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C Caillaud

Publications and source records attributed to C Caillaud.

At least 37 records · Page 2Linked to original sources
PubMed1999

Microcephaly, microphthalmia, congenital cataract, optic atrophy, short stature, hypotonia, severe psychomotor retardation, and cerebral malformations: a second family with micro syndrome or a new syndrome?

We report on four children of both sexes from a highly inbred family with hypotonia, spastic diplegia, microcephaly, microphthalmia, congenital cataract, optic atrophy, ptosis, kyphoscoliosis, short stature, severe mental retardation, and cerebral malformations. Six other children may also have been affected. The differential diagnosis and the possibility of a second family with the micro syndrome are discussed.

Abnormalities, Multiple↗
PubMed1998

Exhaustive screening of the acid beta-glucosidase gene, by fluorescence-assisted mismatch analysis using universal primers: mutation profile and genotype/phenotype correlations in Gaucher disease.

Gaucher disease (GD) is one of the most prevalent lysosomal storage disorders and one of the rare genetic diseases now accessible to therapy. Outside the Ashkenazi Jewish community, a high molecular diversity is observed, leaving approximately 30% of alleles undetected. Nevertheless, very few exhaustive methods have been developed for extensive gene screening of a large series of patients. Our approach for a complete search of mutations was the association of fluorescent chemical cleavage of mismatches with a universal strand-specific labeling system. The glucocerebrosidase (GBA) gene was scanned by use of a set of six amplicons, comprising 11 exons, all exon/intron boundaries, and the promoter region. By use of this screening strategy, the difficulties due to the existence of a highly homologous pseudogene were easily overcome, and both GD mutant alleles were identified in all 25 patients studied, thus attesting to a sensitivity that approaches 100%. A total of 18 different mutations and a new glucocerebrosidase haplotype were detected. The mutational spectrum included eight novel acid beta-glucosidase mutations: IVS2 G(+1)-->T, I119T, R170P, N188K, S237P, K303I, L324P, and A446P. These data further indicate the genetic heterogeneity of the lesions causing GD. Established genotype/phenotype correlations generally were confirmed, but notable disparities were disclosed in several cases, thus underlining the limitation in the prognostic value of genotyping. The observed influence of multifactorial control on this monogenic disease is discussed.

Adolescent↗
PubMed1998

Exercise training reduces myocardial lipid peroxidation following short-term ischemia-reperfusion.

PURPOSE: The purpose of these experiments was to test the hypothesis that endurance exercise training will reduce myocardial lipid peroxidation following short-term ischemia and reperfusion (I-R). METHODS: Female Sprague-Dawley rats (4 months old) were randomly assigned to either a sedentary control group (N = 13) or to an exercise training group (N = 13). The exercise trained animals ran 4 d.wk-1 (90 min.d-1) at approximately 75% V02max. Following a 10-wk training program, animals were anesthetized, mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 5 min followed by a 10-min period of reperfusion. RESULTS: Although training did not alter (P > 0.05) myocardial activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase), training was associated with significant increase (P > 0.05) in heat shock protein (HSP72) in the left ventricle. Compared with controls, trained animals exhibited significantly lower levels (P < 0.05) of myocardial lipid peroxidation following I-R. CONCLUSION: These data support the hypothesis that exercise training provides protection against myocardial lipid peroxidation induced by short-term I-R in vivo.

Animals↗
PubMed1997

Metachromatic leukodystrophy: identification of the first deletion in exon 1 and of nine novel point mutations in the arylsulfatase A gene.

Metachromatic leukodystrophy (MLD), a lysosomal storage disease caused by the deficiency of arylsulfatase A (ASA), is inherited as an autosomal recessive trait, and its frequency is estimated to be 1 in 40,000 live births. Genomic DNA from 21 MLD patients (14 late-infantile and 7 juvenile cases) was amplified in four overlapping PCR fragments and tested by allele-specific oligonucleotide (ASO) for the two common mutations 459 + 1G-->A and P426L. These mutations were found in only 28.6% of the alleles studied. The remaining alleles were analyzed by chemical mismatch cleavage (CMC) and automatic sequencing. In addition to five previously reported mutations (459 + 1G-->A, A212V, R244C, R390W, P426L), 10 novel mutations were identified: 9 missense mutations (S95N, G119R, D152Y, R244H, S250Y, A314T, R384C, R496H, K367N) and one 8 bp deletion in exon 1, the first mutation reported in this exon. These methods allowed us to identify 76% of the alleles tested. Genotype-phenotype correlations could be established for some of these mutations. These results confirm the heterogeneity of mutations causing MLD and suggest that CMC is a reliable and informative screening method for point mutation detection in the arylsulfatase A gene.

Alleles↗
PubMed1997

Inhibition of histamine release by nedocromil sodium reduces exercise-induced hypoxemia in master athletes.

During exercise in highly-trained older master athletes (MA), the impairment of pulmonary gas exchanges has been shown to be associated with a concomitant increase in histamine release (2). To determine the role of the histamine released (% H) during exercise-induced hypoxemia, seven MA (age 63.2 yr +/- 1.9), all of whom were known to develop exercise-induced hypoxemia, performed two maximal incremental exercise tests at a one-month interval after administration of nedocromil sodium (which inhibits histamine and other mediator release) or placebo in random double-blind order. During exercise testing, blood samples for arterial blood gas analysis and histamine assay were drawn at rest, exercise and recovery. Nedocromil sodium induced an inhibition in % H (0.57 +/- 0.03 at maximal load (Pmax) with placebo vs 0.24 +/- 0.02 with nedocromil sodium) linked with an improvement of pulmonary gas exchange (PaO2: 71.1 +/- 1.4 at Pmax with placebo vs 83.4 +/- 3 with nedocromil sodium; D(Ai-a)O2: 37.5 +/- 1.4 at Pmax vs 19.1 +/- 3.1, respectively). These results confirm the link established between the increase in histamine and exercise-induced hypoxemia in master athletes.

Aged↗
PubMed1996

Influence of post-surgery time after cardiac transplantation on exercise responses.

Influence of post-surgery time after cardiac transplantation on exercise responses. Med. Sci. Sports Exerc., Vol. 28, No. 2, pp. 171-175, 1996. To test the hypothesis that exercise response changes with time after cardiac transplantation, we investigated the cardiorespiratory responses of nine orthotopic heart transplant patients (52.4 +/- 2 yr) during graded exercise tests (30 W.3 min-1) done at 1, 3, 6, 9 and 12 months post-surgery. At peak exercise, 1) oxygen uptake per kg of body weight (VO2), minute ventilation (VE) and oxygen pulse (O2 pulse) did not change significantly between 1 and 12 months postsurgery; 2) transplanted heart rate (HRt) and delta heart rate (peak exercise heart rate--resting heart rate) increased significantly over time (P < 0.01; P < 0.05) with a marked increase between 1 and 3 months (P < 0.05); and (3) a significant negative correlation existed between O2 pulse and HRt (r = -0.36, P < 0.05), whereas no correlation was found between delta heart rate and delta VO2 (peak exercise VO2- resting VO2, l.min-1). During submaximal exercise, HRt increased significantly over time (P < 0.001); VO2, VE, and O2 pulse showed no significant change; and the VO2-HRt relationship shifted toward higher values of HRt. We conclude that, in the absence of formal physical training, the exercise response of denervated transplanted heart increases in relation to post-surgery time but does not affect oxygen uptake at submaximal and peak levels of exercise.

Blood Pressure↗
PubMed1995

Computerized tomography and pulmonary diffusing capacity in highly trained athletes after performing a triathlon.

We investigated the computerized tomographies (CTs) of the thorax and the pulmonary diffusing capacity for CO (DLCO) in eight male athletes before and after a triathlon. DLCO and alveolar volume (VA) were simultaneously measured during 9 s of breath holding. The transfer coefficient (KCO = DLCO/VA) was then calculated. CT scanning was performed during breath holding with the subjects in the supine position. Scanner analysis was done by 1) counting the linear and polygonal opacities (index of interstitial fluid accumulation) and 2) calculating the physical mean lung density and the mean slice mass. Results showed a significant reduction in DLCO (44.9 +/- 2.3 vs. 42.9 +/- 1.7 ml.min-1.mmHg-1; P < 0.05) and KCO (6.0 +/- 0.3 vs. 5.6 +/- 0.3 ml.min-1.mmHg-1.l of VA-1; P < 0.05) after the triathlon and an increase in mean lung density (0.21 +/- 0.009 vs. 0.25 +/- 0.01 g/cm3; P < 0.0001). The number of polygonal and linear opacities increased after the race (P < 0.001). This study confirmed that DLCO and KCO decrease in elite athletes after a long-distance race and showed a concomitant increase in CT lung density and in the number of opacities.

Adult↗
PubMed1995

Gene delivery into the central nervous system by nasal instillation in rats.

Replication-deficient adenoviruses have been used successfully to transfer foreign DNA into postmitotic cells. This article demonstrates that it is possible to transfer the Escherichia coli lacZ gene in vivo into the central nervous system structures of rats after nasal instillation of replication-defective adenoviral vector AdRSV beta gal. Mitral cells from the olfactory bulb, neurons from the anterior olfactory nucleus, locus coeruleus and area postrema expressed beta-galactosidase for at least 12 days. No cytopathic effect was observed in the CNS structures studied at the viral titer used (1-3 x 10(9) plaque-forming units (p.f.u.)). This method could be useful for the gene therapy of diseases affecting different CNS structures.

Adenoviridae↗
PubMed1994

In vivo transfer of a marker gene to study motoneuronal development.

Adenovirus vectors containing a marker gene (lacZ from Escherichia coli) are potent for transferring the gene to neurones after intraparenchymal injections. Expression of the marker gene may lead to the synthesis of an enormous amount of beta-galactosidase which diffuses throughout the entire neurone, providing a 'Golgi-like' staining. This suggested that the technique may be used to study the morphology of specific neuronal populations. We have validated this hypothesis by analysing the postnatal development of motoneurones in the rat cervical cord. Injections of the viral suspension into one ventral horn were performed at different ages after birth. Histochemical staining using X-Gal revealed morphological changes occurring within the first 3 weeks with enlargement of the perikaryon and increased dendritic complexity. Immunoreactivity for CGRP was visualized in double-staining experiments. In vivo transfer of a marker gene therefore provides a new way to analyse neuronal morphology which allows selection of the cells to be studied and double-labelling with immunohistochemical markers.

Adenoviridae↗
PubMed1994

Release of cytokines by blood monocytes during strenuous exercise.

During strenuous exercise in endurance athletes, monocytes are activated and there is an acute inflammation and hypoxemia possibly due to lesional pulmonary edema. IL-6 and TNF-alpha released by monocytes may be implicated in the acute phase of lesional pulmonary edema. A study was carried out to determine whether TNF-alpha and IL-6 are released during strenuous exercise, and, if adrenalin released during exercise alters their generation. Ten young and six master athletes underwent an incremental exercise test. Arterial blood was drawn at rest, at the end of the exercise, and 20 minutes afterwards. Monocytes were isolated and incubated for 18 hours in the presence or absence of adrenalin. Il-6 and TNF-alpha were measured in monocyte supernatants. The spontaneous release of IL-6 or TNF-alpha was increased in young athletes when compared to older subjects. The spontaneous release of TNF-alpha was increased, but not significantly, by exercise and there was no correlation between the release of IL-6 and TNF-alpha and lung function measured during hypoxemia. Adrenalin inhibited the release of IL-6 or TNF-alpha. Correlations were observed between the in vitro release of IL-6 or TNF-alpha and age, VO2max, maximal ventilation and maximal power output of the subjects.

Adult↗
PubMed1994

Exercise-induced hypoxemia in older athletes.

To determine whether exercise induces hypoxemia in highly trained older "master" athletes (MA), as it does in certain elite endurance-trained young athletes (YA), 10 MA (65.3 +/- 2.6 yr), 10 control subjects (CS; 68.3 +/- 2.2 yr), and 10 endurance-trained YA (23.3 +/- 1.1 yr) performed an incremental exercise test. During testing, blood samples for arterial blood gas analysis were drawn during the last 20 s of each load. Lung exchanges were measured using a breath-by-breath automated exercise device. Exercise-induced hypoxemia (EIH) appeared in all MA and 8 of 10 YA, whereas there were no changes in the blood gases of CS. In MA, arterial PO2 decreased significantly from 40% of maximal O2 uptake onward and was associated with a significant increase in the ideal alveolar-arterial O2 difference from 60% onward. The MA also showed a lower ventilation for a given absolute load compared with CS. In all subjects arterial PCO2 rose slightly but significantly during the work, but this increase was most marked in MA. The EIH differed between MA and YA in the following ways: 1) all MA showed a drop in arterial PO2 during exercise, 2) this drop appeared earlier and was significantly greater for a given load in MA, and 3) EIH appeared at a lower level of training regimen in MA. This hypoxemia was at first isolated, probably at least partially due to relative hypoventilation, and then was associated with a widened ideal alveolar-arterial O2 difference, which may have been due to an increase in extravascular lung water.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Histamine and exercise-induced hypoxemia in highly trained athletes.

To determine whether exercise-induced hypoxemia in extreme athletes results from an increase in histamine level during maximal incremental exercise, seven young athletes [YA; age 22.2 +/- 1.23 (SE) yr] and seven master athletes (MA; age 66.2 +/- 2.94 yr), all of whom were known to develop exercise-induced hypoxemia, were compared with age-matched control groups (young controls and older controls, respectively). During maximal incremental exercise, blood samples for arterial blood gas analysis and for plasma and total histamine were drawn at rest and at 50, 75, and 100% of maximal O2 uptake. The percentage of histamine released (%H) was calculated from plasma and total histamine samples. In all athletes (MA and YA groups), exercise induced an increase in %H with a concomitant decrease in arterial PO2 (PaO2); in control groups there was no change in either histamine levels or PaO2. When the data for the YA and MA groups were combined, a correlation was observed between the increase in %H and the drop in PaO2. Nevertheless, further studies are required to establish whether histamine plays a causative role in hypoxemia or is a response to injury.

Adult↗
PubMed1993

Adenoviral vector as a gene delivery system into cultured rat neuronal and glial cells.

Previous studies have demonstrated that a defective recombinant adenovirus can infect a wide range of postmitotic and slowly proliferating cell types such as hepatocytes, myotubes, pneumocytes and intestinal cells (Stratford-Perricaudet et al., Hum. Gene Ther., 1, 241-256, 1990; Quantin et al., Proc. Natl. Acad. Sci. USA, 89, 2581-2584, 1992; Jaffe et al., Nature Genetics, 1, 372-378, 1992). We have used a defective recombinant adenovirus, Ad.RSV beta gal, containing the Escherichia coli beta-galactosidase gene targeted to the nucleus under the transcriptional control of the Rous sarcoma virus long terminal repeat promoter (Stratford-Perricaudet et al., J. Clin. Invest., 90, 626-630, 1992) to infect non-dividing neural cells in primary culture. We show that 80-100% of neuronal and astroglial cells infected with a viral titre lower than 10(9) p.f.u./ml express beta-galactosidase for at least 1 month without cell damage. These results demonstrate the potential usefulness of recombinant adenovirus infection for the analysis of brain-specific gene regulation and for the transfer of genes into neural cells before their transplantation into the brain.

Animals↗
PubMed1993

Pulmonary gas exchange and breathing pattern during and after exercise in highly trained athletes.

Highly trained athletes (HT) have been found to show arterial hypoxaemia during strenuous exercise. A lack of compensatory hyperpnoea and/or a limitation of pulmonary diffusion by pulmonary interstitial oedema have been suggested as causes, but the exact role of each is not clear. It is known, however, that interstitial pulmonary oedema may result in rapid shallow breathing (RSB). The purpose of this study was therefore twofold: firstly, to determine the exact role of a lack of compensatory hyperpnoea versus a widened in ideal alveolar minus arterial oxygen partial pressure difference [PA(i)-aO2] in the decrease in partial pressure of oxygen in arterial blood (PaO2) and, secondly, to detect RSB during recovery in HT. Untrained subjects (UT) and HT performed exhausting incremental exercise. During rest, exercise testing, and recovery, breathing pattern, respiratory gas exchange, and arterial blood gases were measured. The PA(i)-aO2 and the difference in tidal volume (VT) between exercise and recovery for the same level of ventilation, normalized to vital capacity of the subject [delta VT(%VC)], were then calculated. A large positive delta VT(%VC) was considered to be the sign of RSB. HT showed a marked hypoxaemia (F = 11.6, P < 0.0001), higher partial pressure of carbon dioxide in arterial blood (F = 3.51, P < 0.05), and lower ideal partial pressure of oxygen in alveolar gas (P < 0.001). The relationship between PA(i)-aO2 and oxygen consumption was the same for the two groups. The widening PA(i)-aO2 persisted throughout recovery for both HT and UT. The RSB was observed in HT during recovery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Transfer of a foreign gene into the brain using adenovirus vectors.

The ability of a replication-deficient adenovirus vector to transfer a foreign gene into neural cells of adult rats in vivo has been analysed. A large number of neural cells (including neurons, astrocytes and ependymal cells) expressed an E. coli lacZ transgene for at least 45 days after inoculation of various brain areas. Injecting up to 3 x 10(5) pfu in 10 microliters did not result in any detectable cytopathic effects--these were only observed for very high titres of infection (> 10(7) pfu 10 microliters-1). Adenovirus vectors therefore appear to be a promising means for in vivo transfer of therapeutic genes into the central nervous system.

Adenoviridae↗
PubMed1992

Linkage disequilibrium between phenylketonuria and RFLP haplotype 1 at the phenylalanine hydroxylase locus in Portugal.

RFLPs of 36 normal and 41 mutant alleles at the phenylalanine hydroxylase locus were determined in 31 Portuguese kindreds. A total of 14 haplotypes including 10 normal and 7 mutant alleles were observed. Almost 75% of all mutant alleles were confined within only two haplotypes, namely haplotype 9 (17.1%) and haplotype 1 (56.1%). This frequency of mutant haplotype 1 in Portugal is, to our knowledge, the highest for this mutant haplotype in all studies reported to date. Other mutant haplotypes were either rare (haplotype 2, 9.7%) or totally absent (haplotype 3, 0%). Only 24.5% of all mutant alleles were found to consistently carry identified mutations, particularly R261Q (9.8%), R252W (3.3%), R408W (1.6%) and delta I94 (3.3%). A new mutation, L249F, located in the seventh exon of the gene, accounted for 6.5% of all mutant alleles in our series. Interestingly, this mutant genotype was consistently associated with mutant haplotype 1 (P less than 0.01), as also observed for the R261Q mutation. It appears, therefore, that mutant haplotype 1 is genotypically heterogeneous in Portugal and that more than two mutations account for its prevalence in this country.

Alleles↗