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Biomedical subjects

I C Mackenzie

Publications and source records attributed to I C Mackenzie.

At least 37 records · Page 2Linked to original sources
PubMed1991

Epithelial lining of sinus tracts associated with periapical disease: an immunocytochemical study using monoclonal antibodies to keratins.

We examined 30 specimens of mucosal sinus tracts arising in association with periapical inflammation. Immunocytochemistry and a panel of monoclonal antibodies to keratins were used to demonstrate the epithelial lining and its pattern of keratin expression. Half of the specimens were found to have an epithelial lining that was continuous with the mucosal epithelium and showed various degrees of extension into the sinus. The presence of an epithelial lining appeared to correlate with the duration of the sinus tracts. The immunostaining patterns of the epithelial linings were similar to those of the mucosal epithelium near the sinus opening although some differences were found. Proliferating strands of epithelium, presumably derived from the rest of Malassez, were observed deep in the tissues but were not continuous with the epithelial lining. The results suggest that the epithelial lining of sinus tracts is derived not from epithelial rests in the periapical region but from the mucosal epithelium adjacent to the opening of the sinus tract and that the observed changes in the pattern of keratinization are due to the influence of inflammation or of the connective tissue substrate.

Antibodies, Monoclonal↗
PubMed1991

Patterns of cytokeratin expression in human gingival epithelia.

Specimens of human gingiva were collected from teenage and adult subjects and frozen sections were stained with an extensive panel of monoclonal antibodies with defined specificities for individual cytokeratins. The results indicated different and distinctive patterns of keratin expression by the oral gingival, oral sulcular and the junctional epithelia. It was observed that epithelium with staining characteristics of sulcular epithelium extended over the gingival crest onto the oral surface of the gingiva. Junctional epithelium showed the unusual pattern of co-expression of keratins typical of the stratifying and of the simple epithelial phenotypes. The patterns of gingival keratin expression are compared with those of other mucosal epithelia. The findings are discussed in relation to mechanisms that may determine or influence the junctional epithelial phenotype.

Adolescent↗
PubMed1990

Antibody markers of basal cells in complex epithelia.

In the course of immunohistochemical studies it has become apparent that there is a distinct phenotype of keratin expression that is shared by basal epithelial cells in a variety of different tissues. A basal cell can be defined as a cell in contact with a basal lamina but with no free luminal surface; this distinguishes it from a simple epithelial cell, which has a free luminal surface as well as basal lamina contact, and from stratifying suprabasal keratinocytes, which have neither basal lamina contact nor free luminal surface. All basal cells, whether they are in glandular ductal or secretory epithelia, or in stratified squamous epithelia, express the keratin pair K5 and K14. In this paper we describe monoclonal and polyclonal antibodies that are monospecific for both keratins 14 and 5 or are specific for denaturation-sensitive epitopes unique to basal cells, including five new monoclonal antibodies: LL001 and LL002 (to keratin 14), 2.1.D7 (to keratins 5, 6 and 8), and LH6 and LH8 (conformation-specific basal cell markers). These antibodies have been used to monitor the distribution of the basal cell phenotype and to demonstrate the expression of keratins 5 and 14 in this cell type, in both stratified epithelia and mixed epithelial glands. The consistent association of this keratin pair with basal cells suggests a possible specific function for these keratin in reinforcing epithelia under physical stress, whilst expression of these keratins may conflict with the differentiated functions of most simple epithelial cells.

Amino Acid Sequence↗
PubMed1989

The influence of subepithelial connective tissues on epithelial proliferation in the adult mouse.

Subepithelial connective tissue is capable of modulating the pattern of histodifferentiation of stratified epithelia from adult animals, but it is not known whether the supporting connective tissue also influences epithelial proliferative activity. Epithelial and connective tissues of murine skin and oral mucosa, differing in their morphology and proliferative activity, were separated and heterotypically recombined prior to grafting to histocompatible hosts. After 3 or 8 weeks in situ, mitotic activity was determined following the administration of vinblastine sulfate. Although the mitotic activity in each of the epithelia could be modulated by some connective tissues, there was no distinct pattern of behavior. In combination with connective tissues from tongue or palate, the ear epidermis acquired a significantly increased mitotic activity. In contrast, when oral epithelia with high mitotic activity were recombined with dermal connective tissue, there was usually a significant reduction in proliferative activity. As there was no apparent association between mitotic activity and the induced changes in either organization or histodifferentiation, it is suggested that subepithelial connective tissue is capable of directly influencing the mitotic activity in the overlying epithelium.

Animals↗
PubMed1989

Isolation of subpopulations of murine epidermal cells using monoclonal antibodies against differentiation-related cell surface molecules.

Monoclonal antibodies (mAbs) against epithelial cells were prepared by immunization of rats with lyophilized murine epithelia. Screening against tissue sections and epithelial cell suspensions permitted identification of mAbs against surface molecules that are expressed early in cell differentiation. Staining with these mAbs followed by fluorescence-activated cell sorting enabled isolation of subpopulations of basal epithelial cells. Staining these subpopulations with antibodies against known differentiation markers (cytokeratins and bullous pemphigoid antigen) and measurements of cell size indicated that they represented fractions of the basal cell population in sequential stages of early differentiation. Labeling mice with bromodeoxyuridine at various times prior to cell isolation showed that the least-differentiated basal cells cycle more slowly than those at later stages, data which support the concept of a differentiation-related, hierarchical pattern of organization of the proliferative compartment.

Animals↗
PubMed1989

Replacement of Langerhans cells in murine palate.

Palates from C3H mice were implanted onto prepared graft beds in histocompatible F1 hybrid mice. Biopsies taken 1, 2, 4, 8, and 16 wk later were prepared to demonstrate Langerhans cells (LC) of C3H and F1 (host) origin. After 1 wk only occasional LC (all of C3H origin) were present. By 2 wk total LC numbers had increased to a level approximately 50% greater than in control (non-implanted) palate, with most of this increase due to C3H LC proliferation. From 4 through 16 wk total LC numbers were not significantly different from those of control palate. During weeks 2 through 16 the percentages of LC of F1 origin were 31, 70, 39, and 19% respectively. These results indicate an increased proliferation of C3H LC with an initial migration of F1 LC which stops as C3H LC numbers increase.

Animals↗
PubMed1989

Cytokeratin expression of the odontogenic epithelia in dental follicles and developmental cysts.

The patterns of cytokeratin expression in the epithelium of 5 dental follicles, 7 dentigerous cysts, 5 odontogenic keratocysts, 3 nasopalatine cysts and an epidermoid cyst have been studies using a panel of monoclonal antibodies. The epithelium of dental follicles and of developmental odontogenic cysts strongly expressed keratins 5 and 19 and showed weaker expression of keratins typical of stratified non-cornified and of simple epithelia. Staining with mAbs against the latter keratins varied with the degree of epithelial differentiation. Nasopalatine cysts strongly expressed simple epithelial keratins and the epidermoid cyst strongly expressed a marker of cornification. Odontogenic cysts thus appear to differ in their pattern of keratin expression from other oral developmental cysts and all derivatives of odontogenic epithelia appear to share similar basic patterns of cytokeratin expression.

Antibodies, Monoclonal↗
PubMed1989

Expression of blood group antigen-related carbohydrates by human gingival epithelia.

A panel of monoclonal antibodies was used to examine differentiation-related carbohydrate structures on the surfaces of gingival epithelial cells. The patterns of binding observed indicate distinct differences in the expression of the epitopes examined for three regions of the gingival epithelia corresponding approximately to the regions defined anatomically as the junctional, oral sulcular and oral epithelia. However, epithelium with the staining pattern of oral sulcular epithelium consistently extended beyond the sulcular region to cover the gingival crest and often the uppermost part of the oral aspect of the gingiva. Differential staining of basal and suprabasal cells indicated an unusual pattern of differentiation of the junctional epithelium. The phenotype of this epithelium appears to differ from patterns reported for any other oral epithelium and the possible functional significance of this difference is discussed.

Antibodies, Monoclonal↗
PubMed1988

Immunocytochemical examination of immune cells in periapical granulomata and odontogenic cysts.

Monoclonal antibodies (mAbs) were used to determine the presence and distribution of immune cells including lymphocytes, macrophages and Langerhans cells, in normal periodontal ligament, periapical granulomata, periapical cysts and dental developmental cysts. Isolated T-lymphocytes, but not B-lymphocytes, were detected in specimens of non-inflamed periodontal ligament. Increased numbers of T and B lymphocytes were found in all of the lesions examined. Monocytes/macrophages were associated with most periapical granulomata, dental developmental cysts and all periapical cysts. Langerhans cells, intraepithelial lymphocytes, and monocytes/macrophages were not detected in the rests of Malassez but were found in some epithelia within periapical granulomata and in most epithelial linings of odontogenic cysts. Increased numbers of immune cells were seen around proliferative epithelia and adjacent to the epithelial linings of cysts. Epithelium, particularly that of odontogenic cysts, showed positive reactions for HLA-Dr, lysozyme and for alpha-1 antitrypsin. The presence of immune cells in periapical granulomata and odontogenic cysts, suggests that cell-mediated and humoral immunoreactions occur in these lesions and may be associated with the epithelial proliferation within the periapical lesions.

Adult↗
PubMed1988

Patterns of keratin-expression in rests of Malassez and periapical lesions.

Using immunocytochemistry and a panel of monoclonal antibodies directed against various keratin polypeptides we examined specimens of normal periodontal ligament, periapical granulomas and inflammatory dental cysts. Epithelial elements with the appearance of rests of Malassez were identified in 6 specimens of normal periodontium and 10 periapical granulomas. Altered epithelium was present in 16 periapical granulomas and a lining epithelium in 10 inflammatory dental cysts. The patterns of binding of antibodies by these epithelia indicated that (a) keratin 19 was expressed by all epithelia, and (b) rests of Malassez also expressed keratin 5 but not large amounts of other keratins and (c) epithelial proliferation in periapical lesions was associated with increased expression of keratin 14, a marker of stratifying epithelia, new expression of keratins 4 and 13, differentiation markers for non-cornifying epithelia and variable, low levels of keratins 8 and 18, markers of simple epithelia. Proliferation of the epithelial rests of Malassez to form the lining of inflammatory dental cysts thus appears to be associated with a change from an unusual epithelial phenotype to that of a stratified non-cornifying epithelium in which some simple epithelial keratins are coexpressed.

Adolescent↗
PubMed1987

Connective tissue influences on the expression of epithelial cell-surface antigens.

Adult mice were found to show regional variation in the epithelial expression of some molecules of the blood-group antigen series. To investigate connective tissue influences on such differences, heterotypic recombinants of epithelia and connective tissues from various regions were prepared and examined using monoclonal antibodies directed against bloodgroup antigens H and Ley. The results indicate that epithelia may maintain a preexisting regionally specific pattern following recombination but that, in some recombinant matches, the connective tissue is capable of signalling redirection of the pattern of expression towards that typical of the epithelium with which it is normally associated.

Animals↗
PubMed1987

Age-associated changes in Langerhans cells of murine oral epithelium and epidermis.

Oral mucosa and skin of older individuals are immunologically less responsive to a range of allergens, but it is not known whether this is due to changes in the number of Langerhans cells or to impaired cell function. EDTA-separated epithelial sheets from the cheek and palate mucosa, and from ear aN< footpad skin of three-month-old and 24-month-old C57BL/6NNia mice were stained for ATPase, beta-glucuronidase activity and Iab-surface antigen to demonstrate Langerhans cells. The general distribution of such cells was unchanged with age, but those in epithelia from the old mice were more varied in shape, with irregular celL bodies and more elongated dendritic processes. The numerical density of Langerhans cells in old mice was reduced by 30-59 per cent compared with that in young mice.

Aging↗
PubMed1986

Epithelial-mesenchymal interactions control basement membrane production and differentiation in cultured and transplanted mouse keratinocytes.

The effects of mesenchyme and substratum on epidermal differentiation and formation of a basement membrane (BM) were analyzed in vitro and in vivo. Primary epidermal cell cultures (PEC) from neonatal mice were grown: on plastic culture dishes; on lifted collagen gels, either alone or in recombination with mesenchyme; after reimplantation in vivo either directly on mesenchyme or on collagen interposed between keratinocytes and mesenchyme. Differentiation of the epithelium and formation of a BM were examined by electron microscopy, and expression of BM constituents (type IV collagen, laminin, fibronectin, bullous pemphigoid antigen, and heparan sulfate proteoglycan) by indirect immunofluorescence. PEC on plastic or on collagen gels showed poor differentiation, a structured BM was not visible, and the expression and deposition of BM constituents was incomplete. Upon reimplantation in vivo, differentiation was normalized, expression of BM components complete and a structured BM reformed. This effect does not depend on immediate contact of epidermal cells with mesenchyme. When PEC on collagen gel were similarly associated with dermal mesenchyme in vitro, epidermal differentiation and expression of BM components were almost normalized, but a structured BM was absent. These findings demonstrate that formation of the BM in epidermis is a function of keratinocytes and, like differentiation is subject to mesenchymal control. A structural BM is not a prerequisite but rather an additional criterion of normal epidermal differentiation.

Animals↗
PubMed1986

Immunohistochemical studies of basal cell carcinomas transplanted into nude mice.

Xenografting into nude mice forms a system for analysis of human tissues under experimental conditions. In this study, normal skin samples and basal cell carcinomas were investigated, prior to and after transplantation, using immunofluorescence methods with antibodies against keratins, laminin, and collagen type IV. Three groups of transplants were studied: intact tissue samples, human epithelium (either normal or neoplastic) recombined with normal human dermis and, human epithelium recombined with normal mouse dermis. Transplants recovered after 3 weeks showed the following characteristics. The xenograft system was satisfactory in terms of host survival and rate of successful tissue recovery except for recombinants between human epithelium and mouse dermis. Intact and recombined samples of normal skin retained their preexisting patterns of architecture, cytodifferentiation, and basement membrane staining. Solid nonfibrosing basal cell carcinomas showed altered architecture and differentiation of both the epithelium and the basement membrane zone after transplantation: the solid tumor pattern changed towards spreading of tumor cells, a more squamous differentiation pattern was apparent and was confirmed by reactivity with antibodies against large keratins. Discontinuities of the basement membrane zone were detected with antibodies against laminin and collagen type IV. These changes were seen in both intact and recombined tumor transplants.

Animals↗
PubMed1986

Lipid composition of cohesive and desquamated corneocytes from mouse ear skin.

An organ culture system has been used to examine differences in the lipid compositions of materials derived from cohesive and desquamated mouse ear stratum corneum. Within this culture system, skin explants display rates of cell replication and differentiation comparable to those observed in vivo for up to 2 weeks and, during this period, loosened or dishesive material accumulates at the surface. Lipid compositions were determined for both intact and loosened stratum corneum derived from cultured skin and also for freshly prepared stratum corneum. In all 3 cases, the profiles of the nonpolar lipids and the ceramides were essentially the same; some of the nonpolar lipids appeared to be of sebaceous origin. The only changes detected upon desquamation were reductions of cholesteryl sulfate and a second unidentified lipid of similar polarity. Cholesteryl sulfate constitutes 4-5% of the polar lipid in fresh stratum corneum or stratum corneum from organ culture. This is reduced to 0.4% in the desquamated material which accumulates in the culture system. The unidentified lipid decreases from 1-2% of the polar lipid in intact fresh or cultured stratum corneum to 0.1% in the desquamated material. The possible function of cholesteryl sulfate in corneocyte cohesion is discussed.

Animals↗
PubMed1986

Rate of loss of tritiated thymidine label in basal cells in mouse epithelial tissues.

A subpopulation of epithelial cells which retains a tritiated thymidine label (termed label-retaining cells, LRCs) has been previously demonstrated in skin and oral mucosae of mice and hamsters. To examine the rate of decrease in the number of LRCs and the changes in degree of labelling, young mice were labelled with tritiated thymidine and the rate at which label was diluted from basal keratinocytes assessed for up to 90 days. The number of LRCs in each tissue examined decreased from 15 to 90 days after labelling with the epidermal tissues maintaining a higher percentage of LRCs than the oral mucosae. Grain counts for LRCs in each tissue at each time period indicated that the number of silver grains overlying LRCs also decreased with time. The observed decrease in numbers of LRCs and the change in their degree of labelling with time suggest that such cells divide slowly, a property associated with stem cells.

Animals↗
PubMed1985

Label-retaining keratinocytes and Langerhans cells in mouse epithelia.

Slowly cycling cells in murine epithelia can be marked by their retention of a tritiated-thymidine nuclear label. The position and identity of such label-retaining cells in palatal and lingual epithelia and ear epidermis was examined using autoradiography and histochemistry. They were found to be either (a) basally positioned keratinocytes preferentially occupying sites within units of epithelial structure that correspond to those expected for epithelial stem cells, or (b) nonkeratinocytes of the Langerhans cell type which lie suprabasally except in the epidermis where they are present in low numbers and occupy a similar position to label-retaining keratinocytes.

Animals↗