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Biomedical subjects

C Lloyd

Publications and source records attributed to C Lloyd.

At least 37 records · Page 2Linked to original sources
PubMed2000

The CD28-related molecule ICOS is required for effective T cell-dependent immune responses.

While CD28 is critical for expansion of naive T cells, recent evidence suggests that the activation of effector T cells is largely independent of CD28/B7. We suggest that ICOS, the third member of the CD28/CTLA-4 family, plays an important role in production of IL-2, IL-4, IL-5, and IFNgamma from recently activated T cells and contributes to T cell-dependent B help in vivo. Inhibition of ICOS attenuates lung mucosal inflammation induced by Th2 but not Th1 effector populations. Our data indicate a critical function for the third member of the CD28 family in T cell-dependent immune responses.

Abatacept↗
PubMed2000

Non-redundant functional groups of chemokines operate in a coordinate manner during the inflammatory response in the lung.

The understanding of the relative contribution of particular chemokines to the selective accumulation of leukocyte subsets to an organ site during an inflammatory response is made difficult by the simultaneous presence of multiple chemokines with partially overlapping functions at the inflammatory site. The study of several chemokine pathways (expression and function) during the development of a mouse model of allergic airway disease (AAD) has revealed differential expression regulation with distinct cellular sources for individual chemokines with functional bias for the recruitment/localization of regulatory and/or effector leukocyte subsets. In the present review, we propose that distinct functional groups of chemokines co-operate to generate the complete inflammatory response in the lung during AAD. We will also extend these concepts to the specific recruitment of a key cellular subset such as T helper type 2 (Th2) lymphocytes. We propose that the long term recruitment of antigen-specific Th2 cells to target organs, such as airways during chronic lung inflammation, is the result the sequential involvement of several chemotactic axes. Specifically, the CCR3/eotaxin and the CCR4/MDC pathway act in a coordinated co-operative manner, with the CCR3/eotaxin pathway being critical in the acute/early stages of a response, followed by the CCR4/MDC pathway, which ultimately dominates in the recruitment of antigen-specific Th2 cells. Other chemokines/receptors participate in this process possibly by amplifying/priming the Th2 recruitment response.

Animals↗
PubMed2000

Non-organic visual loss in children.

BACKGROUND: Patients with non-organic visual loss (NOVL) can take up a disproportionate amount of clinic time and clinicians often resort to expensive and prolonged investigations to ensure the correct diagnosis. This is especially the case in children. METHODS: The case notes of 30 children (18 girls, 12 boys) were retrospectively reviewed following presentation with a primary complaint of visual impairment and a diagnosis of non-organic visual loss. This figure represents 1% of new paediatric referrals to our unit. Associated symptoms included headache, periorbital pain, diplopia, photopsia and photophobia. Visual field defects were present in 5 patients and spasm of the near reflex in 1 child. RESULTS: Treatment consisted of reassurance and was associated with recovery of normal visual function in all cases. Three children were referred to other health care professionals. All psychophysical, electrophysiological and neuroradiological investigations were negative. CONCLUSION: Our study shows that non-organic visual loss is relatively common in pre-pubertal children and that this condition can be safely diagnosed using standard clinical tests in the majority of cases. Prompt diagnosis prevents unnecessary investigations and prolonged 'disease' course. Coexisting social conflict was common and may be a contributory factor. Careful explanation and reassurance to both the child and parents remains the mainstay of management.

Adolescent↗
PubMed2000

Two kinesin-related proteins associated with the cold-stable cytoskeleton of carrot cells: characterization of a novel kinesin, DcKRP120-2.

We have previously described the biochemical isolation of 65 kDa and 120 kDa microtubule-associated proteins from carrot cytoskeletons. The 65 kDa MAPs have subsequently been shown to be structural MAPs that reconstitute 30 nm cross-bridges of the kind that maintain cortical microtubules in parallel groups. By exploiting its avid binding to microtubules, we have now devised a method for isolating MAP120 from protoplast extracts, and shown that it has properties of a kinesin-related protein. MAP120 segregates with the cold stable pool of microtubules in carrot cytoskeletons, whilst the 65 kDa MAPs are also associated with the cold-sensitive microtubules. On gradient gels, MAP120 resolves as two kinesin-like bands. We report the isolation of a carrot cDNA, DcKRP120-2, corresponding to a novel kinesin of the BimC class known to move to the plus ends of microtubules. Antibodies raised against specific expressed sequences recognize the upper band, while the lower band is recognized by antibodies to the tobacco kinesin-related protein, TKRP125. We have also isolated a partial genomic carrot DNA, DcKRP120-1, homologous to the motor region of tobacco TKRP125. Immunofluorescence of the two proteins produces different staining patterns. Anti-TKRP125 labels the cortical microtubules and the pre-prophase band, but anti-DcKRP120-2 does so only weakly. Both clearly stain the spindle and the phragmoplast, but in a proportion of cells anti-DcKRP120-2 strongly decorates the phragmoplast mid-line where the plus ends of the microtubules overlap. We discuss the potential roles of these proteins during the microtubule cycle.

Amino Acid Sequence↗
PubMed2000

An effective protection factor study of respirators used by primary lead smelter workers.

An industrial hygiene study was conducted at a primary lead smelter to determine the effective protection factors for negative pressure and powered air purifying half-mask respirators. The study involved 99 paired personal samples taken in six different work areas, in which randomly chosen subjects from the workforce wore dual sampling pumps connected to closed-face 37-mm cassettes. The cassettes were attached either to the workers' lapels for exposure measurements outside the respirator or to a ported respirator for exposure measurements inside the respirator. Samples were collected throughout the work shift and analyzed for lead according to National Institute of Occupational Safety and Health (NIOSH) Method 7082. Using particle size distribution data obtained for the same workplaces, the within-mask samples were corrected for sampling bias. The negative pressure half-mask respirators showed a mean effective protection factor of 6.5 and a mean corrected effective protection factor of 4.56, with a 5th percentile less than 0.5. Approximately 80 percent and 90 percent of the effective protection factors and the corrected effective protection factors, respectively, were equal to or less than the assigned protection factor of 10. For the powered air purifying half-mask respirators, the means for effective protection factor and corrected effective protection factor were 18.20 and 11.92, respectively, with a 5th percentile of 1.0 or less. Approximately 90 percent and 95 percent of the effective protection factors and the corrected effective protection factors, respectively, were equal to or less than the assigned protection factor of 50. The uncorrected and corrected within-mask lead concentrations for both types of respirators exceeded the Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) for lead by 19 percent to 58 percent. These results indicate that the straight application of assigned protection factors to actual workplace situations may not always be appropriate.

Adult↗
PubMed1999

Crucial role of the interleukin 1 receptor family member T1/ST2 in T helper cell type 2-mediated lung mucosal immune responses.

T1/ST2 is an orphan receptor of unknown function that is expressed on the surface of murine T helper cell type 2 (Th2), but not Th1 effector cells. In vitro blockade of T1/ST2 signaling with an immunoglobulin (Ig) fusion protein suppresses both differentiation to and activation of Th2, but not Th1 effector populations. In a nascent Th2-dominated response, anti-T1/ST2 monoclonal antibody (mAb) inhibited eosinophil infiltration, interleukin 5 secretion, and IgE production. To determine if these effects were mediated by a direct effect on Th2 cells, we next used a murine adoptive transfer model of Th1- and Th2-mediated lung mucosal immune responses. Administration of either T1/ST2 mAb or T1/ST2-Ig abrogated Th2 cytokine production in vivo and the induction of an eosinophilic inflammatory response, but failed to modify Th1-mediated inflammation. Taken together, our data demonstrate an important role of T1/ST2 in Th2-mediated inflammatory responses and suggest that T1/ST2 may prove to be a novel target for the selective suppression of Th2 immune responses.

Allergens↗
PubMed1999

Chemokine amplification in mesangial cells.

Mesangial cells are specialized cells of the renal glomerulus that share some properties of vascular smooth muscle cells and macrophages. They are implicated in the pathogenesis of many forms of nephritis. The murine CXC-chemokines macrophage inflammatory protein-2 (MIP-2) and KC induce migration of mouse mesangial cells. Mesangial cells also exhibit a unique chemokine feedback mechanism. Treatment with nanomolar concentrations of MIP-2 or KC markedly up-regulates monocyte chemoattractant protein-1 and RANTES expression in mesangial cells. Autoinduction of MIP-2 and KC mRNA was also noted. Low levels of MIP-1alpha, MIP-1beta, and IFN-gamma-inducible protein-10 were induced following treatment with higher doses of MIP-2 or KC. These effects are specific to mesangial cells, as MIP-2 or KC treatment of renal cortical epithelial cells or peritoneal macrophages failed to induce chemokine production. This cascade of chemokine interactions may contribute to renal infiltration and leukocyte activation. The abilities of MIP-2 or KC to stimulate their own synthesis may also contribute to the maintenance and chronic course of glomerular inflammation. The mesangial cell receptor for MIP-2 and/or KC is unknown but is not CXC-chemokine receptor-2.

Animals↗
PubMed1999

How I learned to love carrots: the role of the cytoskeleton in shaping plant cells.

The carrot cell suspension was originally used because it provided a model system for studying directional cell expansion - a key process in plant morphogenesis. Early immunofluorescence studies of plant microtubules, using these cells, provided hints that the cortical array of microtubules was dynamic and this was later confirmed by microinjection studies on plant epidermal cells. A nonfixation approach for detecting F-actin was then developed on these cells and showed that, unlike animal cells, actin filaments remained associated with the nucleus throughout division and could have a role in aligning the plane of cell division. Currently, we are using detergent-extracted carrot cytoskeletons for isolating microtubule-associated proteins (MAPs). I discuss how MAPs may be involved in the oriented deposition of cellulose in the cell wall.

Actins↗
PubMed1999

Prolonged eosinophil accumulation in allergic lung interstitium of ICAM-2 deficient mice results in extended hyperresponsiveness.

ICAM-2-deficient mice exhibit prolonged accumulation of eosinophils in lung interstitium concomitant with a delayed increase in eosinophil numbers in the airway lumen during the development of allergic lung inflammation. The ICAM-2-dependent increased and prolonged accumulation of eosinophils in lung interstitium results in prolonged, heightened airway hyperresponsiveness. These findings reveal an essential role for ICAM-2 in the development of the inflammatory and respiratory components of allergic lung disease. This phenotype is caused by the lack of ICAM-2 expression on non-hematopoietic cells. ICAM-2 deficiency on endothelial cells causes reduced eosinophil transmigration in vitro. ICAM-2 is not essential for lymphocyte homing or the development of leukocytes, with the exception of megakaryocyte progenitors, which are significantly reduced.

Administration, Inhalation↗
PubMed1998

The chemotactic cytokine eotaxin acts as a granulocyte-macrophage colony-stimulating factor during lung inflammation.

During inflammatory processes, inflamed tissues signal the bone marrow (BM) to produce more mature leukocytes in ways that are not yet understood. We report here that, during the development of lung allergic inflammation, the administration of neutralizing antibodies to the chemotactic cytokine, Eotaxin, prevented the increase in the number of myeloid progenitors produced in the BM, therefore reducing the output of mature myeloid cells from BM. Conversely, the in vivo administration of Eotaxin increased the number of myeloid progenitors present in the BM. Furthermore, we found that, in vitro, Eotaxin is a colony-stimulating factor for granulocytes and macrophages. Eotaxin activity synergized with stem cell factor but not with interleukin-3 or granulocyte-macrophage colony-stimulating factor and was inhibited by pertussis toxin. We report also that CCR-3, the receptor for Eotaxin, was expressed by hematopoietic progenitors (HP). Thus, during inflammation, Eotaxin acts in a paracrine way to shift the differentiation of BM HP towards the myeloid lineage.

Animals↗
PubMed1998

Cytokine dysregulation associated with exam stress in healthy medical students.

The mechanisms of stress-related immune alterations have not been fully elucidated. Cell-mediated immune responses as well as antibody and certain cytokines are reported as being suppressed during times of high stress. However, the role of suppression vs dysregulation has not been established in human stress models. The effect of exam stress on regulatory cytokines in 16 healthy medical students was assessed by measuring type-1 (IFN-gamma) and type-2 (IL-10) cytokines from 72-h PHA/PMA-stimulated PBMC 4 weeks before and 48 h after exams. Results demonstrated decreased IFN-gamma accompanied by increased IL-10 during exam stress that resulted in a decreased IFN-gamma:IL-10 ratio. There was a significant correlation between the cytokine response to PHA/PMA and number and subjective adjustment to daily hassles. Additionally, students who reported greater levels of loneliness also reported greater numbers of and poorer subjective adjustment to hassles. The differences were consistent in both males and females but did not correlate with AM cortisol levels. Additionally, when individuals were grouped into high vs low preexam hassle levels, the type-1/type-2 shift in the IFN-gamma:IL-10 ratio occurred in the low hassles group only. These data suggest that psychologically stressful situations shift type-1/type-2 cytokine balance toward type-2 and result in an immune dysregulation rather than overall immunosuppression. This may partially explain the increased incidence of type-2-mediated conditions such as increased viral infections, latent viral expression, allergic/asthmatic reactions, and autoimmunity reported during periods of high stress.

Adult↗
PubMed1998

The role of chemokines in tissue inflammation and autoimmunity in renal diseases.

Chemokines are an expanding family of chemoattractant polypeptides involved in the extravasation of leukocytes during the inflammatory process. This review highlights recent advances in the field, including the discovery of a new class of chemokines, and several novel receptors. In addition, the expanding role of chemokines in pathologic processes other than extravasation and their potential as therapeutic targets are discussed.

Animals↗
PubMed1997

Neurotactin, a membrane-anchored chemokine upregulated in brain inflammation.

Chemokines are small secreted proteins that stimulate the directional migration of leukocytes and mediate inflammation. During screening of a murine choroid plexus complementary DNA library, we identified a new chemokine, designated neurotactin. Unlike other chemokines, neurotactin has a unique cysteine pattern, Cys-X-X-X-Cys, and is predicted to be a type 1 membrane protein. Full-length recombinant neurotactin is localized on the surface of transfected 293 cells. Recombinant neurotactin containing the chemokine domain is chemotactic for neutrophils both in vitro and in vivo. Neurotactin messenger RNA is predominantly expressed in normal murine brain and its protein expression in activated brain microglia is upregulated in mice with experimental autoimmune encephalomyelitis, as well as in mice treated with lipopolysaccharide. Distinct from all other chemokine genes, the neurotactin gene is localized to human chromosome 16q. Consequently we propose that neurotactin represents a new delta-chemokine family and that it may play a role in brain inflammation processes.

Animals↗
PubMed1997

The relationship of parental style to depression and self-esteem in adulthood.

Previous studies have implicated low parental care and parental overprotection as risk factors for depression in adulthood. The present study further examined the association between perceived parental style and depression in two samples of medical students. In general, both low maternal and paternal care were associated with depression. Furthermore, maternal overprotection in the U.S. sample and paternal overprotection in the Scottish sample were also associated with depression. However, when results were analyzed separately for men and women, clear gender differences emerged, indicating that the observed relationships were occurring chiefly in the men, although there were some indications that low paternal care was associated with depression in women. Because such gender differences have not been previously reported, women medical students may be a unique group with respect to these relationships. Also intriguing was that although parental style characteristics demonstrated significant associations with self-esteem, this was clearly true only for men and not for women. Finally, the study provided the first partial support for the hypothesis that self-esteem mediates the relationship between parental style and depression.

Adolescent↗
PubMed1997

A transcultural pattern of drug use: qat (khat) in the UK.

BACKGROUND: This study investigates patterns of qat use among 207 Somalis living in London. METHOD: Subjects were recruited using privileged access interviewing. Somalian interviewers were recruited who shared the same culture as the subjects. Data were collected by means of a structured interview. RESULTS: One hundred and sixty-two subjects (78%) had used qat. The majority (76%) used more qat than in Somalia. Some users reported moderate dependence; a minority reported severe problems. Adverse psychological effects included sleep problems, anxiety and depression. Medical problems associated with qat use were rare. CONCLUSIONS: Qat users who continue to use this drug when it is transplanted from a traditional context may experience difficulties. Qat use can also be seen as playing a positive role in supporting the cultural identity of the Somalian community. Severe problems were rarely reported. Qat consumption should be considered when addressing health-related topics with patients from those communities in which qat use is common.

Adolescent↗