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Biomedical subjects

A Cruchley

Publications and source records attributed to A Cruchley.

11 recordsLinked to original sources
PubMed2001

Mice lacking desmocollin 1 show epidermal fragility accompanied by barrier defects and abnormal differentiation.

The desmosomal cadherin desmocollin (Dsc)1 is expressed in upper epidermis where strong adhesion is required. To investigate its role in vivo, we have genetically engineered mice with a targeted disruption in the Dsc1 gene. Soon after birth, null mice exhibit flaky skin and a striking punctate epidermal barrier defect. The epidermis is fragile, and acantholysis in the granular layer generates localized lesions, compromising skin barrier function. Neutrophils accumulate in the lesions and further degrade the tissue, causing sloughing (flaking) of lesional epidermis, but rapid wound healing prevents the formation of overt lesions. Null epidermis is hyperproliferative and overexpresses keratins 6 and 16, indicating abnormal differentiation. From 6 wk, null mice develop ulcerating lesions resembling chronic dermatitis. We speculate that ulceration occurs after acantholysis in the fragile epidermis because environmental insults are more stringent and wound healing is less rapid than in neonatal mice. This dermatitis is accompanied by localized hair loss associated with formation of utriculi and dermal cysts, denoting hair follicle degeneration. Possible resemblance of the lesions to human blistering diseases is discussed. These results show that Dsc1 is required for strong adhesion and barrier maintenance in epidermis and contributes to epidermal differentiation.

Aging↗
PubMed2001

Release of recombinant human bone morphogenetic protein-2 from heterocyclic methacrylate polymer systems.

The release of recombinant human bone morphogenetic protein-2 (rhBMP-2) from three room temperature polymerising methacrylate systems has been studied. These all contained poly(ethyl methacrylate) powder, but the monomer liquids comprised, respectively, tetrahydrofurfuryl methacrylate (THFM), 90/10 THFM/hydroxyethyl methacrylate (HEMA), and 70/30 THFM/ HEMA. In all cases, rhBMP-2 was released, but the addition of 10% HEMA accelerated release (a nine-fold increase in diffusion coefficient); a further increase to 30% HEMA had no additional effect. For most of the release process, a diffusion process operated, although the early stages were not well defined. At the end of the 15 day period, the release, respectively, for the PEM/THFM, PEM:90/10 THFM/HEMA and PEM:70/30 THFM/HEMA systems was 596, 878 and 923 ng (i.e. up to 92% of the rhBMP-2 added).

Biocompatible Materials↗
PubMed1999

Protease-activated receptor-2 involvement in hypotension in normal and endotoxemic rats in vivo.

BACKGROUND: The protease-activated receptor-2 (PAR-2) is expressed by vascular endothelial cells and upregulated by lipopolysaccharide (LPS) in vitro. PAR-2 is activated by a tethered ligand created after proteolytic cleavage by trypsin or experimentally by a synthetic agonist peptide (PAR-2AP) corresponding to the new amino terminus of the tethered ligand. METHODS AND RESULTS: Intravenous administration of PAR-2AP (0.1, 0.3, and 1 mg/kg) to rats caused a dose-dependent hypotension. A scrambled peptide was without effect. A specific trypsin inhibitor, biotin-SGKR-chloromethylketone, inhibited trypsin-induced hypotension but not that stimulated by PAR-2AP. In animals treated with LPS 20 hours earlier, we found an increased sensitivity to trypsin and PAR-2AP in the hypotensive response. In particular, PAR-2AP caused hypotension at a low concentration of 30 ng/kg. Moreover, PAR-2 was immunolocalized to endothelial and smooth muscle cells in aorta and jugular vein in LPS-treated rats, and increased levels of PAR-2 mRNA were shown by reverse transcription-polymerase chain reaction analysis. CONCLUSIONS: Our findings suggest that PAR-2 is important in the regulation of blood pressure in vivo. A functional upregulation of PAR-2 by LPS was demonstrated by the activity of concentrations of PAR-2AP that were inactive in normal animals. We conclude that PAR-2 may play an important role in the hypotension associated with endotoxic shock and may represent a new therapeutic target.

Animals↗
PubMed1998

Vascular endothelial growth factor in human periodontal disease.

Vascular endothelial growth factor (VEGF) is a multifunctional angiogenic cytokine of importance in inflammation and wound healing but its presence in chronic inflammatory periodontal disease has never been reported. The aims of this study were to investigate the presence of VEGF in human periodontal tissue and gingival crevicular fluid (GCF) in periodontal health and disease. VEGF in tissue was localized by immunohistochemistry. GCF and unstimulated saliva were collected from patients and clinically healthy subjects and VEGF was assessed by using an ELISA. VEGF was detected within vascular endothelial cells, neutrophils, plasma cells and junctional, pocket and gingival epithelium. In periodontitis patients, the volume of GCF and total amount of VEGF collected from diseased sites were both greater than from clinically healthy sites (Wilcoxon test p < 0.01). However, the concentration of VEGF per unit volume of GCF was higher at healthy sites compared with diseased sites (Wilcoxon test p < 0.05). Higher concentrations of VEGF were detected in healthy sites in patients compared with similar sites in clinically healthy subjects (Mann-Whitney U-test p < 0.05). A logistic regression approach indicated that there was variation in VEGF between subjects (p < 0.01), and that age (p < 0.05), plaque (p < 0.05) and pocket depth (p < 0.07) were explanatory variables. VEGF was also detected in all saliva samples and was significantly higher in patients than in healthy controls (p < 0.05). This study suggests that VEGF could be relevant to angiogenic processes in healthy as well as diseased periodontal tissue and that the periodontal status influences the salivary level of VEGF.

Analysis of Variance↗
PubMed1996

In situ detection of the Epstein-Barr virus-encoded nuclear antigen 1 in oral hairy leukoplakia and virus-associated carcinomas.

A new monoclonal antibody has been used to examine immunohistochemically the expression of the Epstein-Barr virus (EBV)-encoded nuclear antigen (EBNA) 1 in virus-associated epithelial lesions. EBNA1 was detected in the tumour cell nuclei of 10/13 undifferentiated nasopharyngeal carcinomas and of 10/10 EBV-associated gastric carcinomas. EBNA1 was also detected in 13 of 16 oral hairy leukoplakia (HL) samples, where its expression was confined to nuclei in the upper epithelial cell layers whilst basal epithelial cells were negative. This observation is in agreement with previous studies demonstrating the absence of latent EBV infection in the basal cell compartment of HL and suggests an essential role for EBNA1, not only in latent EBV infection but also in virus replication.

Antibodies, Monoclonal↗
PubMed1993

Immunocytochemical investigation of the rat cementoblast phenotype.

Recent studies have suggested that cementoblasts may be derived from osteoblast progenitor cells, although the cementoblast phenotype has not been extensively characterized. This immunocytochemical study was carried out to investigate the expression by rat cementoblasts of a number of proteins which are characteristic of the osteoblast phenotype. Paraffin sections from developing rat tooth germs and from fully formed adult rat teeth with surrounding tissues, were incubated with antibodies to type I & III collagen, osteocalcin, transforming growth factor beta (TGE beta), and insulin-like growth factor 1 (IGF1). Frozen sections and unfixed resin-embedded sections were stained for alkaline phosphatase activity. Cementum and bone matrix were strongly positive for type I collagen, although there was only weak staining for type III collagen. Cementum was also positive for osteocalcin, which was particularly strong in the matrix of acellular cementum. Most osteoblasts and cementoblasts of the cellular cementum showed intense staining for TGF beta and IGF1, although some cementocytes and osteocytes were negatively stained. The osteoblast- specific anti-E11 mAb reacted strongly with cementoblasts and newly formed cementocytes in the cellular cementum. Cells associated with acellular cementum did not express TGF beta, IGF1 or stain positively with anti-E11 antibody at any time during root development. Cementoblasts were weakly or negatively stained for alkaline phosphatase in contrast to the osteoblasts examined, which may reflect the low level of synthetic activity in cementoblasts. These results demonstrate that osteoblasts and cementoblasts of cellular cementum share many phenotypic characteristics, and also suggest that there may be phenotypic differences between cementoblasts associated with cellular and acellular cementum.

Animals↗
PubMed1990

Quantification of plasma cells in labial salivary glands: increased expression of IgM in Sjögren's syndrome.

Plasma cells expressing IgG, IgA and IgM were quantified in labial salivary glands from patients with Sjögren's syndrome (SS) and compared with glands showing non-specific inflammatory changes and normal controls. In all glands the predominant isotype was IgA but in SS there was a significant increase in both the number and proportions of IgG and IgM positive cells (P less than 0.002). In particular, all SS cases contained greater than 10% IgM positive cells (mean = 26.8 +/- 15.5). The results suggest that accumulation of IgM positive plasma cells may be a specific finding in SS and support the concept that the glandular lesions may be a site of B-cell clonal expansion. Since most B-cell hyperproliferative states in SS, including lymphoma, are associated with synthesis of IgM simple quantification of plasma cells may have important diagnostic and prognostic significance.

Adolescent↗
PubMed1989

Epithelial HLA-DR expression in labial salivary glands in Sjögren's syndrome and non-specific sialadenitis.

The expression of the Class II major histocompatibility antigen HLA-DR was quantified in the epithelial cells of labial salivary glands from patients with Sjögrens Syndrome (SS) and compared with similar expression in glands showing non-specific sialadenitis and normal controls. In all glands more duct cells were positive than acinar cells but only in sialadenitis and SS was strong epithelial staining seen. The proportions of duct and acinar cells expressing HLA-DR were increased between normals and sialadenitis (P less than 0.01) and between sialadenitis and SS (P less than 0.001). However, for all cases increased expression of HLA-DR correlated to the increased proportion of inflammatory cells in the gland (P less than 0.01). The results indicate that although HLA-DR is expressed on the epithelial cells in the glandular lesions of SS, this is not specific as it is also seen in sialadenitis. This supports the view that such expression is secondary to an inflammatory infiltrate and may not be of importance in initiating autoimmune tissue damage.

Adolescent↗
PubMed1989

The permeability of human oral mucosa and skin to water.

Specimens from four regions of oral mucosa (palate, buccal mucosa, lateral border of the tongue, and the floor of the mouth) and of abdominal skin were taken from 58 individuals at autopsy, for determination of permeability constants (Kp) to tritium-labeled water. Comparisons between fresh specimens and those stored at -80 degrees C revealed no significant effect on Kp as a result of freezing; similar results were found with use of specimens from corresponding regions of the pig. Values for Kp were significantly different for all of the tissue regions examined and ranged from 44 +/- 4 x 10(-7) cm/min for skin to 973 +/- 33 x 10(-7) cm/min for the floor of the mouth, which was the most permeable region. Similar differences were evident among corresponding regions of porcine oral mucosa and skin. Moreover, the Kp values obtained for human tissues were not significantly different from those of the pig, except for the floor of the mouth, which was more permeable in human than in pig tissue. The results reveal interesting differences in the permeability of human oral mucosa that might be related to susceptibility to mucosal disease in those conditions where local extrinsic etiological agents are implicated.

Abdomen↗
PubMed1986

The nature of the inflammatory infiltrates in childhood gingivitis, juvenile periodontitis and adult periodontitis: immunocytochemical studies using a monoclonal antibody to HLADr.

Routinely fixed and processed gingival biopsies from childhood gingivitis, juvenile periodontitis and chronic adult periodontitis patients have been stained immunocytochemically with a monoclonal anti HLADr antibody to aid in the identification and quantification of cell types in the inflammatory infiltrates. Using immunoperoxidase staining and morphological criteria, 9 cell types were quantified in 30 patients. Lesions in the 3 groups were found to differ widely both in size and composition. In the small childhood gingivitis lesions, most cells were small lymphocytes, over half of which were HLADr positive, whereas in juvenile periodontitis biopsies, well over half the infiltrate was plasma cells. The chronic adult periodontitis samples showed greater variability in composition between these 2 extremes, perhaps reflecting differences in disease activity. These results suggest that, when disease is quiescent, the volume of inflamed gingival connective tissue is small and is dominated by B-small lymphocytes, whilst on activation, the lesion increases in size and much of the B-lymphocyte population is transformed to plasma cells. This view corroborates the results of other workers with regard to juvenile periodontitis, but suggests a different interpretation of the quiescent lesion of childhood gingivitis from that current in the literature.

Adult↗