bluuebunny/crossref_metadata_2025 huggingface dataset:
Type I interferon dependence of plasmacytoid dendritic cell activation and migration
Authors: Asselin-Paturel Carine , Brizard Géraldine , Chemin Karine , Boonstra Andre , O'Garra Anne , Vicari Alain , Trinchieri Giorgio
Published: March 2005

Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration.
Serine protease inhibitors serpina1 and serpina3 are down-regulated in bone marrow during hematopoietic progenitor mobilization
Authors: Winkler Ingrid G. , Hendy Jean , Coughlin Paul , Horvath Anita , Lévesque Jean-Pierre
Published: March 2005

Mobilization of hematopoietic progenitor cells into the blood involves a massive release of neutrophil serine proteases in the bone marrow. We hypothesize that the activity of these neutrophil serine proteases is regulated by the expression of naturally occurring inhibitors (serpina1 and serpina3) produced locally within the bone marrow. We found that serpina1 and serpina3 were transcribed in the bone marrow by many different hematopoietic cell populations and that a strong reduction in expression occurred both at the protein and mRNA levels during mobilization induced by granulocyte colony-stimulating factor or chemotherapy. This decreased expression was restricted to the bone marrow as serpina1 expression was maintained in the liver, leading to no change in plasma concentrations during mobilization. The down-regulation of serpina1 and serpina3 during mobilization may contribute to a shift in the balance between serine proteases and their inhibitors, and an accumulation of active neutrophil serine proteases in bone marrow extravascular fluids that cleave and inactivate molecules essential to the retention of hematopoietic progenitor cells within the bone marrow. These data suggest an unexpected role for serpina1 and serpina3 in regulating the bone marrow hematopoietic microenvironment as well as influencing the migratory behavior of hematopoietic precursors.
Laws and Possibilities
Authors: Koslow Arnold
Published: March 2005

The initial part of this paper explores and rejects three standard views of how scientific laws might be systematically connected with physical necessity or possibility. The first concerns laws and their consequences, the second concerns the so-called counterfactual connection, and the third concerns a possible worlds construction of physical necessity. The remaining part introduces a neglected notion of possibility, and, with the aid of some examples, illustrates the special way in which laws reduce or narrow down possibilities.
The Law-Idealization
Authors: Teller Paul
Published: March 2005

There are few, perhaps no known, exact, true, general laws. Some of the work of generalization is carried by ceteris paribus generalizations. I suggest that many models continue such work in more complex form, with the idea of ceteris paribus conditions thought of as extended to more general conditions of application. I use the term regularity guide to refer collectively to cp-generalizations and such regularity-purveying models. Laws in the traditional sense can then be thought of as idealizations, which idealize away from the conditions of application of regularity guides. If we keep clearly in mind the status of laws as such idealizations, problems surrounding traditional topics—such as lawlikeness, corresponding counterfactuals and modality—no longer look to be intractable.
An Inferential Conception of Scientific Representation
Authors: Suárez Mauricio
Published: March 2005

This paper defends an inferential conception of scientific representation. It approaches the notion of representation in a deflationary spirit, and minimally characterizes the concept as it appears in science by means of two necessary conditions: its essential directionality and its capacity to allow surrogate reasoning and inference. The conception is defended by showing that it successfully meets the objections that make its competitors, such as isomorphism and similarity, untenable. In addition the inferential conception captures the objectivity of the cognitive representations used by science, it sheds light on their truth and completeness, and it explains the source of the analogy between scientific and artistic modes of representation.
How Might We Put Gender Politics into Science?
Authors: Koertge Noretta
Published: March 2005

Feminist proposals for reforming scientific method often ask that political evaluations be introduced into the context of justification. How might this work in practice? Fausto-Sterling's alternative conceptualization of biological sex is analyzed and criticized. We then use this case study to comment on recent work on the role of social values in science by Longino and Kitcher.
Human Kinds and Biological Kinds: Some Similarities and Differences
Authors: Dupré John
Published: March 2005

This paper compares human diversity with biological diversity generally. Drawing on the pluralistic perspective on biological species defended in earlier work (2002, chs. 3 and 4), I argue that there are useful parallels to be drawn between human and animal kinds, as there are between their respective sources in cultural evolution and evolution generally. This view is developed in opposition to the insistence by sociobiologists and their successors on minimizing the significance of culture. The paper concludes with a discussion of the relation between cultural difference and individual difference, and the relation of the latter to conceptions of human freedom.
Wesley Salmon's Intellectual Odyssey and Achievements
Authors: Grünbaum Adolf
Published: March 2005

Opening Remarks of the Chairman at “Wesley C. Salmon, 1925–2001”: A Symposium Honoring his Contributions to the Philosophy of Science.
Thought Experiments and the Belief in Phenomena
Authors: McAllister James W.
Published: March 2005

Thought experiment acquires evidential significance only on particular metaphysical assumptions. These include the thesis that science aims at uncovering “phenomena”—universal and stable modes in which the world is articulated—and the thesis that phenomena are revealed imperfectly in actual occurrences. Only on these Platonically inspired assumptions does it make sense to bypass experience of actual occurrences and perform thought experiments. These assumptions are taken to hold in classical physics and other disciplines, but not in sciences that emphasize variety and contingency, such as Aristotelian natural philosophy and some forms of historiography. This explains why thought experiments carry weight in the former but not the latter disciplines.
Laws and Initial Conditions
Authors: Frisch Mathias
Published: March 2005

I discuss two case studies from classical electrodynamics challenging the distinction between laws that delineate physically possible words and initial conditions. First, for many reasonable initial conditions there exist no global solutions to the Maxwell-Lorentz equations for continuous charge distributions. Second, in deriving an equation of motion for a charged point particle one needs to invoke an asymptotic condition that seems to express a physically contingent fact even though it is mathematically necessary for the derivation.
Causal Models, Token Causation, and Processes
Authors: Menzies Peter
Published: March 2005

Judea Pearl (2000) has recently advanced a theory of token causation using his structural equations approach. This paper examines some counterexamples to Pearl's theory, and argues that the theory can be modified in a natural way to overcome them.
Causal Inference of Ambiguous Manipulations
Authors: Spirtes Peter , Scheines Richard
Published: March 2005

Over the last two decades, a fundamental outline of a theory of causal inference has emerged. However, this theory does not consider the following problem. Sometimes two or more measured variables are deterministic functions of one another, not deliberately, but because of redundant measurements. In these cases, manipulation of an observed defined variable may actually be an ambiguous description of a manipulation of some underlying variables, although the manipulator does not know that this is the case. In this article we revisit the question of precisely characterizing conditions and assumptions under which reliable inference about the effects of manipulations is possible, even when the possibility of “ambiguous manipulations” is allowed.
Some Thoughts on Wesley Salmon's Contributions to the Philosophy of Probability
Authors: Humphreys Paul
Published: March 2005

Wesley Salmon provided three classic criteria of adequacy for satisfactory interpretations of probability. A fourth criterion is suggested here. A distinction is drawn between frequency-driven probability models and theory-driven probability models and it is argued that single case accounts of chance are superior to frequency accounts at least for the latter. Finally it is suggested that theories of chance should be required only to be contingently true, a position which is a natural extension of Salmon's ontic account of probabilistic causality and his own later views on propensities.
How Models Are Used to Represent Reality
Authors: Giere Ronald N.
Published: March 2005

Most recent philosophical thought about the scientific representation of the world has focused on dyadic relationships between language-like entities and the world, particularly the semantic relationships of reference and truth. Drawing inspiration from diverse sources, I argue that we should focus on the pragmatic activity of representing, so that the basic representational relationship has the form: Scientists use models to represent aspects of the world for specific purposes. Leaving aside the terms “law” and “theory,” I distinguish principles, specific conditions, models, hypotheses, and generalizations. I argue that scientists use designated similarities between models and aspects of the world to form both hypotheses and generalizations.
Methodology in Practice: Statistical Misspecification Testing
Authors: Mayo Deborah G. , Spanos Aris
Published: March 2005

The growing availability of computer power and statistical software has greatly increased the ease with which practitioners apply statistical methods, but this has not been accompanied by attention to checking the assumptions on which these methods are based. At the same time, disagreements about inferences based on statistical research frequently revolve around whether the assumptions are actually met in the studies available, e.g., in psychology, ecology, biology, risk assessment. Philosophical scrutiny can help disentangle ‘practical’ problems of model validation, and conversely, a methodology of statistical model validation can shed light on a number of issues of interest to philosophers of science.
Causal Processes and Interactions: What Are They and What Are They Good For?
Authors: Hitchcock Christopher
Published: March 2005

Concerning any object of philosophical analysis, we can ask several questions, including the two posed in the title of this paper. Despite difficulties in formulating a precise criterion to distinguish causal processes from pseudoprocesses, and causal interactions from mere spatiotemporal intersections, I argue that Salmon answered the first of these questions with extraordinary clarity. The second question, by contrast, has received very little attention. I will present two problems: in the first, it seems that Salmon has provided exactly the conceptual resources needed to solve the problem; in the second, it is difficult to see how causal processes and interactions may be used to shed any light. In general, the way to carry Salmon's program forward will be to demonstrate that these resources can be made to do real philosophical work.
Evolutionary Theory in the 1920s: The Nature of the “Synthesis”
Authors: Sarkar Sahotra
Published: March 2005

This paper analyzes the development of evolutionary theory in the period from 1918 to 1932. It argues that: (i) Fisher's work in 1918 constituted a not fully satisfactory reduction of biometry to Mendelism; (ii) there was a synthesis in the 1920s but that this synthesis was mainly one of classical genetics with population genetics, with Haldane's The Causes of Evolution being its founding document; (iii) the most important achievement of the models of theoretical population genetics was to show that natural selection sufficed as a mechanism for evolution; and (iv) Haldane formulated a prospective evolutionary theory in the 1920s whereas Fisher and Wright formulated retrospective theories of evolutionary history.
Thought Experiments Rethought—and Reperceived
Authors: Gendler Tamar Szabó
Published: March 2005

Contemplating imaginary scenarios that evoke certain sorts of quasi-sensory intuitions may bring us to new beliefs about contingent features of the natural world. These beliefs may be produced quasi-observationally; the presence of a mental image may play a crucial cognitive role in the formation of the belief in question. And this albeit fallible quasi-observational belief-forming mechanism may, in certain contexts, be sufficiently reliable to count as a source of justification. This sheds light on the central puzzle surrounding scientific thought experiment, which is how contemplation of an imaginary scenario can lead to new knowledge about contingent features of the natural world.
The Heuristic Role of Sewall Wright's 1932 Adaptive Landscape Diagram
Authors: Skipper Robert A.
Published: March 2005

Sewall Wright's adaptive landscape is the most influential heuristic in evolutionary biology. Wright's biographer, Provine, criticized Wright's adaptive landscape, claiming that its heuristic value is dubious because of deep flaws. Ruse has defended Wright against Provine. Ruse claims Provine has not shown Wright's use of the landscape is flawed, and that, even if it were, it is heuristically valuable. I argue that both Provine's and Ruse's analyses of the adaptive landscape are defective and suggest a more adequate understanding of it.
Population Genetics and Population Thinking: Mathematics and the Role of the Individual
Authors: Morrison Margaret
Published: March 2005

Ernst Mayr has criticised the methodology of population genetics for being essentialist: interested only in “types” as opposed to individuals. In fact, he goes so far as to claim that “he who does not understand the uniqueness of individuals is unable to understand the working of natural selection” (1982, 47). This is a strong claim indeed especially since many responsible for the development of population genetics (especially Fisher, Haldane, and Wright) were avid Darwinians. In order to unravel this apparent incompatibility I want to examine the possible sources and implications of essentialism in this context and show why the kind of mathematical analysis found in Fisher's work is better seen as responsible for extending the theory of natural selection to a broader context rather than inhibiting its applicability.
Quantum Reference Frames in the Context of EPR
Authors: Dickson Michael
Published: March 2005

Taking a cue from Bohr's use of the notion of a reference frame in his reply to EPR's argument against the completeness (and consistency) of standard quantum theory, this paper presents an analysis ofthe role of reference frames in the situation considered by EPR, using a quantum-theoretical account of physical reference frames based on the work of Mackey, and Aharonov and Kaufherr. That analysis appears to justify at least some crucial aspects of a Bohrian reply to EPR.
Peeking into Plato's Heaven
Authors: Brown James Robert
Published: March 2005

Examples of classic thought experiments are presented and some morals drawn. The views of my fellow symposiasts, Tamar Gendler, John Norton, and James McAllister, are evaluated. An account of thought experiments along a priori and Platonistic lines is given. I also cite the related example of proving theorems in mathematics with pictures and diagrams. To illustrate the power of these methods, a possible refutation of the continuum hypothesis using a thought experiment is sketched.
Who Invented the “Copenhagen Interpretation”? A Study in Mythology
Authors: Howard Don
Published: March 2005

What is commonly known as the Copenhagen interpretation of quantum mechanics, regarded as representing a unitary Copenhagen point of view, differs significantly from Bohr's complementarity interpretation, which does not employ wave packet collapse in its account of measurement and does not accord the subjective observer any privileged role in measurement. It is argued that the Copenhagen interpretation is an invention of the mid-1950s, for which Heisenberg is chiefly responsible, various other physicists and philosophers, including Bohm, Feyerabend, Hanson, and Popper, having further promoted the invention in the service of their own philosophical agendas.
Emotions as Natural and Normative Kinds
Authors: Griffiths Paul E.
Published: March 2005

In earlier work I have claimed that emotion and some emotions are not ‘natural kinds’. Here I clarify what I mean by ‘natural kind’, suggest a new and more accurate term, and discuss the objection that emotion and emotions are not descriptive categories at all, but fundamentally normative categories.
Realization: Metaphysics, Mind, and Science
Authors: Wilson Robert A.
Published: March 2005

This paper surveys some recent work on realization in the philosophy of mind and the philosophy of science.
Neural Machinery and Realization
Authors: Polger Thomas W.
Published: March 2005

The view that the relationship between minds and brains can be thought of on the model of software and hardware is pervasive. The most common versions of the view, known as functionalism in philosophy of mind, hold that minds are realized by brains. The question arises, What is the realization relation? I approach the question of realization through a case study: David Marr's (1982) computational account of early visual processing. Marr's work is instructive because it is the textbook case of the hierarchy of mechanisms that has seemed to bear out the arguments of functionalist philosophers and cognitive scientists. I argue that realization as employed by Marr has some but not all of the characteristics that it is usually taken to have.
Spacetime and Conventionalism
Authors: Sklar Lawrence
Published: March 2005

Salmon, following Reichenbach and others, maintained that distant simultaneity was conventional in a special relativistic world in a way in which this was not so in prerelativistic spacetime. This paper surveys and criticizes a number of proposals to unpack this claim. It goes on to argue that if the claim has validity, it rests upon differing facts about epistemic accessibility of temporal relations in the different spacetimes, and not directly upon any facts about differing causal structures in these worlds.
Imagination and Imaging in Model Building
Authors: Morgan Mary S.
Published: March 2005

Modelling became one of the primary tools of mathematical economic research in the twentieth century, but when we look at examples of how nonanalogical models were first built in economics, both the process of making representations and aspects of the representing relation remain opaque. Like early astronomers, economists have to imagine how the hidden parts of their world are arranged and to make images, that is, create models, to represent how they work. The case of the Edgeworth Box, a model widely used for theoretical work in twentieth-century economics, provides a good example to explore the process of making mathematical representations of the economy. It shows how, in making these new representations, conceptual elements were developed which could not have been represented in the older verbal forms of economics.
Science as Representation: Flouting the Criteria
Authors: van Fraassen Bas C.
Published: March 2005

Criteria of adequacy for scientific representation of the phenomena pertain to accuracy and truth. But that representation is selective and may require distortion even in the selected parameters; this point is intimately connected with the fact that representation is intentional, and its adequacy relative to its particular purpose. Since observation and measurement are perspectival and the appearances to be saved are perspectival measurement outcomes, the question whether this “saving” is an explanatory relation provides a new focus for the realist/antirealist debate. The Born rule and von Neumann's “collapse” postulate in quantum mechanics provide a telling case for this question in recent physics.
Causation: One Word, Many Things
Authors: Cartwright Nancy
Published: March 2005

We currently have on offer a variety of different theories of causation. Many are strikingly good, providing detailed and plausible treatments of exemplary cases; and all suffer from clear counterexamples. I argue that, contra Hume and Kant, this is because causation is not a single, monolithic concept. There are different kinds of causal relations imbedded in different kinds of systems, readily described using thick causal concepts. Our causal theories pick out important and useful structures that fit some familiar cases—cases we discover and ones we devise to fit.
Using Metascience to Improve Dose-Response Curves in Biology: Better Policy through Better Science
Authors: Shrader-Frechette Kristin
Published: March 2005

Many people argue that uncertain science—or controversial policies based on science—can be clarified primarily by greater attention to social/political values influencing the science and by greater attention to the vested interests involved. This paper argues that while such clarification is necessary, it is not a sufficient condition for achieving better science and policy; indeed its importance may be overemphasized. Using a case study involving the current, highly politicized controversy over the shape of dose-response curves for biological effects of ionizing radiation, the paper argues that the conflict could be significantly resolved through specific methodological improvements in the areas of metascience and philosophy of science. These improvements focus on taking account, respectively, of scale, data trimming, aggregation, measurability, and simplicity.
Explanation in Classical Population Genetics
Authors: Plutynski Anya
Published: March 2005

The recent literature in philosophy of biology has drawn attention to the different sorts of explanations proffered in the biological sciences—we have molecular, biomedical, and evolutionary explanations. Do these explanations all have a common structure or relation that they seek to capture? This paper will answer in the negative. I defend a pluralistic and pragmatic approach to explanation. Using examples from classical population genetics, I argue that formal demonstrations, and even strictly “mathematical truths,” may serve as explanatory in different historical contexts.
Qualitative Theory and Chemical Explanation
Authors: Weisberg Michael
Published: March 2005

Roald Hoffmann and other theorists claim that we ought to use highly idealized chemical models (“qualitative models”) in order to increase our understanding of chemical phenomena, even though other models are available which make more highly accurate predictions. I assess this norm by examining one of the tradeoffs faced by model builders and model users—the tradeoff between precision and generality. After arguing that this tradeoff obtains in many cases, I discuss how the existence of this tradeoff can help us defend Hoffmann's norm for modelling.
Principles and Parameters in Physics and Chemistry
Authors: Scerri Eric
Published: March 2005

The paper examines critically some recently published views by Ramsey on the contrast between ab initio and parametrized theories. I argue that, all things being equal, ab initio calculations are indeed regarded more highly in the physics and chemistry communities. A case study on density functional approaches in theoretical chemistry is presented in order to re-examine the question of ab initio and parametrized approaches in a contemporary context.
David Lewis Meets Hamilton and Jacobi
Authors: Butterfield Jeremy
Published: March 2005

I commemorate David Lewis by discussing an aspect of modality within analytical mechanics, which is closely related to his work on counterfactuals. This concerns the way Hamilton-Jacobi theory uses ensembles, i.e. sets of possible initial conditions. (A companion paper discusses other aspects of modality in analytical mechanics that are equally related to Lewis's work.)
Rescued from the Rubbish Bin: Lewis on Causation
Authors: Hall Ned
Published: March 2005

Lewis's work on causation was governed by a familiar methodological approach: the aim was to come up with an account of causation that would recover, in as elegant a fashion as possible, all of our firm “pre-theoretic” intuitions about hypothetical cases. That methodology faces an obvious challenge, in that it is not clear why anyone not interested in the semantics of the English word “cause” should care about its results. Better to take a different approach, one which treats our intuitions about cases merely as guides in the construction of a causal concept or concepts that will serve some useful theoretical purpose. I sketch one central such purpose, suggesting, first, that an account of causation that, like Lewis's, gives a central role to counterfactuals is well-suited to fulfill it, and, second, that the most famous pre-emption-based counterexamples to a counterfactual account yield an important constraint on a successful account.
Laws, Symmetry, and Symmetry Breaking: Invariance, Conservation Principles, and Objectivity
Authors: Earman John
Published: March 2005

Given its importance in modern physics, philosophers of science have paid surprisingly little attention to the subject of symmetries and invariances, and they have largely neglected the subtopic of symmetry breaking. I illustrate how the topic of laws and symmetries brings into fruitful interaction technical issues in physics and mathematics with both methodological issues in philosophy of science, such as the status of laws of physics, and metaphysical issues, such as the nature of objectivity.
Topiramate Inhibits the Initiation of Plateau Potentials in CA1 Neurons by Depressing R‐type Calcium Channels
Authors: Kuzmiski Joseph Brent , Barr Wendy , Zamponi Gerald W. , MacVicar Brian A.
Published: March 2005

Summary:  Purpose: Cholinergic‐dependent plateau potentials (PPs) are intrinsically generated conductances that can elicit ictal‐type seizure activity. The aim of this study was to investigate the actions of topiramate (TPM) on the generation of PPs.

Methods: We used whole‐cell patch‐clamp recordings from CA1 pyramidal neurons in rat hippocampal slices to examine the effects of TPM on the PPs.

Results: In current‐clamp mode, action potentials evoked PPs after cholinergic receptor stimulation. Therapeutically relevant concentrations of TPM (50 μM) depressed the PPs evoked by action potentials. Surprisingly, in voltage‐clamp mode, we discovered that the cyclic nucleotide–gated (CNG) current that underlies PP generation (denoted as Itail) was not depressed. However, significantly longer depolarizing voltage steps were required to elicit Itail. This suggested that the calcium entry trigger for evoking PPs was depressed by TPM and not Itail itself. TPM had no effect on calcium spikes in control conditions; however, TPM did reduce calcium spikes after cholinergic‐receptor stimulation. We recently found that R‐type calcium spikes are enhanced by cholinergic‐receptor stimulation. Therefore we isolated R‐type calcium spikes with a cocktail containing tetrodotoxin, ω‐conotoxin MVIIC, ω‐conotoxin‐GVIA, ω‐agatoxin IVA, and nifedipine. R‐type calcium spikes were significantly depressed by TPM. We also examined the effects of TPM on recombinant CaV2.3 calcium channels expressed in tsA‐201 cells. TPM depressed currents mediated by CaV2.3 subunits by a hyperpolarizing shift in steady‐state inactivation.

Conclusions: We have found that TPM reduces ictal‐like activity in CA1 hippocampal neurons through a novel inhibitory action of R‐type calcium channels.
Epilepsy and Neurocysticercosis in Atahualpa: A Door‐to‐Door Survey in Rural Coastal Ecuador
Authors: Brutto Oscar H. Del , Santibáñez Rocío , Idrovo Luis , Rodrìguez Silvia , Díaz‐Calderón Enrique , Navas Carlos , Gilman Robert H. , Cuesta Fausto , Mosquera Aurelio , Gonzalez Armando E. , Tsang Victor C. W. , García Hector H.
Published: March 2005

Summary:  Purpose: To determine the prevalence of epilepsy and the role of neurocysticercosis in the occurrence of epilepsy in Atahualpa.

Methods: We used a door‐to‐door survey to detect subjects with epileptic seizures, to collect a blood sample for determination of anticysticercal antibodies, and to evaluate social characteristics of the population, including household pig ownership. Neurologists examined suspected cases and a sample of negative individuals. Then patients with epilepsy, as well as age‐ and sex‐matched controls, underwent a head computed tomography (CT) and a scalp EEG.

Results: The questionnaire was answered by 2,415 of 2,548 residents of Atahualpa, and cysticercosis serology was performed in 1,687 consenting individuals. Cysticercosis seroprevalence was 145 (8.6%) per 1,686). Neurologic examination confirmed 24 patients with epilepsy (crude prevalence, 9.9 per 1,000 population, and 10.8 per 1,000 when adjusted to the United States population). After adjustment by age, sex, and pig raising, positive serology was strongly associated with epilepsy (odds ratio (OR), 4.16; 95% confidence interval (CI), 1.6–11.2). CT findings compatible with neurocysticercosis were found in five patients with epilepsy and also were more frequent than in controls, although this did not reach statistical significance (five of 19 vs. one of 19; p = 0.125, McNemar's test). Besides these five cases, three other patients with epilepsy had positive serology (one with a normal CT and two who did not have a CT).

Conclusions: Neurocysticercosis is associated with one‐third of cases of epilepsy in Atahualpa and may be a major contributory factor for the excess fraction of epilepsy seen in this population.
A 5‐Month Period of Epilepsy Impairs Spatial Memory, Decreases Anxiety, but Spares Object Recognition in the Lithium‐pilocarpine Model in Adult Rats
Authors: Detour Julien , Schroeder Henri , Desor Didier , Nehlig Astrid
Published: March 2005

Summary:  Purpose: In temporal lobe epilepsy (TLE), interictal behavioral disorders affect patients' quality of life. Therefore we studied long‐term behavioral impairments in the lithium‐pilocarpine (li‐pilo) model of TLE.

Methods: Eleven li‐pilo adult rats exhibiting spontaneous recurrent seizures (SRSs) during 5 months were compared with 11 li‐saline rats. Spatial working memory was tested in a radial arm maze (RAM), anxiety in an elevated plus‐maze (EPM), and nonspatial working memory in an object‐recognition paradigm. Neuronal loss was assessed on thionine brain sections after behavioral testing.

Results: In the RAM, the time to complete each session and the number of errors per session decreased over a 5‐day period in li‐saline rats but remained constant and significantly higher in li‐pilo rats. In the EPM, the number of entries in and time spent on open arms were significantly higher in li‐pilo than li‐saline rats. In the object‐recognition task, the two groups exhibited a comparable novelty preference for the new object. Neuronal loss reached 47–90% in hilus, CA1, amygdala, and piriform and entorhinal cortex.

Conclusions: In li‐pilo rats having experienced SRS for 5 months, performance in the object‐recognition task is spared, which suggests that object discrimination remains relatively intact despite extensive damage. Neuronal loss in regions mediating memory and anxiety, such as hippocampus, entorhinal cortex, and amygdala, may relate to impaired spatial orientation and decreased anxiety.
Electrical and Chemical Long‐term Depression Do Not Attenuate Low‐Mg2+–induced Epileptiform Activity in the Entorhinal Cortex
Authors: Solger Jörg , Heinemann Uwe , Behr Joachim
Published: March 2005

Summary:  Purpose: Low‐frequency electrical and magnetic stimulation of cortical brain regions has been shown to reduce cortical excitability and to decrease the susceptibility to seizures in humans and in vivo models of epilepsy. The induction of long‐term depression (LTD) or depotentiation of a seizure‐related long‐term potentiation has been proposed to be part of the underlying mechanism. With the low‐Mg2+‐model of epilepsy, this study investigated the effect of electrical LTD, chemical LTD, and depotentiation on the susceptibility of the entorhinal cortex to epileptiform activity.

Methods: The experiments were performed on isolated entorhinal cortex slices obtained from adult Wistar rats and mice. With extracellular recording techniques, we studied whether LTD induced by (a) three episodes of low‐frequency paired‐pulse stimulation (3 × 900 paired pulses at 1 Hz), and by (b) bath‐applied N‐methyl‐d‐aspartate (NMDA, 20 μM) changes time‐to‐onset, duration, and frequency of seizure‐like events (SLEs) induced by omitting MgSO4 from the artificial cerebrospinal fluid. Next we investigated the consequences of depotentiation on SLEs themselves by applying low‐frequency stimulation after onset of low‐Mg2+–induced epileptiform activity.

Results: LTD, induced either by low‐frequency stimulation or by bath‐applied NMDA, had no effect on time‐to‐onset, duration, and frequency of SLEs compared with unconditioned slices. Low‐frequency stimulation after onset of SLEs did not suppress but induced SLEs that lasted for the time of stimulation and were associated with a simultaneous increase of the extracellular K+ concentration.

Conclusions: Our study demonstrates that neither conditioning LTD nor brief low‐frequency stimulation decreases the susceptibility of the entorhinal cortex to low‐Mg2+–induced epileptiform activity. The present study does not support the hypothesis that low‐frequency brain stimulation exerts its anticonvulsant effect via the induction of LTD or depotentiation.
A Child with Epilepsy in Whom Multifocal VEPs Facilitated the Objective Measurement of the Visual Field
Authors: Yukawa Eiichi , Kim Yeong‐Jin , Kawasaki Kensuke , Taketani Futoshi , Hara Yoshiaki
Published: March 2005

Summary:  Purpose: We investigated whether visual field defects can be objectively evaluated by using multifocal visual evoked potential (multifocal VEP) in children with epilepsy in whom it is difficult to measure the visual field.

Methods: First, to determine normal waves in multifocal VEP, recording was performed by using a VERIS Junior Science (Mayo, Aichi, Japan) in 21 healthy children (21 eyes) consisting of 12 boys and nine girls aged 6 to 15 years (mean age, 11.4 years). Responses from eight sites in each subject were divided into four quadrants (superior and inferior temporal quadrants and superior and inferior nasal quadrants). In each quadrant, two response waves were grouped and averaged; peak latency and amplitude were used for assessment. In a child with epilepsy in whom kinetic or static perimetry was impossible, multifocal VEPs were recorded and compared with the peak latency and amplitude in the healthy subjects.

Results: In the 21 healthy children, no significant differences were observed in the peak latency or amplitude among four quadrants by one‐way analysis of variance. Multifocal VEPs in the child with epilepsy showed abnormal waves in the right hemivisual field, which corresponded to the lesion observed with magnetic resonance imaging.

Conclusions: The objective evaluation of visual field defects by using multifocal VEP may be useful in children with epilepsy in whom kinetic/static perimetry as a subjective examination is difficult.
Hypersomnia in an Epilepsy Patient Treated with Levetiracetam
Authors: Khatami Ramin , Siegel Adrian M. , Bassetti Claudio L.
Published: March 2005

Summary:  We report a patient with focal epilepsy in whom increased sleep needs (hypersomnia) developed in the absence of subjective excessive daytime sleepiness (EDS) during an add‐on treatment with levetiracetam (LEV).
Somatosensory Processing Is Impaired in Temporal Lobe Epilepsy
Authors: Grant Arthur C. , Henry Thomas R. , Fernandez Raquel , Hill Mary Ann , Sathian K.
Published: March 2005

Summary:  Purpose: Growing evidence suggests that temporal lobe epilepsy (TLE) is a network disease. In this view, the seizure focus may produce measurable deficits in specific cortical functions.

Methods: A tactile grating orientation (GrOr) discrimination task associated with parietal lobe function was administered at the index fingertip to 15 subjects with medically intractable TLE and to 19 neurologically normal controls. TLE subjects were tested bilaterally at baseline while taking their usual antiepileptic drugs (AEDs), and off AEDs during inpatient video‐EEG monitoring (n = 9). Three subjects also were tested after temporal lobectomy. t Tests were used to compare baseline performance between TLE subjects and controls, and between hands ipsilateral and contralateral to side of seizure onset, with Bonferroni correction for multiple comparisons. TLE subjects' baseline thresholds were compared with those obtained off AEDs by using a repeated measures analysis of variance.

Results: TLE subjects were severely impaired bilaterally on the GrOr task, with mean discrimination thresholds nearly twice those of controls (p ≤ 0.001 for each hand). No significant difference was found in baseline performance between hands (p = 0.37), or between baseline and off‐AED testing (p = 0.42). The three subjects tested after temporal lobectomy demonstrated improved performance compared with baseline, but statistics were not performed because of the small subject number.

Conclusions: Patients with medically intractable TLE have impaired tactile GrOr discrimination bilaterally that is not due to nonspecific effects of AEDs. This impaired perceptual ability may be reversible with surgical removal of the seizure focus.
Seizure Frequency and Cortisol and Dehydroepiandrosterone Sulfate (DHEAS) Levels in Women with Epilepsy Receiving Antiepileptic Drug Treatment
Authors: Andrea Galimberti Carlo , Magri Flavia , Copello Francesco , Arbasino Carla , Cravello Luca , Casu Massimo , Patrone Vittoriana , Murialdo Giovanni
Published: March 2005

Summary:  Purpose: Hormonal changes occur in epilepsy because of seizures themselves and of antiepileptic drug (AED) effects on steroid production, binding, and metabolism. Conversely, steroids may influence neuron activity and excitability by acting as neuroactive steroids. This cross‐sectional observational study aimed to evaluating cortisol and dehydroepiandrosterone sulfate (DHEAS) levels in female epilepsy patients with different disease severity, as assessed by a seizure frequency score (SFS).

Methods: Morning serum levels of cortisol and DHEAS were assayed in 113 consecutive women, aged 16 to 47 years, with varied epilepsy syndromes, receiving mono‐ or polytherapy with enzyme‐inducing and/or noninducing antiepileptic drugs (AEDs). Hormonal data were correlated with clinical parameters (age, body mass index, epilepsy syndrome, disease onset and duration, SFS, AED therapy, and AED serum levels) and compared with those of 30 age‐matched healthy women.

Results: In epilepsy patients, cortisol levels and cortisol‐to‐DHEAS ratios (C/Dr) were significantly higher, whereas DHEAS levels were significantly lower than those in controls. Patients with more frequent seizures showed higher cortisol and C/Dr values and lower DHEAS levels than did those with rarer or absent seizures during the previous 6 months. SFS mainly explained the increase of cortisol levels and C/Dr in patients with more active disease. Changes in DHEAS levels correlated with SFS and epilepsy syndrome, as well as with AED treatments and ages.

Conclusions: Women with more frequent seizures had alterations of their adrenal steroids characterized by an increase of cortisol and a decrease of DHEAS levels. Such hormonal changes might be relevant in seizure control and in patient health.
Increased thyroidal fat and goitrous hypothyroidism induced by interferon‐γ
Authors: Kimura Hiroaki , Kimura Miho , Westra William H. , Rose Noel R. , Caturegli Patrizio
Published: March 2005

Hashimoto's thyroiditis is associated with a diffuse lymphocytic infiltration of the stroma and a production of several cytokines, such as interferon‐γ (IFN‐γ). We previously reported that transgenic mice expressing IFN‐γ under the control of the thyroglobulin promoter develop primary hypothyroidism. In order to determine the long‐term changes induced by IFN‐γ in the thyroid gland, we analysed cross‐sectionally 202 mice (96 transgenic mice and 106 controls) of 0–650 days of age. Multiple linear regression analysis showed that, after adjusting for age and sex, thyr‐IFN‐γ transgenic mice were 14% (3 g) smaller (P < 0.0001) and had a 5‐ to 6‐fold bigger thyroid (P < 0.0001) than wild‐type littermates. Transgenic thyroids showed striking histopathological changes in follicles, thyrocytes and stroma. Follicles were enlarged, irregular and were lined by thickened, granular and oxyphilic thyrocytes. The stroma contained a moderate and diffuse mononuclear infiltrate – mainly composed of macrophages – and, interestingly, a clear increase in the content of fat. These findings indicate that, in addition to hypothyroidism, chronic exposure of the thyroid to IFN‐γ leads also to macrophage infiltration and subsequent adipocyte expansion, suggesting a link between inflammation and fat accumulation.
Embryonic reversions and lineage infidelities in tumour cells: genome‐based models and role of genetic instability
Authors: Bignold Leon P.
Published: March 2005

Reversions to ‘embryonic precursor’‐type cells and infidelities of tumour cell lineage (including metaplasias) have been recognized as aspects of various tumour types since the 19th century. Since then, evidence of these phenomena has been obtained from numerous clinical, biochemical, immunological and molecular biological studies. In particular, microarray studies have suggested that ‘aberrant’ expressions of relevant genes are common. An unexplained aspect of the results of these studies is that, in many tumour types, the embryonic reversion or lineage infidelity only occurs in a proportion of cases. As a parallel development during the molecular biological investigation of tumours over the last several decades, genetic instability has been found much more marked, at least in some preparations of tumour cells, than that identified by means of previous karyotypic investigations of tumours. This study reviews examples of embryonic reversion and lineage infidelity phenomena, which have derived from the various lines of investigation of cancer over the last 150 or so years. Four categories of circumstances of the occurrence of embryonic reversions or lineage infidelities have been identified – (i) as part of the defining phenotype of the tumour, and hence being presumably integral to the tumour type, (ii) presentab initioin only some cases of the tumour type, and presumably being regularly associated with, but incidental to, the essential features of the tumour type, (iii) occurring later in the course of the disease and thus being possibly a manifestation ofin vivogenetic instability and ‘tumour progression’ and (iv) arising probably by genetic instability, during the processes, especially cell culture, associated withex vivoinvestigations. Genomic models are described which might account for the origin of these phenomena in each of these circumstances.
Newly diagnosed childhood diabetes: a psychosocial transition for parents?
Authors: Lowes Lesley , Gregory John W. , Lyne Patricia
Published: March 2005

Aim.  This paper reports a study to gain a new theoretical understanding of parental grief responses and the process of adaptation to a diagnosis of childhood diabetes.

Background.  A diagnosis of childhood (type 1) diabetes is an anxious and distressing event for the whole family. Little is known about the experience of parents of newly diagnosed children as they cope with and adapt to their new situation. Parkes’ Theory of Psychosocial Transition proposes that life‐change events, or ‘psychosocial transitions’, require people to undertake a major revision of their assumptions about the world. The relevance of this theory to adjusting to a diagnosis of childhood diabetes has not been explored.

Method.  Forty audio taped in‐depth interviews were undertaken with 38 parents of 20 newly‐diagnosed children. The data were subsequently examined using the framework of the Theory of Psychosocial Transition.

Findings.  Before diagnosis, most parents associated their child's symptoms with normal childhood illnesses. The unexpectedness and speed of the diagnosis left all parents ill‐prepared to deal with the situation. Their world suddenly changed, leaving them insecure and uncertain about the future. Diabetes intruded emotionally and practically upon all of their lives. Parents successfully adjusted and adapted their lives and rebuilt a new model of the world to accommodate their child's diabetes. However, this dynamic process has no guaranteed endpoint for parents.

Conclusions.  A diagnosis of childhood diabetes leads to a psychosocial transition for parents. The concept of transition provides a logical explanation of parents’ responses to loss, and allows increased understanding of the grieving and adaptation processes experienced by parents of children diagnosed with a chronic condition such as diabetes. This knowledge should help health care professionals to assist parents in the period of transition.