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Biomedical subjects

B E Hull

Publications and source records attributed to B E Hull.

27 records · Page 2Linked to original sources
PubMed1980

Irreversible photoactivation of a pancreatic secretagogue receptor with cholecystokinin COOH-terminal octapeptides.

The photochemically reactive analog of cholecystokinin octapeptide (CCK-8), 2-nitro-5-azidobenzoyl-Gly-Asp-Tyr-(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2 (NAB-Gly-CCK-8), has been used to stimulate irreversibly the receptor for CCK-8 on preparations of dispersed guinea pig pancreatic acini. When continuously present with acini in the dark, NAB-Gly-CCK-8 is a reversible stimulant of secretory protein discharge with an ED50 of 0.4 nM. After six cycles of photolysis of acini with NAB-Gly-CCK-8 followed by extensive washing and assay in peptide-free medium in the dark, the photoactivated label induces irreversible discharge. Irreversible discharge is proportional to the concentration of NAB-Gly-CCK-8 present during photolysis and is nearly equivalent in intrinsic activity to that induced by CCK-8 in the dark. Inclusion of a 5-fold excess of prephotolyzed NAB-Gly-CCK-8 during photolysis partially protects against irreversible discharge, suggesting that the receptor irreversibly stimulated by NAB-Gly-CCK-8 is likely a receptor for peptides in the CCK family. Irreversible discharge requires metabolic energy supplied by oxidative phosphorylation and is dependent on extracellular Ca2+ and, thus, resembles that induced by reversible secretagogues.

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↗