Biomedical subjects
P Sloan
Publications and source records attributed to P Sloan.
The behaviour of pericytes in vitro: relevance to angiogenesis and differentiation.
Explore the source record for details and available documents.
Trabecular generation de novo. A morphological and immunohistochemical study of primary ossification in the human femoral anlagen.
An understanding of trabecular formation in early skeletal development may provide insight into the problem of trabecular replacement in the aging skeleton. In an optical and scanning electron microscope study of the processes of de novo trabecular generation, the immunohistochemical distribution of collagen Types I, II and III, together with the matrix organising proteins fibronectin and tenascin, has been examined in the ossifying human femoral anlage. In the region of the developing spongiosa, the primary osseous trabeculae that arose by endochondral ossification were assembled around calcified cartilage remnants, consisting almost entirely of aggregates of mineralised microspheres. These structures were specifically recognised by antibodies raised against collagen Type II and fibronectin. In contrast, the primary osseous trabeculae that arose by subperiosteal intramembranous processes, were assembled around a framework of prominent coarse fibres that were recognised by antibodies raised against collagen Type III and tenascin. Irrespective of their origin, all the new trabeculae were similar in their general staining character for collagen Type I and fibronectin. However, throughout the developmental stages examined here endochondral trabeculae were separated from intramembranous trabeculae by a discrete boundary of compressed cells and mineralised cartilage.
Phenytoin hyperplasia occurring under complete dentures: a clinical report.
Explore the source record for details and available documents.
Sequential changes in histologic pattern and extracellular matrix deposition during the healing of chronic venous ulcers.
As part of a major clinical trial, sequential biopsies were taken from the margins of venous leg ulcers during their healing. The changing patterns of tissue architecture and extracellular matrix synthesis during healing were documented histologically and immunocytochemically. Initial biopsies were similar in appearance: prominent fibrin cuffs, variable inflammation, hemosiderin, and red blood cell extravasation. So called "fibrin cuffs" were highly organized structures composed of laminin, fibronectin, tenascin, and collagen as well as trapped leukocytes and fibrin. Fibronectin was absent from the ulcer tissue although collagen was abundant. Major histologic changes were observed after 2 weeks' pressure bandage therapy; hemosiderin, acute inflammation, and granulation tissue with the deposition of fibronectin had all increased and epithelial migration had commenced. Complete epithelialization was frequent by the fourth week of treatment, but the basement membrane was incomplete. At this time, hemosiderin and red blood cell extravasation had decreased and "fibrin cuffs" were virtually absent although chronic inflammation remained. The complex organization of the so-called "fibrin cuffs" may inhibit angiogenesis (but offer protection against increased venous pressure) in addition to their previously ascribed role in causing tissue ischemia.
Differentiation of pericytes in culture is accompanied by changes in the extracellular matrix.
We have previously reported that pericytes derived from retinal and brain microvessels aggregate into nodules soon after reaching confluence. Nodule formation involves a reorganization of the cells resulting in the presence of sparse cells, confluent monolayers, multilayers, sprouts, and nodules within the same culture dish. Extracellular calcification occurs only within the nodules, demonstrating that pericytes are capable of undergoing osteogenic differentiation in culture and that this differentiation is related to nodule formation. Using immunofluorescence we have now studied the distribution of laminin, type IV collagen, type X collagen, and tenascin in pericyte cultures during nodule formation. These matrix macromolecules were also identified by a combination of biochemical techniques, including Northern blot hybridization, immunoblotting and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A molecule that seems to be related to type X collagen was demonstrated by the presence of a pepsin-resistant, collagenase-sensitive polypeptide of molecular weight approximately 45 kDa. The production of laminin, type X-related collagen, and tenascin by pericytes has not been previously reported. Our results suggest that the synthesis or distribution or both of these molecules is dependent on the state of pericyte differentiation. The expression of laminin, type IV collagen, and type X-related collagen was maximal in multilayer areas, sprouts, and nodules. Tenascin appeared homogeneously distributed in monolayer and multilayer areas; when calcified nodules were present, the anti-tenascin serum preferentially decorated a discrete area circumscribing the nodules. Tenascin and type X collagen have been found transiently in vivo preceding calcification; their possible role in this process is not known. Our results also suggest an association between laminin, type IV collagen, and calcification. The in vitro experimental system described here may help to clarify the role of matrix macromolecules in the calcification process.
Association of supraglottic and gingival idiopathic plasmacytosis.
Three cases of gingival plasmacytosis in which laryngeal symptoms eventually developed are reported. Two of the three patients underwent endoscopic biopsy of supraglottic lesions, which proved to be similar to those in the oral cavity. The third patient had supraglottic erythema only and was not subjected to biopsy. Known etiologic factors associated with plasma cell gingivitis were excluded. Treatment with oral and topical steroids resulted in good control of the lesions.
A developing complex odontome associated with delayed premolar formation.
Delayed development of a bicuspid in the right premolar region of the mandible was observed radiographically in a 16-year-old male patient following surgical removal of a developing odontome. Whilst odontomes are commonly associated with a failure of eruption of permanent teeth, this case was unusual in that there was both failure and marked delay of adjacent permanent tooth germ development, suggesting that the odontome was associated with a regional disturbance of odontogenic tissues in the neonatal period.
Current concepts of the role of fibroblasts and extracellular matrix in wound healing and their relevance to oral implantology.
Control of tissue differentiation and modelling are discussed in the context of epithelial-mesenchymal interactions and oral implantology. An accumulating body of evidence points to functional heterogeneity of oral fibroblasts and the use of a cell density migration assay to characterize this is described. Present data indicate that oral mucosal fibroblasts exhibit fetal-like phenotypes except in their responses to peptide growth factors. The hypothesis that clonal expansion of fibroblast subsets plays a role in the development of malignancy and in inflammatory disorders is presented. Production of a newly identified migration-stimulating factor by oral fibroblasts is described along with the heterogeneous distribution of extracellular matrix in the oral mucosa. The development of techniques for extracellular matrix localization in hard tissue is discussed.
Immunolocalization of collagen types I and III, tenascin, and fibronectin in intramembranous bone.
Structural components of the organic bone matrix were located by immunohistochemical techniques in fresh-frozen sections of normal and dysplastic bone. Fine and coarse birefringent fibers were identified as separate and distinctive features in the extracellular matrix by antibodies raised against human collagen Type III. The glycoprotein tenascin was located on a proportion of the fibers in a characteristic beaded pattern, which was absent in dysplastic bone. The fibers originated in the periosteum or in the fibrous stroma of the marrow cavity and were oriented with regard to both the spatial and the lamellar organization of the bone. The disposition and composition of the fibers suggests that they form a preliminary framework on which intramembranous bone modeling proceeds, and that the specific location of tenascin on the fibers in normal developing membrane bone may be important in determining the alignment of the bone tissue. Epitopes recognized by the collagen Type I and fibronectin antibodies were demonstrated throughout the mineralized matrix, but their incorporation into the collagen "Type III" fibers was evident only outside the mineralized matrix.
A double blind comparative study of lisinopril and enalapril in patients with essential hypertension.
The efficacy and safety profiles of lisinopril (10-40 mg) and enalapril (5-20 mg) were compared in 169 hypertensive patients during 12 weeks' treatment in a randomised double-blind parallel group study. BP was measured hourly for the first 8 hours following the first dose of lisinopril 10 mg and enalapril 5 mg. The peak reduction in sitting systolic and diastolic BP occurred approximately 6 hours post dose in both groups. At 8 hours post dose lisinopril had reduced sitting systolic and diastolic BP by 2.9 mmHg and 3.5 mmHg (P = 0.02) respectively, more than enalapril with similar results for standing BP. One patient on enalapril developed first dose postural hypotension. After 12 weeks' therapy lisinopril produced a greater decrease (P less than 0.05) in BP than enalapril. Sitting BP decreased by 25/15 mmHg on lisinopril and 17/12 mmHg with enalapril. Standing BP decreased by 24/14 mmHg compared with 16/10 mmHg on enalapril. Eighteen patients did not complete the study, 8 on lisinopril (6 adverse events, 1 uncontrolled BP, 1 protocol violator) and 10 on enalapril (8 adverse events, 1 uncontrolled BP, 1 protocol violator). Overall, the results indicated that while both drugs are well tolerated, the dose range of lisinopril 10-40 mg may produce a greater antihypertensive effect than enalapril 5-20 mg.
The structure and function of oral mucosa.
Understanding of the functional morphology and biology of the oral mucosa has advanced in recent year, particularly in such areas as epithelial-mesenchymal interaction, fibroblast heterogeneity, extracellular matrix, migration factors and growth factors, and the importance of these areas in the development and maintenance of the oral mucosa is increasingly appreciated. This article reviews current knowledge.
Lectin binding to normal mucosa, leukoplakia and squamous cell carcinoma of the oral cavity.
A panel of fifteen biotinylated lectins was used to study the saccharides associated with the epithelial component of normal and leukoplakic mucosa and squamous cell carcinoma, from a variety of locations in the oral cavity. Lectin binding heterogeneity was found between various sites of normal mucosa. The binding to leukoplakic epithelium closely resembled normal, with similar site heterogeneity. However, the features of cell-capping and cellular expression of the blood group A antigen, as observed in normal and most leukoplakic epithelia, were not observed in squamous cell carcinoma. These results show that neoplasia in oral squamous epithelium is associated with alterations in terminal N-acetyl-D-galactosamine, N-acetyl-D-glucosamine, D-mannose, L-fucose, D-glucosamine and D-galactosamine residues present in the outer parts of both O-linked and N-linked glycoconjugates, along with high levels of terminal sialation of certain residues.
Immunohistochemical study of the heterogeneity of tenascin distribution within the oral mucosa of the mouse.
Immunohistochemical labelling of adult mouse oral mucosa revealed a heterogeneous distribution of the extracellular matrix glycoprotein, tenascin. In masticatory mucosa (palate and gingiva), tenascin was selectively localized to the tips of connective tissue papillae, whilst in lining mucosa (ventral tongue, buccal, labial and vestibular) it was more uniformly distributed in the basement membrane. Tenascin was restricted to the connective tissue of specialized papillary tips in the dorsal lingual mucosa. The heterogeneous distribution of tenascin may be linked to mechanical function, proliferative organization within the overlying epithelium or to continuing epithelial-mesenchymal interactions.
Spindle-cell carcinoma: a case report.
An unusual case of an exophytic spindle-cell carcinoma of the maxilla arising from an area of erythroplakia is presented. The epithelial nature of the spindle cells was demonstrated by electron microscopy and immunohistochemistry. After initial surgery the tumour recurred and was then extensively infiltrative and rapidly destructive. Magnetic resonance imaging (MRI) revealed an invasive tumour of the contra-lateral maxillary antrum suggesting a multicentric origin.
Histopathological and scintigraphic features of condylar hyperplasia.
This investigation was undertaken to correlate the scintigraphic and histological features of condylar hyperplasia to identify consistent diagnostic findings. A series of 34 surgically excised condyles were examined from a 5 year period. Of these, 20 were diagnosed clinically and histologically as condylar hyperplasia. In 18 of these the presentation was one of increasing facial asymmetry. In all 20 cases there was an increased uptake of Technetium 99 as determined by gamma scintigraphy. The thickness of the fibrous articular layer, undifferentiated germinal mesenchyme layer and the hyperplastic cartilage layer were measured using an eyepiece graticule and the presence and frequency of islands of cartilage in the subchondral bone were noted. 7 patients received tetracycline hydrochloride 14 and 4 days pre-operatively in an attempt to quantify the calcification rate. An uninterrupted layer of undifferentiated germinal mesenchyme is a consistent feature of condylar hyperplasia. An increased uptake on scintigraphy is proportionally related to the thickness of the hypertrophic cartilage and not only to the presence but also the frequency of cartilage islands in the subchondral bone.
Pericytes derived from the retinal microvasculature undergo calcification in vitro.
Pericytes isolated from the bovine retinal microvasculature retain characteristic features of their in vivo counterparts, such as the presence of glycogen deposits, long filamentous processes, prominent microfilament bundles and the ability to display two distinct and reversible phenotypes. Time-lapse video-microscopy demonstrated that pericytes tend to overlap and aggregate, even in sparse cultures. After reaching confluence, they form multilayered areas that retract away from each other, resulting in the formation of multicellular nodules. These nodules increase in size and cellularity by going through repeated 5- to 6-h cycles of anchoring, spreading, cell proliferation and retraction. Alkaline phosphatase was not detected in pericytes at subconfluent or confluent densities, but this enzyme was expressed in areas of high cell density, such as multilayers and nodules. Pericytes synthesise and deposit an extracellular matrix at all stages of their in vitro development, including nodule formation. The matrix within the nodules contains cross-striated collagen fibres and matrix vesicles. Needle-like crystals of hydroxyapatite appear to be deposited within the matrix, thus leading to massive calcification of the nodule. Calcification, as assessed by electron microscopy, histochemical staining and X-ray microprobe analysis, occurred on plastic and collagen substrate in the absence of disodium-beta-glycerophosphate. The addition of this compound at 5 or 10 mM or the use of a collagen substratum (rather than plastic), brought forward the process of nodule formation and calcification by 3-6 days. Our results suggest that retinal pericytes may differentiate in vitro along the osteogenic pathway.
In vitro and in vivo studies with collagen/hydroxyapatite implants.
There is limited literature describing the early events that follow subperiosteal suprabony implantation of particulate hydroxyapatite (HA)/collagen composite grafts. This paper investigates, both in vitro and in vivo, the influence of a water-based environment on compressed collagen fiber cylinders and compressed HA/collagen blocks. Following subperiosteal extrabony implantation of an HA/collagen block, the HA particles were not retained within the original dimensions of the preformed dry block. The separation of the particles was related to the expansion of collagen on hydration and to the amount, degree of cross-linking, and degree of compression of the collagen.