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Biomedical subjects

L Shawver

Publications and source records attributed to L Shawver.

11 recordsLinked to original sources
PubMed1999

The activation of protein kinase C induces higher production of reactive oxygen species by mononuclear cells in patients with multiple sclerosis than in controls.

OBJECTIVE: Recent findings have increasingly shown the importance of reactive oxygen species (ROS) in causing oxidative damage to macromolecules and in contributing to tissue degeneration in target organs of autoimmune diseases. This study was aimed at comparing the base line and induced production of ROS by peripheral blood mononuclear cells (PB MNCs) of patients with multiple sclerosis (MS) in remission and relapse, of patients with other neurological diseases (OND) and of healthy controls. In addition, we analyzed the underlying mechanism of ROS production. METHODS: PB MNCs were separated from 28 MS patients in remission and 13 in relapse, and from 29 healthy controls and 10 OND. ROS was measured by spectrofluorometry. Expression of proinflammatory cytokines was assessed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). Mitochondrial (mt) DNA haplotypes were determined by using restriction site polymorphism analysis. RESULTS: The base line and tumor necrosis factor (TNF)-alpha or interferon (IFN)-gamma induced ROS values were similar in the four groups, and the individual measures did not show a correlation with MS associated mtDNA haplotypes. Phorbol ester activation of protein kinase C (PKC) induced higher ROS production in all groups, however, with significantly greater values in the MS remission group. Calphostine C, a PKC inhibitor decreased or eliminated ROS production in a dose-dependent manner, suggesting further that it was predominantly or exclusively generated by PKC activated NADPH oxidase. A trend of increased TNF-alpha and IFN-gamma expression was noted in the MS relapse group, in contrast to the high ROS release in the MS remission group. CONCLUSION: The detected phase difference between the highest ROS production vs TNF-alpha expression is compatible with the hypothesis that different subpopulations of monocytes/macrophages are involved. We suggest that the ROS producing subpopulation preferentially migrates into the central nervous system (CNS) during a relapse. The present study together with our previous observation on oxidative damage to DNA in active plaques delineates a molecular pathway likely involved in the histologic evolution of inflammatory demyelination.

DNA, Mitochondrial↗
PubMed1999

Growth inhibition of psoriatic keratinocytes by quinazoline tyrosine kinase inhibitors.

Psoriasis is characterized by hyperproliferation of keratinocytes associated with an inflammatory infiltrate in the epidermis. Among factors which may be related to hyperplasia of psoriatic keratinocytes is the persistent autocrine stimulation of the epidermal growth factor receptor (EGFR) by transforming growth factor-alpha. Owing to the pivotal role of the EGFR in driving the growth of human psoriatic keratinocytes, we examined two selective inhibitors of EGFR kinase activity: 4-(3-bromophenylamino)-6, 7-dimethoxyquinazoline (AG1517/SU5271) and 4-(3-chlorophenylamino)-6, 7-dimethoxyquinazoline (AG1478) on psoriatic keratinocytes. SU5271 potently inhibits ligand-induced autophosphorylation of EGFR, and downstream signal transduction events, including DNA replication and cell cycle progression. SU5271, at micromolar concentrations, inhibited the proliferation of keratinocytes isolated from psoriatic lesions in excellent correlation with its EGFR kinase inhibitory activity in these cells. Biologically active concentrations of SU5271 penetrated human cadaver skin, suggesting that this compound is a strong candidate as an antipsoriatic agent.

Animals↗
PubMed1998

On the clinical relevance of selected postmodern ideas with a focus on Lyotard's concept of "differend".

Clinical differends are collisions of language-games in which people become baffled as to the other's meaning. This confusion creates anxiety and speechlessness, which disables their linguistic creativity to communicate effectively. In order to dispell this confusion, one needs to acquire the ability to negotiate a mutual set of rules for local conversation and to navigate these local local definitions without offending. Psychoanalysis can promote this flexibility by relying on the common-sense tactic of asking people what they mean by the words they use, by exploring their meaning in some depth, and by negotiating a nonoffensive local and provisional language with the patient that allows the patient to create a vocabulary for saying what needs to be said.

Communication↗
PubMed1977

Research variables in psychology and the logic of their creation.

In their book The Language of Psychology, Mandler and Kessen (1964) have concluded that research psychologists should limit themselves to studying variables that are defined in "response invariant" terms. The present author agrees with this general conclusion. The first part of this article will be a review of Mandler and Kessen's concept of "response invariance" and a probe of the reasoning that suggests such a conclusion. This analysis will prepare the way for outlining three kinds of methodological problems in psychology and corresponding solutions for each. This methodological analysis will be used also to relate two traditions in psychological research: the objective operational tradition that has been concerned, primarily, with the rigor of psychological research, and the phenomenological tradition that has been concerned with elucidating subtle, psychological profundities that are mysteriously entangled in human values and perspective, delicate dimensions of human experience that do not yield easily to rigorous and effective research designs.

Humans↗