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S Martel

Publications and source records attributed to S Martel.

At least 19 recordsLinked to original sources
PubMed2001

FLRG, an activin-binding protein, is a new target of TGFbeta transcription activation through Smad proteins.

The FLRG gene encodes a secreted glycoprotein that binds to activin and is highly homologous to follistatin, an activin ligand. We cloned the promoter region of the human FLRG gene, and defined the minimal region necessary for transcription activation in a reporter-system assay. We showed that the fragment between positions -130 and +6, which consists of multiple consensus Sp1-binding sites, is required for the constitutive expression of the FLRG gene. We demonstrate here that FLRG mRNA expression is rapidly induced by TGFbeta or by transfection with Smad protein expression vectors in human HepG2 cells. We investigated the transcription-regulation mechanism of FLRG expression in HepG2 cells following treatment with TGFbeta. By deletion and point-mutation analysis of the FLRG promoter, we identified a Smad-binding element involved in the TGFbeta-inducible expression of the FLRG gene. Moreover, transactivation of the FLRG promoter by TGFbeta was compromised by dominant-negative mutants of Smad3 and Smad4 proteins. In addition, gel electrophoresis mobility-shift assays demonstrated the specific interaction of Smad3 and Smad4 proteins with the Smad-binding element consensus motif found in the FLRG promoter. Taken together, our data imply that Smad proteins participate in the regulation of expression of FLRG, a new target of TGFbeta transcription activation.

Activins↗
PubMed2001

Expression of FLRG, a novel activin A ligand, is regulated by TGF-beta and during hematopoiesis [corrected].

OBJECTIVE: The human gene FLRG, identified from a B-cell chronic lymphocytic leukemia bearing a t(11;19) translocation, encodes a secreted glycoprotein highly homologous with follistatin. Activin A is a TGF-beta family member involved in the regulation of growth and differentiation of various types of cells, such as those of the hematopoietic system. Its biological activity is antagonized by binding with follistatin. We investigated the binding of FLRG to activin A and the expression pattern of FLRG, follistatin, and activin A during hematopoiesis. MATERIALS AND METHODS: The binding of FLRG with activin A was investigated by immunoprecipitation and Far-Western blot analysis. Gene expression was analyzed by reverse transcriptase polymerase chain reaction (RT-PCR) and Northern Blot in purified hematopoietic populations. RESULTS: We demonstrate that FLRG, like follistatin, is able to bind to activin A. In bone marrow stromal cells, both mRNA and protein FLRG levels were found to be dramatically increased by TGF-beta. FLRG and activin A are expressed in the same cells, with a higher level of expression in the myeloid cells compared with the erythroid and megakaryocytic cells. FLRG and follistatin expression were different in the hematopoietic subpopulations tested. Moreover, we observed that FLRG and activin A expression was up-regulated during hematopoiesis. CONCLUSION: FLRG and activin A are expressed in the same hematopoietic cells and regulated by TGF-beta. Moreover, FLRG interacts with activin A, suggesting that FLRG, like follistatin, participates in the diverse regulatory functions of activin A, such as those in hematopoiesis.

Activins↗
PubMed2000

Use of diethyl(2-methylpyrrolidin-2-yl)phosphonate as a highly sensitive extra- and intracellular 31P NMR pH indicator in isolated organs. Direct NMR evidence of acidic compartments in the ischemic and reperfused rat liver.

The novel phosphorylated pyrrolidine diethyl(2-methylpyrrolidin-2-yl)phosphonate (DEPMPH) was evaluated as a (31)P NMR probe of the pH changes associated with ischemia/reperfusion of rat isolated hearts and livers. In vitro titration curves indicated that DEPMPH exhibited a 4-fold larger amplitude of chemical shift variation than inorganic phosphate yielding an enhanced NMR sensitivity in the pH range of 5.0-7.5 that allowed us to assess pH variations of less than 0.1 pH units. At the non-toxic concentration of 5 mm, DEPMPH distributed into external and cytosolic compartments in both normoxic organs, as assessed by the appearance of two resonance peaks. An additional peak was observed in normoxic and ischemic livers, assigned to DEPMPH in acidic vesicles (pH 5.3-5.6). During severe myocardial ischemia, a third peak corresponding to DEPMPH located in ventricular and atrial cavities appeared (pH 6.9). Mass spectrometry and NMR analyses of perchloric extracts showed that no significant metabolism of DEPMPH occurred in the ischemic liver. Reperfusion with plain buffer resulted in a rapid washout of DEPMPH from both organs. It was concluded that the highly pH-sensitive DEPMPH could be of great interest in noninvasive ex vivo studies of pH gradients that may be involved in many pathological processes.

Animals↗
PubMed2000

AF15q14, a novel partner gene fused to the MLL gene in an acute myeloid leukaemia with a t(11;15)(q23;q14).

In haematopoietic malignancies the MLL gene, located on chromosome 11q23, is frequently disrupted by chromosome rearrangement, generally resulting in fusion to various partner genes. We have previously reported a t(11;15)(q23;q14) in a case of acute myeloblastic leukaemia. Here, we report the cloning of a novel MLL partner, AF15q14, at chromosome 15q14. In this translocation, the breakpoint occurred in exon 8 of MLL and exon 10 of AF15q14. The normal AF15q14 transcripts of approximately 8.5 kb in size, are expressed in different tumoral cell lines, in a variety of normal tissues, and in all the foetal tissues tested. Sequencing of AF15q14 cDNA revealed a putative open reading frame of 1833 amino acids that had no homology with any other known protein. The C-terminal end of the putative AF15q14 contained a bipartite nuclear localization site. The translocation t(11;15) preserved the open reading frame between MLL and the 3' end of AF15q14. The contribution of AF15q14 to the fusion protein was only 85 amino acids. Immunofluorescence staining experiments with expression vectors encoding these 85 amino acids confirmed the functionality of the predicted nuclear localization site.

Amino Acid Sequence↗
PubMed2000

alpha - and beta -phosphorylated amines and pyrrolidines, a new class of low toxic highly sensitive 31P NMR pH indicators. Modeling of pKa and chemical shift values as a function of substituents.

Fourteen linear and cyclic alpha- and beta-aminophosphonates in which the P-atom is substituted by alkoxy groups have been synthesized and evaluated as (31)P NMR pH markers in Krebs-Henseleit buffer. pK(a) values varied with substitution in the range 1.3-9.1, giving potentially access to a wide range of pH. Temperature had a weak influence on pH and a dramatic increase in ionic strength slightly modified the pK(a) of the pyrrolidine diethyl(2-methylpyrrolidin-2-yl)phosphonate (DEPMPH). All compounds displayed a 4-fold better NMR sensitivity than inorganic phosphate or other commonly used phosphonates, as assessed by differences delta(b)-delta(a) between the chemical shifts of the protonated and the unprotonated forms. In isolated perfused rat hearts, a non-toxic concentration window of 1.5-15 mm was determined for three representative compounds. Using empirical linear relationships, the experimental values of pK(a), delta(a), and delta(b) have been correlated with the two-dimensional structure, i.e. the chemical nature of substituents bonded to the secondary amine and P-atom. The data suggest that DEPMPH and its cyclic and linear variants are ideal versatile (31)P NMR probes for the study of tenuous pH changes in biological processes.

Amines↗
PubMed2000

Airway hyperresponsiveness, inflammation, and subepithelial collagen deposition in recently diagnosed versus long-standing mild asthma. Influence of inhaled corticosteroids.

This study aimed at documenting airway inflammation and subepithelial collagen deposition in patients using only inhaled beta(2)-agonists with either recently diagnosed asthma (RDA: </= 2 yr, n = 16) or long-standing asthma (LSA: >/= 13 yr, n = 16) and at the influence of an intense inhaled corticosteroid (ICS) treatment on these parameters, in relation to changes in airway responsiveness. Patients had a methacholine inhalation test and a bronchoscopy with bronchial biopsies before and after an 8-wk treatment with inhaled fluticasone propionate (FP), 1,000 microgram/day. Baseline FEV(1) (mean +/- SEM) was normal and similar in both groups (RDA: 98.1 +/- 2.7, LSA: 94.5 +/- 4.6%). Geometric mean methacholine PC(20) was lower in LSA than in RDA (0.44 versus 3.37 mg/ml) at baseline and improved similarly by 1.85 and 1.86 double concentrations with FP treatment. PC(20) normalized (>/= 16 mg/ml) in five patients with RDA and two patients with LSA. Baseline mean bronchial cell counts (per mm(2) connective tissue surface) for CD3(+), CD4(+), CD8(+), CD25(+), EG1(+), CD45ro(+), and AA1(+) cells were similar in both groups. With FP, EG1(+) (p < 0.001), EG2(+) (p = 0.018), and AA1(+) counts (p = 0.009) decreased significantly in both groups while CD45ro(+) (p = 0.02) counts decreased only in LSA. Baseline type 1 and type 3 collagen deposition underneath the basement membrane was similar in RDA and LSA and did not change significantly after FP. This study shows that recent compared to long-standing mild asthma is associated with a similar degree of airway inflammation and subepithelial fibrosis, and a similar improvement in airway hyperresponsiveness after 8 wk on high-dose ICS. It also indicates that once asthma becomes symptomatic, airway responsiveness cannot normalize in most subjects over such a time period, even with a high dose of ICS.

Administration, Inhalation↗
PubMed1999

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Emergencies↗
PubMed1998

FLRG (follistatin-related gene), a new target of chromosomal rearrangement in malignant blood disorders.

We report here the molecular study of a t(11;19)(q13;p13) translocation observed in a case of B-cell chronic lymphocytic leukemia. This translocation leads to the juxtaposition of the CCND1 gene on chromosome 11 to a new transcriptional unit on chromosome 19. The cDNA of this new evolutionarily conserved gene (named FLRG for Follistatin-Related Gene) codes for a secreted glycoprotein of the follistatin-module-protein family. FLRG is expressed in a wide range of human and murine adult tissues and its expression seems to be tightly regulated during murine embryogenesis. Its transcripts could not be detected in hematopoietic cells from all lineages and in particular in cells from lymphoid B and T lineage except in the t(11;19)-carrying leukemia described here. A great variability of expression is observed among the other tumoral cell lines analysed. Besides the t(11;19)-carrying leukemia described in this work, structural rearrangements of the FLRG locus have been found in a non-Hodgkin lymphoma, suggesting that it may play a role in leukemogenesis.

Amino Acid Sequence↗
PubMed1998

Metallothionein expression in human lung and its varying levels after lung transplantation. Toulouse Lung Transplantation Group.

The aim of this study was to determine the lung levels of metallothionein (MT), a free radical scavenger, because oxygen-derivated free radicals (ODFRs) have been involved both in reperfusion injury of transplanted lungs and in cardiac or renal allograft destruction. First, MT localization was evaluated in 14 normal human lung biopsy specimens. Then, in lung transplant recipients, MT content in BAL fluid (BALF) and its transcription rate in alveolar macrophages (AMs) were determined. The BALFs of 69 patients were separated into six groups: lung transplant recipients in clinically stable condition (CSR), those with acute rejection (AR), asymptomatic cytomegalovirus infection (ACMV), cytomegalovirus pneumonitis (CMVP), bronchiolitis obliterans syndrome (BOS), and patients without transplants who served as control subjects (NTCs). In normal lungs, 83% of AMs were positively stained. MT staining was also observed in pleural endothelial cells and basal cells from bronchial epithelium. In lung transplant recipients, MT levels in BALF were significantly higher in patients with CSR, AR, ACMV, and CMVP compared with NTCs, while during BOS, MT had a significantly lower level compared with other lung transplant groups. However, no difference among groups was found concerning MT-II messenger RNA expression in AMs, showing that, as in normal lung, AMs are not the only cells that produce MT. These data report for the first time to our knowledge MT cell distribution in human lung with specific emphasis on its enhanced levels after lung transplantation, even in the absence of complication. Possible correlation among MT levels, ODFRs, cytokine levels, and corticosteroid treatment during complications of lung transplantation are discussed.

Acute Disease↗
PubMed1998

Cancer trends from 1972-1991 for Registered Indians living on Manitoba Reserves.

BACKGROUND: The objectives of this study were to determine if the incidence of and mortality from cancer have increased between 1972-1991, and to describe the distribution of cancer sites and survival for Registered Indians living on-reserves. METHODS: Cancer cases and deaths on-reserve were obtained from the provincial cancer registry, using a postal code match. Treaty Status was verified using a population registry kept by Health Canada. Population figures on-reserve were obtained from the federal Department of Indian Affairs. RESULTS: The average annual number of cases and deaths increased by 64% and 122%, respectively, between 1972-76 and 1987-91 (NS). The age and sex standardized incidence and mortality rates increased by 7% and 50% (NS). Males had a 1.1 times higher incidence and 1.4 times higher death rate than females. The entire excess male incidence and mortality occurs after age 50. Females have 1.1 to 6.2 times the incidence and mortality between ages 20-49. CONCLUSIONS: Cancer incidence and mortality appear to be increasing on-reserve. The distribution of leading sites and pattern of survival are similar to that of the rest of the population, with the exception of a higher proportion of cases and mortality caused by cervical and gallbladder cancer in females and kidney cancer in both sexes. The lung cancer rate is increasing in women and is the leading cause of cancer mortality for both sexes. It is likely that these trends will continue for some time unless there is reduction in the high rate of smoking, dietary change, and implementation of more widespread and effective Pap screening on-reserves.

Adult↗
PubMed1997

Shigellosis on Indian reserves in Manitoba, Canada: its relationship to crowded housing, lack of running water, and inadequate sewage disposal.

OBJECTIVES: This study compares incidence and hospitalization rates for shigellosis between Indians and the rest of the population in Manitoba, Canada. It examines the relationship between shigellosis and environmental conditions on reserves. METHODS: Rates were calculated with surveillance data and a survey of environmental infrastructure was done. RESULTS: Indians had shigellosis incidence and hospitalization rates that were 29 and 12 times as high, respectively, as those of the rest of the population. Household crowding, lack of piped water, and inadequate sewage disposal were significantly associated with an increased incidence of shigellosis on reserves. CONCLUSIONS: Many cases of shigellosis may be prevented by improving living conditions on Indian reserves.

Adolescent↗
PubMed1996

Tumour necrosis factor-alpha gene expression by alveolar macrophages in human lung allograft recipient with recurrence of sarcoidosis. Toulouse Lung Transplantation Group.

Recurrence of sarcoidosis in lung allografts is an interesting model to study the pathogenesis of this disease. We report a case of sarcoidosis recurrence in a single lung allograft recipient 2 years after transplantation. The expression of tumour necrosis factor-alpha (TNF-alpha) gene by alveolar macrophages was monitored. The TNF-alpha gene was not expressed at the time of recurrence of sarcoidosis, but only later when prominent granulomas were observed.

Adult↗
PubMed1996

[Alveolar lavage cytological data in lung transplants free of bronchial superinfection. Toulouse Lung Transplantation Group].

Total and differential cells counts from 173 bronchoalveolar lavages (BAL) carried out in 19 lung transplanted recipients have been analysed. The patients were separated into seven groups: (a) those without detectable complications (86 BAL); (b) those with acute rejection (AR) (26 BAL); (c) those with bronchiolitis obliterans (BO) (21 BAL); (d) those with intra-alveolar cytomegalovirus (CMV) but asymptomatic (11 BAL); (e) those with an associated intra-alveolar CMV and AR (7 BAL); (f) those with CMV pneumonia (11 BAL); (g) those with infectious pneumonia excluding CMV (11 BAL). The alveolar cytological data were compared to those from control subjects who were smokers (7 BAL) or non-smokers (8 BAL). Excluding the BO group, the total cell count from the BAL of transplanted patients was significantly higher than in the non-smoking controls and was approaching that of the smoking controls. The lymphocytes count was significantly higher in transplanted patients without complication and in the AR group than in the controls, but there was no significant difference between the two groups. There was a significantly greater eosinophilia at the time of AR than either before or after. Eosinophilia was also higher in grade 3 AR than in grade 1 or 2 AR. These data stress the absence of any correlation between the lymphocyte count in the BAL and the existence of AR. Alternatively, the alveolar eosinophilia observed at the time of AR does not allow the possibility of an infection to be elimitated with certainty.

Adult↗
PubMed1996

[Lung pathology in heart, liver and kidney transplantation in adults].

Currently transplantation constitutes the only treatment for terminal heart, liver or renal failure. Post-transplantation complications remain numerous and sometimes fatal. The rejection of the organ, acute or chronic, and secondary infections due to immunosuppression are the most frequent complications that are observed. Added to this are the complications of the surgery itself and also the non-infectious complications of the immunosuppressive drugs. Pulmonary complications contribute an important factor to the post-graft morbidity and mortality. The majority of heart and liver transplants develop pulmonary complications principally in the first six months after graft. The immediate post-operative complications such as atelectasis, pleural effusion and pulmonary oedema are the most frequent but the infectious complications are much the most serious and are responsible for a significant part of the mortality. In renal transplantation pulmonary complications are above all infectious and are much less common than in cardiac or hepatic transplantation. An early diagnosis of the type of complication constitutes a major prognostic factor in immunodepressed patients. Thus, the practising pneumologist must thoroughly know the principal respiratory complications of solid organ transplant.

Acute Disease↗
PubMed1990

[Severe suicides: short- and long-term outcome. Assessment of their quality of life].

From January 1977 to December 1982, 160 patients (10 to 55 years old) were admitted in a traumatic Intensive Care Unit after serious attempted suicides. Hospital mortality rate was about 34%. A questionnaire was sent to alive patients in 1983 (median delay between attempted suicide and questionnaire: 3.5 years); 68 were alive in 1983, 46 answered to questionnaire, 3 were died (two according to a new suicide); 32 could not be found; 85% of contacted patients answered (they were comparable in age, sex and means used in their suicide attempts, to the others). One patient about two must be rehospitalised one or more times. One patient about two must be always take drugs; 85% worked. Over 50% of the patients considered they had returned to their former way of life but 50% presented increased difficulty to work, and 25% said that they had no sequelae. Any of these 46 patients had made an other attempt suicide.

Adolescent↗
PubMed1987

[Myocardial metabolism in angina with angiographically normal coronary arteries].

Myocardial metabolism was studied during rapid atrial pacing in 22 patients with angina and angiographically normal coronary arteries. Pyruvate, non esterified fatty acid and lactate levels were measured in the coronary arteries and veins under basal conditions, at the peak of atrial pacing and during the recovery phase. A control group of 8 patients had neither angina, ST depression, or lactate production during atrial pacing. A correlation was observed between the coronary arterio-venous difference and arterial pyruvate and non esterified fatty acid levels in the 22 patients during the 3 periods of study. The control patients did not differ significantly from the rest of the population. There was a correlation between the coronary arterio-venous difference and arterial lactate levels under basal conditions in all of the study and control groups. This correlation remained significant during atrial pacing and the recovery period only in the control group. It was possible to distinguish a group of 14 patients (64 p. 100) (Group A) with a correlation coefficient of lactate production similar to the control group (+/- 2 standard deviations) during atrial pacing, from a second group of 8 patients (36 p. 100) (Group B) with abnormal myocardial metabolism. The arterial lactate concentrations were similar in both groups in the 3 periods of study. A coefficient of lactate extraction less than 10 p. 100 was observed in 2 patients in Group A and in 7 patients in Group B (88 p. 100, p less than 0.01). One patient in Group B had a coefficient of lactate extraction greater than 10 p. 100 (+ 13 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Serious suicides. Short and long-term results. One hundred and fifty six cases with a follow-up period of 1 to 7 years.

By serious suicides we mean all suicide attempts in which the wish to die was clearly expressed by the patient. Hospitalization in intensive care is indispensable (lasting 3 days on average, 1 to 34 days in extreme cases). From January 1977 to December 1982, 156 patients, aged 10 to 55, were admitted on the basis of this criterion (i.g. 6 1/2% of all our patients), 60% of them men. The mode of suicide was often violent: voluntary fall: (44 or 28%) 15 dead; hanging: (11 or 7%) 3 dead; fire arms: (48 or 30%) 23 dead; knife wounds: (13 or 7%) 2 dead; drug and/or chemical poisoning: (33 or 23%) 6 dead; others: (7 or 5%) 4 dead. In 34% of the cases (54 cases), death was immediate. For longterm results the follow-up lasts from 6 months to 6 years. Only 12 patients (7 1/2%) had attempted to kill themselves prior to their admission in our service. Out of the 103 patients still alive, 30 (29%) were contacted on the phone, and agreed to answer the questionnaire, whatever their mode of suicide, sex or age. The survey focused on their medico-surgical problems, their socio-professional activities, both previous and subsequent to hospitalization. Whatever the diagnosis at the moment of hospitalization, no disabling after-effects were noticed among the subjects. Only 3 of our patients (2,8%) have made a second attempt, 2 of which have been fatal. The results of this survey show the beneficial action of emergency medical aid and intensive care in the treatment of suicides, which represent a unique event in the patient's life rather than a chronic psychiatric syndrome. In the long term these results preclude further attempts or advice to commit suicide.

Adolescent↗