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Biomedical subjects

C Walker

Publications and source records attributed to C Walker.

At least 199 records · Page 11Linked to original sources

Differential cytokine profiles in peripheral blood lymphocyte supernatants and skin biopsies from patients with different forms of atopic dermatitis, psoriasis and normal individuals.

There is increasing evidence that the activation of a selected T helper cell population producing a Th2-related cytokine pattern with IL-4 and IL-5 but not IL-2 and interferon-gamma (IFN-gamma) may be involved in the pathogenesis of IgE-mediated atopic diseases and in particular of atopic dermatitis (AD). However, the existence of a 'nonatopic' (intrinsic) form of AD (NAD) with normal serum IgE levels, negative RAST tests, negative immediate type skin reactions towards environmental allergens and a negative patients and family history for IgE-mediated allergies raised the question whether this form may be explained by a different T cell activation and cytokine pattern. In the present study we compared the distribution of peripheral blood leukocyte and lymphocyte subpopulations, their activation state and cytokine production in peripheral blood lymphocyte supernatants and skin biopsies of patients with AD (n = 19), NAD (n = 14), psoriasis (n = 6) and normal individuals (n = 13). A characteristic eosinophilia was present in AD and NAD but not in psoriasis and normal controls. The three patient groups showed significantly increased numbers of activated CD4+ and CD8+ cells as measured by IL-2R and HLA-DR expression. Determination of spontaneously released IL-2, IL-4, IL-5 and IFN-gamma from peripheral blood lymphocytes demonstrated a Th2-related cytokine pattern with elevated levels for IL-4 and IL-5 in AD patients only. Increasingly enough, patients with NAD displayed high IL-5 but low IL-4 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Cytokines↗

Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia.

Increasing evidence suggests an important role for cytokines in the regulation of eosinophilic inflammation. In the present study we investigated the distribution of leukocytes, lymphocyte subsets, their activation state, and the cytokine profile present in BAL fluid from patients with various lung diseases associated with eosinophilia. For this purpose, we analyzed the levels of IL-1 beta, IL-2, IL-4, IL-5, IL-6, IL-8, GM-CSF, TNF-alpha, and IFN-gamma, as well as soluble IL-2 and TNF receptors, in concentrated bronchoalveolar lavage (BAL) fluid obtained from clearly defined patients with allergic and nonallergic asthma, eosinophilic pneumonia, allergic bronchopulmonary aspergillosis (ABPA), hypersensitivity pneumonitis, and idiopathic pulmonary fibrosis. BAL fluid from normal individuals and sarcoidosis patients was analyzed as noneosinophilic controls. BAL cytokine levels were compared with the cellular infiltrate and the activation state of CD4+ and CD8+ T cells as measured by the expression of IL-2 receptors (CD25), HLA-DR, and the very late activation antigen VLA-1. Beside the characteristic leukocyte infiltrate in the various lung diseases, all patients demonstrated significantly increased numbers of activated CD4 and CD8 T cells compared with normal individuals. The analysis of the cytokine profile present in BAL fluid revealed a T helper type 2 (Th2) cell cytokine pattern, with elevated IL-4 and IL-5 but normal levels of IL-2 or IFN-gamma in allergic asthma. ABPA patients demonstrated significantly increased levels of IL-4 and IL-5, with low but significantly elevated concentrations of IL-2 and IFN-gamma. In contrast, the analysis of the cytokine profile in sarcoidosis patients revealed a Th1 cell cytokine pattern characterized by increased concentrations of IL-2 and IFN-gamma but normal levels of IL-4 or IL-5. All other patient groups showed a cytokine pattern incompatible with a pure Th1 or Th2 cell response, because IL-5, IL-2, and IFN-gamma were found to be significantly increased. The BAL fluid analysis of the other, mainly non-T cell-derived cytokines and soluble receptors showed increased levels in all patients compared with normal individuals and may represent the ongoing inflammatory responses. In conclusion, whereas increased IL-4 levels were found only in diseases characterized by increased IgE production, IL-5 was elevated in all patients with increased numbers of eosinophils. The close correlation between IL-5 levels, number of eosinophils, and activated T cells further supports a role for IL-5 in causing tissue eosinophilia.

Adult↗

Pulmonary immune cells in health and disease: the eosinophil leucocyte (Part I).

Increasing evidence has accumulated to suggest that eosinophils play a key role in the pathogenesis of asthma and other pulmonary diseases by damaging infiltrated bronchial tissue and lung parenchyma. The first part of this review on eosinophils describes the cellular characteristics and properties of the cell, which help in understanding its role in disease. The article focuses on origin, maturation and differentiation of the eosinophil, its morphological and phenotypical properties, as well as its preformed and newly generated mediators of inflammation. The cause and putative significance of eosinophil heterogeneity in respect to function and density will also be discussed. In addition, the naturally occurring mediators through which eosinophils are activated and communicate with other inflammatory cells are outlined. The first part closes with new aspects of eosinophil recruitment from the circulation into perivascular tissue, including nonselective and putative selective adhesion mechanisms and chemotaxis.

Eosinophils↗

Balancing workloads under GP attachment.

Alignment with a GP practice resulted in fluctuating workloads for health visitors Lynda Brooks, Caro Fickling and Caroline Walker. Here they describe how the introduction of a corporate caseload helped to restore balance.

Community Health Nursing↗

Isolation, propagation, and characterization of rat liver serosal mesothelial cells.

Although rat liver epithelial cell (RLEC) lines have been developed by a number of laboratories, the identity of the clonogenic nonparenchymal progenitors is unknown. To provide insight into the derivation of RLEC, we immunoisolated serosal liver mesothelial cells (LMC) and bile duct epithelial cells and attempted to propagate each epithelial cell population using culture conditions routinely employed to establish RLEC lines. Briefly, the selective reactivity of LMC with two bile duct cell surface markers, OC.2 and BD.2, was exploited to develop an immunocytochemical technique to isolate LMC. Livers were collagenase dissociated, the mesothelial capsule was "peeled" and digested with pronase to destroy contaminating hepatocytes, and rare biliary ductal epithelial cells were immunodepleted using OC.2. LMC were subsequently isolated by selective binding to magnetic beads adsorbed with BD.2 and cultured in supplemented Waymouths 752/1 media containing 10% fetal calf serum. Proliferating BD.2+ LMC rapidly formed epithelial-like monolayers that could be continuously subcultured after trypsinization. In contrast, attempts to establish cell lines from purified OC.2+ bile duct epithelial cells were unsuccessful. Results from reverse transcriptase polymerase chain reaction analysis confirmed that LMC expressed Wilms' tumor transcripts, a lineage marker for mesodermally-derived cells. In summary, our findings clearly demonstrate that LMC can be continuously propagated using culture conditions routinely employed to establish RLEC lines, an observation that supports the contention that some RLEC lines may be derived from LMC.

Animals↗

Induction of muscle pioneers and floor plate is distinguished by the zebrafish no tail mutation.

Dorsal mesoderm is thought to provide important signals for axis formation and neural differentiation in vertebrate embryos. We have examined induction and patterning in a zebrafish mutant, no tail, that lacks a derivative of dorsal mesoderm, the notochord. Despite the absence of a differentiated notochord, development of the central nervous system including floor plate appears normal, likely owing to the presence of notochord precursor cells. In contrast, somites are misshapen, and muscle pioneer cells are absent. Wild-type cells transplanted into mutant hosts can autonomously differentiate into notochord and thereby rescue somitic defects, suggesting that interactions between notochord and paraxial mesoderm are necessary for proper somite patterning. Thus, cells derived from dorsal mesoderm may have multiple signaling functions during zebrafish embryogenesis.

Animals↗

Production of multiple growth factors by a human non-small cell lung carcinoma cell line.

The 1PT cell line, derived from an undifferentiated bronchial carcinoma, produced, in conditioned medium, immunoreactive basic fibroblast growth factor (bFGF), insulin-like growth factors I and II (IGF-I and IGF-II), epidermal growth factor (EGF), transforming growth factor alpha (TGF alpha), and transforming growth factor beta-2 (TGF beta 2) in its latent form, but not platelet-derived growth factor (PDGF), tumour necrosis factor alpha (TNF alpha), or transforming growth factor beta-1 (TGF beta 1). Comparative studies of growth stimulation of human umbilical vein (HUV) endothelial cells indicated that the growth factors detected in 1PT-conditioned medium do not solely account for its proliferative effects on these cells. These results support previous characterization studies [1,2] that suggest the production of a potentially novel tumour-derived endothelial cell growth factor by the 1PT cell line.

Carcinoma, Non-Small-Cell Lung↗

Asthma.

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Asthma↗

Increased expression of CD11b and functional changes in eosinophils after migration across endothelial cell monolayers.

Eosinophils from sputum, nasal polyps, and bronchoalveolar lavages of asthmatics demonstrated a considerably increased CD11b expression, compared with blood eosinophils. Furthermore, the tissue eosinophils expressed ICAM-1 (CD54) and HLA-DR, whereas peripheral blood eosinophils did not. In vitro migration of peripheral blood eosinophils across IL-1-activated human umbilical vein endothelial cell monolayers caused a considerable up-regulation of CD11b and CD35 expression, no induction of ICAM-1 or HLA-DR, and a small but significant decrease in CD11a, CD29, and CD32 expression. These changes were only partially inducible with supernatants from nonactivated or IL-1-activated endothelial cells, platelet-activating factor, or a variety of recombinant cytokines. Thus, cell-cell interactions mediated by receptor-ligand binding or endothelial cell membrane-bound mediators, rather than soluble factors, are responsible for the altered eosinophil surface marker expression. Indeed, preparations of membrane fragments from IL-1-stimulated endothelial cells were able to induce up-regulation of CD11b, which was not inhibitable with the platelet-activating factor antagonist WEB 2086 or antibodies against ELAM-1, VCAM-1, or ICAM-1. Investigation of the functional significance of the increased CD11b expression on eosinophils revealed only minimal changes in the adherence or transmigration capacity. Nevertheless, increased CD11b expression was related to an increased capacity to generate superoxide after stimulation with opsonized zymosan. Thus, cell-cell interactions between eosinophils and endothelial cells induce a considerable up-regulation of CD11b and CD35 on eosinophils and an increased capacity to generate an oxidative burst.

Antigens, CD↗

Cryptosporidial diarrhoea in South Australia. An exploratory case-control study of risk factors for transmission.

OBJECTIVE: To identify risk factors for transmission of cryptosporidiosis in South Australia. DESIGN: Case-control study of 51 cases of laboratory confirmed cryptosporidiosis and 51 age and sex matched controls. SETTING: Subjects from greater Adelaide, with cases notified by local pathology laboratories to the Communicable Disease Control Unit, South Australian Health Commission, during the summer of 1990/1991. PARTICIPANTS: One in 10 cases was selected systematically from 479 laboratory notifications, and permission was obtained from the treating physicians to contact the patients. Subjects nominated age and sex matched controls living in the same area. METHODS: By means of a structured questionnaire, participants were asked by telephone about exposure to possible risk factors in the two weeks preceding the illness/interview. The risk factors included those most commonly cited in the literature as resulting in zoonotic, waterborne and person-to-person infection. The number and percentage of cases and controls exposed was recorded for each risk factor. The probability of having been exposed to selected risk factors was compared between cases and controls by the exact test for matched pairs. RESULTS: The proportion of cases and controls exposed was similar for all risk factors except water sources. Controls were more likely to have consumed only rain water than were cases (P < 0.005). Cases tended more than controls to have consumed only spring water (P = 0.06) or only mains water (P = 0.09). CONCLUSIONS: The consumption of spring water or mains water contaminated with cryptosporidial oocysts may be the mode of transmission of cryptosporidiosis in South Australia. The advent of specific methods for detecting Cryptosporidium sp. in water will allow this hypothesis to be tested.

Adolescent↗

Human peripheral blood eosinophils produce and release interleukin-8 on stimulation with calcium ionophore.

We present evidence that human blood eosinophils produce interleukin (IL)-8 when stimulated with calcium ionophore. Following in vitro culture of 99% pure eosinophils with calcium ionophore, released IL-8 was detectable by enzyme-linked immunosorbent assay in supernatants. Eosinophil IL-8 production was considerably greater than that of IL-3 or granulocyte macrophage colony-stimulating factor. Furthermore, eosinophil production of IL-8 in the presence of calcium ionophore could be inhibited with the immunomodulating agent cyclosporin A and the protein synthesis inhibitor cycloheximide. In addition, following stimulation of highly purified blood eosinophils with calcium ionophore, IL-8 mRNA was detectable after polymerase chain reaction amplification. In comparison with other cells on stimulation with calcium ionophore, eosinophils produce about half as much IL-8 as neutrophils but significantly more than purified T cells. In contrast to monocytes and neutrophils, IL-8 production was not inducible with IL-1 or tumor necrosis factor. Finally, following calcium ionophore stimulation blood eosinophils were shown to contain cytoplasmic IL-8 by employing a monoclonal antibody against IL-8 in conjunction with immunohistochemistry. These observations demonstrate that eosinophils are capable of IL-8 production and release, which may contribute to defense against parasites and to the pathophysiology of allergic and asthmatic disease.

Calcimycin↗

Eosinophils and cytokines.

Cytokines act on eosinophils to regulate eosinophil function, with IL-5 recognised to be especially important in control of eosinopoiesis, eosinophil survival and eosinophil priming. In addition, eosinophils have the capacity to produce cytokines involved in acute and chronic inflammatory and repair processes, as well as to produce cytokines that stimulate eosinophils within an autocrine loop. This paper describes (A) an immunomagnetic selection technique for the purification of human blood eosinophils, and (B) a method that employs immunofluorescence with flow cytometry for measurement of blood and sputum eosinophil surface markers. Having demonstrated that sputum eosinophils express HLA-DR, highly purified blood eosinophils were used to analyse (C) the induction and function of eosinophil HLA-DR. Cytokines have the capacity to induce eosinophil HLA-DR, and are produced by eosinophils as an accessory function during antigen presentation. Finally, preliminary data on (D) eosinophil production of IL-8 is presented. Hence, eosinophils have the capacity to act as immunomodulatory cells within cells networks in allergic and asthmatic inflammation.

Antigens, Surface↗

The immunology of extrinsic and intrinsic asthma.

It is now widely accepted that chronic mucosal inflammation plays an important role in the pathogenesis of asthma. This response involves the interaction of various cell types and is not the result of a single inflammatory cell acting in isolation. The present review describes the possible role of T lymphocytes in the inflammatory response of extrinsic (allergic) and intrinsic (nonallergic) asthma, focusing mainly on analysis of lymphocyte subpopulations, their activation state and cytokines produced in peripheral blood and bronchoalveolar lavages. Recent research suggests that there may be fundamental immunological differences between intrinsic and extrinsic asthma. In particular, intrinsic asthmatics have different patterns of T cell activation and cytokine production.

Asthma↗

Brief communication: dietary habits of first-year medical students as determined by computer software analysis of three-day food records.

Nutrition training for medical students has long been a low priority for most medical schools. Given the growing body of knowledge linking health promotion to proper dietary habits, there is a need to increase the quantity and quality of nutrition training for medical students. In the present study, first-year medical students recorded food intake for 3 days and analyzed their diets for nutrient contents with a computer software program. Use of the interactive software created a personalized approach to increasing nutrition knowledge as the students became aware of their own dietary habits. Female students had a low consumption of kilocalories, dietary fiber, calcium, iron, zinc, potassium, and polyunsaturated fat. Male students exceeded current recommended intakes for fat, saturated fat, cholesterol, and sodium.

Diet Records↗