[Work-related musculoskeletal disorders of the upper limbs: Presentation of the "Health Passport"].
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Accidents, Occupational↗
Biomedical subjects
D Sassoon
Publications and source records attributed to D Sassoon.
[Musculoskeletal disorders of the upper extremity associated with work: from presentation to work maintenance].
The so called Musculo-Squeletal-Disorders in the upper extremity are frequent and are responsible for a significant cost. The increase in registered work-related affections has been quite impressive in the past few years. The type of social undertaking is determinant on the evolution and final outcome of the pathology. Our proposal for a "Passport to work continuation" follows two goals: facilitate and enhance the relations between medical and social workers concerned by the patient's course reduce the time off-work, improve prevention of work related pathologies, avoid dismissal for inaptitude, start earlier a vocational training, a rehabilitation or an adaptation of the work station.
Arm↗
[Eight days of hand emergencies. Report of the audit carried out at the FESUM centers from June 3 to June 9, 2002].
All the FESUM centers in France, Belgium and Switzerland were invited to participate in this prospective audit, during 1 week in June 2002. In these FESUM centers, the patients are operated by senior hand surgeons or trainees graduated with a microsurgical and a hand surgery University degrees. All acute hand disorders, requiring surgery or not, were to be included. For every case, a standardized form was to be filled. This form included 22 fields concerning the specificities of the patient, the circumstances of the accident, the lesions and initial treatment up to exit of the patient out of the Hand Center. Out of the 43 French centers, 38 (90%) participated in this study, but only 30% in the other French speaking countries. A total of 2360 forms were completed and analyzed, representing a mean of 8 forms per day center (6-147). The population was predominantly active men with a mean age of 31. Manual workers represented 41%, scholars 33%. Most of them came to the Hand Center with a non-specilized vehicle (86%). Emergency medical transportation was required in 130 cases (5.8%). A majority of the patients were treated on an outdoor basis. A 1-day admission concerned 29% of the patients, and 4.6% have been admitted on an indoor basis during several days. Work accident represented 28% of all the cases, while the majority was daily living (62%) or sport (15%) accidents. Closed trauma represented 50% of the cases. Amongst open trauma (974 cases), 862 were simple skin lacerations, 156 skin loss, 140 extensor tendon lacerations, 70 flexor tendon lacerations. A preliminary wound exploration had been performed in a non-specialized center in 124 cases (12%). Complete amputation of some part was observed in 33 cases. In 32%, the initial severity of the lesion led to expect some degree of definitive consequences. Some kind of anesthesia was required in 43% of the cases (local in 41%, troncular in 19%, plexical in 28% and general in 9%). A surgical procedure was performed in 45% of the patients. Microsurgery was necessary in 15%, six of which were replantations. The period between presentation to the Hand Center and treatment was less than 1 day in 95% of the cases. Time of treatment was considered to be delayed in 113 cases (5%). Following this audit, it is considered that the FESUM centers make provision for the care of 120,000 cases per year, 54,000 of which needing a surgical procedure. This may be a small part of the total load of emergency hand surgery throughout the country (generally estimated over 1.4 million), but compares quite favorably with other European studies. We believe that improvement relies essentially on a better orientation of the patients whether they need a simple skill or specialist skill treatment. An information leaflet about orientation of hand trauma has been distributed to non-specialized emergency centers. Hand surgery training must be reevaluated inside the universitary system to avoid a dramatic lack of hand surgeons within a few years. A new audit will be presented next year.
Adolescent↗
Visualization and functional characterization of the developing murine cardiac conduction system.
The cardiac conduction system is a complex network of cells that together orchestrate the rhythmic and coordinated depolarization of the heart. The molecular mechanisms regulating the specification and patterning of cells that form this conductive network are largely unknown. Studies in avian models have suggested that components of the cardiac conduction system arise from progressive recruitment of cardiomyogenic progenitors, potentially influenced by inductive effects from the neighboring coronary vasculature. However, relatively little is known about the process of conduction system development in mammalian species, especially in the mouse, where even the histological identification of the conductive network remains problematic. We have identified a line of transgenic mice where lacZ reporter gene expression delineates the developing and mature murine cardiac conduction system, extending proximally from the sinoatrial node to the distal Purkinje fibers. Optical mapping of cardiac electrical activity using a voltage-sensitive dye confirms that cells identified by the lacZ reporter gene are indeed components of the specialized conduction system. Analysis of lacZ expression during sequential stages of cardiogenesis provides a detailed view of the maturation of the conductive network and demonstrates that patterning occurs surprisingly early in embryogenesis. Moreover, optical mapping studies of embryonic hearts demonstrate that a murine His-Purkinje system is functioning well before septation has completed. Thus, these studies describe a novel marker of the murine cardiac conduction system that identifies this specialized network of cells throughout cardiac development. Analysis of lacZ expression and optical mapping data highlight important differences between murine and avian conduction system development. Finally, this line of transgenic mice provides a novel tool for exploring the molecular circuitry controlling mammalian conduction system development and should be invaluable in studies of developmental mutants with potential structural or functional conduction system defects.
Animals↗
The emergence of molecular gynecology: homeobox and Wnt genes in the female reproductive tract.
Reproductive tissues respond to steroid hormones and thus are particularly vulnerable to the effects of exogenous steroid 'mimic' compounds (endocrine disrupters). One such endocrine disrupter, diethylstilbestrol (DES), is linked to gynecological cancers and changes in uterine structure that reduce or completely abrogate reproductive competence. Until recently, little was known about the identity of target genes and signaling pathways involved in pathologies linked to endocrine disrupters such as DES. We outline genetic, cellular and molecular roles for patterning genes, with emphasis on homeobox and Wnt genes. There is evidence that changes in the expression of Wnt and homeogenes underlie many of the defects induced by DES. Data obtained from murine systems will likely apply to a broad spectrum of gynecological pathologies involving abnormal cell behaviors ranging from fibroids to malignant tumors. Knowledge garnered from modern molecular genetics should lead to progress in the emerging field of molecular gynecology.
Animals↗
Wnt genes and endocrine disruption of the female reproductive tract: a genetic approach.
Reproductive tract development and function is regulated by circulating steroid hormones. In the mammalian female reproductive tract, estrogenic compounds direct many aspects of cytodifferentiation including uterine gland formation, smooth muscle morphology, and epithelial differentiation. While it is clear that these hormones act through their cognate nuclear receptors, it is less clear what signaling events follow hormonal stimulation that govern cytodifferentiation. Recent advances in molecular embryology and cancer cell biology have identified the Wnt family of secreted signaling molecules. Discussed here are recent advances that point to a definitive role during uterine development and adult function for one member of the Wnt gene family, Wnt-7a. In addition, recent data is reviewed that implicates Wnt-7a deregulation in response to pre-natal exposure to the synthetic estrogenic compound, DES. These advances point to an important role for the Wnt gene family in various reproductive tract pathologies including cancer.
Animals↗
Msx2 is a transcriptional regulator in the BMP4-mediated programmed cell death pathway.
Homeobox-containing genes play an important role in patterning processes that occur during embryogenesis. Programmed cell death is a key process during pattern formation. The mechanisms by which programmed cell death is spatially regulated are not well characterized. Msx1 and Msx2 are two closely related homeobox-containing genes that are expressed at sites where cellular proliferation and programmed cell death occur, including the developing limb and the cephalic neural crest. Tissue interactions are necessary for the maintenance of Msx1 and Msx2 expression and programmed cell death. It has been demonstrated that BMP4 can regulate cell death at these same sites as well as induce Msx expression. These observations lead to the hypothesis that Msx2 is a key regulator of cell death in the BMP-mediated pathway. Embryonic stem cell lines will undergo processes typical of early embryogenesis upon aggregation and have recently been shown to provide a model system for programmed cell death. In contrast to ES cells, we see that P19 cells do not undergo pronounced cell death upon aggregation; however, constitutive ectopic Msx2 expression in P19 cells results in a marked increase in apoptosis induced upon aggregation but has no effect when cells are grown as a monolayer. If aggregates are allowed to interact with a substrate, the process of programmed cell death is completely inhibited. Addition of BMP4 to aggregated P19 cells also results in cell death; however, BMP4 does not increase levels of cell death in Msx2-expressing cells. Addition of BMP4 to P19 cells results in an induction of Msx2 transcription consistent with its proposed role in cell death in the embryo. Our data support a model by which BMP4 induces programmed cell death via an Msx2-mediated pathway and provide direct functional evidence that Msx2 expression is a regulator of this process.
Apoptosis↗
Pw1, a novel zinc finger gene implicated in the myogenic and neuronal lineages.
The cellular and molecular processes leading to the establishment of the skeletal muscle lineage in the vertebrate are not well understood. The MyoD-related family of myogenic regulatory factors (MRFs) are expressed during somitogenesis although cells with myogenic capacity are present prior to gastrulation. We propose that regulatory genes exist that guide the skeletal muscle lineage during early development. In an effort to identify these regulatory genes, we performed a differential screening to isolate transcripts that are present in myogenic cells and in the embryo prior to MRF expression but absent in nonmyogenic fibroblasts. We report here the identification of Pw1. The Pw1 transcript is approximately 8.5 kb long and encodes a large protein containing 12 widespread C2H2 zinc fingers and 3 motifs containing periodic prolines and acidic residues. Consistent with the possibility that Pw1 is a transcription factor, we observe nuclear localization of the protein. Pw1 is strongly expressed upon gastrulation and subsequently becomes restricted to skeletal muscle and subregions of the central nervous system. Pw1 is initially expressed in all mesodermal cells early in development; however, its maintained expression in adult differentiated muscle suggests a specific role in the skeletal muscle lineage. Pw1 expression is cell cycle specific with levels highest during late M-phase. The gene is intronless which may facilitate transcription during cell division. At present, the precise function of Pw1 is not understood; however, we note that Pw1 maps to the proximal region of chromosome 7 near the axial segmentation mutant pudgy which shows severe perturbation of axial skeletal and muscle structures.
Animals↗
Notch4/int-3, a mammary proto-oncogene, is an endothelial cell-specific mammalian Notch gene.
The int-3 oncogene was identified as a frequent target in Mouse Mammary Tumor Virus (MMTV)-induced mammary carcinomas and encodes the intracellular domain of a novel mouse Notch gene. To investigate the role of the int-3 proto-oncogene in mouse development and carcinogenesis, we isolated cDNA clones corresponding to the entire coding potential of the int-3 proto-oncogene. We propose to name this gene Notch4 and reserve the int-3 nomenclature for references to the oncogenic form. The deduced amino acid sequence of Notch4 contains conserved motifs found in Notch proteins; however Notch4 has fewer epidermal growth factor (EGF)-like repeats and a shorter intracellular domain than other mouse Notch homologues. Comparison of the coding potential of the int-3 gene to that of Notch4 suggests that loss of the extracellular domain of Notch4 leads to constitutive activation of this murine Notch protein. In situ hybridization revealed that Notch4 transcripts are primarily restricted to endothelial cells in embryonic and adult life. Truncated Notch4 transcripts were detected in post-meiotic male germ cells. The distinct Notch4 protein features and its restricted expression pattern suggests a specific role for Notch4 during development of vertebrate endothelium.
Amino Acid Sequence↗
MSX1 inhibits myoD expression in fibroblast x 10T1/2 cell hybrids.
Transfer of human chromosome 11, which contains the myoD locus, from primary fibroblasts into 10T1/2 cells results in activation of myoD. In contrast, hybrids that retain human chromosome 11 and additional human chromosomes fail to activate myoD. We show that human chromosome 4 inhibits myoD activation. myoD enhancer/promoter reporter constructs show that repression is at the transcriptional level. Chromosome fragment-containing hybrids localize the repressing activity to the region of 4p that contains the homeobox gene MSX1. MSX1 is expressed in primary human fibroblasts and in 10T1/2 cells containing human chromosome 4, while parental 10T1/2 cells do not express Msx1. Forced expression of Msx1 represses myoD enhancer activity. Msx1 protein binds to the myoD enhancer and likely represses myoD transcription directly. Antisense MSX1 relieves repression mediated by chromosome 4. We conclude that MSX1 inhibits transcription of myoD and that myoD is a target for homeobox gene regulation.
Animals↗
Ectoderm-mesenchyme and mesenchyme-mesenchyme interactions regulate Msx-1 expression and cellular differentiation in the murine limb bud.
The apical ectodermal ridge (AER) is a specialized thickening of the distal limb mesenchyme that has been demonstrated to support limb outgrowth and proper limb development. The homeobox gene, Msx-1, is associated with the distal limb mesenchyme (progress zone) and its expression depends upon the presence of the AER in chick limbs. We demonstrate here that the expression of Msx-1 is dependent upon the limb ectoderm in the mouse, but that the inductive capacity of murine limb ectoderm is not restricted to the AER. Msx-1 can also be maintained in limb mesenchyme by the substitution of FGF 4 for the ectoderm; however, we see that local cell-cell interactions are required for high levels of expression. Disruption of cell-cell interactions in the limb mesenchyme results in a dramatic decrease in Msx-1 levels and a precocious expression of MyoD1, suggesting that the limb environment represses differentiation and promotes cell proliferation during early development. BMP 4 and FGF 2 can also maintain Msx-1 expression in limb mesenchyme as well as retinoic acid which is usually associated with polarizing activity in the early limb. Msx-2 expression does not appear to be dependent upon cell-cell interactions as measured in these experiments. Taken together, our data suggest that the expression of Msx-1, but not Msx-2, not only requires factors from the limb ectoderm, but also relies upon cues from local cell interactions and that the spatial distribution of inductive capacities in limb ectoderm differs between the avian and murine systems.
Animals↗
Restricted expression of type-II TGF beta receptor in murine embryonic development suggests a central role in tissue modeling and CNS patterning.
The type-II TGF beta receptor mediates many of the biological responses to TGF beta. An examination of the expression of the type-II TGF beta receptor during mouse embryogenesis therefore provides specific information about the role of TGF beta during embryogenesis than has been available to date. We have isolated the genomic murine homologue of the human type-II TGF beta receptor corresponding to exon 2. The murine and human sequences show a high degree of homology. Using the murine probe, we found that type-II TGF beta receptor expression is regulated in both a spatial and a temporal fashion by using in situ hybridization and ribonuclease protection assays. Type-II TGF beta receptor expression is localized to the mesenchyme during critical interactions with adjacent epithelium such as developing hair follicles, whisker follicles and tooth anlage. In the central nervous system, type-II TGF beta receptor expression is highly restricted to the floor plate. Strong expression is also detected in migrating neural crest cells, meninges, and choroid plexus. Specific mesenchymal localization of type-II TGF beta receptor is also observed in lung, kidney, intestine, stomach, and bladder. The restricted expression of type-II TGF beta receptor in mesenchymal cells at sites of epithelial-mesenchymal interactions suggests that type-II TGF beta receptor plays a major role in mediating the establishment of embryonic organ systems. The highly restricted expression of type-II TGF beta receptor in the developing CNS suggests an important role for a serine/threonine kinase in patterning of the nervous system.
Aging↗
Digit tip regeneration correlates with regions of Msx1 (Hox 7) expression in fetal and newborn mice.
We report that during mouse fetal development transcripts of Msx1 and Msx2 become progressively restricted to cells that will form more distal digit structures; the Msx2 expression domain is always more distal than Msx1. At birth both Msx1 and Msx2 are expressed in cells of the nail bed and hair follicle. We have found that the regenerative ability of mouse digit tips is restricted to levels in which the amputation plane is within the region of Msx1, but not Msx2, expression in early fetal digits and to levels where both Msx1 and Msx2 are expressed in late fetal and neonatal digits. Fetal digit tip regeneration is rapid and completed by birth, whereas neonatal digit tip regeneration requires 4 weeks and is sometimes imperfect. In both fetal and neonatal digits, we find that both Msx1 and Msx2 are expressed during regeneration, but not during wound healing associated with proximal amputations where no regenerative response is observed. These data support the hypothesis that the expression of Msx genes are important for digit cells to initiate and participate in a regenerative response.
Animals↗
[The organization of hand rehabilitation in France in 1993].
Analysis of a questionnaire sent to members of the French Hand Society revealed the following information: the concept of a surgical team is very important, physiotherapists are usually our primary coworkers. Splints are frequently prescribed and must correspond to precise criteria. Surgeons are globally satisfied with their practice and their results, but are dissatisfied with the nomenclature concerning medical splints. Analysis of this nomenclature reveals marked inequalities concerning prices and refunds.
Equipment Design↗
Developmental cell-specific regulation of Na(+)-K(+)-ATPase alpha 1-, alpha 2-, and alpha 3-isoform gene expression.
Na(+)-K(+)-activated adenosine triphosphatase (Na(+)-K(+)-ATPase) is the integral membrane protein that maintains the Na(+)-K(+) electrochemical gradient across the plasma membrane. Because of the importance of the Na(+)-K(+) electrochemical gradient to fundamental and specialized cell functions, we investigated the cell-specific modulation of Na(+)-K(+)-ATPase alpha-subunit isoform (alpha 1, alpha 2, and alpha 3) gene expression in different stages of postimplantation mouse embryos and neonatal rat tissues by in situ hybridization with use of isoform-specific rat-derived antisense RNA probes. At early organogenesis (9.5-10.5 days postcoitus), we demonstrated generalized coexpression of alpha 1- and alpha 2-isoforms throughout the mouse embryo with greater levels in the developing but already functional heart, in contrast to the distinct spatially restricted alpha 3-isoform gene expression in the early developing neural tube. At midorganogenesis (15.5-16.5 days postcoitus), differential spatial variation in alpha 1-, alpha 2-, and alpha 3-isoform gene expression was already evident in all organs. Interestingly, region-specific expression patterns within single cell types were noted throughout development and were exemplified by 1) alpha 3-isoform gene expression in marginal cells of the 10.5-day-postcoitus developing neural tube; 2) alpha 1-, alpha 2-, and alpha 3-isoform gene expression in cerebellar granular cells of the 4-day-old rat brain; and 3) alpha 1- and alpha 3-isoform gene expression in 4-day-old rat ventricular cardiomyocytes. These isoform-specific changes in cellular and regional Na(+)-K(+)-ATPase alpha-isoform gene expression may play an active role in development and specialized cell functions.
Animals↗
Msx1 (Hox-7.1) in the adult mouse uterus: cellular interactions underlying regulation of expression.
We report here that Msx1 (formerly Hox-7.1) is expressed at high levels in uterine epithelial cells of the non-pregnant adult. These cells undergo pronounced changes in morphology in response to embryo implantation and show a concomitant decrease in Msx1 levels. While Msx1 is restricted to the uterus in adulthood, we observe Msx1 expression throughout the entire perinatal Müllerian duct epithelium in the prospective uterus, cervix and vagina. Through analysis of tissue recombinants, the expression of Msx1 in the epithelium was shown to be dependent upon an interaction with the underlying mesenchyme of uterine origin. The capacity of uterine mesenchyme to support or induce Msx1 expression in Müllerian epithelium is correlated with mesenchymal expression of Wnt-5a. Whereas Msx1 expression in the epithelium results from interaction with uterine mesenchyme, Wnt-5a expression is an intrinsic property of the uterine mesenchyme and does not depend upon the epithelium. The observation that Msx1 is expressed in the adult uterine epithelium and that conversion of the presumptive vaginal epithelium to uterine epithelium can be elicited only during the first week of postnatal development when Msx1 expression is detected suggests that, in addition to regulating various aspects of uterine epithelial morphology and function (e.g. gestation), this homeobox-containing gene plays a role in maintaining the uterus in a morphogenic and developmentally responsive state prerequisite for its unique function.
Animals↗
Detection of messenger RNA by in situ hybridization.
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Animals↗
Expression of Hox-7.1 in myoblasts inhibits terminal differentiation and induces cell transformation.
The terminal differentiation of myogenic cells initiates in the proximal portion of the limb bud whereas the distal region remains undifferentiated and proliferative. The apical ectodermal ridge maintains the progress zone in an undifferentiated state and induces proliferation of limb mesenchymal cells. Hox-7.1, a homeobox-containing gene, is expressed throughout the limb bud when limb outgrowth begins, whereas transcripts are later restricted to distal limb mesenchyme which is the proposed site of positional specification. Transplantation of proximal limb bud tissue into the distal portion of the limb results in a re-expression of Hox-7.1 in the transplanted mesenchyme. Similar grafts result in a positional reassignment to distal structures as well as de-differentiation of the grafted proximal tissue. Because of the association of Hox-7.1 expression with proliferative and undifferentiated cells, we tested whether Hox-7.1 regulates differentiation by transfection of Hox-7.1 complementary DNA into determined myogenic cells which represent one mesenchymal lineage in the limb. Here we report that forced expression of Hox-7.1 blocks terminal differentiation and results in a corresponding decrease in steady-state levels of MyoD1. Consistent with the association of Hox-7.1 with proliferation, Hox-7.1-expressing cells also acquire a transformed phenotype. Forced expression of Hox-8.1, a related Hox-gene, does not affect terminal differentiation indicating that the effects of Hox-7.1 are specific.
Actins↗