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Biomedical subjects

R Martin

Publications and source records attributed to R Martin.

At least 289 records · Page 16Linked to original sources
PubMed1997

The proxy model of social comparison for self-assessment of ability.

One purpose of the social comparison of abilities is to determine action possibilities-"Can I do X?" By comparing ourselves with a proxy who has attempted X, we can determine our likelihood of success. A good proxy is one who has performed the same as us on an initial task requiring the ability. In addition, however, a good proxy must be similar on related attributes so that we can be confident that the proxy's performance on the initial task was maximal. In the case of a task requiring multiple abilities, more than one proxy may be used.

Journal Article↗
PubMed1997

Interferon-beta interferes with the proliferation but not with the cytokine secretion of myelin basic protein-specific, T-helper type 1 lymphocytes.

Interferon-beta (IFN-beta) has beneficial effects on the frequency and severity of relapses, as well as on disease progression in patients suffering from relapsing-remitting MS. Its mode of action, however, is not completely understood. Previous studies on T-lymphocyte bulk cultures and T-lymphocyte lines with specificity for different antigens suggested that the drug might partially act via suppression of T-cell proliferation and secretion of proinflammatory cytokines like interferon-gamma (IFN-gamma) and/or tumor necrosis factor-alpha (TNF-alpha). In this study we investigated the effects of human recombinant IFN-beta 1b on proliferation, interleukin 2 (IL-2) receptor (IL-2R) alpha-chain upregulation, and cytokine and chemokine secretion of myelin basic protein-reactive, MS patient-derived T-cell clones secreting T-helper type 1 (Th1) cytokines. IFN-beta partially suppressed both antigen- and IL-2-driven proliferation of these cells without affecting the expression of either IL-2 or IL-2R alpha-chain. There was no inhibitory effect on the secretion of IFN-gamma, TNF-alpha, and macrophage inflammatory protein (MIP)-1 alpha, but release was rather slightly enhanced. In conclusion, while IFN-beta does reduce proliferation of Th1-like, MBP-specific T cells in vitro, the drug does not result in overall dysfunction of these cells. Therefore, the effect of IFN-beta on MS may not depend on a primary inhibition of potentially encephalitogenic T lymphocytes.

Adjuvants, Immunologic↗
PubMed1997

Human T-cell response to myelin basic protein peptide (83-99): extensive heterogeneity in antigen recognition, function, and phenotype.

Multiple sclerosis (MS) is considered a T cell-mediated autoimmune disease, and myelin proteins are the most likely candidate autoantigens. Based on experiments performed in experimental allergic encephalomyelitis (EAE), innovative immunotherapies have been developed that target either the specific trimolecular complex of encephalitogenic T cells, consisting of T-cell receptor (TCR), major histocompatibility complex (MHC; HLA in humans) class II molecule, and autoantigenic peptide, or the effector functions of these cells. To provide the basis for the transfer of these specific immunotherapies to MS, we extensively characterized the human T-cell response to one major myelin epitope, the myelin basic protein peptide (83-99). We analyzed restriction element, TCR usage and affinity, fine specificity, cytokine production, cytolytic activity, and expression of surface molecules on 41 T-cell clones (TCCs) derived from MS patients and normal controls. We demonstrate a high degree of complexity of recognition patterns as well as of functional phenotypes among T cells responding to the same epitope. In contrast to results from animal models, these findings indicate that the design of epitope-based specific immunotherapies for MS is more difficult than previously thought.

Antigens↗
PubMed1997

Narcan therapy.

Explore the source record for details and available documents.

Drug Overdose↗
PubMed1997

Dentin bond strength of Dyract Cem.

PURPOSE: To evaluate the influence of provisional cements and of a dentin bonding agent on the adhesion of a self-curing polyacid-modified resin composite (Dyract Cem) on pressurized human dentin. MATERIALS AND METHODS: Freshly prepared dentin specimens of human teeth were perfused with physiologic saline. Three different types of surface treatment were evaluated. (1) Dyract Cem was applied to freshly prepared dentin without (Group 1.1) or with (Group 1.2) the respective dentin bonding agent (Prime & Bond 2.0) and cured. (2) Freegenol (Groups 2.1 and 2.2) or Temp Bond (Groups 2.3 and 2.4) were applied first on the dentin surface for 24 hours. Only then was Dyract Cem (with or without Prime & Bond 2.0) added onto the dentin after cleaning the dentin surface with pumice. 3) Prime & Bond 2.0 was applied first on the dentin surface and cured. Then Freegenol (Group 3.1) or Temp Bond (Group 3.2) were added for 24 hours. After cleaning with pumice, Prime & Bond 2.0 was applied for a second time on the dentin (= dual application) and finally Dyract Cem was added. As control, a conventional glass ionomer cement (Ketac-Cem Maxicap; Groups 4.1-4.3) was used in a similar way. After 1,500 thermal cycles with constant imitation of intrapulpal pressure, shear bond strengths were measured. Resulting shear bond strength values were displayed by means of a box plot and they were analyzed statistically by Mann-Whitney, Kruskal-Wallis or one way ANOVA tests. RESULTS: Lowest and highest mean shear bond strength values were 0.27 +/- 0.42 MPa (Group 2.4; single use of Prime & Bond 2.0 with prior application of TempBond) and 5.84 +/- 3.36 MPa (Group 3.1; dual use of Prime & Bond 2.0 with intermediate application of Freegenol). A clearly significant difference between groups could only be found when a single or dual use of the dentin bonding agent Prime & Bond 2.0 were combined with either Freegenol (Groups 2.1, 2.2 and 3.1; Kruskal-Wallis: P < 0.01) or Temp Bond (Groups 2.3, 2.4 and 3.2; Kruskal-Wallis: P < 0.001) as additional dentin surface treatment.

Adhesiveness↗
PubMed1996

Lithium-responsive affective disorders: no association with the tyrosine hydroxylase gene.

Family, adoption, and twin studies have demonstrated the involvement of genetic factors in the etiology of major affective disorders. In an attempt to identify the involved genes, several linkage and association studies have focused on the gene coding for tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. The discrepant results to date could be explained by etiological heterogeneity, which may be substantially reduced by selecting patients according to lithium response. Therefore, we investigated 54 patients who had shown definite long-term response to lithium monotherapy in spite of a high risk of recurrence as indicated by the previous clinical course. All the subjects suffered from major affective disorder by Research Diagnostic Criteria (48 bipolar, 6 recurrent unipolar). They were compared to 94 population controls of similar ethnic background to test for association with a penta-allelic microsatellite marker found within the tyrosine hydroxylase gene. No significant differences in allele and genotype frequencies were observed between the two groups, providing further evidence against a major role for the tyrosine hydroxylase gene in the etiology of major affective disorders.

Adult↗
PubMed1996

Human T lymphocytes specific for the immunodominant 83-99 epitope of myelin basic protein: recognition of golli MBP HOG 7.

Myelin basic protein (MBP) is a candidate autoantigen in the disease multiple sclerosis. Although MBP was thought to be sequestered behind the blood-brain barrier, isoforms of MBPs have recently been demonstrated in lymphoid tissues. These isoforms, termed golli MBPs, contain sequences that are shared with "classic" MBP within the CNS. In the present study, we have determined that epitopes within golli MBP isoforms may be recognized by human T lymphocyte clones specific for classic MBP. Ten of 12 T-cell clones recognized golli MBP. Although 11 clones were specific for the immunodominant 83-99 sequence, the clones differed with respect to human leukocyte antigen (HLA) restriction, T-helper phenotype, cytolytic activity, and T-cell receptor usage. Greater responses to classic MBP than to golli MBP suggested a difference in the ability of the two proteins to be processed and to present epitopes therein. These data advance the hypothesis that golli MBP sequences expressed within lymphoid tissues may be recognized by classic MBP-specific T lymphocytes during central or peripheral tolerance.

Antibody Specificity↗
PubMed1996

Cytokine phenotype of human autoreactive T cell clones specific for the immunodominant myelin basic protein peptide (83-99).

Experimental allergic encephalomyelitis (EAE), an animal model resembling multiple sclerosis (MS), is mediated by myelin antigen-specific CD4+ T cells secreting cytokines such as interferon-gamma (IFN-gamma), tumor necrosis factor-beta (TNF-beta), and the proinflammatory cytokine TNF-alpha-all associated with the T-helper-1 (Th1) T cell subset. Based on numerous similarities between MS and EAE, it has been postulated that Th1-like T cells are involved in the pathogenesis of MS. Production of proinflammatory cytokines such as IFN-gamma and, in particular, TNF-alpha/beta by autoreactive T cells is considered crucial for the initiation and amplification of inflammatory brain lesions and possibly also for direct myelin damage. In contrast, regulatory cytokines such as interleukin-4 (IL-4), IL-10, and IL-13, which are associated with the Th2-like phenotype, may play a role in the resolution of relapses. Although the human T cell response to myelin basic protein (MBP) is well characterized in terms of antigen specificity, HLA restriction, and T cell-receptor (TCR) usage, little is known about the cytokine pattern of these autoreactive T cells. To gain such information, conditions for studying cytokine secretion by human autoreactive T cell clones (TCC) were established. The cytokine secretion profile of human autoreactive CD4+ TCC, specific for myelin basic protein peptide (83-89) [MBP(83-99)], a candidate autoantigen in MS, was investigated. Our results show that TCC cytokine production in long-term culture was stable. In addition, the correlation of various cytokines within specific TCC revealed differences compared to murine T cells. The comparison of 30 human MBP (83-99)-specific TCC demonstrated heterogeneity in cytokine secretion, with a continuum between Th1- and Th2-like cells rather than distinct Th1 or Th2 subsets. These data are important for further investigation of the potential role of cytokines in the inflammatory process of MS, and provide a powerful tool to investigate therapeutic interventions with respect to their influence on cytokine secretion of autoreactive T cells.

Amino Acid Sequence↗
PubMed1996

A novel population of CD4+CD56+ myelin-reactive T cells lyses target cells expressing CD56/neural cell adhesion molecule.

CD56 is a member of the neural cell adhesion molecule family expressed on cells of the central nervous system and also on NK cells. Previous studies suggest the involvement of CD56 in effector-to-target cell conjugation mediated by NK cells. It was shown recently that CD56 is also expressed by subpopulations of CD8+ and CD4+ T cells. The present study describes the functional characteristics of CD4+CD56+ T cell lines established from blood of multiple sclerosis patients by stimulation with myelin basic protein (MBP). CD4+CD56+, MBP-specific T cell lines were able to lyse MBP-pulsed target cells in an HLA class II-restricted fashion. At the same time, they mediated MHC-unrestricted lysis of CD56+ target cells such as CD56+ lymphoid or glial tumor cells, but not of the typical NK target, K562. A number of experimental results including separation of CD4+CD56+ T cells into CD56 high and low expressing populations, cold target inhibition, as well as killing of CD56-transfected cells indicate that homotypic CD56 interactions are involved in the MHC-unrestricted lysis. CD56 interactions are not sufficient but are required for effector/target interaction. Our findings raise the possibility that CD4+CD56+ T cells sharing properties of both typical Ag-specific Th0-like T cells and NK cells might be involved in damage of tissues expressing CD56/neural cell adhesion molecule, such as the central nervous system. Thus, we provide evidence for a novel mechanism that could lead to organ-specific autoreactivity.

Biomarkers↗
PubMed1996

No association between chromosome-18 markers and lithium-responsive affective disorders.

An allelic association study of excellent responders to lithium was conducted with a candidate gene (Golf, a G-protein receptor gene) and five other chromosome-18p markers. Golf is of special interest because it maps to a region of chromosome 18 where two independent groups (Berrettini et al., 1994; Stine et al., 1995) have found linkage to bipolar disorder. It has been proposed that G proteins are involved in the pathogenesis of bipolar disorder, and lithium, an effective prophylactic agent, is known to impair G-protein activation. To reduce heterogeneity--a common obstacle to genetic investigation--only patients who showed excellent response to lithium prophylaxis were studied. Fifty-five genetically unrelated excellent responders to lithium prophylaxis were compared with 94 normal subjects of similar ethnic background. The groups did not differ in either allele or genotype frequency for the tested markers. The data do not support the hypothesis that the tested loci confer a major susceptibility for affective disorders.

Adult↗
PubMed1996

Nurses taking on junior doctors' work: a confusion of accountability.

The number of hospital based posts in which nurses take over clinical work previously done by junior doctors is growing. Accountability for the scope of such new roles and the standards of practice which apply to them are still unclear. When analysed together and compared, the regulations arising from the professional bodies (GMC and UKCC), civil law concerning certain wrongs to patients, and employment law are sometimes contradictory and hard to interpret. The resulting uncertainties about appropriate management for clinical roles evolving between the professions, coupled with an increasingly litigious public, put the nurses and consultants involved at risk of complaints and of disciplinary and legal action. Drawing on our current research into changing clinical roles at the medical-nursing interface, we suggest strategies to reduce risk. Doctors and nurses should be equal partners in planning and managing these new posts, patients should be informed adequately about the nature of the postholder's role and training, significant changes in the work of such postholders should be formally acknowledged by the employer and relevant insurers, individuals taking up new roles should have access to legal advice and support to cover legal risk, and national regulatory bodies need to work together to harmonise their codes of practice in relation to changing clinical roles between the professions.

Humans↗
PubMed1996

Cortical plaque-like structures identify ribosome-containing domains in the Mauthner cell axon.

The hypothesis that ribosomes are present, but may have a restricted distribution, in the Mauthner (M) axon was evaluated in isolated M-cell axoplasm after (1) staining with YOYO-1 and (2) inspection by electron spectroscopic imaging (ESI) of ribosomal RNA (rRNA) phosphorus (P). Discrete periaxoplasmic plaques, identified by their ribonuclease-sensitive fluorescence, were located circumferentially at the surface boundary of isolated axoplasm and distributed longitudinally at random intervals. Conditions that destabilized plaques, and surface blotting of plaques onto a coverslip, revealed that fluorescent puncta were probably a significant source of plaque fluorescence. Fluorescent puncta were also distributed in a delimited volume of axoplasm, subjacent to the plaque. The notably higher density of F-actin in the latter region suggested that the actin cytoskeleton may govern the spatial distribution of puncta in subcortical axoplasm. Some fluorescent plaques were superficial to the cortical F-actin layer, whereas others formed inclusions within the F-actin layer; however, plaques did not appear to contain F-actin. Periaxoplasmic plaques were also identified in ordinary myelinated axons. ESI, in which rRNA emits bright signals in the phosphorus (P) spectral line against a low-contrast background, showed that isolated axoplasm contained characteristic 25 nm P signals, which were associated or in direct contact with a pleiomorphic structural matrix, located at the surface boundary. Polyribosomal P signals were also distributed in peripheral axoplasm below the matrix. The concept of a distinct polyribosome-populated domain, distributed intermittently in the cortical zone of the axon is described. This domain is spatially defined by a plaque-like periaxoplasmic structural matrix, and a confluent volume of subcortical axoplasm integrated through an actin cytoskeleton.

Animals↗