Biomedical subjects

R K Simmons

Publications and source records attributed to R K Simmons.

8 recordsLinked to original sources

PubMed2006

How much might achievement of diabetes prevention behaviour goals reduce the incidence of diabetes if implemented at the population level?

AIMS/HYPOTHESIS: Randomised trials targeting high-risk people with impaired glucose tolerance have halved progression to diabetes using behavioural interventions aimed at achieving five goals related to weight, diet and physical activity. The number of people currently meeting these goals in the general population is unknown. The potential impact on the incidence of diabetes of increasing the proportion of people who meet these goals is also unclear. We quantified the association between the achievement of behavioural goals for the prevention of diabetes and the incidence of diabetes in a population-based cohort study. SUBJECTS AND METHODS: European Prospective Investigation into Cancer (EPIC)-Norfolk is a prospective cohort of 24,155 participants aged 40-79 years who attended a baseline health check and completed validated diet and activity questionnaires. We assessed the association between achievement of five diabetes healthy behaviour prevention goals (BMI <25 kg/m(2), fat intake <30% of energy intake, saturated fat intake <10% of energy intake, fibre intake > or =15 g/4,184 kJ, physical activity >4 h/week) and risk of developing diabetes at follow-up (mean 4.6 years). RESULTS: Only 20% of EPIC participants met three or more diabetes prevention goals. Diabetes incidence was inversely related to the number of goals achieved (p<0.001). None of the participants who met all five goals developed diabetes, whereas diabetes incidence was highest in those who did not meet any goals. If the entire population were able to meet one more goal, the total incidence of diabetes would be predicted to fall by 20%. CONCLUSIONS/INTERPRETATION: In this population-based study, the risk of diabetes was inversely associated with the number of behaviour goals for diabetes prevention that were met. Interventions that promote achievement of these goals in the general population could significantly reduce the growing burden of diabetes-related morbidity and mortality.

Adult↗

PubMed2005

Patch test value.

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Dental Amalgam↗

PubMed2001

Identification of ocular cicatricial pemphigoid antibody binding site(s) in human beta4 integrin.

PURPOSE: To identify specific site(s) on human ss4 molecule to which sera from ocular cicatricial pemphigoid (OCP) patients bind and to determine its role in the process of blister formation. METHODS: Clone the fragments representing the extracellular and intracellular domain of ss4 molecule from normal human conjunctival mRNA into an expression vector; map the region to which sera from OCP patients bind by Western blot analysis. Determine the role of the immunodominant region in pathogenesis by demonstrating the ability of the rabbit antibody to the immunodominant region to produce separation of basement membrane zone (BMZ) from the basal epithelial layer when incubated with normal human conjunctiva in an in vitro organ culture model. RESULTS: Majority of the OCP sera tested bound to the C-terminal end of the intracellular domain (IC3.0) of the human ss4 integrin. Further subcloning of IC3.0 demonstrated that a smaller fragment extending from 1489 aa to 1572 aa (IC3.4) was responsible for this binding. This region may have multiple antibody binding sites. Antibody to human IC3.0 and IC3.4 produced in rabbit, resulted in BMZ separation, histologically identical with that observed when normal human conjunctiva was cultured with OCP sera in an human conjunctival organ culture model. CONCLUSIONS: These observations identify IC3.4 as the antibody binding site for sera of OCP patients and suggest a possible role for it in blister formation. Indirectly it highlights certain important aspects of the structural and functional dynamics of the biology of the hemidesmosomes and basement membranes.

Animals↗

PubMed2001

Transferring genes to salivary glands.

This review provides a brief description of gene transfer studies using salivary glands as the target tissue. The aggregate results demonstrate the potential clinical value of this methodological approach for managing several conditions lacking fully satisfactory conventional treatments. Routine clinical applications are still seven to ten years away, primarily because of the need for improved gene transfer vectors. Overall, this body of work provides the dental educator with a substantive example of how biotechnological progress will significantly affect the treatment of oral problems in the near future.

Adenoviridae↗

PubMed2000

The autoantibodies to alpha 6 beta 4 integrin of patients affected by ocular cicatricial pemphigoid recognize predominantly epitopes within the large cytoplasmic domain of human beta 4.

This study was undertaken to characterize the antigenic determinants recognized by the autoantibodies of patients with ocular cicatricial pemphigoid (OCP). OCP is a subepithelial, blistering, autoimmune disease that mainly affects the conjunctiva and other mucous membranes. We previously demonstrated that a cDNA clone, isolated from a keratinocyte expression library by using immunoaffinity-purified OCP autoantibody, encoded the cytoplasmic domain of beta 4 integrin subunit. Our subsequent studies showed that sera from all the OCP patients that were tested recognize the human beta 4 integrin subunit. To identify the prevalent epitopes of the anti-beta 4 autoantibodies of OCP, we have used cell lines transfected with vectors encoding a wild-type beta 4 subunit, a tailless beta 4 subunit, or a beta 4 subunit lacking the extracellular domain. Nontransfected cell lines were used as controls. Lysates from these cell lines were analyzed with OCP sera, IgG fractions from OCP sera, and immunoaffinity-purified OCP autoantibodies. Abs to extracellular and cytoplasmic domains of human beta 4 integrin were used as positive controls, whereas normal human sera and normal human IgG fractions were used as negative controls. The reactivity of OCP Abs was determined by using immunoblotting, immunoprecipitation, and FACS analysis. The results of this study indicate that OCP sera, OCP IgG fractions, and immunoaffinity-purified OCP autoantibodies react with the intracellular and not the extracellular domain of human beta 4 integrin subunit. In vitro cell culture experiments demonstrated that OCP autoantibody binds to the cytoplasm of the cells. The relevance of these findings to the pathogenesis of OCP is discussed.

Animals↗

PubMed1999

Contemporary issues in the diagnosis of oral pemphigoid: a selective review of the literature.

Pemphigoid is a group of bullous diseases that have a diversified morphologic presentation and affect the skin, oral mucosa, and other mucosal membranes, alone or in combination. In the literature, the condition has been subclassified into bullous pemphigoid and cicatricial pemphigoid (mucous membrane pemphigoid) on the basis of the primary organ of involvement. In addition to the clinical presentation and a subepithelial vesicle or bullae on routine histologic analysis, the diagnosis is based on direct and indirect immunofluorescence studies. Recent investigations indicate that different clinical groups of patients with pemphigoid produce autoantibodies to different molecules within the basement membrane zone. Based on these recent observations and a review of the literature, a viewpoint is presented that not all patients with cicatricial pemphigoid should be grouped together. Rather, they should be classified into subgroups-ocular, oral, etc-on the basis of the clinical phenotype and long-term follow-up. Such a division will facilitate the provision of appropriate and relevant treatment plans; if the clinical course changes, the diagnosis can be adjusted. This strategy will prevent patients with disease limited to the oral cavity from receiving systemic drugs or agents that may be more harmful than beneficial.

Fluorescent Antibody Technique↗

PubMed1999

Biology of IL-5 in health and disease.

LEARNING OBJECTIVES: Reading this article will increase the readers' knowledge of the biology of interleukin-5 (IL-5), an important cytokine. The immune and inflammatory responses of any organism are the basis of the defense mechanism ensuring its survival. The role of IL-5 in these processes, as well as in the pathogenesis of various diseases has been discussed along with the effects of various pharmacologic agents on the production and function of IL-5. DATA SOURCES: A detailed literature search was performed. Studies considered relevant and important, in all languages, which involved humans and animals were used. STUDY SELECTION: Information was obtained only from peer reviewed journals. RESULTS: Interleukin-5 is normally produced by T-cells, mast cells, and eosinophils while Reed Sternberg and Epstein Barr virus (EBV) transformed cells also produce IL-5. Monoclonal antibodies (mAb) to IL-5 are potent inhibitors of IL-5 mediated tissue damage, secondary to eosinophil infiltration. The majority of the studies on IL-5 are preliminary, often the information is obtained from animal studies or in vitro systems and occasionally from pathologic tissue analysis. This along with the absence of confirmatory studies is a limiting factor. Nonetheless, the role of IL-5 in allergic and immunologic disease and asthma may be central to their pathogenesis. CONCLUSIONS: Interleukin-5 is an important molecule that is participant to many processes that maintain health and are involved directly or indirectly in the pathogenesis of disease. Some pharmacologic agents can modify IL-5 production in vivo. Development of selective inhibitors of IL-5 may have a potential use for specific therapy of certain autoimmune, inflammatory, and neoplastic diseases.

Animals↗

PubMed1999

The role of antibody to human beta4 integrin in conjunctival basement membrane separation: possible in vitro model for ocular cicatricial pemphigoid.

PURPOSE: To demonstrate the specific binding of autoantibodies present in the sera of patients with ocular cicatricial pemphigoid (OCP) to human beta4 integrin present in the normal human conjunctiva (NHC) and to study the role of OCP autoantibodies and antibody to human beta4 integrin in the pathogenesis of subepithelial lesion formation in OCP. METHODS: Indirect immunofluorescence assay and in vitro organ culture method using NHC were used. Sera and IgG fractions from 10 patients with OCP; immunoaffinity-purified OCP autoantibody; antibodies to human beta4, beta1, alpha6, and alpha5 integrins; and sera from patients with pemphigus vulgaris, bullous pemphigoid (BP), and chronic atopic and chronic ocular rosacea cicatrizing conjunctivitis; and normal human serum (NHS) were used. RESULTS: Nine of 10 OCP sera or IgG fractions, immunoaffinity-purified OCP autoantibody, antibodies to human beta4 and alpha6 integrins, and sera from patients with BP showed homogenous, smooth linear binding along the basement membrane zone (BMZ) of the NHC. NHS, antibodies to other integrins, and sera from patients with chronic cicatrizing conjunctivitis from other causes showed no such binding. When NHC was first absorbed with OCP sera and then reacted with anti-beta4 antibodies or vice versa, the intensity of the BMZ binding was dramatically reduced or completely eliminated, indicating that there were autoantibodies in OCP sera specific for the beta4 integrin. BMZ separation developed 48 to 72 hours after addition of total OCP sera, IgG fractions from OCP sera, immunoaffinity-purified autoantibodies from sera of patients with OCP, or anti-beta4 antibodies to the NHC cultures, but not after addition of normal control sera, sera from patients with chronic cicatrizing conjunctivitis from causes other than OCP, or sera from patients with OCP in clinical remission. CONCLUSION: Circulating anti-beta4 integrin antibody may have an important role in the pathogenesis of OCP.

Antigens, CD↗