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Biomedical subjects

N A Robinson

Publications and source records attributed to N A Robinson.

At least 19 recordsLinked to original sources
PubMed2004

Low frequency of anti-endomysial antibodies in recurrent aphthous stomatitis.

INTRODUCTION: The aetiology of recurrent aphthous stomatitis (RAS) remains unknown. An association between RAS and coeliac diseases (CD) has previously been suggested, but the supporting evidence remains equivocal. The aim of the present study was to determine the likely frequency of CD in a large cohort of patients with well-defined RAS, by detailed haematological and serological analysis, including the detection of anti-endomysium and anti-reticulin antibodies. MATERIALS AND METHODS: The study comprised 87 patients with minor RAS. Full blood counts and the presence of IgA anti-endomysial and IgA anti-reticulin antibodies were estimated in all patients. RESULTS: The frequency of anti-endomysium and anti-reticulin antibodies was not elevated in patients with RAS and no patients with RAS had other serological features of CD. CONCLUSIONS: It is concluded that there is little significant aetiological link between RAS and CD, and that screening RAS patients for key serological markers of CD is of little clinical value.

Adolescent↗
PubMed2004

Bisphosphonates--a word of caution.

There have been recent reports from various centres of a possible association between avascular necrosis of the jaws and the use of bisphosphonates. This commentary reviews the available data and alerts clinicians to a possible adverse reaction in the oral cavity to a group of drugs that are commonly prescribed.

Diphosphonates↗
PubMed2004

Oral pemphigus vulgaris: a case report and literature update.

INTRODUCTION: Pemphigus vulgaris is a rare cause of oral mucosal ulceration. CLINICAL PICTURE: A 47-year-old Chinese man presented with a 3-month history of oral ulceration. There were no lesions on the skin or other mucosal sites. Histology and immunostaining were consistent with pemphigus vulgaris. TREATMENT: Systemic and topical corticosteroids were instituted, together with topical antifungals. Conventional periodontal therapy was carried out to improve gingival/oral health. OUTCOME: Control of oral ulceration was achieved with re-establishment of normal oral function. No other sites to date have been involved. CONCLUSIONS: Chronic oral ulceration can be the sole manifestation of pemphigus vulgaris, at least initially. Early recognition of this lesion may prevent delayed diagnosis and inappropriate treatment of a potentially chronic dermatological condition.

Antifungal Agents↗
PubMed2003

Desquamative gingivitis: a sign of mucocutaneous disorders--a review.

Desquamative gingivitis is a clinical term to describe red, painful, glazed and friable gingivae which may be a manifestation of some mucocutaneous conditions such as lichen planus or the vesiculobullous disorders. It is important to be aware of this rare clinical entity so as to distinguish desquamative gingivitis from plaque induced gingivitis which is an extremely common condition, easily recognized and treated daily by the dental practitioner. This article gives an overview of desquamative gingivitis, its presentation, the possible causes, diagnosis and treatment. Early recognition of these lesions may prevent delayed diagnosis and inappropriate treatment of potentially serious dermatological diseases.

Diagnosis, Differential↗
PubMed2001

Gene flow on the ice: genetic differentiation among Adélie penguin colonies around Antarctica.

Each summer Adélie penguins breed in large disjunct colonies on ice-free areas around the Antarctic continent. Comprising > 10 million birds, this species represents a dominant feature of the Antarctic ecosystem. The patchy distribution within a large geographical range, natal philopatry and a probable history of refugia, suggest that this species is likely to exhibit significant genetic differentiation within and among colonies. We present data from seven microsatellite DNA loci for 442 individuals from 13 locations around the Antarctic continent. With the exception of one locus, there was no significant genic or genotypic heterogeneity across populations. Pairwise FST values were low with no value > 0.02. When all colonies were compared in a single analysis, the overall FST value was 0.0007. Moreover, assignment tests were relatively ineffective at correctly placing individuals into their respective collection sites. These data reveal a lack of genetic differentiation between Adélie penguin colonies around the Antarctic continent, despite substantial levels of genetic variation. We consider this homogeneity in terms of the dispersal of individuals among colonies and the size of breeding groups and discuss our results in terms of the glacial history of Antarctica.

Animals↗
PubMed2000

The carboxy-terminal hydrophobic domain of TIG3, a class II tumor suppressor protein, is required for appropriate cellular localization and optimal biological activity.

TIG3 is a recently discovered class II tumor suppressor protein, originally isolated from retinoid-treated cultured epidermal keratinocytes, that suppresses the proliferation of a variety of epithelial cell types. In the present study, we examine the ability of this protein to reduce CHO, T47D and HaCaT cell proliferation, and the role of the carboxy-terminal hydrophobic domain in this regulation. Vector-mediated expression of the full length TIG3 protein, TIG31-164, results in a 50-70% reduction colony formation efficiency. Expression of a truncated mutant, TIG31-134, that lacks the putative carboxy-terminal membrane-anchoring domain, results in a partial loss of ability to suppress colony formation. The fact that the truncated protein remains partially active suggests that both the amino- and carboxy-terminal regions of TIG3 are required for optimal growth suppression. The full-length protein is distributed in a perinuclear location, and is not present in the nucleus. TIG31-134, in contrast, is distributed in the cytoplasm. Thus, a change in location is associated with the partial loss of activity. We also monitored the distribution of green fluorescent protein (GFP)-TIG3 fusion proteins. GFP-TIG31-164 was localized in a pattern similar to that observed for TIG31-164, while GFP-TIG31-134 displayed a distribution pattern similar to GFP. This suggests that the c-terminal hydrophobic domain has an important role in determining the intracellular localization of TIG3. In addition, GFP-TIG31-164 retains the ability to inhibit cell function, while GFP-TIG31-134 is inactive.

Amino Acid Sequence↗
PubMed2000

Expression of a retinoid-inducible tumor suppressor, Tazarotene-inducible gene-3, is decreased in psoriasis and skin cancer.

Tazarotene-induced gene-3 (TIG-3), isolated from human keratinocytes treated with the retinoic acid receptor-selective retinoid Tazarotene, is homologous to H-rev, a class II tumor suppressor. TIG-3 gene localized to chromosome 11q23, a site of loss of heterozygosity in several malignancies. Retinoids influence epidermal differentiation and are used to treat and prevent skin cancer. Therefore, we studied TIG-3 mRNA expression in psoriasis and in basal and SCCs by in situ hybridization and a quantitative QT-RT-PCR assay. Psoriasis lesions had significantly lower staining (median, 3) than paired normal control skin (median, 4; P = 0.012). TIG-3 mRNA was significantly higher in normal control skin (P = 0.001), in paired adjacent skin (median, 3; P = 0.007), and in overlying epidermis (median, 3.0; P = 0.0001) than in 21 SCC specimens as a group (median, 1.5).

Aged↗
PubMed2000

Lichenoid tissue reactions of the oral mucosa.

The lichenoid tissue reaction (LTR) is characterised by epidermal basal cell damage and a variable subepithelial inflammatory infiltrate. There is a range of mucosal lesions exhibiting the LTR, chief of which is Oral Lichen Planus (OLP). The other oral lichenoid lesions resemble OLP clinically and histologically and at times it can be difficult to differentiate between the lesions. The important oral lichenoid lesions are reviewed in this paper.

Dental Amalgam↗
PubMed1999

Should UK emergency physicians undertake diagnostic ultrasound examinations?

From the published evidence there is no doubt that emergency physicians in America can undertake focused ultrasound examinations and that, by extrapolation, this would also be the case for UK emergency physicians. If this skill is to become part of the diagnostic armamentarium of the emergency physician, however, it needs to be demonstrated to be cost effective compared with the alternatives already available to the hospital. Trials to test for this benefit should adopt a hospital and not an emergency department perspective if the results are to influence health policy and specialty training.

Clinical Competence↗
PubMed1998

Identification of transglutaminase-reactive residues in S100A11.

The recent finding that S100A11 is a component of the keratinocyte cornified envelope (CE) (Robinson, N. A., Lapic, S., Welter, J. F., and Eckert, R. L. (1997) J. Biol. Chem. 272, 12035-12046) suggests that S100A11 is a transglutaminase (TG) substrate. In the present study we show that S100A11 forms multimers when cultured keratinocytes are challenged by increased levels of intracellular calcium and that multimer formation is inhibited by the TG inhibitor, cystamine. These S100A11 multimers appear to be incorporated into the CE, as immunoreactive S100A11 is detected in purified envelopes prepared from cultured cells and from foreskin epidermis. To study S100A11 as a transglutaminase substrate, recombinant human S100A11 (rhS100A11) was used in a cell-free cross-linking system. [14C]Putrescine, a primary amine, labels rhS100A11 in a TG-dependent manner. Trypsin digestion of [14C]putrescine-labeled rhS100A11 releases one radiolabeled peptide, Ala98-Lys103. The glutamine residue in this segment, Gln102, is the site of radiolabel incorporation indicating that Gln102 functions as an amine acceptor. The ability of S100A11 to form multimers indicates that it also has a reactive lysine residue that functions as an amine donor. To identify the reactive residue, we compared the high pressure liquid chromatography profile of trypsin-digested rhS100A11 monomer to that of cross-linked rhS100A11. A unique cross-linked peptide was purified and identified as Met-Ala-Lys3-Ilu-Ser-Ser-Pro-Thr-Glu-Thr-Glu-Arg cross-linked via an Lys3-Gln102 isopeptide bond to Ala-Val-Pro-Ser-Gln102-Lys. These studies show that S100A11 is post-translationally modified by transglutaminase, that it can be cross-linked to form multimers, that it is present in CEs from cultured keratinocytes and in vivo epidermis, and that Lys3 and Gln102 are specific sites of cross-link formation.

Cell Compartmentation↗
PubMed1998

In vitro cross-linking of recombinant human involucrin.

Human involucrin (hINV) is a constituent of the scaffolding of the cornified envelope. In the present study, we describe an in vitro model system to study the role of hINV in scaffold formation. We characterize the in vitro cross-linking of full-length (585 amino acid) recombinant hINV, rhINV(1-585). When reacted with detergent-solubilized, particulate transglutaminase type 1 (TG1) or partially purified type 2 transglutaminase (TG2), rhINV(1-585) functions as a TG substrate in a calcium-dependent manner. When the reaction is supplemented with 14C-putrescine tracer, the radiolabeled cosubstrate is incorporated into a high-molecular-weight product in a calcium-, rhINV(1-585)- and time-dependent manner. 35S-rhINV(1-585) is also cross-linked to form a high-molecular-weight product. These results suggest that rhINV(1-585) is extensively multimerized. Products having a molecular weight smaller than authentic rhINV(1-585) are also formed, providing evidence for intramolecular cross-link formation. Transmission electron microscopy of cross-linked product reveals immunoreactive large-molecular-weight loop-string-loop and branched structures. Our studies (1) show that rhINV(1-585) is a substrate for both TG1 and TG2, (2) indicate that rhINV(1-585) can be cross-linked to form macromolecular products having distinct structural features, (3) demonstrate that rhINV(1-585) forms intramolecular cross-links when hINV concentration is limiting and (4) establish that hINV possesses reactive Gln and Lys residues.

Bacteria↗
PubMed1997

S100A11, S100A10, annexin I, desmosomal proteins, small proline-rich proteins, plasminogen activator inhibitor-2, and involucrin are components of the cornified envelope of cultured human epidermal keratinocytes.

The cornified envelope (CE) is an insoluble sheath of epsilon-(gamma-glutamyl)lysine cross-linked protein, which is deposited beneath the plasma membrane during keratinocyte terminal differentiation. We have probed the structure of the CE by proteolytic cleavage of purified CE fragments isolated from CEs formed spontaneously in cell culture. CNBr digestion, followed by trypsin and then proteinase K treatment released 25%, 42%, and 18%, respectively, of the CE protein. Purification and sequencing of released peptides has identified two novel CE precursors, S100A11 (S100C, calgizzarin) and S100A10 (calpactin light chain). We also sequenced peptides derived from annexin I and plasminogen activator inhibitor 2, two putative envelope precursors, as well as portions of the well established CE precursor proteins SPR1A, SPR1B, and involucrin. Many desmosomal components were identified (desmoglein 3, desmocolin A/B, desmoplakin I, plakoglobin, and plakophilin), indicating that desmosomes become cross-linked into the CE. Fragments derived from envoplakin, the recently sequenced 210-kDa membranous CE precursor protein, which also appears to be a desmosomal component, were also identified. Analysis of the pattern of peptide release following the sequential digestion indicates that S100A11 is anchored to the envelope via Gln102 and/or Lys103 at the carboxyl terminus and at Lys3, Lys23, and/or Gln22 in the amino terminus. A similar type of analysis indicates that small proline-rich proteins 1A and 1B (SPR1A and SPR1B) become cross-linked at the amino terminus (residues 1-23) and the carboxyl terminus (residues 86-89). No loricrin, cystatin A, or elafin peptides were detected.

Amino Acid Sequence↗
PubMed1997

The epidermal keratinocyte as a model for the study of gene regulation and cell differentiation.

The epidermis is a dynamic, continually renewing structure that provides the organism with a life-sustaining interface with the environment. The major cell type of the epidermis, the epidermal keratinocyte, undergoes a complex and carefully choreographed program of differentiation. Aberrations in this process result in the genesis of a variety of debilitating and life-threatening diseases. In the present paper, we discuss the keratinocyte differentiation program and the exogenous agents that regulate differentiation. We describe the marker genes that have been utilized to study the process of gene regulation in epidermis. We describe the keratin proteins and studies that have identified keratin mutations that cause epidermal disease. We present recent information on regulation of keratinocyte gene expression and attempt to summarize current knowledge on the role of transcription factors in this process. We also discuss the process of cornified envelope assembly and the structure and function of the proteins that are thought to be precursors of this structure.

Animals↗
PubMed1996

Involucrin is a covalently crosslinked constituent of highly purified epidermal corneocytes: evidence for a common pattern of involucrin crosslinking in vivo and in vitro.

Involucrin (hINV) is an important structural component of the keratinocyte cornified envelope that is expressed early in the keratinocyte differentiation process and is thought to be a component of the initial envelope scaffolding. We have previously shown that cyanogen bromide (CNBr) cleavage of cornified envelopes isolated from cultured foreskin keratinocytes releases several discrete involucrin-immunoreactive peptides. In this study, we compare the pattern of release of immunoreactive hINV fragments from envelopes prepared from human breast skin and foreskin, and from spontaneous and induced envelopes prepared from cultured keratinocytes. We also identify one of the released products. Envelopes prepared from human breast skin or foreskin, or spontaneous or induced envelopes prepared from cultured cells differ significantly in structure. The envelopes isolated from epidermis appear to be structurally complete, whereas spontaneous envelopes appear less complete and the induced envelopes appear to be the least complete. In spite of these structural differences, CNBr cleavage releases an identical quartet of hINV-immunoreactive peptides migrating between 68 and 81 kDa from each preparation. Immunoblots indicate that the quantity of hINV-immunoreactive material released per microg of envelope protein is as follows: induced > spontaneous > foreskin > breast skin. The fastest migrating peptide (68 kDa) comigrates with a peptide that is released after CNBr cleavage of bacterially produced-recombinant hINV. Amino-terminal amino acid sequencing of this peptide from recombinant hINV and from the cornified envelopes yields the sequence G-Q-L-K-H-L-E-Q-Q-E-G-Q-P-K-H. These results suggest that this fragment is the 275-amino acid segment of hINV beginning at G311 and extending to K585, and that this peptide is not crosslinked to another protein. These results indicate that a population of the envelope-associated hINV present in cultured and in vivo keratinocytes is crosslinked in the amino-terminal half. It is possible that this species represents an early intermediate in the involucrin crosslinking process.

Amino Acid Sequence↗
PubMed1996

Microsatellite differentiation between Phillip Island and mainland Australian populations of the red fox Vulpes vulpes.

Predation by the red fox Vulpes vulpes is believed to be threatening the little penguin Eudyptula minor on Phillip Island in Victoria. Polymorphism at seven microsatellite loci was examined to estimate the extent of differentiation between Phillip Island and mainland populations of V. vulpes. Loss of alleles has occurred on Phillip Island where foxes first appeared approximately 88 years ago compared with mainland populations. Genetic differentiation between the Phillip Island and mainland populations was high. The relatively high differentiation found between the two populations could be due to either low migration rates, the effect of the composition of founder animals or both effects. Further ecological and historical information about the populations is needed to explore the likely significance of these effects.

Alleles↗