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Biomedical subjects

K Barton

Publications and source records attributed to K Barton.

At least 37 records · Page 2Linked to original sources
PubMed1997

Inflammatory cytokines in the tears of patients with ocular rosacea.

OBJECTIVE: The purpose of the study is to compare tear fluid concentrations of interleukin-1alpha (IL-1alpha), tumor necrosis factor-alpha (TNF-alpha), and epidermal growth factor (EGF) in ocular rosacea with those in control subjects and to examine the relation between tear functions, such as production and clearance rate, and the concentrations of cytokines in tear fluid. PARTICIPANTS AND INTERVENTION: Fourteen patients with severe meibomian gland disease, facial rosacea, and symptoms of ocular irritation were examined for ocular surface disease, tear production, and tear clearance rate (TCR). Twelve control subjects, frequency-matched for age, and 15 ideal normal subjects with no ocular symptoms and normal tear function were assessed using the same parameters. Minimally stimulated tear samples (20 microl) were drawn from each subject and analyzed using a sandwich enzyme-linked immunosorbent assay to detect IL-1alpha, TNF-alpha, and EGF. RESULTS: Tear IL-1alpha concentration was significantly higher in patients with rosacea than in age-matched (P = 0.003) and ideal control subjects (P < 0.001). Tumor necrosis factor-alpha was not detected in patients or control subjects, indicating levels of less than 10 pg/ml. Epidermal growth factor was not significantly higher in patients with rosacea than in age-matched control subjects. Tear turnover LN(TCR) was lower in patients with rosacea than in both age-matched (P = 0.048) and ideal control subjects (P = 0.002). Schirmer I scores were statistically lower in patients with rosacea than in ideal control subjects (P = 0.013), but not age-matched control subjects. Interleukin-1alpha was correlated inversely with LN(TCR) (r= -0.58, P < 0.0001) and Schirmer I (r = -0.39, P = 0.012). CONCLUSIONS: Concentrations of IL-1alpha are present in normal tears but are elevated in ocular rosacea, whereas TNF-alpha is not present in either case. The reduced tear turnover, LN(TCR), its inverse correlation with IL-1alpha, and the absence of TNF-alpha in the tears of these patients suggest that the increased concentration of IL-1alpha observed may be largely because of clearance failure of cytokine normally produced at the ocular surface.

Adult↗
PubMed1997

Comparison of conjunctival autografts, amniotic membrane grafts, and primary closure for pterygium excision.

OBJECTIVE: The purpose of the study is to determine whether amniotic membrane can be used as an alternative to conjunctival autograft after pterygium excision. DESIGN: A prospective study of amniotic membrane grafts (group A) and primary closure (group B) was compared retrospectively with conjunctival autografts (group C) in patients with pterygia. PARTICIPANTS: Group A included 46 eyes with primary pterygia and 8 eyes with recurrent pterygia, group B had 20 eyes with primary pterygia, and group C consisted of 78 eyes with primary and 44 eyes with recurrent pterygia. INTERVENTION: For the above three different surgeries, the amount of tissue removed was estimated from histopathologic analysis, and the result was evaluated by clinical examination. MAIN OUTCOME MEASURES: Recurrence, survival analysis, and final appearance were compared. RESULTS: In group A, the recurrence rate was 10.9%, 37.5%, and 14.8% for primary, recurrent, and all pterygia, respectively (mean follow-up, 11 months). These three rates were significantly higher than 2.6%, 9.1%, and 4.9% noted in group C (mean follow-up, 23 months) (P < 0.001, 0.018, and 0.01, respectively). However, the latter recurrence rate was significantly lower than 45% (mean follow-up, 5.2 months) in group B for primary pterygia (P < 0.001). The onset of recurrence was delayed significantly in group C as compared with that of groups A and B. CONCLUSIONS: The relatively low recurrence rate for primary pterygia allows one to use amniotic membrane transplantation as an alternative first choice, especially for advanced cases with bilateral heads or those who might need glaucoma surgery later.

Adolescent↗
PubMed1997

Corneal chromoblastomycosis.

PURPOSE: We sought to illustrate the difficulty in managing uncommon, pigmented mold-related corneal ulceration and to highlight the role of itraconazole in treating these patients. METHOD: We describe the management and clinical course of a patient with a recurring corneal infection caused by Fonsecaea pedrosoi and discuss this experience in the light of existing literature on management of cutaneous chromoblastomycosis. RESULTS: A corneal ulcer caused by this organism healed initially on treatment with topical and systemic antifungal medication, but infection recurred in the deep stroma 4 months after cessation of therapy. After failure to respond to a further period of medical therapy, a small therapeutic penetrating keratoplasty was performed. Culture of a fibrinous membrane from the anterior iris surface demonstrated intraocular fungal infection, and postoperatively, an episode of marked fibrinous uveitis developed, suggesting the presence of viable intraocular fungal elements. A large penetrating keratoplasty was therefore performed with excision of involved iris in combination with extracapsular cataract extraction. F. pedrosoi was again cultured from the fibrinous membrane adherent to the iris and from the anterior lens capsule. Postoperatively the patient received a 5-month course of systemic itraconazole, and no further recurrences have been encountered after a further 2 months. CONCLUSION: F. pedrosoi is the organism most commonly isolated from the chronic cutaneous mycosis, chromoblastomycosis, and is relatively resistant to medical therapy. As has been reported for cutaneous disease, surgery in combination with systemic itraconazole may provide the best chance of cure in corneal chromoblastomycosis.

Antifungal Agents↗
PubMed1997

The effects of age, gender, and fluid dynamics on the concentration of tear film epidermal growth factor.

PURPOSE: To identify the relationship between epidermal growth factor (EGF) concentration in human tears and clinical tear-flow parameters and how these vary with age and gender. METHODS: Tear samples were collected with minimal stimulation from 68 healthy and asymptomatic adults (33 men, 35 women), aged 21-88 years. EGF concentrations were determined by sandwich enzyme-linked immunosorbent assay (ELISA) in 65 cases. Schirmer tests were performed without anesthesia, and the clearance of fluorescein from the tear film assessed. The Tear Function Index (TFI) was calculated from these values. RESULTS: There were approximately equal numbers of male and female subjects with a similar age distribution for each gender (48 +/- 3 and 51 +/- 3 years, mean +/- SEM, respectively). Ninety percent of tear EGF concentrations were between 0.75 and 7.1 ng/ml. Tear EGF level correlated significantly with Schirmer I value, but not with age. Schirmer I value correlated with tear clearance [LN(TCR)] but not with age. Tear EGF concentrations were significantly higher for men (3.4 +/- 0.3 ng/ml) than for women (2.4 +/- 0.3 ng/ml; p = 0.043). CONCLUSIONS: EGF concentrations is tear samples from normal humans were found to correlate with gender and Schirmer I value but not with tear clearance.

Adult↗
PubMed1996

Defective thymocyte proliferation and IL-2 production in transgenic mice expressing a dominant-negative form of CREB.

The basic/leucine zipper (bZip) transcription factor, CREB, binds to the CRE element (TGANNTCA). The transcriptional activity of CREB requires phosphorylation of the protein on a serine residue at position 119 (ref. 6). CREs are present in a number of T-cell genes but the precise role of CREB in T-cell differentiation and function was unknown. Here we show that resting thymocytes contain predominantly unphosphorylated (inactive) CREB, which is rapidly activated by phosphorylation on Ser 119 following thymocyte activation. T-cell development is normal in transgenic mice that express a dominant-negative form of CREB (CREBA119, with alanine at position 119) under the control of the T-cell-specific CD2 promoter/enhancer. In contrast, thymocytes and T cells from these animals display a profound proliferative defect characterized by markedly decreased interleukin-2 production, G1 cell-cycle arrest and subsequent apoptotic death in response to a number of different activation signals. This proliferative defect is associated with the markedly reduced induction of c-jun, c-fos, Fra-2 and FosB following activation of the CREBA119 transgenic thymocytes. We propose that T-cell activation leads to the phosphorylation and activation of CREB, which in turn is required for normal induction of the transcription factor AP1 and subsequent interleukin-2 production and cell-cycle progression.

Activating Transcription Factors↗
PubMed1996

The role of cytology in the diagnosis of periocular basal cell carcinomas.

The accurate diagnosis of eyelid tumors such as basal cell carcinoma (BCC) requires histological confirmation, usually obtained by biopsy. Cytology provides a rapid alternative that can yield a diagnosis during the initial outpatient appointment. The accuracy of this technique has been reported to be very good but its sensitivity in the diagnosis of periocular lesions is unknown. In order to assess the accuracy of cytology in eyelid lesions suspected clinically to be BCCs, the cytological and histopathological diagnoses were compared retrospectively in 20 lesions from 17 consecutive patients who underwent cytology followed by excision biopsy. The sensitivity of cytology for the diagnosis of BCC was 92% compared with 88% for the diagnosis of malignant tumor. The predictive accuracy was 75% for either diagnosis. This was compared with a second group of 26 clinical BCCs from 22 consecutive patients who had incisional biopsy and histological examination followed by excision with histological confirmation, in which case the sensitivity was 100% and accuracy 96%. It was concluded that cytology was sufficiently accurate to plan excision and reconstructive surgery, when a confirmatory tissue diagnosis can be made, but not sufficiently sensitive for conservative regimens such as radiotherapy because of the small risk of false negative diagnoses.

Biopsy↗
PubMed1995

Defective activation and survival of T cells lacking the Ets-1 transcription factor.

The Ets-1 proto-oncogene is a member of the Ets family of eukaryotic transcription factors. Members of this family play important roles in regulating gene expression in response to multiple developmental and mitogenic signals. Ets-1 is preferentially expressed at high levels in B and T cells of adult mice and is regulated during both thymocyte development and T-cell activation. To study the role of Ets-1 in T-cell development and function we have used the RAG-2-/- complementation system and murine embryonic stem (ES) cells containing homozygous deletions in the Ets-1 gene (Ets-1-/-). Ets-1-/(-)-RAG-2-/- chimaeric mice displayed markedly decreased numbers of mature thymocytes and peripheral T cells. Ets-1-/- T cells expressed normal levels of CD3 and T-cell antigen receptor (TCR)-alpha/beta. However, they displayed a severe proliferative defect in response to multiple activational signals and demonstrated increased rates of spontaneous apoptosis in vitro. These findings demonstrate that Ets-1 is required for the normal survival and activation of murine T cells.

Animals↗
PubMed1995

The kinetics of cytokine mRNA expression in the retina during experimental autoimmune uveoretinitis.

Experimental autoimmune uveoretinitis (EAU) was induced in Lewis rats and the inflamed retinas were examined for IFN-gamma, IL-2, IL-4, and IL-10 mRNA production at serial time points using the reverse transcriptase-polymerase chain reaction. IFN-gamma, IL-2, IL-4, and IL-10 mRNAs were all detected 24 hr before the earliest time point at which histological changes have previously been detected. IFN-gamma, IL-2, and IL-4 mRNA expression peaked during the active phase of the disease and declined in parallel with lymphocyte numbers as the inflammation resolved. IL-10 mRNA levels increased more slowly, reaching a maximum at later stages of disease. The observed pattern of cytokine mRNA expression in the retina in EAU is similar to that reported in experimental autoimmune encephalomyelitis (EAE). The increase in IL-10 mRNA expression in late disease may reflect a role in disease resolution as previously proposed in EAE.

Animals↗
PubMed1995

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

AIDS-Related Opportunistic Infections↗
PubMed1995

Adenovirus-mediated over-expression of the cyclin/cyclin-dependent kinase inhibitor, p21 inhibits vascular smooth muscle cell proliferation and neointima formation in the rat carotid artery model of balloon angioplasty.

Vascular smooth muscle cell (VSMC) proliferation after arterial injury is important in the pathogenesis of a number of vascular proliferative disorders, including atherosclerosis and restenosis after balloon angioplasty. Thus, a better understanding of the molecular mechanisms underlying VSMC proliferation in response to arterial injury would have important therapeutic implications for patients with atherosclerotic vascular disease. The p21 protein is a negative regulator of mammalian cell cycle progression that functions both by inhibiting cyclin dependent kinases (CDKs) required for the initiation of S phase, and by binding to and inhibiting the DNA polymerase delta co-factor, proliferating cell nuclear antigen (PCNA). In this report, we show that adenovirus-mediated over-expression of human p21 inhibits growth factor-stimulated VSMC proliferation in vitro by efficiently arresting VSMCs in the G1 phase of the cell cycle. This p21-associated cell cycle arrest is associated both with significant inhibition of the phosphorylation of the retinoblastoma gene product (Rb) and with the formation of complexes between p21 and PCNA in VSMCs. In addition, we demonstrate that localized arterial infection with a p21-encoding adenovirus at the time of balloon angioplasty significantly reduced neointimal hyperplasia in the rat carotid artery model of restenosis. Taken together, these studies demonstrate the important role of p21 in regulating Rb phosphorylation and cell cycle progression in VSMC, and suggest a novel cytostatic gene therapy approach for restenosis and related vascular proliferative disorders.

Adenoviridae↗
PubMed1994

T lymphocyte effector mechanisms in the retina in posterior uveitis.

Loss of vision in posterior uveitis is often the consequence of chronic retinal oedema and immune-mediated damage to the retinal parenchyma. Research in other putative autoimmune diseases such as rheumatoid arthritis, and in animal models of autoimmune disease, has uncovered a number of mechanisms which may contribute to the development of inflammatory disease within the eye. With recent developments in specific anti-cytokine therapy an understanding of these mechanisms, most of which are cytokine-mediated, is essential in order to plan more effective therapeutic strategies. In this paper we review recent research investigating the functional characteristics of the T cells which are recruited into the retina in experimental autoimmune uveoretinitis, including activation status, antigen-specific proliferation in vitro and cytokine mRNA production in the inflamed retina.

Animals↗
PubMed1994

Uveitis presenting de novo in the elderly.

Seventy-one consecutive patients presenting with their first episode of uveitis at the age of 60 or more years, were studied retrospectively. The majority were found to have idiopathic uveitides on investigation. In those who did have associated systemic disease, the commonest finding was non-insulin-dependent diabetes mellitus or an autoimmune disease. There were no cases of ocular lymphoma in this series. We conclude that, contrary to some previous reports, idiopathic uveitis may occur in the elderly, and that the relative frequencies of acute anterior, chronic anterior, intermediate and posterior uveitides are similar to those seen in young patients.

Age Factors↗
PubMed1994

Corneal endothelial changes in cytomegalovirus retinitis.

Reticular deposits on the corneal endothelium together with fundus changes typical of cytomegalovirus (CMV) retinitis have been noted in patients with acquired immune deficiency syndrome (AIDS). The aim of this study was to characterise this finding using specular microscopy and to assess the potential of this clinical sign as a screening tool which could be performed rapidly at the slit lamp without the need for dilatation of the pupil. Sixty male homosexual patients with a diagnosis of AIDS as defined by the Center for Disease Control (Atlanta, 1987) were examined at their first visit to the ophthalmic clinic. The cornea was examined at the slit lamp prior to fundal examination and the presence or absence of the characteristic endothelial changes noted. CMV retinitis was diagnosed on the basis of the fundal appearance together with confirmation of the diagnosis by analysis of a vitreous sample. As a diagnostic sign of CMV retinitis the endothelial changes had a positive predictive value of 94.7% and a negative predictive value of 75.6%. Although the presence of the endothelial changes always indicates the presence of CMV retinitis it is not a sign which is found in a high enough proportion of patients to allow its reliable use as a screening tool.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Stress reduction in child-abusing families: global and specific measures.

This study compared in-home treatment to traditional county services for their ability to reduce stress in child-abusing families. 47 families who were at risk for having at least one child removed from the home for child abuse were referred to Families First for an intensive 6-wk., in-home therapy program. A comparison group of 29 families who were also at risk for having at least one child removed for abuse received traditional county services but no in-home therapy. Stress scores used were derived from a factor analysis of the Family Inventory of Life Events and Changes (FILE) that had identified 10 stress factors. The stress data were analyzed by a series of 2 x 2 analyses of variance, group and time being the independent variables and the stress factors the dependent variables. Total stress was significantly reduced over time for both groups, and several specific stress factors were also significantly reduced over time. In secondary analyses, 2 x 3 (group by time) analyses identified interactions for total stress and three of the individual stress factors. In-home treatment was effective in reducing stress, but traditional services were also effective. Some possible explanations were discussed. A major finding was that, by including analyses using the specific stress factors (rather than just the Total Stress score), a much richer understanding of the role stress plays in abusive families is provided. It was concluded that, although global stress may be reduced by different methods, some specific types of stress are more likely to be reduced than others.

Adaptation, Psychological↗
PubMed1993

The nature of stress in child-abusing families: a factor analytic study.

An instrument for measuring stress (the Family Inventory of Life Events and Changes: FILE) was administered to 151 parents of abused children. A factor analytic treatment of the results indicated that ten different aspects of stress (factors) best explained the data. Several of these factors seemed to be unique to the abusing environment while the rest were similar to those found in less atypical samples. The results suggest that (a) "local factor analyses" should be employed with atypical samples and (b) both measures of types of stress as well as general stress may be useful. The ten stress factors identified were (1) Trouble with Teenagers, (2) Violence and Separation, (3) Legal Violations, (4) Work, (5) Family Loss, (6) Financial Strains, (7) Illness and Family Care Strains, (8) Public Assistance, (9) Major Changes in Family Situation, and (10) Young Child Management Focus. The "unique" factors that only appeared in our child-abusing sample were (1) Trouble with Teenagers, (2) Violence and Separation, and (8) Public Assistance.

Adolescent↗
PubMed1993

Isolation of retinal lymphocytes in experimental autoimmune uveoretinitis: phenotypic and functional characterization.

Lymphocytes were obtained from the inflamed retinas of Lewis rats with S antigen (S-Ag)-induced experimental autoimmune uveoretinitis (EAU). In early disease 81% of these were CD4+ T cells. Thirty-four per cent of retinal CD4+ T cells expressed the interleukin-2 receptor (IL-2R) and 95% were CD45R-. These phenotypes contrast sharply with those of peripheral blood and lymph node CD4+ T cells isolated from EAU rats and confirm a high level of CD4+ T-cell activation in the retina in early disease. Although the relative proportions of CD8+ T cells increased in late disease, so did those of B cells and CD45R+ CD4+ T cells. We did not find clear evidence of a selective retention of CD8+ T cells in the retinas in late disease. Proliferation assays using retinal preparations demonstrated modest but significant responses to both S-Ag and the purified protein derivative of Mycobacterium tuberculosis (PPD) compared with lymph node preparations. The S-Ag response was abrogated by anti-major histocompatibility complex (MHC) class II monoclonal antibody (mAb). Lymphocyte preparations from inflamed retinas have not been examined previously in vitro but are likely to be useful in defining the precise function of CD4+ T cells during the course of EAU.

Animals↗
PubMed1993

Effects of CD8 depletion on retinal soluble antigen induced experimental autoimmune uveoretinitis.

During the later stages of soluble-antigen (sAg)-induced experimental autoimmune uveoretinitis (EAU), an increase in the relative number of CD8+ lymphocytes has been observed at the site of inflammation in the retina. It has been suggested that these late-appearing CD8+ cells might down-regulate this acute disease process. To determine the role of the CD8+ cells in EAU, Lewis rats were depleted of CD8+ cells prior to and during disease and the enucleated eyes examined histologically. The spleen cells from CD8-depleted rats were also examined for their ability to respond to concanavalin A (Con A) and to allogeneic targets as determined by mixed lymphocyte reaction (MLR) and cytotoxicity assays. The results suggest that depleting CD8+ cells had no effect on the course of disease and that CD8+ cells do not play a crucial role in the immunoregulation of EAU.

Animals↗