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Biomedical subjects

A J Potts

Publications and source records attributed to A J Potts.

At least 37 records · Page 2Linked to original sources

Beta 1 integrins isolated from embryonic chicken fibroblasts bind to monomers and polymers of type I collagen.

The avian integrin beta 1 subfamily consists of multiple alpha-beta subunit heterodimers. We employed two different physical states of type I collagen, monomers and fibrils, in the isolation and characterization of avian collagen integrins. Affinity chromatography showed that three integrins, tentatively designated alpha 155 beta 1 (band 1), alpha 5a beta 1, and alpha 3 beta 1 (band 2), bind fibrillar and monomeric collagen under physiological ionic conditions and require divalent cations for binding activity. Sodium chloride gradients (0-0.5 M) were used to assess the functional ability of the integrins to remain bound to the two forms of type I collagen. The results show that integrins elute from the two forms of collagen with distinct fractionation profiles. One integrin, alpha 155 beta 1, binds fibrillar collagen with relatively higher affinity than the other beta 1 receptors. This same avian integrin, alpha 155 beta 1, is immunoreactive with an antiserum (Hynes et al., 1989) raised against a peptide that corresponds to the entire alpha 5 cytoplasmic domain, and coincidently, part of the alpha 6 cytoplasmic domain (de Curtis et al., 1991). Cell biological studies employing double immunofluorescence show that integrins recognized by this antiserum co-localize with extracellular deposits of type I collagen.

Animals↗

Detection of Epstein-Barr virus antigens and DNA in major and minor salivary glands using immunocytochemistry and polymerase chain reaction: possible relationship with Sjogren's syndrome.

This study has investigated the presence of Epstein-Barr virus (EBV) in parotid (n = 12), submandibular (n = 15), and minor salivary glands (n = 25) using immunohistochemical methods for detection of EBV-encoded antigens and the polymerase chain reaction (PCR) for detection of viral DNA. Major salivary glands were from patients without connective tissue disease. Labial glands were from patients with primary Sjogren's syndrome (n = 10), rheumatoid arthritis (n = 8), or from normal individuals (n = 7). None of the glands exhibited specific reactivity for lytic (EA-D, EA-R, VCA) or latent (EBNA-2, LMP) viral antigens. Antibodies to EA-D, when used at 20-50 times their optimal concentration, gave lumenal staining of ducts and acini of all the specimens tested (n = 14), irrespective of the presence (n = 8) or absence (n = 6) of EBV-DNA by PCR. Ductal immunoreactivity for the EBV/C3d (CR2, CD21) receptor was found in 40 per cent of specimens. PCR detected EBV-DNA in 64 per cent submandibular, 46 per cent parotid, and 80 per cent of minor glands. There were no significant differences in the detection of EBV-DNA between specimen/patient groups. Only type A EBV was detected by strain typing PCR. These results indicate that EBV (type A), undetected immunocytochemically, is commonly present at low copy numbers within salivary glands irrespective of a clinical diagnosis of Sjogren's syndrome.

Adult↗

Primed and naive helper T cells in labial glands from patients with Sjogren's syndrome.

This study has investigated the presence and distribution of B cells, T cells and T-cell subsets within labial glands of patients with primary Sjogren's syndrome (n = 9) and secondary Sjogren's syndrome associated with rheumatoid arthritis (n = 8) using a sequential double immunoperoxidase technique and true colour image analysis. The composition of the inflammatory infiltrates was similar in glands from both patient groups. B cells were normally present within large foci with few detected in diffuse infiltrates such that the ratio of T:B cells in foci (2.4:1) was significantly lower than in diffuse infiltrates (7.3:1; P less than 0.001). In all infiltrates helper T cells (CD8-, CD3+) predominated over suppressor/cytotoxic cells (CD8+, CD3+; 2.7:1). Analysis of primed (CD45RA-, CD45RO+) and naive (CD45RA+, CD45RO-) CD8- T cells showed that the ratio of the primed to naive subset was significantly higher in focal (4.2:1) compared to diffuse (1.5:1; P less than 0.001) areas of lymphoid infiltration. These results indicate that the focal lymphocytic infiltrates characteristic of Sjogren's syndrome contain B cells associated with a T-cell population consisting predominantly of primed CD8- helper T cells. This latter population may be responsible for upregulating glandular B-cell activity in Sjogren's syndrome.

Antigens, CD↗

Expression of rheumatoid factor associated cross-reactive idiotopes by glandular B cells in Sjögren's syndrome.

B cell expression of the germline gene-encoded, kappa IIIb-associated, rheumatoid factor (RF) cross-reactive idiotope (CRI) 17-109 and three VHI associated RF CRIs (G6, G8, H1) was investigated immunocytochemically in labial salivary glands from nine patients with primary and six with secondary Sjögren's syndrome, and in inflamed submandibular salivary glands from 10 patients with no history of connective tissue disease. Expression of CRIs by B cell infiltrates in labial glands from patients with primary and secondary Sjögren's syndrome were similar. Lymphoid infiltrates of labial glands from Sjögren's syndrome patients contained a higher proportion of kappa III+ cells reactive for the kappa IIIb-associated 17-109 idiotope (P less than 0.01) and larger G6 (P less than 0.02) and H1 (P less than 0.01) positive B cell populations than those within inflamed submandibular salivary glands. Furthermore, in labial glands there was a significant correlation between numbers of 17-109 and G6 idiotope reactive cells (r = 0.61; P less than 0.02), reflecting the known association between these H and L chain CRIs in RF IgM paraproteins. These results indicate that B cells bearing both VKIII and VHI-associated CRI are increased in the glandular infiltrates in Sjögren's syndrome and support the idea that this condition is associated with proliferation of immature B cell clones retaining germ-line V genes.

B-Lymphocytes↗

Embryonic chicken fibroblast collagen binding proteins: distribution, role in substratum adhesion, and relationship to integrins.

Collagen binding proteins (CBP) are hydrophobic, cell surface polypeptides, isolated by collagen affinity chromatography. Antibodies to CBPs inhibit the attachment of embryonic chicken heart fibroblasts to native type I collagen fibrils in a dose-dependent manner. The CBP antibodies also induce rounding and detachment of cells adherent to a planar substratum. This process of antibody-mediated substratum detachment resulted in a clustering of CBP and cell-associated extracellular matrix at the cell surface, and the rearrangement of filamentous actin. Other functional studies showed that cells grown within a three-dimensional gel of type I collagen cannot be immunostained at the cell surface with CBP antibodies. However, treatment of cultures with purified collagenase, unmasks immunoreactive sites and permits strong cell surface immunolabeling. This result suggests that collagen sterically blocks antibody access to CBP. Finally, we show that antibodies to CBP recognize purified avian integrin beta subunits; and that antibodies to avian integrins recognize a 100,000 Mr CBP. These data demonstrate that chicken embryonic fibroblasts possess surface polypeptides that mediate adhesion to type I collagen, and suggest that two of these proteins are related to the integrin family.

Animals↗

The medication of patients with oral lichen planus and the association of nonsteroidal anti-inflammatory drugs with erosive lesions.

While the cause of lichen planus remains unclear, a number of drugs are known to produce oral and cutaneous lesions that clinically and histologically resemble lichen planus. In this study, the medication taken by 225 consecutive patients with oral lichen planus was compared with the drug histories of 202 age- and gender-matched control patients who were treated at the same clinics. Fifty-three percent of the patients with lichen planus and 44% of the control patients were taking one or more drugs (p greater than 0.05). However, 17% of the patients with lichen planus were taking nonsteroidal anti-inflammatory drugs (NSAID) compared with 9% of the control patients (p less than 0.05). There were no significant differences in the use of antihypertensive, oral hypoglycemic, or psychotropic drugs between the two groups. Almost 30% of the patients with the more severe erosive form of lichen planus were taking NSAID while fewer than 9% of the patients without erosions were taking this type of medication indicating a relationship between NSAID and the more severe form of lichen planus (p less than 0.01). Withdrawal from NSAID resulted in resolution or marked clinical improvement in the 12 patients tested. These results indicate that oral lichen planus may be aggravated or precipitated by NSAID and that withdrawal from the drug may benefit some patients.

Anti-Inflammatory Agents, Non-Steroidal↗

Immunoglobulin-producing cells in labial salivary glands of patients with rheumatoid arthritis and systemic lupus erythematosus.

The distribution of immunoglobulin-producing cells within labial salivary glands from normal individuals (n = 7) and patients with rheumatoid arthritis (n = 10) and systemic lupus erythematosus (n = 9) was studied using morphometric and indirect immunoperoxidase methods. Cell counts revealed a significant increase in the density of IgG cells within glands from both patient groups compared with glands from normal individuals. No significant differences in the density of IgA- or IgM-producing cells between the 3 groups were observed although large individual variations were apparent. Histomorphometric studies showed an increase in the lymphoid compartment and a decrease in glandular elements within glands from the 2 patient groups. When data for all specimens were pooled a significant positive correlation was obtained between the percent area of stromal lymphoid tissue and density of IgG and IgM cells.

Adult↗

Relationship between fibronectin and lymphoid cells in buccal mucosa, labial salivary glands and palatine tonsil.

The distribution of fibronectin in human buccal mucosa and labial salivary glands and its relationship to lymphoid cells was studied using an immunoperoxidase technique and monoclonal and polyclonal antibodies. In all specimens fibronectin was associated with basement membranes of epithelia, vascular endothelium and perineural sheaths. In histologically normal areas of buccal mucosa fibronectin was distributed as a sparse network in the superficial lamina propria. A more extensive network of fibronectin was found within the lamina propria of mucosal specimens infiltrated with T lymphocytes, whereas fibronectin was absent in areas occupied by B lymphocytes. A similar relationship between lymphocyte type and the presence of a fibronectin network was found in labial glands and palatine tonsil. Fibronectin was not detected within oral, salivary gland, tonsillar crypt or capsular epithelium.

B-Lymphocytes↗

An immunohistochemical study of lymphocyte subsets and expression of glandular HLA-DR in labial salivary glands from patients with symptomatic xerostomia, rheumatoid arthritis and systemic lupus erythematosus.

Lymphocyte subsets, T+6 cells and glandular expression of HLA-DR within labial salivary glands from patients with symptomatic xerostomia (n = 9), RA (n = 24) and SLE (n = 25) were studied using an immunoperoxidase method and monoclonal antibodies. The results indicate that common immune cellular reactions are involved in glandular changes irrespective of patient group and that the appearance of T+6 cells and glandular expression of HLA-DR are unlikely to play a role in initiation of lymphoid infiltration.

Arthritis, Rheumatoid↗

T6 antigen-positive cells in human labial salivary glands.

The distribution of T6-positive cells in glands from three healthy individuals and 18 patients suffering from various systemic disorders was studied using OKT 6 and NA1/34 monoclonal antibodies in an indirect immunoperoxidase method on frozen sections. Although no positive cells were seen in the glands of healthy controls, 10 of the 18 biopsies from the patient-group contained T6-positive cells which were mostly within glandular epithelium. The presence of T6-positive cells appeared to correlate with lymphoid infiltration of the glands. Only one of the 8 patient biopsies showing normal or minimally-altered structure contained T6-positive cells. Thus these cells are unlikely to play a role in the normal physiological function of labial salivary glands.

Adult↗

Lichen planus and liver disease: how strong is the association?

One hundred and thirteen patients with histologically confirmed oral lichen planus, from three stomatology clinics, were examined for evidence of liver disease. No patient had clinical evidence of liver disease. Nine patients (7.9%) had a raised serum concentration of a single enzyme; 6 patients had raised gamma-glutamyl transpeptidase, 2 had raised alkaline phosphatase, and 1 had raised aspartate transaminase levels. No patient had serum auto-antibodies suggestive of primary biliary cirrhosis or chronic active hepatitis. Most patients presenting with oral lichen planus are unlikely to have liver disease.

Adolescent↗

Macrophages in oral lichen planus.

The presence and distribution of macrophages within 15 non-ulcerated lesions of oral lichen planus was investigated using an immunoperoxidase technique for the detection of the macrophage markers lysozyme and alpha 1 antitrypsin. All specimens contained mononuclear lysozyme and alpha 1 antitrypsin positive cells which were concentrated in a band immediately beneath the epithelium and often associated with areas of damaged basal cells. Cell counts revealed that 11% of the positive cells were in the epithelium and 89% in the lamina propria. Approximately 61% of all positive cells were found within a 125 micron wide zone centred on the basement membrane. These results suggest that in oral lichen planus macrophages are in close proximity to the epithelial basal cells, where cell damage occurs, and play a role in the pathogenesis of this condition.

Cell Count↗

Immunoglobulin-containing cells in normal human labial salivary glands.

The distribution of immunoglobulin-containing cells within 8 normal human labial salivary glands was studied using an immunoperoxidase technique. Cell counts revealed that IgA-containing cells pre-dominated in all specimens and that the mean percentage class ratios for IgG:IgA:IgM:IgD cells were 4:92:3:1. IgE cells were rare and only detected in one gland. The density of IgA cells (191 cells/mm2 of labial gland section) was greater than those previously reported for the parotid and submandibular glands. These results support the view that minor salivary glands play an important role in the synthesis and secretion of salivary antibody.

Adult↗

Oral lichen planus: an immunoperoxidase study using monoclonal antibodies to lymphocyte subsets.

Sixteen biopsies from patients with oral lichen planus (10), simple keratosis (3) and lichenoid reactions (3) were studied using monoclonal antibodies directed against lymphocyte markers. T lymphocytes predominated in the cellular infiltrates of the epithelium and lamina propria of all biopsies, and cells positive with Leu 3a and Leu 2a antibodies were also present at both sites in all specimens. However, many of the Leu 3a positive intraepithelial cells had a dendritic appearance and distribution consistent with their being Langerhans cells. Limited results from cell counts on three lichen planus specimens suggested that the majority of intraepithelial T cells were of the cytotoxic/suppressor phenotype (OKT3 and Leu 2a positive).

Antibodies, Monoclonal↗