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Biomedical subjects

I C Mackenzie

Publications and source records attributed to I C Mackenzie.

At least 55 records · Page 3Linked to original sources
PubMed1984

Connective tissue influences on patterns of epithelial architecture and keratinization in skin and oral mucosa of the adult mouse.

Epithelial-mesenchymal interactions play an important role during embryogenesis but it is uncertain whether such interactions influence the maintenance of epithelial structure in the adult. To examine this problem, separated epithelial and connective tissue components of skin and mucosae from various regions of adult mice were homo-or heterotypically recombined and transplanted to histo-compatible hosts. The patterns of tissue architecture and keratinization of the resultant epithelia were examined for changes indicative of mesenchymal influences on the epithelial phenotype. Each type of epithelium, in some recombinations, fully conserved its normal pattern of phenotypic expression indicating that subepithelial connective tissue from all regions is permissive and that regionally-specific connective tissue influences are not necessary for conservation of epithelial specificity. In other recombinations, however, the epithelium acquired features of tissue architecture or keratinization typical of the epithelium normally associated with the connective tissue component, indicating directive influences from the connective tissue. The patterns of epithelial response observed suggest that there may be separate connective tissue influences on epithelial architecture and cyto-differentiation and that there is a regionally-related variation in the competence of epithelia to respond to these influences.

Animals↗
PubMed1984

The influence of differing connective tissue substrates on the maintenance of adult stratified squamous epithelia.

The interaction between adult stratified squamous epithelium and its supporting connective tissue possibly involves both permissive and directive influences. To examine the effect of vitality and specificity of connective tissue on the maintenance of epithelial structure and histodifferentiation, specimens of skin and oral mucosa from various regions of adult mice were separated using either EDTA or trypsin. Prior to transplantation, the epithelium was recombined with either inverted homologous connective tissue or with connective tissue that had been killed either by heating or repeated freeze-thawing. Epithelial sheets were also transplanted onto the graft bed alone or in combination with striated muscle or tendon. Normal patterns of cytodifferentiation were maintained when the epithelium was recombined with inverted or frozen-thawed subepithelial connective tissue but there was a loss of spatial organization on the frozen-thawed connective tissue. In contrast, heat-killed or trypsin-treated frozen-thawed subepithelial connective tissue and non-dermal connective tissue failed to maintain a viable epithelium. These observations suggest that subepithelial connective tissues (dermis, lamina propria) but not deep connective tissues facilitate epithelial proliferation and histodifferentiation.

Animals↗
PubMed1984

The distribution of blood group antigens in rodent epithelia.

The pattern of distribution of antigens cross-reacting with antibodies to human blood group antigens A and B and two precursor molecules was examined by immunofluorescence in the epidermis, oral mucosa and forestomach of rats and mice. Staining for blood group antigen A was negative. In all epithelia examined, blood group antigen B was present at the surface of basal and parabasal cells, and the H antigen at the surface of spinous cells. N-acetyllactosamine was present on the cell membranes in the upper spinous and granular cell layers of epidermis and forestomach epithelium and was not expressed in the oral epithelia except for a limited area in the dorsal tongue epithelium. Thus, the expression of antigen varies both regionally and, as earlier shown in human epithelium, with the stage of maturation of cells within a given epithelium. The observed sequence of expression of these antigens during maturation differs from that of human epithelia, but the present study provides a basis for further experimental studies of the role of cell surface antigens in epithelial homeostasis and maturation.

ABO Blood-Group System↗
PubMed1984

Identification and localization of label-retaining cells in hamster epithelia.

A subpopulation of basal epithelial cells which retains tritiated thymidine label for extended periods was previously demonstrated in skin and oral mucosae of mice. The present study examined the presence of similar cells in hamsters. Five-day-old hamsters were labeled with tritiated thymidine and the rate at which label was diluted from the basal cells observed. A small percentage of basal cells was found to retain label for up to 69 days. The location of such label-retaining cells ( LRCs ) in the palatal epithelium and in tongue papillae was examined. Thirty and 69 days after labeling, approximately 80% of LRCs in palate were located in the proximal halves of papillae and 80% of LRCs in tongue were positioned basally with approximately 30% of such LRCs occupying positions previously suggested to be stem cell locations. The finding that slowly cycling keratinocytes are related to patterns of tissue architecture is compatible with a function of these cells as epithelial stem cells.

Animals↗
PubMed1984

The keratin polypeptide patterns in heterotypically recombined epithelia of skin and mucosa of adult mouse.

Epithelial-mesenchymal interactions were investigated considering both morphologic criteria and keratin polypeptide expression in homotypic and heterotypic recombinants of adult mouse skin and oral mucosa. Two series of cross-recombinants of epithelia with different morphology and keratin patterns were chosen: (a) footpad epidermis/ear dermis and ear epidermis/footpad dermis; (b) palate epithelium/cheek connective tissue and cheek epithelium/palate connective tissue. Homotypic and heterotypic recombinants were prepared after EDTA-separation of the original tissues and then grown on syngeneic mice in subcutaneously prepared protected graft chambers. EDTA-separation is especially suited to completely separate the epidermal-dermal union, and the transplantation procedure used strictly prevents contamination with host epithelium. Five weeks after implantation keratins were analyzed by one and two-dimensional gel electrophoresis and peptide mapping. In both series, homotypic recombination of the tissues did not alter the original morphology and keratin polypeptide composition of the individual epithelial components. Ear epidermis displayed no significant changes in structure or keratin pattern in heterotypic recombinants. Recombined with ear dermis, footpad epidermis showed acquisition of some morphologic features typical for ear epidermis and slight changes in keratin composition which were, however, difficult to interpret due to the normal similarities of footpad keratin with that of ear. In contrast, the heterorecombinants of the palate/cheek series exhibited considerable alterations in their keratin patterns. Either epithelium showed suppression of distinct keratin subunits and de novo expression of subunits characteristic of the epithelium normally associated with the connective tissue component. The keratin patterns of both matches closely resembled each other and represented patterns intermediate between the normal patterns. This partial, however, significant modulation in the expression of differentiation markers was paralleled by similarly directed changes in the architecture of the heterotransplanted tissues, thus indicating that both morphogenesis and cytodifferentiation of certain adult epithelia can be influenced by extrinsic mesenchymal factors.

Animals↗
PubMed1984

Effects of the anti-inflammatory agents indomethacin, metiamide and acetylsalicylic acid on the induction of hyperplasia in hamster cheek-pouch epithelium and ear epidermis.

Previous studies have shown that agents such as indomethacin and hydrocortisone act to reduce the level of epidermal hyperplasia produced by various chemical, but little information is available about the effects of such anti-inflammatory agents on the induction of hyperplasia in oral mucosa. Hamster cheek-pouch epithelium and ear epidermis were treated with indomethacin, metiamide and acetylsalicylic acid prior to treatment with turpentine, podophyllin or TPA. The levels of hyperplasia induced were monitored by rates of epithelial glycolysis, protein synthesis and mitosis. The response of the metabolic assays to epinephrine was also examined. Alone, turpentine, podophyllin and TPA each caused a 3-5 fold increase in the metabolic assays and loss of the normal tissue response to epinephrine. Tissues pretreated with indomethacin showed significant reductions in the levels of hyperplasia produced and they retained a normal response to epinephrine. No reduction in hyperplasia was observed following pretreatment with acetylsalicylic acid, an alternative inhibitor or prostaglandin synthesis or with metiamide, a histamine blocker. The results indicate that the production of epithelial hyperplasia by turpentine, podophyllin and TPA can be inhibited by indomethacin.

Animals↗
PubMed1984

Proliferation of mast cells in normal and DMBA-treated mouse skin.

To examine the pattern of proliferation of mast cells in the skin of Swiss Webster mice, single or multiple pulses of 3H-thymidine, autoradiography and selective staining techniques were combined to detect DNA synthesis. A very low labelling index was found for the mast cells of normal skin but alteration of the mast-cell population using the chemical carcinogen dimethylbenzathracene led to increased labelling of mast cells. A series of studies of experimentally altered skin showed a pattern of mast cell labelling which suggested derivation of new mast cells by local self-replication. The labelling pattern indicated that mast cells labelled after 1 h divided to produce 2 daughter cells and that the rate of increase in the number of labelled mast cells following repeated labelling for up to 20 days was linear. These data do not suggest major recruitment of mast cells from a distant source during this period.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1984

Fatty-acid metabolism in oral mucosal epithelium of the hamster.

Little is known about the role of lipid metabolism in oral mucosal epithelia, although lipids probably play significant roles in the barrier function and in the production of energy for the various epithelial biosynthetic activities. The metabolic fate of exogenously added 14C-labelled oleic acid in pure epithelial sheets from hamster cheek-pouch has been investigated. Significant amounts of the label from the fatty acid were found in phosphatidyl choline, sphingomyelin and triglyceride fractions. Lesser amounts were found in cholesterol, cholesterol ester, ceramide and phosphatidyl ethanolamine. Estimations of the amount of ATP produced by both glycolysis and by fatty-acid beta-oxidation indicated that the 2 activities were essentially equal, which is in contrast to that reported for the epidermis. The results suggest that the oral mucosal epithelium, like the epidermis, is an active lipid-metabolizing tissue.

Animals↗
PubMed1983

Effects of histological processing on lectin binding patterns in oral mucosa and skin.

The effects of fixation and wax processing on lectin binding to C3H mouse palate and tail skin were evaluated using eight FITC-conjugated lectins. Sections and blocks of tissue were fixed in acetone, ethanol, methanol, formalin, glutaraldehyde or Bouin's picric-acetic-formalin fixative. Tissue blocks were then processed to paraffin wax. Compared to unfixed cryostat sections, there was a weaker but similar pattern of surface binding to sections of fixed and wax-processed tissues with acetone, alcohols and Bouin's fixative. Basement membrane binding was much weaker with acetone-wax and absent when alcohols or Bouin's fixatives were used. Tissues fixed in formalin showed very weak general binding, while glutaraldehyde fixation resulted in considerable non-specific cytoplasmic binding. Acetone, alcohols or Bouin's fixative followed by processing to paraffin wax provided convenient acceptable alternatives to the use of unfixed cryostat sections. Lipid extraction prior to lectin incubation resulted in complete elimination of detectable binding to epithelium suggesting that lectin-binding sites in the cell surface are associated with glycolipid or lipid.

Acetone↗
PubMed1983

Regeneration of organized epithelial structure.

The role of connective tissue in facilitating and directing the growth of epithelia during adult life is uncertain. The basic processes associated with maintenance of epithelial structure and previous work concerning the role of mesenchyme in this process in the embryo and adult are reviewed. A series of experiments examining the role of connective tissue in facilitating epithelial growth and development in vitro and after transplantation in vivo is described. These confirm the requirement for dermal elements if normal structure is to be reestablished and point to the requirement of dermal, as opposed to deep, connective tissues for facilitation of the growth of adult epithelia in vivo. The in vitro experiments suggest the presence of diffusible dermally produced factors that facilitate epithelial growth.

Animals↗
PubMed1983

Etiology of oral squamous cell carcinoma.

The traditional list of etiological factors related to oral squamous cell carcinoma namely, tobacco, alcohol, syphilis, and oral sepsis has been expanded to include iron deficiency, chronic candidosis, and herpes simplex virus. The development of current concepts in these areas is discussed. In evaluating the need for future research, special emphasis is given to the concepts of multifactorial etiology and the role of mutagens. Suggestions for future research are discussed.

Alcoholic Beverages↗
PubMed1983

Sequential histological changes and mast cell response in skin during chemically-induced carcinogenesis.

Skin tumors experimentally induced by dimethylbenzanthracene (DMBA) are associated with dense subepithelial accumulations of mast cells. To investigate the sequential changes of the mast cell population during carcinogenesis, and to provide a model with which to examine mast cell proliferation, the back skin of 48 Swiss Webster mice was painted with 0.5% DMBA in benzene twice weekly for 12 weeks. Control and DMBA-treated tissues were processed for histological examination. The observed pattern of tissue changes fell into four phases: a) inflammation and necrosis followed by epithelial regeneration and hyperplasia, b) development of localized regions of acanthosis, c) loss of normal organization with downgrowth of epithelial cells and formation of keratin pearls, d) appearance of well-defined nodules resembling verrucous carcinoma. Subepithelial mast cells varied greatly in number during the above sequence of changes. Dense foci of cells were seen, particularly beneath the regions of hyperplastic epithelium. Mast cells may play a role in abnormal epithelial proliferation and, further, DMBA treatment may provide a suitable model with which to examine the origin and kinetics of mast cells.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1983

Effects of repeated treatment of hamster ear epidermis and cheek-pouch mucosa with 12-0-tetradecanoylphorbol-13-acetate.

The effects of repeated stimulation of hamster oral mucosa and epidermis with 12-0-tetradecanoylphorbol-13-acetate (TPA), were examined using in vitro assays of glycolysis and amino acid incorporation. The response of control and hyperplastic tissues to epinephrine and cAMP, and their rates of incorporation of histidine and leucine, were also examined. Repeated treatment with TPA in the concentration range of 1 X 10(-8) to 1 X 10(-5) M resulted in increased rates of glycolysis, amino acid incorporation and mitosis in both tissues. During the induction of hyperplasia, a loss of the normal epithelial response to epinephrine was observed at Day 8, suggesting re-establishment of mechanisms controlling homeostasis. Application of TPA resulted in a reduction in the amount of histidine incorporated relative to leucine.

Amino Acids↗
PubMed1983

Recent advances in oral mucosal research.

Major progress in investigation of the normal structure and function of the oral mucosa has been made within the last ten years and has come principally from the application of various techniques developed in basic science disciplines to specific mucosal problems. However, it is apparent that many gaps still exist in our knowledge of the oral mucosa and, although it is to be expected that different workers will have distinct views on which of these are the most significant, some basic areas for further investigation can clearly be identified. For example, little is known about epithelial control systems and their disturbance by epithelial disease processes, about the nature of the interactions occurring during development and maintenance of the oral mucosal epithelia, or about the epithelial cell surface and its role in normal function. The specific properties and behavior of the cell populations of the subepithelial connective tissues appears to be poorly understood and the existence and significance of functional changes in mucosa with age and malnutrition are uncertain. It is increasingly apparent that successful progress in such investigations involves approaches using diverse methodologies. For example, epithelial-mesenchymal interactions are likely to involve multiple mesenchymal factors acting in concert to establish and maintain epithelial form and, because of this complexity, the nature of the inductive influences is not likely to be elucidated in model systems unless individual variables can be rigidly controlled. Defining the cellular and acellular elements in mesenchyme and reconstructing a functional mesenchyme from purified components may not be a simple task, but with current methods for cultivating mucosal keratinocytes and fibroblasts, as well as for purifying various components of the ground substance, it should be possible to initiate such a program of study. Some of the most dramatic advances made over the past 5-6 years in epidermal research have come about through the utilization of newly developed biochemical investigative techniques, examples of which include the use of gene cloning to study the organization of the keratin gene family, and the use of immuno-fluorescence with monoclonal antibodies to discern when various keratin proteins appear during differentiation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1982

Reformation of organized epidermal structure by transplantation of suspensions and cultures of epidermal and dermal cells.

The development of epidermis and epidermal appendages from dissociated cells of neonate mouse skin was examined by transplantation of cell suspensions to subdermally prepared, protected graft beds. Using Ficol gradients and culture procedures, we prepared subfractions of primary cell suspensions consisting of essentially pure epidermal cells or fibroblasts. Reformation of an epithelium structurally similar to the epidermis was observed from transplanted epidermal-cell suspensions, but formation of hair follicles and development of normal epidermal microarchitecture was observed only when epidermal cells were transplanted together with cells of dermal origin. This pattern was observed following transplantation of either fresh-cell isolates or cells cultured up to 7 days prior to transplantation.

Animals↗