Biomedical subjects

M D McMillan

Publications and source records attributed to M D McMillan.

At least 19 recordsLinked to original sources

PubMed2000

Coinvasion of dentinal tubules by Porphyromonas gingivalis and Streptococcus gordonii depends upon binding specificity of streptococcal antigen I/II adhesin.

Cell wall-anchored polypeptides of the antigen I/II family are produced by many species of oral streptococci. These proteins mediate adhesion of streptococci to salivary glycoproteins and to other oral microorganisms and promote binding of cells to collagen type I and invasion of dentinal tubules. Since infections of the root canal system have a mixed anaerobic bacterial etiology, we investigated the hypothesis that coadhesion of anaerobic bacteria with streptococci may facilitate invasive endodontic disease. Porphyromonas gingivalis ATCC 33277 cells were able to invade dentinal tubules when cocultured with Streptococcus gordonii DL1 (Challis) but not when cocultured with Streptococcus mutans NG8. An isogenic noninvasive mutant of S. gordonii, with production of SspA and SspB (antigen I/II family) polypeptides abrogated, was deficient in binding to collagen and had a 40% reduced ability to support adhesion of P. gingivalis. Heterologous expression of the S. mutans SpaP (antigen I/II) protein in this mutant restored collagen binding and tubule invasion but not adhesion to P. gingivalis or the ability to promote P. gingivalis coinvasion of dentin. An isogenic afimbrial mutant of P. gingivalis had 50% reduced binding to S. gordonii cells but was unaffected in the ability to coinvade dentinal tubules with S. gordonii wild-type cells. Expression of the S. gordonii SspA or SspB polypeptide on the surface of Lactococcus lactis cells endowed these bacteria with the abilities to bind P. gingivalis, penetrate dentinal tubules, and promote P. gingivalis coinvasion of dentin. The results demonstrate that collagen-binding and P. gingivalis-binding properties of antigen I/II polypeptides are discrete functions. Specificity of antigen I/II polypeptide recognition accounts for the ability of P. gingivalis to coinvade dentinal tubules with S. gordonii but not with S. mutans. This provides evidence that the specificity of interbacterial coadhesion may influence directly the etiology of pulpal and periapical diseases.

Adhesins, Bacterial↗

PubMed1999

Neutrophils in the molar tooth extraction wound in the rat: a transmission electron microscope (TEM) study.

Neutrophils have been ascribed a number of functions from ultrastructural studies of healing wounds. All of the wounds so far examined have been relatively aseptic. This study investigates, by TEM, the structure of neutrophils in healing molar tooth sockets in rats. Prior to epithelial coverage, a dense infiltrate of neutrophils separated the viable wound tissues from the overlying debris and bacteria. The more deeply situated neutrophils contained many granules and only occasional phagosomes. More superficial neutrophils contained fewer granules and phagosomes with engulfed bacteria undergoing lysis. The most superficial neutrophils were degenerate, lacked granules and often contained viable bacteria. There were varying numbers of neutrophils containing granules in the blood clot, granulation tissue, wound epithelium and adjacent tissue. No extracellular neutrophil granules nor extracellular discharge of granules was found. These findings differ from those of previous ultrastructural studies of relatively aseptic healing wounds. Ultrastructurally, the only function of neutrophils in healing tooth extraction wounds appears to be phagocytosis of bacteria, which supports a role in the prevention of infection.

Animals↗

PubMed1997

Differential expression of type I cytokeratins in hamster cheek pouch epithelium following treatment with dimethylbenzanthracene.

Cytokeratin (CK) expression in untreated, paraffin-treated or dimethylbenzanthracene (DMBA)-treated hamster cheek pouch epithelium was investigated utilizing monoclonal antibodies AE1 or AE3, which react with type I or type II CKs, respectively, and by in situ hybridization utilizing type I CK-specific probes. The latter were isolated from a cDNA library of hamster cheek pouch mRNA and designated CK 13 and CK 10 based on their respective homologies (> 95% amino acids) with murine CK 13 and human CK 10. Treatment of hamster cheek pouch epithelium with DMBA resulted in increased expression of type I CK, detected immunohistochemically with monoclonal AE1, but decreased expression of type II CKs detected with AE3. Despite an overall increase in type I CKs, in situ hybridization demonstrated differential expression of type I CKs with altered distribution of CK 13 mRNA and reduced expression of CK 10 mRNA, providing additional sensitive markers for DMBA-associated changes in CKs. These changes were constant at 2 to 22 weeks in the pre-neoplastic and neoplastic epithelium following the initial application of DMBA.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1997

A comparison of 2 polytetrafluoroethylene membranes in guided tissue regeneration in sheep.

The purpose of this study was to evaluate the sheep as a suitable animal model in which to compare periodontal wound healing after surgically induced Class II furcation defects were treated with different guided tissue regeneration (GTR) membranes. 22 mandibular second premolar sites in 11 sheep were used. The experimental design included untreated control teeth, sites treated by surgery alone, and others where surgery included placement of either Gore-Tex Periodontal Material (GTPM) or Gore-Tex Soft Tissue Patch (GTSTP). Sheep were killed 7 wk after surgery. Mesiodistal sections through decalcified second mandibular premolars were evaluated histologically. Histomorphometric analysis of digitized images allowed both area and linear measurements of newly regenerated furcal tissues. Percentage areas of cementum, bone, epithelium and connective tissue filling the furcation region were calculated. Coronal regeneration of alveolar bone and cementum were expressed as a percentage of the original height of the defect. Mean values for each group were subsequently analysed by 1-way ANOVA. Significantly greater regeneration was achieved with both of the GTR membranes, by comparison with the non-GTR surgical control group, with respect to percentage areas of cementum, bone and connective tissue, and the linear measurement of cementum (p < or = 0.05). This study demonstrates successfully the use of the sheep animal model for GTR research, and shows that few differences exist between GTR healing when either GTPM or GTSTP is used in the treatment of class II furcation defects.

Alveolar Bone Loss↗

PubMed1997

Invasion of dentinal tubules by oral streptococci is associated with collagen recognition mediated by the antigen I/II family of polypeptides.

Cell surface proteins SspA and SspB in Streptococcus gordonii and SpaP in Streptococcus mutans are members of the antigen I/II family of polypeptides produced by oral streptococci. These proteins are adhesins and mediate species-specific binding of cells to a variety of host and bacterial receptors. Here we show that antigen I/II polypeptides are involved in the attachment of oral streptococci to collagen and that they also determine the ability of these bacteria to invade human root dentinal tubules. Wild-type S. gordonii DL1 (Challis) cells showed heavy invasion of tubules to a depth of approximately 200 microm, whereas the abilities of cells of isogenic mutant strains OB220 (sspA) and OB219 (sspA sspB) to invade were 50 and >90% reduced, respectively. Likewise, wild-type S. mutans NG8 cells invaded dentinal tubules, whereas cells of isogenic mutant strain 834 (spaP) did not. The invasive abilities of strains OB220 and OB219 were restored by heterologous expression of S. mutans SpaP polypeptide in these strains. The extents of tubule invasion by various wild-type and mutant strains correlated with their levels of adhesion to type I collagen, a major component of dentin. Furthermore, S. gordonii DL1 cells exhibited a growth response to collagen by forming long chains. This was not shown by ssp mutants but was restored by the expression of SpaP in these cells. The production of SspA polypeptide by S. gordonii DL1, but not production of SspB polypeptide by strain OB220 (sspA), was enhanced in the presence of collagen. These results are the first to demonstrate that antigen I/II family polypeptides bind collagen and mediate a morphological growth response of streptococci to collagen. These antigen I/II polypeptide activities are critical for intratubular growth of streptococci and thus for establishment of endodontic infections.

Adhesins, Bacterial↗

PubMed1996

Scanning electron microscopy of dimethylbenzanthracene (DMBA)-treated hamster cheek pouch.

The aim of the present study was to describe changes which could be regarded as a result of neoplastic rather than inflammatory processes. Fifty-five weeks after 6 weeks of DMBA application to the cheek pouches of 5 male hamsters there were 4 types of lesion: larger ulcerated sessile; smaller non-ulcerated sessile; non-ulcerated pedunculated; conical projections. These and the rest of the pouches were examined by scanning electron and light microscopy. The interlesional mucosa, non-ulcerated sessile lesions and conical projections were covered by flat polygonal cells with either a honeycomb surface pattern of interconnecting microridges, or microridges arranged into more parallel lines. Cell imprints and boundaries were formed by linear ridges, grooves or both. Pedunculated lesions had flat smooth-surfaced cells and cells with a honeycomb surface pattern. None of these lesions were carcinomas by light microscopy but the ulcerated sessile lesions were. The appearance of the cells on the ulcerated lesions varied: flat, with a variable number of short microvilli that were often knob-like, isolated short microridges, or both; plump, giving a cobblestone appearance with surfaces that were smooth, covered by microvilli, short microridges or both. Such appearances have been described as characteristic for dysplastic and malignant stratified squamous epithelium in a number of sites. Further study of both experimental and naturally occurring mucosal disease is needed to validate this.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1995

Structure of hamster palatal gingiva and intermolar mucosa after intraperitoneal dosing with N-methyl-N-nitrosourea: a scanning electron microscope study.

The palatal gingiva and intermolar mucosa from normal hamsters and from hamsters that had received N-methyl-N-nitrosourea (NMU) intraperitoneally were examined by scanning electron microscopy over a 22-week period. The normal gingiva and rostral two-thirds of the intermolar mucosa were covered by flat polygonal cells that had a regular honeycomb surface pattern of interconnecting micro-ridges, distinct cell boundaries and imprints of cells that had been desquamated. The caudal third of the intermolar mucosa in normal and NMU-treated hamsters was covered by soft-palate type mucosa whose smooth surfaced cells surrounded scattered fungiform-like papillae. In NMU-treated hamsters changes were more common in the rostral two-thirds of the intermolar mucosa than in the gingiva. At 10 weeks there were sessile and conical surface projections and saucer-shaped and conical epithelial-lined depressions. At 16 weeks these projections and depressions were larger and more numerous, and groups of conical projections formed papillomatous-like lesions. At 22 weeks the projections and depressions were further increased in number and size and there were distinct papillomas. At 10 and 16 weeks the entire epithelium showed cells, cell boundaries and cell imprints resembling those in the controls, except that there were defects or dilated intercellular spaces at the base of the conical depressions and some of the cells were thicker. Much of the 22-week epithelial had a similar structure, but in some areas that did not show the projections or depressions the cells varied in size and shape and were covered by elongated micro-ridges. Here the surface was irregular as were the cell boundaries. Examination of sections by light microscopy, both from these irregular areas and from areas that appeared normal by scanning electron microscopy, revealed that the deeper epithelial strata could be either normal, dysplastic or at times malignant. However, scanning electron microscopy failed to reveal dysplastic or malignant epithelium.

Animals↗

PubMed1995

Scanning electron microscope study of the healing molar tooth extraction socket in the rat.

Healing molar tooth extraction wounds in rats were examined by scanning electron microscopy from 15 minutes to 40 days following tooth removal. The wound epithelium, which was derived mainly from the gingiva but also from the cheek and hard palate, migrated beneath the superficial socket contents. The contents were lost between 5 to 11 days, thus leaving a central epithelial-lined depression. This decreased in width with time as the level of the wound epithelium approached that of the hard palate but was still present at 40 days. Between 5 and 7 days, the wound epithelium became more regular. However, from 11 days on, it became more irregular with increasing numbers of saucer-shaped depressions, circular defects and circular whorls of epithelial cells. The surface structure of the epithelial cells changed as it migrated and matured. The initially plump, then flattened cells mostly had smooth areas along with variable numbers of irregular microridges and microvilli, although cells derived from the cheek had only smooth surfaces. With further maturation, all cells developed a regular honeycomb surface pattern of interconnecting microridges similar to that on the hard palate. Why the wound epithelium became more uneven after 11 days is not known.

Animals↗

PubMed1994

The effect of intraperitoneal N-methyl-N-nitrosourea on hamster palatal gingiva and intermolar mucosa.

Fifty 4- to 6-week-old male random-bred golden hamsters were injected intraperitoneally with a weight-related dose (12.5 mg/kg body weight) of N-methyl-N-nitrosourea (NMU) three times a week for 4 weeks. Groups of seven animals were killed 10, 16 and 22 weeks after the first injection. The palatal gingiva from six animals and the intermolar mucosa from 21 animals was examined. Seven male age-matched untreated control animals were killed at each period. Although all NMU-treated hamsters showed dysplastic and neoplastic changes similar to those in human oral squamous-cell carcinoma, other changes such as acantholytic dyskeratosis, invading cysts, duct-like structures and basaloid islands and cords were not. The extent and severity of the changes increased with time so that by 22 weeks there was extensive involvement of the palatal bone and marrow spaces, the molar periodontal ligament and the greater palatine neurovascular bundle by neoplastic epithelium. The invading epithelium was derived from the junctional, crevicular and palatal gingival and intermolar epithelium. The latent period for the crevicular and junctional epithelia was shorter than that for the palatal gingival and intermolar epithelium. The invasive changes from the latter epithelium were often preceded by exophytic changes such as epithelial projections, papillae and papillomas. Such changes were infrequent for the gingival, crevicular and junctional epithelia. The study shows that intraperitoneal NMU acts as a complete carcinogen on the palatal gingival and intermolar epithelium in hamsters.

Animals↗

PubMed1994

Changes in cytokeratins following treatment of hamster cheek pouch epithelia with hyperplastic or neoplastic agents.

The effects of four different hyperplastic agents and of the carcinogen DMBA on cytokeratin expression in hamster cheek pouch epithelia were compared. Reversible hyperplasia was produced by the application of either oil of turpentine, vitamin A or TPA. No hyperplastic changes were produced by application of EPP. Apart from the transient appearance of a 45 kDa cytokeratin in one group treated with vitamin A, the immunohistochemical staining patterns and immunoblot profiles of cytokeratins from cheek pouches treated with each of the hyperplastic agents were identical to controls. Following application of DMBA, the cytokeratins stained with increased intensity in the spinous and granular cell layers. This was associated with increased amounts of 42-56 kDa cytokeratins and decreased production of 62-75 kDa cytokeratins. Monoclonal antibody AE1 detected a 45 kDa cytokeratin in extracts of DMBA-treated epithelia that was not detected in untreated epithelial extracts. Monoclonal antibody AE3 detected an additional 54 kDa cytokeratin band in extracts of DMBA-treated epithelia. These cytokeratin changes were present in preneoplastic epithelia and maintained in neoplastic epithelia.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1993

Canalicular adenoma: report of five cases with ultrastructural observations.

Canalicular adenomas from five patients were examined by light and electron microscopy. All patients were over 50 years of age; 4 of the lesions were from the upper lip, 4 were cystic, 2 showed capsular invasion and 1 was multifocal. Histopathologically there were epithelial duct-like or canalicular structures cut at various angles and epithelial islands surrounded by hyalinized and mucinous connective tissue that contained little collagen. Ultrastructurally the epithelial islands contained many small lumina and connective tissue islands. The characteristic epithelial cell was columnar or cuboidal, extended from the lumina to the connective tissue, had almost straight lateral cell boundaries with desmosomes that predominated near the lumina, and possessed gap junctions and a small number of tight junctions. Their main cytoplasmic constituents were ribosomes, mitochondria, rough-surfaced endoplasmic reticulum and microfilaments. These findings show that canalicular adenomas are truly monomorphic and support the concept that they are derived from the cells of excretory ducts.

Actin Cytoskeleton↗

PubMed1993

Evaluation of a 10 percent carbamide peroxide gel vital bleaching agent.

A clinical study determined the whitening effect of a 10 percent carbamide peroxide gel on the teeth of 10 subjects. Histological evaluation of the effect of this agent on human tooth pulps and hamster cheek pouch tissues was also undertaken. The gel provided a modest, but unpredictable, whitening of discoloured teeth. A localised mild to moderate inflammatory response was found in some of the pulps of teeth that had been bleached. No soft-tissue changes were observed in the hamster cheek pouches.

Adolescent↗

PubMed1992

A scanning electron microscopic study of rete ridges in the cheek pouch of normal young, adult and aged Syrian hamsters.

Cheek pouches were removed from BIO 87.20 male hamsters 4 weeks, 8 months or 18 months of age. One pouch from each animal was routinely processed for light microscopy. The epithelium and connective tissue of the remaining pouches were separated with EDTA and routinely processed for scanning electron microscopy. Two types of rete ridge were found: simple, consisting of a single epithelial ridge or blunt projection and complex, made up of multiple interconnecting ridges. The simple type predominated at 4 weeks (90%) but the complex type predominated at 8 (58%) and 18 months (73%). Although the 8- and 18-month pouches were significantly larger than the 4-week ones, the total number of rete ridges was similar at all ages. This, taken in association with the shift in type with age, suggests that the simple rete ridges develop into the complex ones. With increasing age more of the complex rete ridges took on the characteristics of touch domes. These changes in the shape of the rete ridges with age need to be taken into account in studies on experimentally altered cheek pouches so that they are not mistaken as pathological changes.

Aging↗

PubMed1992

Effects of chronic Candida albicans in the hamster cheek pouch.

Sixty-four adult male hamsters had a suspension of either C. albicans (UO1) or C. albicans (ATCC 10261) placed in their cheek pouches once a week for up to 9 months. Four hamsters from both experimental groups, along with two untreated control hamsters, were killed at monthly intervals after the initial inoculation. Sections taken from the hamsters and examined in the light microscope showed that all experimental pouches had some or all of the following localized changes: inflammation and increased vascularity of the connective tissue; epithelial inflammation and microabscesses; hyperkeratosis; and isolated rete ridges similar to those in control pouches. C. albicans, usually the yeast form, was present on the exposed surface and between hyperplastic keratin squames. There was no hyphal invasion of the epithelium. Rather than being a true long-term study of chronic infection by C. albicans, the changes seen were probably the result of repetitive, more short-term responses after multiple inoculations.

Animals↗

PubMed1992

Temporalis muscle as a disc replacement in the temporomandibular joint of sheep.

Temporalis muscle flaps were evaluated in sheep. Flaps placed following discectomy were examined at 2, 4, 12, and 24 weeks. Histologic evaluation showed avascular necrosis and subsequent displacement and loss of tissue from the joint resulting in close contact between the condyle and fossa. Muscle flaps placed lateral to the joint in operative controls were examined at 4, 12, and 24 weeks. This muscle remained viable while undergoing fibrous replacement. Although the surface layers of the condyle and fossa were initially lost, the tissues were reformed with time. This experiment showed that in the sheep, temporalis muscle does not withstand functional loading within the joint. However, despite the lack of interpositional material, the condyle and fossa can remodel.

Animals↗

PubMed1992

Mucus-producing adenopapillary carcinoma of the oral cavity.

Mucus-producing adenopapillary carcinoma is a rare neoplasm of the oral cavity. The literature is reviewed and a case described, with histological and ultrastructural findings of a tumour which involved the upper lip and recurred following local excision.

Adenocarcinoma, Mucinous↗

PubMed1991

Ultrastructural examination of experimentally induced premalignant lesions.

Lesions induced in hamster cheek pouch using dimethylbenz(alpha)anthracene were studied by transmission electron microscopy and compared with normal tissue. Features regarded as suggestive of progression towards malignancy were: increased numbers of membrane-bound vesicles in basal cells, gaps in the lamina densa associated with widening of the lamina lucida and an irregular epithelial-connective tissue junction, the presence of cerebriform cells and frequent close association of 2 or more intra-epithelial cells (lymphocytes, cerebriform cells, Langerhans cells).

9,10-Dimethyl-1,2-benzanthracene↗

PubMed1991

Comparison of the effects of four hyperplastic agents on hamster cheek pouch mucosa.

Hyperplasia in the hamster cheek pouch was examined using 4 different hyperplastic agents: oil of turpentine 50% v/v in liquid paraffin; vitamin A palmitate 10% w/v in liquid paraffin; 12-O-tetradeconyl-phorbol-13-acetate 16nM in acetone; and ethylphenylpropiolate 0.04mM in acetone. Acetone, paraffin and untreated control groups were also examined. Cheek pouches were painted 3 times a week for up to 4 weeks with each solution. Samples were removed and prepared for light microscopy 24 hours after 2 weeks of painting and 24 hours, 6, 12 and 18 weeks after 4 weeks of painting. Hyperplasia was produced by application of turpentine, vitamin A and TPA after 2 weeks of application. Further increases in epithelial width occurred after 4 weeks of painting in the turpentine and vitamin A groups but a decrease was seen in the TPA group. Six weeks (vitamin A and TPA groups) or 12 weeks (turpentine group) after the completion of treatment the epithelium had a normal histological appearance. No differences between the control or EPP treated cheek pouch mucosa could be detected. Turpentine and vitamin A can be used as models of reversible hyperplasia in the hamster cheek pouch.

Alkynes↗