams by Ouachi, Roger and Gastaut in 1961, are encountered with relative frequency in specific forms of infantile epilepsy and they establish the principal nucleus of the appearing manifestations in some cases of childhood epileptic encephalopathy. We have studied 43 epileptic children who have displayed tonic-axial crises, taking into consideration the absence or existence of concrete antecedents of cerebral attack, the moment of appearance of the tonix-axial crises in relation to the commencement of the critical manifestations, the type or types of epileptic crises, the circumstances of appearance of tonic-axial crises and its influence upon the further development of the child. Its physiopathology is questioned and the tonic-axial crises is considered as a semiologic crossroad in the evolution in the secondary generalized epilepsy.

Brain↗

PubMedDate not supplied

[Contribution to studies of seizures in Rett's syndrome. Analysis of critical forms of four cases].

Twenty girls were diagnosed as having Rett's Syndrome (RS) based on criteria decided upon in 1988. Fifteen suffered epileptic fits, four of which were possible to record by EEG. In this work we report on the clinical EEG semiology of these girls. All underwent clinical, biochemical, electroneurophysical, neuroimaging and cytogenetic studies. Periodic EEG were carried out while the girls were awake and the recorded fits were so obtained. All had night-time EEG. Four girls had their first fits between 5 years 4 months and 6 years 5 months (average 6 years). The ages at which their attacks were recorded varied from seven to eleven years. Two girls presented tonic-axial attacks expressed graphically by desynchronisation in the EEG in one case and rhythmically in the other, one having had atypical simple absences expressed on EEG as point-wave complexes at a rate of two per second, the other presenting two types of attack: initially tonic-axial fits expressed as a low amplitude rhythm and a year later generalised clonal fits expressed as slow waves with sharp waves in between. Outstanding is the fact that despite the diversity of epileptic fits described in RS all such attacks recorded were of a generalised type.

Anticonvulsants↗

PubMedDate not supplied

[Single photon emission tomography (SPECT) in severe infantile myoclonic epilepsy (EMS)].

Ten children, three boys and seven girls, with an average age of 7.5 years diagnosed as having severe myoclonic epilepsy (SME) underwent single photon emission computerised tomography (SPECT) with HMPAO. All had CT, nuclear MR and various EEG studies, these findings made at the same time as SPECT. CT and nuclear MR produced no relevant data. EEG, although without paroxystic abnormalities in two cases, showed generalised discharge in the remaining eight, predominantly in the right hemisphere in five. SPECT was normal in two cases (of 20 and 30 months) and showed areas of hypoperfusion localised in one hemisphere in five cases, three in the left and two in the right, and in both hemispheres in three cases. Areas of hypoperfusion were located in frontal and/or temporal and/or parietal regions. In two cases there was concordance with the prevalence of EEG paroxystic activity and in two other cases there was discordance. Our findings, with SPECT abnormalities after two years of age, suggest SME could be considered as a multifocal epilepsy brought on by secondary structural irregularities.

Adolescent↗