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Biomedical subjects

B E Hull

Publications and source records attributed to B E Hull.

10 recordsLinked to original sources
PubMed1990

Coverage of full-thickness burns with bilayered skin equivalents: a preliminary clinical trial.

A total of six patients have received bilayered skin-equivalent coverage of full-thickness burns, with takes of 50% to 70% in the later patients. These skin-equivalent grafts are constructed by combining allogeneic fibroblasts with collagen to form a sheet and adding a suspension of autologous epidermal cells to the surface of the collagen matrix. These bilayered skin-equivalent grafts have provided an expansion of at least fifteenfold to twentyfold for the area covered by the donor epidermis. By 8 months after grafting, the skin-equivalent grafts appeared smooth and approximated the color of normal skin. Long-term problems associated with hypertrophic scarring or graft fragility have not developed during the 18-month period of follow-up.

Adolescent↗
PubMed1986

Toxic cardiomyopathy: the effect of antipsychotic-antidepressant drugs and calcium on myocardial protein degradation and structural integrity.

In the nonrecirculating isolated perfused rat heart it has recently been described that basal myocardial protein degradation is suppressed by 30% within 5 min of maximal beta-adrenergic receptor occupancy under 5 X 10(-7) M isoproterenol (Lockwood, 1985, Biochem. J. 231, 299-308). This adrenergic-controlled proteolytic process presumably contributes to the well-known normal coordination of myocardial protein mass with functional demand. It is presently reported that elevated intracellular calcium is among the messengers that somehow suppress protein degradation. Acute elevation of extracellular calcium to a maximal concentration of 9.0 mM mimicked the simultaneous effects of isoproterenol on increasing inotropy and decreasing protein degradation, although this concentration was eventually lethal. Conversely, infusion of trifluoperazine (TFP), a calmodulin-blocking antipsychotic drug, caused stimulation of protein degradation above basal levels within 5 min. The stimulation of degradation by 30-60% was transient at 5 X 10(-7) M and returned to the control level in 5-10 min. However, TFP produced massive irreversible release of amino acid peptides and proteins at 10(-5) M within 30 min, followed by grossly observable cell structural disruption and cell separation. The degradative stimulation caused by TFP was potentiated by lowering the normal 2.5-mM extracellular Ca2+ concentration to 1.25 mM. Trifluoperazine at 10(-5) M caused longitudinal separation of myofibrils by disrupting lateral attachments between adjacent Z lines, leading to a loss of lateral myofibrillar registry followed by myofibrillar degeneration. Spot desmosomes were disrupted, leading to lateral cell separation; however, the fascia adherens region of the intercalated disks remained intact and cells maintained end-to-end attachment. Perfusion under the low extracellular Ca2+ concentration of 0.1 mM for 0.5 hr caused separation of the fascia adherens region and spot desmosomes of the intercalated disks as well as disruption of cytoplasmic myofibrils and other changes. Although the structural disorganization caused by perfusion with low (0.1 mM) Ca2+ were similar to those caused by TFP, cells also lost end to end attachment under low Ca2+. Amitriptyline (10(-5) M), thioridazine (10(-5) M), and calmidazolium (10(-6) M) stimulated protein degradation and caused structural damage. It is speculated that the above Ca2+-related phenomena describe the mechanism of the well-known toxic cardiomyopathy resulting from overdoses of some of the antipsychotic-antidepressant drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1979

The terminal web. A reevaluation of its structure and function.

The apical cytoplasm of epithelial cells of the small and large intestines has been examined by freeze-etch techniques as well as conventional and high voltage electron microscopy of sectioned material to gain a better understanding of the fine structural organization of the terminal web region. In the small intestine the terminal web exhibits a distinct stratification caused by the association of different sets of filaments with the three members of the junctional complex. Individual filaments of this network are closely associated with the sealing elements of the tight junctions, the surface of the core microfilament bundles, and the intermicrovillar plasma membrane. This region of the terminal web is the apical zone. The adherens zone appears as a band of interwoven filaments of two different diameters extending across the cytoplasm at the level of the intermediate junction. Within this region of the terminal web, individual 60-70 A actin-like filaments separate from the bundles of core microfilaments to interact with one another and with filaments of similar diameter from the zonula adherens. 100 A tonofilaments also contribute to the adherens zone, presumably stabilizing the orientation of the actin-like filaments. The basal zone which underlies the adherens zone consists of closely interwoven bundles of tonofilaments that are anchored to and interconnect the spot desmosomes. Within the large intestine the cytoplasmic microfilaments form a looser and less clearly stratified network which nevertheless retains the same basic organization found in the small intestine. Transmembrane linkers appear to originate within the cytoplasmic plaques of the spot desmosomes, pass through the plasma membranes, and meet in a staggered configuration in the intercellular space; these linkers may thus mediate the actual mechanical coupling between the cytoskeletal networks of tonofilament bundles of adjacent cells. This integrated system of cytoplasmic filaments and intercellular junctions endows the apical cytoplasm with both the flexibility and the stability necessary for the normal functioning of the epithelium.

Animals↗
PubMed1976

Functional significance of the variations in the geometrical organization of tight junction networks.

Using freeze-fracture techniques, we have examined the morpholog of tight junction networks found along the length of the alimentary tract of Xenopus laevis before and after metamorphosis. We have developed the hypothesis, based on these observations, that the geometrical organization of the network determined by the stress-induced shape changes normally experienced by the cells linked by the network. Consistent with this theory, tight junctions can be classified into two distinct types of network organization which differ in their response normal and experimentally induced stress conditions: (a) loosely interconnected networks which can stretch or compress extensively under tension, thereby adapting to stress changes in the tissue; and (b) evenly cross-linked networks which retain their basic morphology under normal stress conditions. The absorptive cells of the large intestine as well as the mucous cells of the gastrointestine or stomach are sealed by the first, flexible type of tight junction. The second type of junctional organization, the evenly cross-connected network, is found between absorptive cells of the small intestine and ciliated cells of the esophagus, and reflects in its constant morphology the relative stability of the apical region of both of these cell types. Networks intermediate between these two types arise when a cell which would normally form a lossely interconnected network borders a cell which tends to form a more evenly cross-linked network, as is found in the esophagus where ciliated and goblet cells adjoin. Despite the change in the animal's diet during metamorphosis from herbivorous to carnivorous, the basic gemetrical organization of the networks associated with each tissue of the alimentary tract remains the same.

Animals↗
PubMedDate not supplied

The role of allogeneic epidermis in murine graft rejection.

Skin equivalents containing allogeneic fibroblasts in a collagen matrix and overlaid with isologous epidermal cells have been successfully grafted to rodents. By contrast, skin equivalents containing isologous fibroblasts and allogeneic epidermal cells provoke a strong rejection response, characterized by the infiltration of mononuclear cells into the epidermis at 1 week and occlusion of the microvasculature and destruction of the epidermis by lymphocytes 2 weeks after grafting. Based on these findings, skin equivalents containing allogeneic fibroblasts could be used in the treatment of burn injuries, but the epidermis should be obtained from the patient.

Animals↗
PubMedDate not supplied

Replacement of full-thickness burns on mice with isogeneic skin equivalents.

A copper slug heated with a soldering iron was used to produce full- and partial-thickness burns on the backs of mice. The untreated partial-thickness burns healed by outgrowth of epidermal cells from the hair follicles and adjoining skin, and the full-thickness burns formed linear scars. Skin equivalents containing isogeneic fibroblasts and epidermal cells were used to replace full-thickness burns; these grafts were fully vascularized and covered with a cornified epidermis within 2 weeks. The grafts maintained 34% of their original area at 180 days, but the full-thickness burns retained only 4.5% of the initial area. For the first 2 weeks, the splenic index in animals that received burns followed by surgical excision and grafting was significantly greater than in the animals that had burns not followed by excision, but the difference was no longer significant by 21 days.

Animals↗
PubMedDate not supplied

Cornification and basement membrane formation in a bilayered human skin equivalent maintained at an air-liquid interface.

Human keratinocytes that were grown in a skin equivalent at an air-liquid interface were analyzed morphologically and biochemically to demonstrate differentiation approaching that of human skin. Within 3 weeks of growth at the interface, cuboidal basal cells, distinct spinous and granular zones, and a fully developed cornified layer of enucleated cells formed the multilayered epidermis. Ultrastructurally, the keratinocytes in the upper granular layer contain tonofilament bundles and membrane-coating granules. These cells form cornified squames that are resistant to degradation by sodium dodecyl sulfate/dithiothreitol. Basal cells are attached to a developing basement membrane with hemidesmosomes. Immunogold silver staining analysis with monoclonal antibodies demonstrated the expression of basement membrane collagens IV and VII. This level of differentiation might improve "take" of human grafts and provides a useful system with which to study topical carcinogens and tumor promoters in vitro.

Artificial Organs↗