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Biomedical subjects

M Sauvage

Publications and source records attributed to M Sauvage.

At least 19 recordsLinked to original sources
PubMed2003

Cancer incidence and mortality in France over the period 1978-2000.

BACKGROUND: Monitoring cancer incidence and mortality time trends is essential for cancer research and health-care planning. French cancer registries do not cover the entire population and do not provide a representative sample of the national population. Our study aimed at estimating national cancer incidence and mortality trends over the longest period available. METHODS: Incidence and mortality data were collected over the period 1978-1997. Twenty-seven cancer sites were selected and age, sex and site specific incidence and mortality rates were estimated for each year from 1978 up to 2000. Observed incidence and mortality data in the population covered by cancer registries were modelled using age-cohort methods. An estimation of the incidence/mortality ratio was obtained from these models and applied to the mortality rates predicted from an age-cohort model for the entire French population. The person-years of observation were calculated cohort-wise from census data provided by the national institute of statistics RESULTS: Cancer incidence increased by 63% throughout the study period, from 170,000 new cases in 1980 to 278,000 in 2000. This evolution was due to demographic changes but also to an increase in the risk of cancer which was estimated to more than 35% during the same period. In men, this change is largely explain by the increase of prostate cancer incidence. Among women, the increase was dominated by the continuing increase in breast cancer incidence. Large increases were also seen for non-Hodgkin lymphoma, melanoma, and thyroid cancer in both genders and for lung cancer in women. Cancer mortality increased by 20% from 125,000 deaths in 1980 to 150,000 in 2000. This increase is less than that predicted from changes in demographic factors and corresponds in fact to a decrease in the risk of death estimated to about 8%, slightly greater for women than for men. This decrease is associated with a decreasing incidence for stomach cancers for both sexes, alcohol-related cancer for men and cervical cancer for women. Colo-rectal cancer decreasing mortality contributes to this improvement despite an incidence increase. CONCLUSION: Between 1980 and 2000, the study showed a large change in the cancer burden both quantitatively and qualitatively. Decrease in exposure, earlier diagnosis and therapeutic improvement explained part of this change, but overall the distribution of cancer cases shifted toward a distribution including less aggressive cancers. A striking divergence between incidence and mortality trends is observed for a great number of cancers. Prostate cancer shares with breast cancer the same pattern of a severe increasing incidence and a stable mortality. This points to important changes in medical practice and needs further analysis. The trend of lung cancer mortality among women should be emphasised since the situation will inevitably worsen in the coming years. It is already the third cause of cancer death among women.

Age Distribution↗
PubMed2001

Detection of corticotropin-releasing hormone receptor 1 immunoreactivity in cholinergic, dopaminergic and noradrenergic neurons of the murine basal forebrain and brainstem nuclei--potential implication for arousal and attention.

Corticotropin-releasing hormone (CRH) interacts with noradrenergic, dopaminergic and cholinergic systems of the brain, and these interactions are thought to be of relevance for the stress response, anxiety-related behavior, and cognitive function. CRH mediates its central effects through two high-affinity membrane receptors, CRH receptor subtypes 1 and 2. It is however unclear at present whether cholinergic or catecholaminergic cells express these receptors themselves or whether the effects of CRH are indirectly mediated through interaction with other neurotransmitter systems. Therefore, this study investigated whether choline acetyltransferase immunoreactive neurons of the murine basal forebrain and brainstem nuclei, and tyrosine hydroxylase immunoreactive neurons located within the locus coeruleus, ventral tegmental area and substantia nigra co-express CRH receptor 1, employing a double-immunocytochemical procedure. Using an antibody against the C-terminus of the CRH type 1 receptor (CRH-R1), CRH-R1-like immunoreactivity was found in all cholinergic basal forebrain nuclei except the nucleus basalis magnocellularis. In particular, the diagonal band of Broca (vertical and horizontal limbs) showed a high degree of co-localization of CRH-R1 immunoreactivity and choline acetyltransferase immunoreactivity (both limbs >90%). A less intense immunoreactivity but still high rate of co-localization was detected in the cholinergic neurons of the medial septum (80%), while lowest co-localization was observed in choline acetyltransferase immunoreactive neurons of the substantia innominata (58%). An intermediate degree of co-localization (75%) was seen in the brainstem pedunculopontine tegmental nucleus, while the other major brainstem cholinergic nucleus, the laterodorsal tegmental nucleus, showed an even higher degree of choline acetyltransferase immunoreactivity-positive cells also immunoreactive for CRH-R1 (92%). All catecholaminergic structures studied displayed a pattern of CRH-R1 immunoreactivity strongly overlapping the pattern of tyrosine hydroxylase immunoreactivity. The intensity of the CRH-R1 signal was relatively low within the ventral tegmental area and the substantia nigra pars compacta, while the CRH-R1 signal was very intense and detected in almost all of the neurons of the locus coeruleus. These results clearly demonstrate that the cholinergic and catecholaminergic systems provide direct anatomical substrates for CRH action through the CRH-R1. These findings are of particular relevance for understanding the action of recently developed CRH-R1 antagonistic drugs which may offer a new therapeutic approach to treat stress-related disorders such as anxiety and depression and their concomitant alterations in arousal and cognitive functions.

Acetylcholine↗
PubMed2001

[Assessing the quality of patients' medical records at the Claudius-Regaud Institute].

In 1999, the Claudius-Regaud Institute of Toulouse, France, specialized in oncology, set up a workshop in order to assess the quality of its patients medical records. A retrospective evaluation was performed on a 100-chart-sample drawn from all the charts in the institution. Results show that the medical records are subdivised into three parts: medical care, nursing care and imaging. Some of the explored charts show a lack of data, and a certain inconsistency in the charts' organization and in the structure of information was reported. Patient's record is a key to communication between the different care providers in oncology. To improve its quality, efforts will have to be done in restructuring the charts, creating guidelines and training the different caregivers.

Cancer Care Facilities↗
PubMed2001

[Regulation of elastin synthesis].

Elastin is the main protein of elastic fibers and confers the property of elastic recoil to the tissues such as arteries, lung, elastic cartilage,... Elastin synthesis goes through several steps: gene transcription, alternative splicing of pre-mRNA, mRNA translation, hydroxylation of some proline residues of the newly synthesized protein-tropoelastin-, association of with a 67 kDa chaperone protein, secretion of tropoelastin molecules in the extracellular space, and their deposition on the microfibrillar scaffold which contains fibrillin 1, fibrillin 2, MAGP 1 and MAGP 2,.... After the synthesis of cross-links-lysinonorleucine, desmosine, isodesmosine-, elastin becomes insoluble and elastic. The elastogenic pathway is regulated at many levels. The most recently described regulatory mechanism of elastin synthesis is the control of elastin mRNA stability. Elastogenesis is well controlled during development and aging but remains responsive to external factors such as soluble compounds-cytokines, vitamins, hormones,...- and hemodynamic stress. In order to ensure its function, both quantity and quality of elastin should be and should remain optimal in elastic tissues.

Alternative Splicing↗
PubMed2000

Mild deficits in mice lacking pituitary adenylate cyclase-activating polypeptide receptor type 1 (PAC1) performing on memory tasks.

Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor subtype 1 (PAC1) have been suggested to play a role in the modulation of learning and memory. However, behavioral evidence for altered mnemonic function due to altered PAC1 activity is missing. Therefore, the role of PAC1 in learning and memory was studied in mouse mutants lacking this receptor (PAC1 knock-out mice), tested in water maze two-choice spatial discrimination, one-trial contextual and cued fear conditioning, and multiple-session contextual discrimination. Water maze spatial discrimination was unaffected in PAC1 mutants, while a mild deficit was observed in multiple session contextual discrimination in PAC1 knock-out mice. Furthermore, PAC1 knock-out mice were able to learn the association between context and shock in one-trial contextual conditioning, but showed faster return to baseline than wild-type mice. Thus, the effects of PAC1 knock-out on modulating performance in these tasks were subtle and suggest that PAC1 only plays a limited role in learning and memory.

Animals↗
PubMed2000

Insulin stimulates NHE1 activity by sequential activation of phosphatidylinositol 3-kinase and protein kinase C zeta in human erythrocytes.

The signaling cascade linking insulin receptor stimulation to the activation of Na/H exchanger (NHE) was investigated in human erythrocytes, a simple cell model expressing the NHE1 isoform and protein kinase C (PKC) alpha and zeta isoforms only. Our results demonstrate the presence of phosphatidylinositol (PtdIns) 3-kinase in these cells and its activation by insulin. With a similar time-course, insulin also promoted both the translocation and activation of PKC zeta, but had no effect on PKC alpha. Inhibition of PtdIns 3-kinase with wortmannin prevented the activation of PKC zeta by insulin. Stimulation of NHE1 was observed after 10 min of insulin treatment and persisted for at least 60 min. This effect was totally abolished by wortmannin or GF 109203X, an inhibitor of all PKC isoforms, but not by Gö 6976, a specific inhibitor of conventional and novel PKCs (e.g. PKC alpha). These data indicate that PKC zeta activation is mediated by a PtdIns 3-kinase-dependent mechanism and that NHE1 stimulation involves the sequential activation of PtdIns 3-kinase and PKC zeta. In addition, insulin stimulation of NHE1 occurred without altering the phosphorylation state of the exchanger, suggesting that the phosphorylation of an ancillary protein by PKC zeta would be responsible for activation of the transporter.

Androstadienes↗
PubMed2000

Glucocorticoid receptor impairment enhances impulsive responding in transgenic mice performing on a simultaneous visual discrimination task.

Transgenic mice with impaired glucocorticoid receptor (GR) function were tested for their ability to learn and perform a series of simultaneous visual discriminations which allowed a dissociation between accuracy of discrimination from those of motivation and behavioural disinhibition. Animals were first trained on an operant five-choice simultaneous discrimination autoshaping procedure, followed by a continuous reinforcement schedule on that task. Subsequently, the number of choices was limited to two and data were analysed according to the mathematical methods of signal detection theory (SDT). The effects of GR-antisense expression on accuracy when different rates of responding were required were studied under different fixed ratio response requirements (FR1-FR10). Autoshaping was retarded in transgenic animals and accuracy was impaired in both the five-choice and the two-choice discrimination tasks, although transgenic mice showed clear evidence for learning. Under conditions of low response requirements, transgenic mice showed increased response and cognitive biases, but reduced perceptual bias, and a behavioural disinhibition, characterized by a reduction in errors of omission, decreased response latencies and increased number of responses during the inter-trial interval. Increasing the response requirement improved performance in transgenic animals as reflected by enhanced accuracy. Moreover, transgenics were less susceptible to the deleterious effects of higher response requirements, as indicated by relatively unaffected bias measures in this group, while bias increased in controls. These results indicate that altered performance in GR-antisense transgenic animals cannot simply be interpreted as a mnemonic deficit, but that altered motivation and enhanced impulsive responding may account for some of these impairments.

Animals↗
PubMed2000

[A study based on national DRG data to evaluate work load and practice relating to cancer patients in not-for-profit hospitals].

BACKGROUND: In France there is no reliable information describing the organisation of hospital care for patients with cancer. The present study attempts to clarify this issue taking advantage of an information source that has up to now been unused, namely the national PMSI (Information System Medical program) data base. METHODS: A quantitative study has been carried out regarding cancer management in France using information filed with the PMSI which compiles data related to hospital admissions in all institutions with more than 100 beds and subject to a defined global budget. The "cancer" component of hospital activity was extracted using a specific algorithm which utilized the diagnostic and intervention codes included in the admission summaries. By using the unit of activity as defined by the ISA (Activity Synthetic Index) and the scale of relative cost according to the GHM (Homogeneous Group of patients) it was possible to analyse the information in terms of a balance sheet. RESULTS: The study provided information regarding the costs and methods of management, including therapeutic strategies, for each type of hospital establishment. It is shown that with one death out of six, cancer covers a quarter of all hospital stays, and one sixth of annual hospital expenses. This accounts for 16.2% of ISA ie approximately 29 billion francs (4.6 billion dollars) for the public and semipublic sectors. Surgery, which accounted for 32% of expenditures, appeared to be the most expensive intervention, ahead of chemotherapy (16.3%) and radiotherapy (9.1%). Each type of hospital organisation (university, cancer centre, district hospital) had their own relative figures. CONCLUSION: Through this study the current situation regarding cancer care in hospital has been documented. It has also demonstrated the value of the PMSI data base as a source of information for large scale quantitative studies of health care economics. However, the PMSI does not yet provide details regarding infrastructure or succession of hospital stay. Ultimately, this analysis does not provide any information on the quality or efficacy of care but does define a typological system for health care organisations which could provide information on distribution of resources.

Costs and Cost Analysis↗
PubMed1999

Disrupted allocentric but preserved egocentric spatial learning in transgenic mice with impaired glucocorticoid receptor function.

Spatial and non-spatial learning of mice with an incorporated antisense RNA complementary to a fragment of cDNA coding for the glucocorticoid receptor (GR) were evaluated in allocentric and egocentric radial maze and water maze tasks, and in spontaneous object recognition and sensorimotor learning paradigms. Mice with impaired GR function did not acquire two maze paradigms based on allocentric spatial navigation, radial maze non-matching to position and water maze spatial discrimination learning. Comparison of performance in spaced and massed trials indicated that this may be due to a general inability to store information into allocentric reference memory or in retrieval processes. However, both groups of animals learned the rules of an egocentric radial maze task at similar rates and there was no difference in their ability to recognise objects once animals had equal opportunity to explore the sample objects. Sensorimotor performance was impaired in transgenic animals, but it is suggested that this is due to non-specific factors rather than to disrupted sensorimotor learning per se. These results are consistent with a disruption of hippocampal function. Histological examination of the hippocampus revealed no obvious structural abnormalities in transgenic animals. Therefore, the data suggest that functional underactivity of GRs at the level of the hippocampus induces a deficit in allocentric navigation while sparing egocentric navigation and object recognition.

Animals↗
PubMed1999

Excitotoxic hippocampal lesions disrupt allocentric spatial learning in mice: effects of strain and task demands.

Spatial discrimination of ibotenic acid-lesioned C57BL/6 (B6) and DBA/2 (D2) mice was tested in two-choice water maze and plus maze tasks. B6 but not D2 mice learned the spatial discrimination in the water maze, but strains did not differ in learning a spatial discrimination in the plus maze paradigm. Ibotenic acid lesions of the hippocampus impaired percentage correct choices in the water maze spatial discrimination task in B6 but not in D2 mice, the latter of which may have been due to a floor effect. Furthermore, lesioned mice were more thigmotaxic, the distance travelled until a choice was made was longer and animals made more errors of omission. Despite the poor performance during water maze acquisition, lesioned animals, as well as sham-lesioned D2 mice, eventually acquired some place response in the water maze, as was evident when the location of the platform was reversed. However, hippocampus-lesioned mice of both strains were impaired when tested in the plus maze spatial discrimination task. Thus, ibotenic acid-induced lesions of the hippocampus impair acquisition of spatial discrimination in mice. These deficits were strain-dependent and likely comprise impaired accuracy as well as changes in non-mnemonic types of behaviour. Importantly, lesions in both strains impaired spatial learning, and whether a deficit was seen in mice of the D2 strain seemed to depend on the demands of the task.

Animals↗
PubMed1999

Influence of elastin gene polymorphism on the elastin content of the aorta: A study in 2 strains of rat.

The elastin content in the thoracic aorta of male Brown-Norway (BN) rats is 31.4+/-1.2% (dry weight), whereas that of male LOU rats is 37.2+/-1.0%. A similar difference in the elastin content of the thoracic aorta is also observed in female animals. Furthermore, in the thoracic aorta of young, growing rats as well as in cultured aortic smooth muscle cells, the steady-state level of elastin mRNA is significantly lower in the BN than in the LOU strain. These results suggested that 1 or more genes control the elastin mRNA level and the elastin content in the aortas of BN and LOU rats. A possible relationship between a polymorphism in the elastin gene and the elastin content of the aorta was tested. For this purpose, the aortic elastin content was measured in F(1) and F(2) generations bred from LOU and BN rats and was compared with that of the F(0) (parental) generation. A polymorphic marker located in intron 25 of the elastin gene has been used to genotype the F(2) rats. The degree of genetic determination of aortic elastin content was estimated to be 73% in the F(2) cohort, but the elastin locus accounts for only 3. 9% of the total variance in aortic elastin content. Other genes are thus responsible for the major part of the observed interstrain difference by regulating the transcription of the gene, the stability of elastin mRNA, and/or posttranslational events.

Alleles↗
PubMed1998

Involvement of deoxygenation-induced increase in tyrosine kinase activity in sickle cell dehydration.

Deoxygenation of sickle (SS) cells causes cationic alterations leading to cell dehydration by various mechanisms, including activation of Ca2+-sensitive K channels and possibly of K-Cl cotransport. Since an abnormal tyrosine kinase (TK) activity exists in SS cells we investigated the possible role of tyrosine phosphorylation in SS cell dehydration. In density-fractionated SS reticulocytes and discocytes, but not in normal red cells, deoxygenation increased membrane and cytosolic TK activities and tyrosine phosphorylation of band 3, independently of external Ca2+. These effects were abolished by the TK inhibitors methyl 2, 5-dihydroxycinnamate (DiOH) or tyrphostin 47 (T47). Deoxygenation-induced Ca2+ uptake was not affected by the inhibitors and Na+ gain was reduced by T47 and not by DiOH. Both inhibitors decreased the loss of K+ and cellular dehydration. The effect of the inhibitors on K+ efflux was still observed in the absence of external Ca2+. These data indicate that the TK inhibitors do not interfere with deoxygenation-induced membrane permeabilization, but affect Ca2+-independent K+ efflux. It cannot be excluded, however, that the TK inhibitors also attenuate Ca2+-sensitive K+ efflux. Based on recent evidence from the literature, it is suggested that the diminution of K+ efflux results in part from inhibition of K-Cl cotransport activity.

Anemia, Sickle Cell↗
PubMed1998

Localization of elastin mRNA and TGF-beta1 in rat aorta and caudal artery as a function of age.

Several in vitro studies have previously demonstrated that the addition of TGF-beta to aortic smooth muscle cells or skin fibroblasts stimulates elastin synthesis. It is not clear however whether, in vivo, TGF-beta participates in the regulation of elastin synthesis, especially in physiological conditions. The aim of our study was to explore the localization of elastin mRNA and TGF-beta1 in the rat thoracic aorta (an elastic artery) and caudal artery (a muscular artery). Elastin mRNA was localized by in situ hybridization and quantified using Northern blot analysis. TGF-beta1 was detected using immunohistochemistry. The study was carried out as a function of age (rats of 3, 10, 20, and 30 months). We observed that TGF-beta1 immunoreactivity is present predominantly, but not exclusively, at the sites of elastin synthesis as determined by elastin mRNA detection: in smooth muscle cells in the aorta and in endothelial cells in the caudal artery. The ability of exogenously added TGF-beta1 (0.001-10 ng/ml) to modulate the steady-state levels of elastin mRNA in primary cultures of endothelial cells, smooth muscle cells, and fibroblasts isolated from the thoracic aorta was also studied. At the highest concentration used, elastin mRNA levels increased 5-fold in endothelial cells and 11-fold in smooth muscle cells. The demonstration that TGF-beta1 immunoreactivity is present at the sites of elastin synthesis in the thoracic aorta and in the caudal artery and the observation that TGF-beta1 induces an increase in elastin mRNA levels in cultured endothelial cells and smooth muscle cells suggest that TGF-beta1 may be implicated, at least in part, in the physiological regulation of elastin gene expression.

Aging↗
PubMed1997

Expression of c-fos in bulbar nuclei involved in cardiovascular control following the electrical stimulation of sensorimotor cortex in the rat.

Previous studies have shown that electrical stimulation of the sensorimotor cortex (SMC) induces responses of the autonomic nervous system such as variations in heart rate and arterial pressure. Neuroanatomical studies have shown the existence of monosynaptic projections from the SMC to the nucleus tractus solitarius (NTS), the rostral ventrolateral medulla (RVLM) and the dorsal nucleus of the vagus nerve (DNV), which are bulbar nuclei involved in cardiovascular control. The aim of the present study was to establish whether there exists a functional connectivity between the SMC and these nuclei. Electrical stimulation applied to the SMC of 7 rats for 1 h induced the expression of c-fos-protein-like immunoreactivity in the nucleus of some neurons in NTS, RVLM and DNV. These data support the view that the SMC has functional connections with bulbar neurons involved in cardiovascular control.

Animals↗
PubMed1997

Effects of PKC alpha activation on Ca2+ pump and K(Ca) channel in deoxygenated sickle cells.

We have previously shown that a pretreatment with phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C (PKC), reduced deoxygenation-induced K+ loss and Ca2+ uptake and prevented cell dehydration in sickle anemia red blood cells (SS cells) (H. Fathallah, E. Coezy, R.-S. De Neef, M.-D. Hardy-Dessources, and F. Giraud. Blood 86: 1999-2007, 1995). The present study explores the detailed mechanism of this PMA-induced inhibition. The main findings are, first, the detection of PKC alpha and PKC zeta in normal red blood cells and the demonstration that both isoforms are expressed at higher levels in SS cells. The alpha-isoform only is translocated to the membrane and activated by PMA and by elevation of cytosolic Ca2+. Second, PMA is demonstrated to activate Ca2+ efflux in deoxygenated SS cells by a direct stimulation of the Ca2+ pump. PMA, moreover, inhibits deoxygenation-induced, charybdotoxin-sensitive K+ efflux in SS cells. This inhibition is partly indirect and explained by the reduced deoxygenation-induced rise in cytosolic Ca2+ resulting from Ca2+ pump stimulation. However, a significant inhibition of the Ca2+-activated K+ channels (K(Ca) channels) by PMA can also be demonstrated when the channels are activated by Ca2+ plus ionophore, under conditions in which the Ca2+ pump is operating near its maximal extrusion rate, but swamped by Ca2+ plus ionophore. The data thus suggest a PKC alpha-mediated phosphorylation both of the Ca2+ pump and of the K(Ca) channel or an auxiliary protein.

Anemia, Sickle Cell↗
PubMed1993

Characterization of structural and functional phosphoinositide domains in human erythrocyte membranes.

In the erythrocyte membrane, only a fraction (50-60%) of phosphatidylinositol 4,5-bisphosphate (PIP2) and of phosphatidylinositol 4-phosphate (PIP) is rapidly turned over by specific kinases and phosphatases and accessible to hydrolysis by the polyphosphoinositide (PPI)-specific phospholipase C (PLC). To investigate whether the metabolic segregation of PPI resulted from preferential interactions with proteins, we have measured the accessibility of PPI to bee venom phospholipase A2 (PLA2) in native erythrocyte membranes, or after treatments designed to remove peripheral proteins and cytoplasmic domains of integral proteins. In native membranes, PPI, as well as the other major phospholipids, behaved as two distinct fractions (R1 and R2) differing by their sensitivity to PLA2. Such a behavior was not observed in PIP and PIP2 containing artificial vesicles. Evidence was provided that the highly sensitive fraction of PIP and PIP2 (R1) may be identical to the PLC-sensitive and rapidly metabolized pool. Removal of peripheral proteins, followed by proteolysis of the cytoplasmic domain of integral proteins, mainly glycophorins and band 3, led to a reduction of the R1 fraction of PIP and of PIP2. It is proposed that the rapidly metabolized pool of PIP2 and PIP, involved in the regulation of major cellular functions, would be maintained in its functional state through interactions with integral proteins.

Blood Proteins↗