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Biomedical subjects

Anthony P Corfield

Publications and source records attributed to Anthony P Corfield.

9 recordsLinked to original sources
PubMed2006

Alterations in the composition of the supramucosal defense barrier in relation to disease severity of ulcerative colitis.

Mucin glycoproteins and trefoil peptides play an important role in protection and repair of the gastrointestinal epithelium. This study investigates alterations in mucin and trefoil peptide gene expression and product localization in ulcerative colitis (UC). Product localization and message expression of mucin MUC1 to 6 and trefoil peptide TFF1 to 3 genes was analyzed in rectosigmoid tissue from a cohort of patients with active UC and compared with that of normal colorectal mucosa. MUC1 expression was upregulated in severe UC at the site of rupture of crypt abscesses. Reduction in MUC2 expression occurred in UC adjacent to ulceration. No alteration in MUC3 or MUC4 gene expression was detectable in UC compared with normal colorectal mucosa. No ectopic expression of MUC5AC, MUC5B, or MUC6 was identified in UC. Ectopic TFF1 expression was identified in tissues eliciting histological features of severe disease. Decreased TFF3 localization was demonstrated in UC tissues, but no TFF2 expression was detected in any colorectal specimens. Subtle alterations in composition of the supramucosal defense barrier exist in UC and vary in relation to clinical severity of disease. There is upregulation in mucin MUC1 at crypt abscesses and neo-expression of TFF1 trefoil peptide in severe disease.

Adult↗
PubMed2005

A novel bacterial mucinase, glycosulfatase, is associated with bacterial vaginosis.

The modifications to the vaginal habitat accompanying a change to vaginal flora in bacterial vaginosis (BV) are poorly understood. In this study enzymes involved in mucin degradation were measured, including a novel glycosulfatase assay. Women attending an emergency walk-in sexually transmitted disease clinic were studied. One high vaginal swab (HVS) was used to prepare a gram-stained smear to determine BV status, using Ison and Hay's criteria, and a separate swab was used for the purposes of the assays. The median glycosulfatase activity was 8.5 (range, -1.2 to 31.9) nmol h(-1) 1.5 ml(-1) of HVS suspension in patients with BV compared to 0.5 (range, -0.7 to 9.4) nmol h(-1) 1.5 ml(-1) of HVS suspension in patients without BV (P = <0.001). The median glycoprotein sialidase activity was 29.2 (range, -17 to 190) nmol h(-1) 1.5 ml(-1) of HVS suspension in patients with BV compared to -1.1 (range, -41 to 48) nmol h(-1) 1.5 ml(-1) of HVS suspension in patients without BV (P < 0.001). A rapid spot test for sialidase was positive in 22/24 patients with BV (sensitivity, 91.7%; 95% confidence interval [CI], 73 to 99%) and negative in 32/35 patients without BV (specificity, 91.4%; 95% CI, 76.9 to 98.2%) (P < 0.001). Glycosulfatase activity significantly correlated with both glycoprotein sialidase activity and the sialidase spot test (P = 0.006 and P < 0.001, respectively). The results are consistent with the hypothesis that the consortium of bacteria present in BV requires the ability to break down mucins in order to colonize the vagina and replace the normal lactobacilli.

Adolescent↗
PubMed2004

Glycopolymer charge density determines conformation in human ocular mucin gene products: an atomic force microscope study.

Atomic force microscopy (AFM) has been applied to the study of heterogeneity in the structure and function of individual biopolymers with complex structures such as glycoproteins, polysaccharides and nucleic acids. In this work we describe experiments which shed light on the heterogeneity of human ocular mucin gene products. By separating samples of native human ocular mucins on a caesium chloride density gradient, at least three populations consisting predominantly of products of the gene MUC5AC can be identified. Separation on the caesium chloride density gradient is governed by molecular architecture and charge density, and thus provides a route to the discrimination between different glycoforms within a glycoprotein sample. AFM images of these populations show that each is characterised by different conformational properties and polymer diameters, both of which can be attributed to differences in the degree and nature of glycosylation. These differences in glycosylation are likely to be the result of post-translational processing and may also have functional consequences. The AFM's ability to examine the composition of a predominantly single gene product population at the level of the single molecule allows the consequences of post-translational process heterogeneity to be examined at high resolution.

Biopolymers↗
PubMed2004

Increased airway mucins after cardiopulmonary bypass associated with postoperative respiratory complications in children.

OBJECTIVE: Airway mucins may play an important role in the mechanism of respiratory complications after cardiopulmonary bypass in infants and children. Our aim was to measure airway mucin levels before and after cardiopulmonary bypass and to determine whether changes in mucin levels were associated with the development of respiratory complications. METHODS: Airway glycoprotein and mucins (MUC5AC, MUC5B, and MUC2) in serial small-volume airway lavage samples from 39 young children who underwent cardiac operations with cardiopulmonary bypass were measured by slot-blot assay with specific antimucin peptide antibodies. The relationship between mucin changes and post-cardiopulmonary bypass respiratory complications was investigated. Airway lavage samples were also collected from 11 children before and after operation without cardiopulmonary bypass, and changes in mucin levels were compared with those in subjects who underwent cardiopulmonary bypass. Airway lavage sample DNA was also measured to investigate the relationship between mucin changes and lung injury. RESULTS: Glycoprotein, MUC5AC, and MUC5B levels were significantly increased after cardiopulmonary bypass (P <.001) whereas MUC2 level was not. Children with respiratory complications showed significantly higher glycoprotein and MUC5AC levels than did children without respiratory complications before and after cardiopulmonary bypass (P <.05). Increase of total mucin (MUC5AC, MUC5B, and MUC2) during cardiopulmonary bypass showed positive correlation with DNA increase during cardiopulmonary bypass (r = 0.73), PaCO(2) (r = 0.62) and alveolar-arterial oxygen difference (r = 0.55) immediately after cardiopulmonary bypass. Increase of total mucin was associated with postoperative respiratory complications and their severity. There were no significant changes detected in airway mucin during operations without cardiopulmonary bypass. CONCLUSIONS: Airway mucins were increased during cardiopulmonary bypass, and this increase was associated with markers of lung injury after cardiopulmonary bypass and with the development of postoperative respiratory complications.

Biomarkers↗
PubMed2003

Patterns of mucin adherence to contact lenses.

PURPOSE: Contact lens wear alters the preocular fluid through factors that include tear deposits on the lens. In the current study, lens-adherent material was extracted to assess whether contact lenses sample mucins from the preocular fluid. METHODS: Discarded extended-wear contact lenses were collected from patients with no ocular surface disease. Mucins were extracted in guanidine hydrochloride (GuHCl) with protease inhibitors. After the supernatant was removed, the extraction was repeated twice with the addition of 10 mM dithiothreitol, making a total of three extractions. Mucins were isolated by cesium chloride (CsCl) gradient centrifugation and size fractionated on Sepharose CL2B. Charge distribution was analyzed on ion-exchange chromatography with a lithium perchlorate (LiClO(4)) gradient. RESULTS: Contact lens-adherent mucins comprised soluble mucins and mucins that required solubilization by (repeated) dithiothreitol treatment. MUC1, MUC4, MUC2, and MUC5AC mucins eluted mainly at low buoyant densities in extractions from lenses worn long term without disinfection and at successively higher buoyant densities from monthly disposable contact lenses. Mucins with little negative charge, which were observed in all extractions, and very highly negatively charged species, present in the second and third extractions from contact lenses, had no equivalents in tissue-extracted mucins. CONCLUSIONS: Mucins adhering to contact lenses are altered forms of intracellular mucins. Different degrees of adherence of mucins to contact lenses may occur, either because of mucin characteristics or after mucin complexation with adherent materials. In the context of good contact lens hygiene, their presence may offer some protection from toxicants in the tear film, because mucins could function as acceptors for charged moieties such as free radicals.

Chromatography, Ion Exchange↗
PubMed2003

Characterization of mucins in human lacrimal sac and nasolacrimal duct.

PURPOSE: Mucins are polymers that may reduce drag and enhance tear outflow. Mucin expression and distribution in human efferent tear ducts were tested in the physiological state, and potential differences in the expression pattern were investigated in the presence of primary acquired dacryostenosis (PANDO). METHODS: Expression of mucins in human lacrimal sac and nasolacrimal ducts was monitored by reverse transcription-polymerase chain reaction analysis. The presence and distribution of MUC1, -2, -4, -5AC, -5B, -6, and -7 in epithelia of the efferent tear duct passage are assessed with antisera to mucin peptide cores. Twenty normal tissues from cadavers and surgical specimens from 20 patients with PANDO were tested. RESULTS: mRNAs for all mucins investigated were detected in healthy human lacrimal sacs and nasolacrimal ducts. MUC6 mRNA was detected in only about half of the investigated samples. A reduced level of MUC2, -5AC, and -5B mRNAs was observed in PANDO. Immunohistochemistry revealed MUC2 in goblet cells and single epithelial cells. Both MUC5AC and -5B were detected in goblet cells forming intraepithelial mucous glands. MUC7 was present only in columnar epithelial cells of the efferent tear duct system. No immunoreactivity was observed with antibodies against MUC1, -4, and -6 peptide cores. CONCLUSIONS: Human efferent tear ducts express and produce a broad spectrum of mucins that is partly comparable with that in the conjunctiva and the salivary glands. The mucin diversity of the efferent tear ducts could enhance tear transport and antimicrobial defense. Reduced levels of mucin mRNA in a nonfunctioning though patent segment of the lacrimal passage, which is associated with epiphora, suggests that mucins ease tear flow through the efferent tear ducts.

Adult↗
PubMed2002

Mucin expression in the ileoanal reservoir reflects incomplete mucosal adaptation.

Restorative proctocolectomy is regarded as a standard surgical procedure for patients who require a proctocolectomy for ulcerative colitis and familial adenomatous polyposis. The ileal mucosa undergoes colonic phenotypic change with time, but the extent and relevance of these changes to the long-term safety of the ileoanal pouch are unclear. The aim of this study was to study the mucin biology of this adaptive process in order to assess its extent and possible impact on pouch safety. Ileoanal pouch biopsies from a cohort of patients and normal ileal and colonic controls were subjected to histological, biochemical, histochemical, and immunohistochemical mucin analysis. Mucin sulphation and sialic acid O-acetylation were studied as parameters of colonic phenotypic change. Fifty-one patients, 16 ileal, and 22 colonic controls were studied. Seventy per cent of biopsies retained villous mucosal architecture, with no cases of dysplasia detected. Ileoanal pouch mucosal sulphation and sialic acid O-acetylation did not reach colonic levels, thus indicating limited evidence for a more colonic phenotype. The data from this study suggest that colonic phenotypic change within the ileoanal reservoir is incomplete, with no cases of dysplasia detected. The degree of phenotypic change is less than in previous studies, which may support, but not prove, our hypothesis that there may be a process of reversion to an ileal type mucosa in the ileoanal reservoir with time.

Adaptation, Physiological↗