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Biomedical subjects

S Dumas

Publications and source records attributed to S Dumas.

At least 19 recordsLinked to original sources
PubMed2003

[Intravenous immunoglobulins for relapsing-remitting multiple sclerosis after failure of treatment with other immuno-modulators].

Intravenous immunoglobulins are used in the treatment of different autoimmune diseases. Recent trials suggest their efficacy in relapsing remitting multiple sclerosis. We report the results of an efficacy and safety trial using monthly intravenous injections of immunoglobulins for patients with secondary progressive multiple sclerosis. Eighteen patients in clinical progression, who have been previously treated with immunomodulatory or immunosuppressive drugs, were given monthly intravenous immunoglobulin infusions (0.4 g/kg/d for 5 days). At the beginning, the mean EDSS score was 6.77. At the end of the study, an improvement of EDSS was noted in 61.1 p. cent of patients, with less than 1 and 0.75 for secondary and primary progressive diseases respectively. No worsening was reported. Surprisingly, some patients had partial improvement of neurological functions which were considered as sequelae. Indications for intravenous immunoglobulins in the treatment of the multiple sclerosis need to be evaluated.

Adjuvants, Immunologic↗
PubMed2002

A novel sensitive microarray approach for differential screening using probes labelled with two different radioelements.

We have developed a novel microarray approach for differential screening using probes labelled with two different radioelements. The complementary DNAs from the reverse transcription of mRNAs from two different biological samples were labelled with radioelements of significantly different energies (3H and 35S or 33P). Radioactive images corresponding to the expressed genes were acquired with a MicroImager, a real time, high resolution digital autoradiography system. An algorithm was used to process the data such that the initially acquired radioactive image was filtered into two subimages, each representative of the hybridisation result specific for one probe. The simultaneous screening of gene expression in two different biological samples requires <100 ng mRNA without any amplification. In such conditions, the technique is sensitive enough to directly quantify the amount of mRNA even when present in small amounts: 10(7) molecules in the probe as assessed with an added control sequence and 2 x 10(5) molecules with an endogenous tyrosine hydroxylase mRNA. This novel technique of double radioactive labelling on a microarray is thus suitable for the comparison of gene expression in two different biological samples available in only small quantities. Consequently, it has great potential for various biological fields, such as neuroscience.

Animals↗
PubMed2002

Age-dependent differential regulation of genes encoding APP and alpha-synuclein in hippocampal synaptic plasticity.

We investigated the modulation of the messenger RNA encoding the amyloid precursor protein (APP) and alpha-synuclein following induction of long-term potentiation (LTP) in the dentate gyrus of young and aged rats. Three hours after tetanic stimulation, LTP induced in the young rats was maintained; the aged rats, however, fell into two subgroups: those in which LTP was maintained, and those in which LTP had declined to basal levels. In young rats, the global expression of mRNAs of all isoforms of APP and in particular that of the isoform lacking the KPI domain were significantly upregulated. In aged rats, the global expression of mRNAs of all isoforms of APP was not modified, regardless of whether LTP was maintained or not. The level of mRNA encoding the Kunitz protease-inhibitory (KPI)-minus isoform of APP, however, was increased in aged rats in which LTP was maintained, suggesting that the gene of this isoform may be more specifically regulated by synaptic plasticity. In contrast, we found that the gene encoding alpha-synuclein showed a trend towards being downregulated at the mRNA level in young rats following LTP, and significantly so in aged rats in which LTP was maintained, whereas it was not downregulated in aged rats with decremental LTP. These data suggest that the regulated expression of APP isoforms is part of the tanscriptional response associated with the enduring forms of synaptic plasticity and is altered with age. Whereas the level of alpha-synuclein mRNA is not apparently modified in normal LTP, it may reflect a mechanism of apoptotic cell death in aging that is in part responsible for decremental synaptic plasticity.

Aging↗
PubMed2002

Spatio-temporal heterogeneity and cell-specificity of long-term potentiation-induced mRNA expression in the dentate gyrus in vivo.

Gene expression in neurones can vary in response to neuronal activation. In this study, to analyse the spatio-temporal dynamics of the transcriptional response of three genes following the induction of long-term potentiation within the entire dentate gyrus in vivo, two new complementary approaches based on in situ hybridisation were developed: three-dimensional reconstruction of the pattern of mRNA expression within the entire dentate gyrus; and radioactive co-detection of two mRNA species allowing quantification of two different mRNAs in the same brain section. Zif268, Homer and syntaxin 1B genes were studied, and their regulated expression was examined three times after the induction of long-term potentiation. Constitutive expression of each gene under control conditions was homogeneous, but the spatial distribution of mRNA was heterogeneous along the rostro-caudal axis of the dentate gyrus following the induction of long-term potentiation, and different for each gene. In addition, the intensity of each gene-specific pattern of expression varied over time following the induction of long-term potentiation. Our results reveal that long-term potentiation differentially modulates the expression of mRNA species in cells of the dentate gyrus depending on their position along the rostro-caudal axis, on the gene and on time. We suggest that there are several molecular mechanisms of long-term potentiation, differing from one cluster of cells of the dentate gyrus to another, or that the different signaling pathways involved in long-term potentiation are used with varying efficiencies by different cells.

Animals↗
PubMed2001

Selective cardiorespiratory and catecholaminergic areas express the hypoxia-inducible factor-1alpha (HIF-1alpha) under in vivo hypoxia in rat brainstem.

Under severe oxygen deprivation, all cells are able to express the transcription factor HIF-1, which activates a wide range of genes. Under tolerable hypoxia, chemosensory inputs are integrated in brainstem areas, which control cardiorespiratory responses. However, the molecular mechanisms of this functional acclimatization are unknown. We investigated when and where the inducible HIF-1alpha subunit is expressed in the rat brainstem in vivo, under physiological hypoxia. The regional localization of HIF-1alpha mRNA and protein was determined by in situ hybridization and immunocytochemistry in adult male rats exposed to moderate hypoxia (10% O2) for 1-6 h. HIF-1alpha protein was found in cell types identified by immunocytochemistry as catecholaminergic neurons. Hypoxia induced HIF-1alpha mRNA and protein in only some parts of the brainstem located dorsomedially and ventrolaterally, which are those involved in the cardiorespiratory control. No labelling was detected under normoxia. The protein was detected in glia and neurons after 1 and 6 h of hypoxia, respectively. A subset of A2C2 and A1C1 catecholaminergic neurons colocalized tyrosine hydroxylase and HIF-1alpha proteins under hypoxia, but no HIF-1alpha was detected in more rostral catecholaminergic areas. In contrast to cardiorespiratory areas, HIF-1alpha protein was already present under normoxia in glial cells of brainstem tracts but was not overexpressed under hypoxia, although HIF-1alpha mRNA was up-regulated. In conclusion, there appear to be two regulatory mechanisms for HIF-1alpha expression in the brainstem: hypoxic induction of HIF-1alpha protein in cardiorespiratory-related areas and constitutive protein expression unaffected by hypoxia in brainstem tracts.

Animals↗
PubMed2000

Rectal cancer and occupational risk factors: a hypothesis-generating, exposure-based case-control study.

In 1979, a hypothesis-generating, population-based case-control study was undertaken in Montreal, Canada, to explore the association between occupational exposure to 294 substances, 130 occupations and industries, and various cancers. Interviews were carried out with 3, 630 histologically confirmed cancer cases, of whom 257 had rectal cancer, and with 533 population controls, to obtain detailed job history and data on potential confounders. The job history of each subject was evaluated by a team of chemists and hygienists and translated into occupational exposures. Logistic regression analyses adjusted for age, education, cigarette smoking, beer consumption, body mass index, and respondent status were performed using population controls and cancer controls, e.g., 1,295 subjects with cancers at sites other than the rectum, lung, colon, rectosigmoid junction, small intestine, and peritoneum. We present here the results based on cancer controls. The following substances showed some association with rectal cancer: rubber dust, rubber pyrolysis products, cotton dust, wool fibers, rayon fibers, a group of solvents (carbon tetrachloride, methylene chloride, trichloroethylene, acetone, aliphatic ketones, aliphatic esters, toluene, styrene), polychloroprene, glass fibers, formaldehyde, extenders, and ionizing radiation. The independent effect of many of these substances could not be disentangled as many were highly correlated with each other.

Adult↗
PubMed2000

[Metacarpophalangeal prosthesis modeling. Comparison of stress factors in a normal and a prosthetic metacarpophalangeal joint using finite element analysis].

INTRODUCTION: Prosthetic replacement of the metacarpophalangeal joints of long fingers is a problematical technique for the surgeon. The aim of the present study was to examine and compare, by means of finite element analysis, stress distribution in a normal metacarpophalangeal joint and to compare this with the findings in a similar joint with a prosthesis in order to better determine the risk of aseptic loosening, and also to examine possible solutions to limit these risks. METHOD: Finite element modelling was carried out using Abaqus software. Various criteria were taken into account including anatomical data, stress distribution, mechanical characteristics of the materials used, and different positions of the phalanx. RESULTS: A comparison of the results showed two significant stress distribution factors, i.e., a reduction of normal stress in the cortical bone of the finger fitted with a prosthesis; and the appearance of a flexion moment which completely modified the stress distribution throughout the metacarpal and therefore also in the opposite phalanx. DISCUSSION: To reduce the risk of aseptic loosening, two solutions were proposed: a) to reduce Young's module. The problem which arises, as in the case of total hip prosthesis, is that of finding a material with a Young's module which is closer to that of cortical bone, and which at the same time has a high elastic limit and breakage point and good biocompatibility; b) to reduce the inertia of the prosthesis, which seems the more likely of the two propositions, as it is based on the results of the modelling. The inertia of the prosthesis on stress distribution can be reduced by modifying two parameters, namely by producing a hollow section and shortening the structure of the prosthesis.

Elasticity↗
PubMed2000

Spatial and temporal distribution of chloroplast DNA polymorphism in a tropical tree species.

The level and the spatial organization of chloroplast DNA polymorphism were investigated in Dicorynia guianensis Hamshoff (Caesalpiniaceae) at different spatial and temporal scales. D. guianensis is a canopy tree of the rain forest that is distributed throughout the Guiana plateau in small aggregates. Twelve different haplotypes were identified using restriction analysis of polymerase chain reaction (PCR) amplified fragments of the chloroplast genome. When populations from different areas of French Guiana were compared, a clear geographical pattern of haplotype frequencies was identified along the Atlantic coast. This pattern is most likely the result of the restriction-expansion dynamics of the tropical forest during the Quaternary. At the local level, D. guianensis was characterized by a high level of within population diversity. Maintenance of within population diversity results from the dynamics of the aggregates; stochastic demography associated with the turnover of aggregates generates genetic differentiation among them. At the stand level, a strong spatial aggregation of haplotypes persisted from the adult to the seedling cohort indicating limited seed flow. There was also a strong difference in levels of diversity between the cohorts which suggested that recruitment over several years is needed in order to maintain genetic diversity during regeneration.

DNA, Chloroplast↗
PubMed2000

Dysfunctional regulation of alphaCaMKII and syntaxin 1B transcription after induction of LTP in the aged rat.

Syntaxin 1B and alphaCaMKII are two genes that are upregulated after the induction of LTP and appear to underlie different mechanisms of synaptic plasticity. alphaCaMKII is directly implicated in strengthening the synapses that have been modified, whereas syntaxin 1B has been implicated in a mechanism for the propagation of synaptic plasticity within neural circuits. In these experiments we have investigated whether the regulation of these genes is altered after the induction of LTP in aged rats. We found, three hours after the induction of LTP in the dentate gyrus, that aged rats could be subgrouped into those in which LTP was maintained and those in which LTP had decayed back to basal levels. Both genes were upregulated in young adult rats, whereas there was a differential pattern of LTP-induced expression in the aged rats. Dendritic alphaCaMKII was upregulated in aged rats only when LTP was maintained. In contrast, regulation of syntaxin 1B and alphaCaMKII was absent in the granule cell bodies of the aged rats regardless of whether LTP was maintained or not. These results suggest that molecular mechanisms implicated in two aspects of hippocampal synaptic plasticity malfunction during normal ageing and therefore may have some contributory role in the decline in memory function routinely observed in ageing.

Aging↗
PubMed2000

O2-sensing after carotid chemodenervation: hypoxic ventilatory responsiveness and upregulation of tyrosine hydroxylase mRNA in brainstem catecholaminergic cells.

Ventilatory responses to acute and long-term hypoxia are classically triggered by carotid chemoreceptors. The chemosensory inputs are carried within the carotid sinus nerve to the nucleus tractus solitarius and the brainstem respiratory centres. To investigate whether hypoxia acts directly on brainstem neurons or secondarily via carotid body inputs, we tested the ventilatory responses to acute and long-term hypoxia in rats with bilaterally transected carotid sinus nerves and in sham-operated rats. Because brainstem catecholaminergic neurons are part of the chemoreflex pathway, the ventilatory response to hypoxia was studied in association with the expression of tyrosine hydroxylase (TH). TH mRNA levels were assessed in the brainstem by in situ hybridization and hypoxic ventilatory responses were measured in vivo by plethysmography. After long-term hypoxia, TH mRNA levels in the nucleus tractus solitarius and ventrolateral medulla increased similarly in chemodenervated and sham-operated rats. Ventilatory acclimatization to hypoxia developed in chemodenervated rats, but to a lesser extent than in sham-operated rats. Ventilatory response to acute hypoxia, which was initially low in chemodenervated rats, was fully restored within 21 days in long-term hypoxic rats, as well as in normoxic animals which do not overexpress TH. Therefore, activation of brainstem catecholaminergic neurons and ventilatory adjustments to hypoxia occurred independently of carotid chemosensory inputs. O2-sensing mechanisms unmasked by carotid chemodenervation triggered two ventilatory adjustments: (i) a partial acclimatization to long-term hypoxia associated with TH upregulation; (ii) a complete restoration of acute hypoxic responsivity independent of TH upregulation.

Adaptation, Physiological↗
PubMed2000

Sensitive and quantitative co-detection of two mRNA species by double radioactive in situ hybridization.

A better understanding of biological phenomena involving modulations of gene expression requires quantitative analysis of the expression of several genes in the same structure. For this purpose, we have developed a novel in situ hybridization method to quantify two different mRNA species in the same tissue section simultaneously. Two probes labeled with radioelements of significantly different energies ((3)H and (33)P or (35)S) were used to detect the mRNA species. Radioactive images corresponding to the detected mRNA species were acquired with a Micro Imager, a real-time, high-resolution digital autoradiography system. An algorithm was used to process the data such that the initial radioactive image acquired was filtered into two subimages, each representative of the hybridization result specific to one probe. This novel method allows local discrimination and quantification of the respective contributions of each label to each pixel and can therefore be used for quantitative analysis of two mRNAs with a resolution of 15-20 microm.

Algorithms↗
PubMed2000

How organizational factors contribute to innovations in service delivery.

Twelve staff members from three community centers providing services to people with mental retardation were interviewed about the implementation of a new approach to service delivery that utilized Essential Lifestyle Planning. Findings indicate that although the innovation proposed and the technical assistance provided were quite similar, the outcomes varied greatly across the three sites. By highlighting the importance of organizational factors, such as timing and agency supports, these findings provide direction for future training and technical assistance activities of those who promote change in service-delivery philosophy and methods.

Adult↗
PubMed2000

[Retinal complications of cataract surgery].

Main retinal complications of cataract extraction are retinal detachment and cystoid macular edema. The incidence of retinal detachment after ex traction is 1 %, and may increase after Nd: YAG laser capsulotomy to 4 %. Cystoid macular edema in aphakic or pseudophakic patients is unusually transient, with a decrease of visual acuity in about 3 % of cases; a long lasting cystoid macular edema with prolonged visual deficiency is described in only 1 % of cases. The incidence of photic macular injuries is estimated at between 7 and 28 % of cases; most photoretinal injuries are asymptomatic or minimally symptomatic because of their extrafoveolar location. Finally, the visual prognosis after cataract surgery is poor in diabetic patients, because of the frequency of cystoid macular edema and progression of diabetic retinopathy.

Aphakia↗
PubMed1999

A human tyrosine hydroxylase isoform associated with progressive supranuclear palsy shows altered enzymatic activity.

A novel human tyrosine hydroxylase (HTH) messenger RNA subgroup generated by alternative splicing and characterized by the absence of the third exon was recently identified. The corresponding putative protein lacks 74 amino acids including Ser31 and Ser40, two major phosphorylation sites implicated in the regulation of HTH activity. These mRNA species are detected in adrenal medulla and are overexpressed in patients suffering from progressive supranuclear palsy, a neurodegenerative disease mostly affecting catecholaminergic neurons of the basal ganglia. In the present work, an HTH protein isoform lacking exon 3 was identified in human adrenal medulla. For this purpose, an antibody was raised against the HTH exon 3. The effect of the removal of exon 3 on the enzymatic activity of HTH was studied in vitro by comparing a purified recombinant fusion protein without exon 3 (glutathione S-transferase (GST)-HTHDelta3) to the equivalent protein containing exon 3 (GST-HTH3). In initial velocity conditions, GST-HTHDelta3 has 30% of the maximal velocity of GST-HTH3. Moreover, the skipping of exon 3 results in the absence of activation of GST-HTH by heparin and increases by 10-fold the retroinhibition constant for dopamine, demonstrating the involvement of exon 3 in the regulation of HTH enzymatic activity. The identification of a variably expressed HTH isoform that lacks an exon implicated in activity regulation supports the view that HTH alternative splicing contributes to the functional diversity within the catecholaminergic system and may be implicated in some neurological diseases.

Adrenal Glands↗
PubMed1999

A single adenovirus vector mediates doxycycline-controlled expression of tyrosine hydroxylase in brain grafts of human neural progenitors.

Ex vivo gene transfer is emerging as a promising therapeutic approach to human neurodegenerative diseases. By combining efficient methodologies for cell amplification and gene delivery, large numbers of cells can be generated with the capacity to synthesize therapeutic molecules. These cells can then be transplanted into the degenerating central nervous system (CNS). Applying this approach to human diseases will require the development of suitable cellular vehicles, as well as safe gene delivery systems capable of tightly controlled transgene expression. For such brain repair technologies, human neural progenitors may be extremely valuable, because of their human CNS origin and developmental potential. We have used these cells to develop a system for the regulated expression of a gene of therapeutic potential. We report the construction of a single adenovirus encoding human tyrosine hydroxylase 1 (hTH-1) under the negative control of the tetracycline-based gene regulatory system. Human neural progenitors infected with this vector produced large amounts of hTH-1. Most importantly, doxycycline allowed a reversible switch of transgene transcription both in vitro and in vivo. This system may be applied to the development of therapies for human neurodegenerative diseases.

Adenoviridae↗
PubMed1996

Plasticity of tyrosine hydroxylase gene expression in the rat nucleus tractus solitarius after ventilatory acclimatization to hypoxia.

The aim of this study was to define the influence of long-term hypoxia on gene expression of tyrosine hydroxylase (TH) in the rat nucleus tractus solitarius (NTS). Animals were exposed to normobaric hypoxia (10% O2 in nitrogen) for 2 weeks. At this time, the hypoxia-induced hyperventilation reached a plateau, indicating ventilatory acclimatization. In horizontal brainstem sections, hypoxia-induced changes in TH protein and TH mRNA were assessed by immunocytochemistry and in-situ hybridization, respectively. Long-term hypoxia increased TH mRNA levels seen as both an increase in the number of grains per cell and an extension of the labeled area. The highest degree of labeling was found selectively located in caudal NTS. Hypoxia also enhanced TH immunoreactivity in the caudal NTS but this labeling extended more rostrally than that of TH mRNA. The data suggest that there is an hypoxia-induced plasticity of gene expression at the gene level in the NTS, which is associated with ventilatory acclimatization. The hypoxia model described in this study may serve as a framework for future regulatory studies.

Animals↗