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Biomedical subjects

M D Henry

Publications and source records attributed to M D Henry.

15 recordsLinked to original sources
PubMed1999

Dystrophic phenotype induced in vitro by antibody blockade of muscle alpha-dystroglycan-laminin interaction.

alpha-dystroglycan is a glycoprotein expressed on the surface of skeletal muscle fibres and other cell types. In muscle, alpha-dystroglycan provides a link between the myofibre cytoskeleton through its indirect binding to dystrophin, and the basal lamina through its binding to laminin-2, a protein of the extracellular matrix. The disruption of this linkage between the myofibre cytoskeleton and the extracellular matrix is a common feature of Duchenne and other muscular dystrophies, though the pathogenic mechanisms leading to muscle wasting remain unknown. By treating primary mouse muscle cultures with a monoclonal antibody which blocks alpha-dystroglycan binding to laminin, we show here the induction of a dystrophic phenotype in vitro. The phenotype is inducible in differentiated cultures only, is characterised by reduced myotube size, myofibril disorganisation, loss of contractile activity, reduced spontaneous clustering of acetylcholine receptors and is reversed by addition of excess exogenous laminin-2. Thus, alpha-dystroglycan may be part of a signalling pathway for the maturation and maintenance of skeletal myofibres. Detailed knowledge of this signalling pathway may provide insights into the molecular pathology of the various inherited muscular dystrophies, and identify valuable pharmacological targets and new therapeutic strategies.

Animals↗
PubMed1998

A role for dystroglycan in basement membrane assembly.

Basement membranes are composed of ordered arrays of characteristic extracellular matrix proteins, but little is known about the assembly of these structures in vivo. We have investigated the function of dystroglycan, a cell-surface laminin receptor expressed by cells contacting basement membranes in developing and adult tissues. We find that dystroglycan is required for the formation of a basement membrane in embryoid bodies. Our results further indicate that dystroglycanlaminin interactions are prerequisite for the deposition of other basement membrane proteins. Dystroglycan may exert its influence on basement membrane assembly by binding soluble laminin and organizing it on the cell surface. These data establish a role for dystroglycan in the assembly of basement membranes and suggest fundamental mechanisms underlying this process.

Animals↗
PubMed1998

Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus.

A peripheral membrane protein that is interactive with lymphocytic choriomeningitis virus (LCMV) was purified from cells permissive to infection. Tryptic peptides from this protein were determined to be alpha-dystroglycan (alpha-DG). Several strains of LCMV and other arenaviruses, including Lassa fever virus (LFV), Oliveros, and Mobala, bound to purified alpha-DG protein. Soluble alpha-DG blocked both LCMV and LFV infection. Cells bearing a null mutation of the gene encoding DG were resistant to LCMV infection, and reconstitution of DG expression in null mutant cells restored susceptibility to LCMV infection. Thus, alpha-DG is a cellular receptor for both LCMV and LFV.

Amino Acid Sequence↗
PubMed1998

Dystroglycan in development and disease.

Our understanding of the structure and function of dystroglycan, a cell surface laminin/agrin receptor, has increased dramatically over the past two years. Structural studies, analysis of its binding partners, and targeted gene disruption have all contributed to the elucidation of the biological role of dystroglycan in development and disease. It is now apparent that dystroglycan plays a critical role in the pathogenesis of several muscular dystrophies and serves as a receptor for a human pathogen as well as being involved in early development, organ morphogenesis, and synaptogenesis.

Animals↗
PubMed1998

Distribution of dystroglycan in normal adult mouse tissues.

Dystroglycan is a cell surface protein which, in muscle, links the extracellular matrix protein laminin-2 to the intracellular cytoskeleton. Dystroglycan also binds laminin-1 and the binding occurs via the E3 fragment of laminin-1. Recently, it was found that dystroglycan is expressed in developing epithelial cells of the kidney. Moreover, antibodies against dystroglycan can perturb epithelial development in kidney organ culture. Therefore, dystroglycan may be an important receptor for cell-matrix interactions in non-muscle tissues. However, information about the tissue distribution of dystroglycan is limited, especially in adult tissues. Here we show that dystroglycan is present in epithelial cells in several non-muscle organs of adult mice. Dystroglycan is enriched towards the basal side of the epithelial cells that are in close contact with basement membranes. We suggest that dystroglycan is involved in linking basement membranes to epithelial and muscle cells. Dystroglycan may be important for the maintenance of tissue integrity.

Animals↗
PubMed1997

Dystroglycan is essential for early embryonic development: disruption of Reichert's membrane in Dag1-null mice.

Dystroglycan is a central component of the dystrophin-glycoprotein complex (DGC), a protein assembly that plays a critical role in a variety of muscular dystrophies. In order to better understand the function of dystroglycan in development and disease, we have generated a null allele of dystroglycan (Dag1neo2) in mice. Heterozygous Dag1neo2 mice are viable and fertile. In contrast, homozygous Dag1neo2 embryos exhibit gross developmental abnormalities beginning around 6.5 days of gestation. Analysis of the mutant phenotype indicates that an early defect in the development of homozygous Dag1neo2 embryos is a disruption of Reichert's membrane, an extra-embryonic basement membrane. Consistent with the functional defects observed in Reichert's membrane, dystroglycan protein is localized in apposition to this structure in normal egg cylinder stage embryos. We also show that the localization of two critical structural elements of Reichert's membrane--laminin and collagen IV--are specifically disrupted in the homozygous Dag1neo2 embryos. Taken together, the data indicate that dystroglycan is required for the development of Reichert's membrane. Furthermore, these results suggest that disruption of basement membrane organization might be a common feature of muscular dystrophies linked to the DGC.

Amino Acid Sequence↗
PubMed1997

Testing surfactant treatment responses: a comparison of two models.

We have compared treatment responses of two surfactants in two animal models of respiratory distress syndrome. Preterm rabbits at 27 days gestation and premature lambs at 126 days gestation were treated with natural sheep surfactant Survanta (Ross Laboratories), or no surfactant and then were ventilated with the same ventilation style to achieve tidal volumes of 8 ml/kg. Dynamic compliances at 15 min were higher for control and surfactant-treated rabbits than for preterm lambs. Sheep surfactant and Survanta increased compliances in rabbits, but only sheep-surfactant-treated lambs had compliances higher than controls at 15 min of age. Maximal lung volumes (milliliters per kilogram) of the rabbits (after 15 min ventilation) were about twice those of the lambs (after 4 h of ventilation). Lung volumes of sheep-surfactant-treated rabbits were larger than for Survanta-treated rabbits, but no differences in lung volume were evident between the surfactant-treated lambs. The two models for testing surfactants do not give the same results when directly compared.

Analysis of Variance↗
PubMed1997

Overdenture retention and stabilization with ball-and-socket attachments: principles and technique.

Implant attachments of various designs are used to retain, stabilize and sometimes support overdentures. Tissue supported overdentures stabilized and retained by two to four implants are often the restorations of choice due to patient preference, limitations in finances, insufficient available bone to accommodate a greater number of implants, or needed improvements in esthetics, phonetics and oral hygiene. Female retentive sockets in the overdenture base that snap onto male ball abutments offer such advantages as reduction in hydraulic resistance to coupling, lower functional stress on the implants, retention that can be adjusted downward, easy component replacement and only relatively parallel abutments.

Dental Abutments↗
PubMed1996

Dystroglycan: an extracellular matrix receptor linked to the cytoskeleton.

Dystroglycan provides a crucial linkage between the cytoskeleton and the basement membrane for skeletal muscle cells. Disruption of this linkage leads to various forms of muscular dystrophy. Significant recent advances in understanding the structure and function of dystroglycan include detailed in vitro and in vivo analyses of its binding partners in muscle, an examination of its function at the neuromuscular junction, and emerging evidence of its roles in nonmuscle tissues.

Amino Acid Sequence↗
PubMed1996

Ultrasonic nebulized in comparison with instilled surfactant treatment of preterm lambs.

To evaluate the efficiency and distribution of ultrasonic nebulized versus instilled surfactant in the treatment of surfactant deficiency at varying degrees of maturation, twin or triplet lamb fetuses were delivered at 125 to 137 d gestational age and received nebulized natural surfactant (Neb Only), instilled surfactant followed by a second instilled dose (Inst/Inst), instilled surfactant followed by nebulized surfactant (Inst/Neb), or no surfactant (Control). The lambs were ventilated for 6 h. Twenty-eight lambs were categorized into two groups (low compliance versus moderate compliance) based on initial physiologic lung characteristics. Efficiency of deposition of nebulized surfactant directly correlated with the compliances and ventilatory efficiency indices measured at 15 min of age. The low-compliance group (Low Comp) had significantly lower efficiency of surfactant deposition (7.6 +/- 1.6%) than did the moderate-compliance group (Mod Comp) (23.4 +/- 2.5%) (p < 0.01). Overall, instilled surfactant had a reasonably homogeneous distribution, whereas nebulized surfactant had a less homogeneous distribution, except for the Low Comp, Inst/Neb group, which had a distribution pattern similar to that for instilled surfactant. The potential for nebulized surfactant therapy for respiratory distress syndrome (RDS) may be limited by the nonhomogeneous nature of ventilation in the preterm lung.

Administration, Inhalation↗
PubMed1995

Interdomain interactions of radixin in vitro.

We have assayed the domains of the ERM protein radixin for binding activities in vitro. Affinity columns bearing the amino-terminal domain of radixin selectively bound a small subset of the proteins of the chicken erythrocyte cytoskeleton. Two of those proteins were identified as radixin itself and band 4.1. In contrast, the carboxyl-terminal domain of the molecule bound neither protein, and full-length radixin did not bind band 4.1 (binding of full-length radixin to itself was not evaluated). Columns bearing a mixture of the amino- and carboxyl-terminal domains of radixin also failed to bind radixin and band 4.1. These results suggested that the amino- and carboxyl-terminal sequences can interact with one another either in cis or in trans, and so interfere with radixin's interactions with other ligands. Using affinity co-electrophoresis, we confirmed a direct interaction in solution between the two radixin domains; the data are consistent with the formation of a 1:1 complex with a dissociation constant of approximately 5 x 10(-8) M. Competition between intramolecular and intermolecular interactions may help to explain the provocative and dynamic localization of ERM proteins within cells.

Animals↗
PubMed1995

Molecular dissection of radixin: distinct and interdependent functions of the amino- and carboxy-terminal domains.

The ERM proteins--ezrin, radixin, and moesin--occur in particular cortical cytoskeletal structures. Several lines of evidence suggest that they interact with both cytoskeletal elements and plasma membrane components. Here we described the properties of full-length and truncated radixin polypeptides expressed in transfected cells. In stable transfectants, exogenous full-length radixin behaves much like endogenous ERM proteins, localizing to the same cortical structures. However, the presence of full-length radixin or its carboxy-terminal domain in cortical structures correlates with greatly diminished staining of endogenous moesin in those structures, suggesting that radixin and moesin compete for a limiting factor required for normal associations in the cell. The results also reveal distinct roles for the amino- and carboxy-terminal domains. At low levels relative to endogenous radixin, the carboxy-terminal polypeptide is associated with most of the correct cortical targets except cleavage furrows. In contrast, the amino-terminal polypeptide is diffusely localized throughout the cell. Low level expression of full-length radixin or either of the truncated polypeptides has no detectable effect on cell physiology. However, high level expression of the carboxy-terminal domain dramatically disrupts normal cytoskeletal structures and functions. At these high levels, the amino-terminal polypeptide does localize to cortical structures, but does not affect the cells. We conclude that the behavior of radixin in cells depends upon activities contributed by separate domains of the protein, but also requires modulating interactions between those domains.

3T3 Cells↗
PubMed1995

Avoiding implant overload.

Implant overload can be caused by a great number of factors, including suboptimal implant design and size; an insufficient number of implants to support the restoration; improperly splinted abutments; violation of conventional prosthetic limitations for natural dentition; excessively cantilevered pontics; splinting to natural dentition, even with a stress-breaking attachment; improperly positioned implants; the wrong type of restoration for the clinical condition; loss of supporting bone; excessive parafunctional forces; and non-maintenance of the components. Screws loosening or crestal bone loss are frequently the first detectable signs of implant overload, and warrant immediate action. Other signs of occlusal overload include infection, inflammation and peri-implant radiolucency. Balancing the whole arch, reducing contacts and surface area of the implant-supported areas, and shortening or eliminating cantilevers whenever possible are initial steps that can be taken to eliminate or lessen the excessive stress. The strongest possible implant and restorative materials should be used, and the patient should also be instructed as to proper implant function. As oral implantology develops at a seemingly exponential rate, it is extremely important to keep abreast of the latest advancements. Overload, rather than component design, is the primary factor in the majority of prosthetic and implant failures. Safeguarding the long-term integrity of the restoration should be a shared responsibility involving the patient and the health care team.

Dental Abutments↗
PubMed1992

Role of the heat shock response in stability of mRNA in Escherichia coli K-12.

The heat shock response in Escherichia coli involves extensive induction of the heat shock proteins, with the concomitant suppression of the synthesis of the non-heat shock proteins. While the induction of the heat shock proteins has been shown to occur primarily at the transcriptional level, the suppression of non-heat shock proteins is poorly understood. We have investigated the possibility that an increased decay of non-heat shock mRNAs is a means of decreasing the synthesis of non-heat shock proteins during the heat shock response. Heat shock response-defective strains were compared with wild-type controls by several criteria to evaluate both mRNA stability and the induction of enzymes known to be involved in mRNA turnover. Our results indicate that increased mRNA decay is not a mechanism used to regulate the synthesis of non-heat shock proteins.

Bacterial Proteins↗