PubMed Health⌕ Search

Biomedical subjects

J Michaud

Publications and source records attributed to J Michaud.

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

Stroke-like episodes in autosomal recessive cytochrome oxidase deficiency.

Stroke-like episodes, defined as periods of acute localized neurological dysfunction during which brain imagery suggests cerebral ischemia but vascular anatomy is normal, occurred in 3 patients with autosomal recessive Saguenay-Lac St-Jean (SLSJ) cytochrome oxidase (COX) deficiency. The patients developed focal neurological deterioration and frontal hypodensities on cerebral computerized tomography (CT). Arteriography, performed in 1 patient during an acute episode, showed normal vascular anatomy. Nevertheless, capillary shunting was evident both in regions that appeared abnormal on the initial cerebral CT study and in regions that appeared normal but subsequently developed Leigh disease. Stroke-like episodes did not exacerbate systemic acidosis, and acidotic decompensations occurred independently of stroke-like episodes. In conclusion, stroke-like episodes occur in autosomal recessively inherited congenital lactic acidoses as well as in those caused by mitochondrial DNA mutations. In some cases, acute localized neurovascular changes occur in regions that subsequently develop Leigh disease.

Brain↗
PubMed1999

[Is it necessary to legislate euthanasia?].

There are no specific articles on the end of life in French law. Thus an act of euthanasia can be qualified as murder, murder with premeditation or non-assistance to a person in danger. Recent events and debates have raised the question of enacting new legislation to deal with this problem. Two contrary positions could be considered: either create a special offence or explicitly authorize acts of euthanasia. There are major objections to both these propositions. The first one would require taking account of various situations, --unbearable suffering, loss of dignity, and precise requests,--that would be impossible to specify in legislative terms. The second proposition would be open to the same objection; it would also derogate from the major principle of respect for the life of persons and thus risk setting a precedent that could be used in other circumstances to evade this principle. Finally, if a law were enacted to this effect, it would constitute a threat for the development of palliative care.

Euthanasia↗
PubMed1998

Analysis of the genetic pathway leading to formation of ectopic apical ectodermal ridges in mouse Engrailed-1 mutant limbs.

The apical ectodermal ridge (AER), a rim of thickened ectodermal cells at the interface between the dorsal and ventral domains of the limb bud, is required for limb outgrowth and patterning. We have previously shown that the limbs of En1 mutant mice display dorsal-ventral and proximal-distal abnormalities, the latter being reflected in the appearance of a broadened AER and formation of ectopic ventral digits. A detailed genetic analysis of wild-type, En1 and Wnt7a mutant limb buds during AER development has delineated a role for En1 in normal AER formation. Our studies support previous suggestions that AER maturation involves the compression of an early broad ventral domain of limb ectoderm into a narrow rim at the tip and further show that En1 plays a critical role in the compaction phase. Loss of En1 leads to a delay in the distal shift and stratification of cells in the ventral half of the AER. At later stages, this often leads to development of a secondary ventral AER, which can promote formation of an ectopic digit. The second AER forms at the juxtaposition of the ventral border of the broadened mutant AER and the distal border of an ectopic Lmx1b expression domain. Analysis of En1/Wnt7a double mutants demonstrates that the dorsalizing gene Wnt7a is required for the formation of the ectopic AERs in En1 mutants and for ectopic expression of Lmx1b in the ventral mesenchyme. We suggest a model whereby, in En1 mutants, ectopic ventral Wnt7a and/or Lmx1b expression leads to the transformation of ventral cells in the broadened AER to a more dorsal phenotype. This leads to induction of a second zone of compaction ventrally, which in some cases goes on to form an autonomous secondary AER.

Animals↗
PubMed1998

[The notion of medical responsibility. Current evolution].

Medical responsibility can be evaluated from a penal or a civil standpoint. In the first case it is referable to common law or other specific provisions, notably those included in the laws voted on July 29 1994. In the second case it is viewed within the contractual relationship, since the physician's obligation is theoretically one of means and not of results. The circumstances under which medical responsibility is questioned have evolved under the influence of three factors affecting the medical art: it is now characterized by techniques that have often become scientific; team practice; an increase in patients' demands. Nonetheless it is most important to maintain a genuine relationship of trust between physician and patient.

Ethics, Medical↗
PubMed1997

Expression of the mouse Gli and Ptc genes is adjacent to embryonic sources of hedgehog signals suggesting a conservation of pathways between flies and mice.

The three mouse Gli genes are putative transcription factors which are the homologs of cubitus interruptus (ci) in Drosophila. Along with the gene patched (Ptc), ci has been implicated in the hedgehog (Hh) signal transduction pathway. To assess the role of Gli in embryogenesis, we compared its expression with that of Ptc and Hh family members in mouse. We found that Gli and Ptc are expressed in similar domains in diverse regions of the developing mouse embryo and these regions are adjacent to Hh signals. We also show that Gli is expressed ectopically along with Ptc and Shh in Strong's luxoid mutant mice. These results are consistent with conservation of the Hh signal transduction pathway in mice with Gli potentially mediating Hh signaling in multiple regions of the developing embryo.

Animals↗
PubMed1997

Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases.

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.

Animals↗
PubMed1997

Specific and redundant functions of Gli2 and Gli3 zinc finger genes in skeletal patterning and development.

The correct patterning of vertebrate skeletal elements is controlled by inductive interactions. Two vertebrate hedgehog proteins, Sonic hedgehog and Indian hedgehog, have been implicated in skeletal development. During somite differentiation and limb development, Sonic hedgehog functions as an inductive signal from the notochord, floor plate and zone of polarizing activity. Later in skeletogenesis, Indian hedgehog functions as a regulator of chondrogenesis during endochondral ossification. The vertebrate Gli zinc finger proteins are putative transcription factors that respond to Hedgehog signaling. In Drosophila, the Gli homolog cubitus interruptus is required for the activation of hedgehog targets and also functions as a repressor of hedgehog expression. We show here that Gli2 mutant mice exhibit severe skeletal abnormalities including cleft palate, tooth defects, absence of vertebral body and intervertebral discs, and shortened limbs and sternum. Interestingly, Gli2 and Gli3 (C.-c. Hui and A. L. Joyner (1993). Nature Genet. 3, 241-246) mutant mice exhibit different subsets of skeletal defects indicating that they implement specific functions in the development of the neural crest, somite and lateral plate mesoderm derivatives. Although Gli2 and Gli3 are not functionally equivalent, double mutant analysis indicates that, in addition to their specific roles, they also serve redundant functions during skeletal development. The role of Gli2 and Gli3 in Hedgehog signaling during skeletal development is discussed.

Animals↗
PubMed1997

Effects of basic fibroblast growth factor on the differentiation, growth, and viability of a new human medulloblastoma cell line (UM-MB1).

We presently report the effects of human recombinant basic fibroblast growth factor (bFGF) on a newly established medulloblastoma cell line, UM-MB1. This predominantly adherent cell line has a mean doubling time of 39.3 hours and was found, by karyotypic analysis, to be near triploid. UM-MB1 consists of undifferentiated cells expressing markers of neuronal lineage such as the three neurofilament subunits as well as neuron-specific enolase, synaptophysin, and microtubule-associated proteins 1 and 5. In contrast, no immunoreactivity for glial fibrillary acidic protein was evident. When exposed to nanomolar amounts of bFGF, UM-MB1 cells began to extend neurite-like processes with arborizations and growth-cone-like structures. In addition, UM-MB1 cells treated with bFGF exhibited ultrastructural alterations that reflect their enhanced differentiation as well as the increased expression of at least one of the neurofilament subunits as evidenced both immunocytochemically and on Western blots. Furthermore, bFGF significantly decreased UM-MB1 cell growth as well as induced their death. UM-MB1 cells treated with bFGF for several days displayed DNA cleavage, nuclear shrinkage, and chromatin condensation while retaining their cytoplasmic and mitochondrial membrane integrity, all early indices of apoptosis. After this, cell death was evident with the concomitant appearance of the classical apoptotic bodies. By flow cytometry, bFGF was found to increase the proportion of cells in G1 before inducing their death by apoptosis. In conclusion, UM-MB1 cells can, when appropriately stimulated, be induced to differentiate along their neuronal lineage pathway. Their differentiation induced by bFGF, although incomplete, appears to promote or inhibit the expression of apoptotic effectors or suppressors in these cells, respectively, so to induce their death by an apoptotic-like mechanism.

Antigens, Differentiation↗
PubMed1996

The mouse Engrailed-1 gene and ventral limb patterning.

During vertebrate limb development, positional information must be specified along three distinct axes. Although much progress has been made in our understanding of the molecular interactions involved in anterior-posterior and proximal-distal limb patterning, less is known about dorsal-ventral patterning. The genes Wnt-7a and Lmx-1, which are expressed in dorsal limb ectoderm and mesoderm, respectively, are thought to be important regulators of dorsal limb differentiation. Whether a complementary set of molecules controls ventral limb development has not been clear. Here we report that Engrailed-1, a homeodomain-containing transcription factor expressed in embryonic ventral limb ectoderm, is essential for ventral limb patterning. Loss of Engrailed-1 function in mice results in dorsal transformations of ventral paw structures, and in subtle alterations along the proximal-distal limb axis. Engrailed-1 seems to act in part by repressing dorsal differentiation induced by Wnt-7a, and is essential for proper formation of the apical ectodermal ridge.

Animals↗
PubMed1996

Dynamic expression of cell-surface antigens probed with Candida albicans-specific monoclonal antibodies.

IgG hybridomas were produced with preferentially reacted with cell-surface antigens of either yeast cells or hyphae of Candida albicans. Four mAbs were used in an immunostaining procedure to follow the expression dynamics of these antigens in media supplemented with glucose or galactose. Yeast cell growth was analysed during the lag phase, the early- and late-exponential phases and the stationary phase, and mycelium formation was analysed between 0.5 and 24 h induction at 37 degrees C. It appears that yeast cell-surface antigens 5C11 and 2E11 are expressed throughout all phases of yeast cell growth as well as on young hyphae after up to 1 h induction. Longer hyphae only faintly react with these two mAbs as they switch to hyphal cell-surface antigens 2G8 and 4E1 after 3 h induction. The reactivity to mAbs 2G8 and 4E1 was induced after a 3 h temperature shift and was confined to the terminal third of growing mycelia. Growth and hyphae induction in galactose prolonged the reactivity of young hyphae with the two anti-yeast-cell mAbs, whereas the expression of surface antigens 2G8 and 2E11 appeared delayed and desynchronized on hyphae. Whereas a similar reactivity was found with ten ATCC strains of C. albicans, four clinical isolates had a unique pattern of reactivity. Immunoblot analyses of DTT extracts of cell-surface constituents indicated that the antigens were proteinaceous in nature and showed that yeast-cell antigens 5C11 and 2E11 are detected in four bands between 68 and 104 kDa, whereas mycelial antigens 4E1 and 2G8 are detected in 117 kDa and 104 kDa bands found in mycelial but not in yeast-cell extracts. Present data support the concept of a dynamic balance in the expression of phase-specific antigens in C. albicans.

Antibodies, Fungal↗
PubMed1995

Prenatal diagnosis of retinal nonattachment in the Walker-Warburg syndrome.

We report on the prenatal ultrasonographic diagnosis of Walker-Warburg syndrome based on cerebral and ocular findings. The ultrasound study done at 37 weeks gestation documented hydrocephalus and retinal nonattachment consistent with this syndrome. The ability to detect retinal nonattachment prenatally may have implications for the prenatal diagnosis of other conditions which have early retinal nonattachment as one of their findings. However, it is uncertain how early in pregnancy this defect can be detected.

Abnormalities, Multiple↗
PubMed1995

New autosomal recessive form of amelia.

Amelia is a rare, usually sporadic malformation. We report on a family in which three fetuses had amelia of the upper limbs and variable deficiency of the lower limbs. The fetuses also had minor facial anomalies. Recurrence of the condition in sibs of both sexes suggests autosomal recessive inheritance. Recurrent amelia has been documented in only a few families most often associated with a different set of malformations. Possibly, mutations in more than one gene with different modes of transmission can lead to this severe limb deficiency. We speculate that the mutation found in our cases interferes with formation of the apical ectodermal ridge in the upper limbs and results in its premature degeneration in the lower limbs.

Abnormalities, Multiple↗
PubMed1995

Neuronal expression of human immunodeficiency virus type 1 env proteins in transgenic mice: distribution in the central nervous system and pathological alterations.

It is now well documented that human immunodeficiency virus type 1 (HIV-1) induces encephalopathy in patients with AIDS. In vitro studies have implicated the envelope protein (gp120) as a factor which causes neuronal death. To better evaluate the role and elucidate the mechanisms of gp120 neurotoxicity, we have developed transgenic mice carrying a segment of the HIV-1 genome that expresses the viral gp160 protein under the control of the human neurofilament light gene promoter. In two separate lines of transgenic mice, the Env protein was found to be expressed in several nuclei of the brain stem and in the anterior horns of the spinal cord. The two lines showed identical patterns of Env expression. Neuropathological evaluation revealed numerous abnormal dendritic swellings in the immunostained motor neuron structures. Large and numerous neuritic swellings were also prominent in the nucleus gracilis and in the gracilis and cuneate fascicles. In addition, reactive astrocytosis was observed in several immunoreactive areas of the central nervous system. These transgenic mice offer a unique model to further investigate the role of HIV-1 Env protein in neuronal toxicity and to help elucidate the mechanisms that are involved.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Marketing hospital wellness products to service companies.

The authors examine service firm employee attitudes towards wellness programs among twenty-three service companies in three states. Program components that were considered to be most desirable by service industry workers are identified in a regression model. The results indicate that hospital administrators need to adopt a marketing approach during the design phase of employee wellness programs.

Attitude to Health↗