bluuebunny/crossref_metadata_2025 huggingface dataset:
Reformation of the marginal band of avian erythrocytes in vitro using calf-brain tubulin: peripheral determinants of microtubule form.
Authors: Swan J A , Solomon F
Published: May 2004

The microtubules of nucleated erythrocytes form an extraordinary structure: they are organized into a marginal band at the periphery of the cell. This unusual organelle, recurring in detail in each cell, provides an excellent opportunity to study the determinants of microtubule form. We have been able to reform the marginal band, using detergent-extracted erythrocytes that have been depleted of microtubules in vivo and phosphocellulose-purified tubulin from calf brain. We find that detergent-extracted cytoskeletons incubated under these conditions again have microtubules, and that the pattern of these microtubules recapitulates several features of the intact marginal band. In particular, most of the microtubules after regrowth are located in a band at the periphery of the cell, and curve to form an ellipse. These results support the hypothesis that the specification of microtubule location and shape in these cells is governed by determinants that reside at the periphery of the cell.
Pericellular coat of chick embryo chondrocytes: structural role of hyaluronate.
Authors: Goldberg R L , Toole B P
Published: May 2004

Chondrocytes produce large pericellular coats in vitro that can be visualized by the exclusion of particles, e.g., fixed erythrocytes, and that are removed by treatment with Streptomyces hyaluronidase, which is specific for hyaluronate. In this study, we examined the kinetics of formation of these coats and the relationship of hyaluronate and proteoglycan to coat structure. Chondrocytes were isolated from chick tibia cartilage by collagenase-trypsin digestion and were characterized by their morphology and by their synthesis of both type II collagen and high molecular weight proteoglycans. The degree of spreading of the chondrocytes and the size of the coats were quantitated at various times subsequent to seeding by tracing phase-contrast photomicrographs of the cultures. After seeding, the chondrocytes attached themselves to the tissue culture dish and exhibited coats within 4 h. The coats reached a maximum size after 3-4 d and subsequently decreased over the next 2-3 d. Subcultured chondrocytes produced a large coat only if passaged before 4 d. Both primary and first passage cells, with or without coats, produced type II collagen but not type I collagen as determined by enzyme-linked immunosorbent assay. Treatment with Streptomyces hyaluronidase (1.0 mU/ml, 15 min), which completely removed the coat, released 58% of the chondroitin sulfate but only 9% of the proteins associated with the cell surface. The proteins released by hyaluronidase were not digestible by bacterial collagenase. Monensin and cycloheximide (0.01-10 microM, 48 h) caused a dose-dependent decrease in coat size that was linearly correlated to synthesis of cell surface hyaluronate (r = 0.98) but not chondroitin sulfate (r = 0.2). We conclude that the coat surrounding chondrocytes is dependent on hyaluronate for its structure and that hyaluronate retains a large proportion of the proteoglycan in the coat.
Sorting and secretion of adrenocorticotropin in a pituitary tumor cell line after perturbation of the level of a secretory granule-specific proteoglycan.
Authors: Burgess T L , Kelly R B
Published: May 2004

A mouse anterior pituitary tumor cell line (AtT-20) that secretes adrenocorticotropin and beta endorphin sorts the proteins it transports to the surface into two exocytotic pathways. AtT-20 cells also synthesize a secretory granule-specific sulfated molecule and secrete it on stimulation (Moore, H.-P., B. Gumbiner, and R. B. Kelly, 1983, J. Cell Biol., 97:810-817). We show here that this molecule is sensitive to proteolysis and that the residual sulfated material co-migrates with a chondroitin sulfate standard on thin-layer electrophoresis. Furthermore, this sulfated molecule is completely sensitive to chondroitinase ABC digestion. Thus the secretory granule-specific sulfated molecule is a proteoglycan with chondroitin sulfate side chains. We examined the role of proteoglycans in the sorting and secretion of adrenocorticotropin in AtT-20 cells by severely decreasing the amount of this vesicle-specific proteoglycan in two ways. First, a xyloside was used to inhibit proteoglycan biosynthesis; second, a variant of the AtT-20 cell line was isolated that synthesized little of the sulfated proteoglycan. In neither case was the sorting or secretion of adrenocorticotropin detectably altered, suggesting that the proteoglycan is not required for these processes.
Transmembrane signaling: an ion-flux-independent model for signal transduction by complexed Fc receptors.
Authors: Pfefferkorn L C
Published: May 2004

Fluxes of Na+/K+ that precede effector functions in stimulated phagocytes are thought to play a role in signal transduction. To examine this hypothesis, phagocytosis, phagosomal acidification, and superoxide anion generation (O2-) were stimulated in media in which the Na+ was replaced with K+ or choline+. Counts of particles internalized and assessment of acidification of the phagosomes by acridine orange staining indicated that Na+/K+ fluxes were not necessary for phagocytosis or phagosomal acidification in J774.2 macrophages. Phagocytosis mediated by the ionophoretic Fc receptor gamma 2b/gamma 1 of J774.2 macrophages was equally independent of a Na+ gradient. Na+/K+ fluxes did not dictate the rate of O2- generation in human monocytes. Therefore, in at least these three effector functions, Na+/K+ fluxes stimulated by Fc- and non-specific receptor binding play neither a signaling nor an enhancing role. An ion-flux-independent model for transmembrane signaling by the Fc receptor is proposed. Others have shown that there is an apparent dependence on the external Na+ concentration for O2- generation and lysosomal secretion by neutrophils. These neutrophils had been pre-treated with NH4+ during a routine purification step. O2- generation stimulated by opsonized zymosan or phorbol myristate acetate, by monocytes or monocyte-derived macrophages, and phagocytosis of opsonized zymosan by J774.2 macrophages, showed dependence on external Na+ only if these cells had been pre-treated with NH4+. Brief NH4+ pre-treatment would be expected to acidify the cytoplasm of the cells. The reversal of this acidification is known to require Na+ for H+ extrusion through the Na+/H+ antiport, thus explaining the apparent Na+ dependence.
The relationship between stress fiber-like structures and nascent myofibrils in cultured cardiac myocytes.
Authors: Dlugosz A A , Antin P B , Nachmias V T , Holtzer H
Published: May 2004

The topographical relationship between stress fiber-like structures (SFLS) and nascent myofibrils was examined in cultured chick cardiac myocytes by immunofluorescence microscopy. Antibodies against muscle-specific light meromyosin (anti-LMM) and desmin were used to distinguish cardiac myocytes from fibroblastic cells. By various combinations of staining with rhodamine-labeled phalloidin, anti-LMM, and antibodies against chick brain myosin and smooth muscle alpha-actinin, we observed the following relationships between transitory SFLS and nascent and mature myofibrils: (a) more SFLS were present in immature than mature myocytes; (b) in immature myocytes a single fluorescent fiber would stain as a SFLS distally and as a striated myofibril proximally, towards the center of the cell; (c) in regions of a myocyte not yet penetrated by the elongating myofibrils, SFLS were abundant; and (d) in regions of a myocyte with numerous mature myofibrils, SFLS had totally disappeared. Spontaneously contracting striated myofibrils with definitive Z-band regions were present long before anti-desmin localized in the I-Z-band region and long before morphologically recognizable structures periodically link Z-bands to the sarcolemma. These results suggest a transient one-on-one relationship between individual SFLS and newly emerging individual nascent myofibrils. Based on these and other relevant data, a complex, multistage molecular model is presented for myofibrillar assembly and maturation. Lastly, it is of considerable theoretical interest to note that mature cardiac myocytes, like mature skeletal myotubes, lack readily detectable stress fibers.
Differential proliferative responses of cultured Schwann cells to axolemma- and myelin-enriched fractions. I. Biochemical studies.
Authors: Yoshino J E , Dinneen M P , Lewis B L , Meador-Woodruff J H , Devries G H
Published: May 2004

Cultured rat Schwann cells were treated for 72 h with axolemma- and myelin-enriched fractions prepared from rat brainstem. [3H]Thymidine was added to the cultures 48 h before the termination of the experiment. Although, both fractions produced a dose-dependent uptake of label into Schwann cells, the shape of the dose response curves and rates at which [3H]thymidine was incorporated were different. The axolemma-enriched fraction produced a sigmoid dose response curve with a Hill coefficient of 2.05. The dose response curve for myelin rose sharply and saturated at a level that was approximately 50% of the maximal response observed with axolemma. Schwann cells that had been treated with axolemma exhibited little change in the rate of [3H]thymidine incorporation from 36-72 h after the addition of the membranes. In contrast, Schwann cells accumulated label three times faster during the 48-72-h period following the addition of myelin to the cultures when compared with the rate during the preceding 12-h interval. Furthermore, the mitogenic activity of the myelin-enriched fraction was decreased by the addition of ammonium chloride, a lysosomal inhibitor, whereas the activity of the axolemmal fraction was not impaired.
Differential expression and distribution of chicken skeletal- and smooth-muscle-type alpha-actinins during myogenesis in culture.
Authors: Endo T , Masaki T
Published: May 2004

Antibodies to chicken fast skeletal muscle (pectoralis) alpha-actinin and to smooth muscle (gizzard) alpha-actinin were absorbed with opposite antigens by affinity chromatography, and four antibody fractions were thus obtained: common antibodies reactive with both pectoralis and gizzard alpha-actinins ([C]anti-P alpha-An and [C]anti-G alpha-An), antibody specifically reactive with pectoralis alpha-actinin ([S]anti-P alpha-An), and antibody specifically reactive with gizzard alpha-actinin ([S]anti-G alpha-An). In indirect immunofluorescence microscopy, (C)anti-P alpha-An, (S)anti-P alpha-An, and (C)anti-G alpha-An stained Z bands of skeletal muscle myofibrils, whereas (S)anti-G alpha-An did not. Although (S)anti-G alpha-An and two common antibodies stained smooth muscle cells, (S)anti-P alpha-An did not. We used (S)anti-P alpha-An and (S)anti-G alpha-An for immunofluorescence microscopy to investigate the expression and distribution of skeletal- and smooth-muscle-type alpha-actinins during myogenesis of cultured skeletal muscle cells. Skeletal-muscle-type alpha-actinin was found to be absent from myogenic cells before fusion but present in them after fusion, restricted to Z bodies or Z bands. Smooth-muscle-type alpha-actinin was present diffusely in the cytoplasm and on membrane-associated structures of mononucleated and fused myoblasts, and then confined to membrane-associated structures of myotubes. Immunoblotting and peptide mapping by limited proteolysis support the above results that skeletal-muscle-type alpha-actinin appears at the onset of fusion and that smooth-muscle-type alpha-actinin persists throughout the myogenesis. These results indicate (a) that the timing of expression of skeletal-muscle-type alpha-actinin is under regulation coordination with other major skeletal muscle proteins; (b) that, with respect to expression and distribution, skeletal-muscle-type alpha-actinin is closely related to alpha-actin, whereas smooth-muscle-type alpha-actinin is to gamma- and beta-actins; and (c) that skeletal- and smooth-muscle-type alpha-actinins have complementary distribution and do not co-exist in situ.
Lateral diffusion of wild-type and mutant Ld antigens in L cells.
Authors: Edidin M , Zuniga M
Published: May 2004

We have compared the lateral diffusion of intact transmembrane proteins, wild-type H-2Ld antigens, with that of mutants truncated in the cytoplasmic domain. Diffusion coefficients and mobile fractions were similar for all molecules examined, from wild-type Ld antigens with 31 residues on the cytoplasmic side of the plasma membrane to mutants with only four residues in the cytoplasmic domain. This result limits ways in which the lateral diffusion of a major histocompatibility antigen, a transmembrane protein, can be constrained by interactions with other molecules.
The Current Account, Fiscal Policy, and Medium‐Run Income Determination
Authors: Makin Anthony J.
Published: May 2004

This article presents a new framework for analyzing the simultaneous determination of current account imbalances and the path of national income. Using standard macroeconomic behavioral relationships, it first examines how and why current account deficits matter by investigating links between domestic consumption, government spending, output, saving, investment, interest rates, and capital flows. Central to the model is the distinction between aggregate output and expenditure that enables dissection of the effects of discretionary fiscal change on the current account and national income. The framework yields results relevant to the twin deficits hypothesis that are contrary to those of standard models. (JEL E10, F32)
Central Bank Behavior, the Institutional Framework, and Policy Regimes: Inflation Versus Noninflation Targeting Countries
Authors: Siklos Pierre L.
Published: May 2004

This article estimates central bank reaction functions for 20 OECD countries. It bridges the gap between the Taylor reaction function literature and the political‐economy literature. Central banks react to both inflation and the output gap. Moreover, inflation‐targeting countries have been able to reduce nominal interest rate to a greater extent than have non‐inflation‐targeting countries. Countries with fixed exchange rates react more strongly to inflation but not at all to the output gap, unlike countries with floating rates. Political influences also seem relatively more important in fixed exchange rate countries. Central bank independence also helps reduce nominal interest rates. (JEL E58, C31, C32, C53)
The Inflation‐Output Variability Trade‐off: OECD Evidence
Authors: Lee Jim
Published: May 2004

This article employs a multivariate GARCH model to empirically estimate a possible trade‐off between output variability and inflation volatility in light of OECD data over the 1984–2001 period. Statistical support for the hypothesized volatility trade‐off is equivocal across countries. The mixed findings can be associated with central banks' varying monetary policy responses to exogenous shocks. The trade‐off estimates are also found to be consistent with earlier studies that reveal different degrees of central bank commitment to price vis‐à‐vis output stability. (JEL E30, E58, C32)
The Economic Cost of Fatal Occupational Injuries in the United States, 1980–97
Authors: Biddle Elyce Anne
Published: May 2004

According to the National Traumatic Occupational Fatalities (NTOF) surveillance system, occupational injuries claimed the lives of over 100,000 American workers from 1980 to 1997. Previous estimates presented aggregate values of life, providing no information on the cost variations for different case or worker characteristics. This research developed an interactive computer program that estimates comprehensive national costs for all occupational fatal injuries reported through NTOF, nearly $85 billion for 1980–97, and specific estimates for the burden on selected groups and characteristics of the fatality. These estimates provide an additional basis for targeting and evaluating the effectiveness of investments in prevention of occupational fatalities. (JEL I18)
Further Evidence on the Labor Market Effects of Addiction: Chronic Drug Use and Employment in Metropolitan Miami
Authors: Alexandre Pierre Kébreau , French Michael T.
Published: May 2004

This study used data collected from 1996 to 1997 in low‐income and high‐crime neighborhoods in Miami, Florida, to analyze the effects of chronic drug use on employment. Given the significant gender differences in substance use patterns and labor market behavior, separate models were estimated for males and females. The analysis estimated univariate probit models of employment and bivariate probit models that allow for possible correlation among missing or unobserved determinants of drug use and employment. The key finding was that regardless of gender and specification, chronic drug use significantly reduced the probability of being employed. (JEL I12, J22, J24)
‘Our common room in Geneva’ and the early exploration of the Alps of Savoy
Authors: Rowlinson J. S.
Published: May 2004

The polite world took little interest in the Alps before the 18th century. The local inhabitants had ventured far enough to shoot chamois and to search for crystal (i.e. quartz), but few of the educated took any notice. The earliest natural philosophers to study the botany and mineralogy of these regions were from the German–speaking towns of Switzerland. Their first conclusions have not always stood the test of time; one of them, J.J. Scheuchzer (F.R.S., 1703) even reported the presence of dragons. Such frivolities did not appeal to the Calvinists of the city republic of Geneva. They could see the ‘montagnes maudites’ of Savoy to the south–east, but they never went to them. The first serious attempts to describe this world of snow and ice were made in 1741 and 1742.
Jagadis Bose, Augustus Waller and the discovery of ‘vegetable electricity’
Authors: Dasgupta S.
Published: May 2004

On 6 June 1901, the Indian science pioneer (later Sir) Jagadis Chandra Bose (1858–1937) read a paper before the Royal Society on ‘The electric response of inorganic substances’. This paper, though never published, was of considerable importance in the annals of Bose's personal scientific life. For one thing, coming in the wake of a Friday Evening Discourse delivered at the Royal Institution the month before, it served notice of Bose's transmutation from a highly respected physicist, indeed India's first physicist in the ‘Western scientific tradition’ to a controversial, again his country's first, plant physiologist, the latter so controversial that a later American botanist would note acerbically that the botanical community could be divided into ‘Bosephobes’ and ‘Bosephiles’.
Grounding Human Dignity
Authors: Shannon Thomas A.
Published: May 2004

Abstract:  What is the future of human dignity? Is there a limit on what can be done to human organisms? To approach such questions this article reviews some traditional understandings of human dignity and then offers a shift in perspective. Traditional areas in which human dignity has been grounded include the doctrine of the image of God, the notion of humanity as a reconciliation of opposites, the chronological place of humans in the process of creation, God's free grace, and the human capacity for union with the divine. Maintaining that dignity is reserved for the later stages of human development, the author suggests we shift our thinking from notions of dignity to those of value. A fertilized egg as a living organism is to be valued for its uniqueness and nature, but it does not acquire dignity until it individualizes within the larger process of embryogenesis.
Levetiracetam in Focal Epilepsy and Hepatic Porphyria: A Case Report
Authors: Paul Friedemann , Meencke Heinz‐Joachim
Published: May 2004

Summary:  We report a patient with focal epilepsy and latent hereditary coproporphyria who had exacerbation of clinical symptoms of porphyria under treatment with valproate and primidone and was then treated with levetiracetam without exacerbation of clinically latent porphyria.
Gamma Knife Surgery in Mesial Temporal Lobe Epilepsy: A Prospective Multicenter Study
Authors: Régis Jean , Rey Marc , Bartolomei Fabrice , Vladyka Vilibald , Liscak Roman , Schröttner Oskar , Pendl Gerhard
Published: May 2004

Summary:  Purpose: This article is the first prospective documentation of the efficacy and safety of gamma knife surgery (GKS) in the treatment of drug‐resistant epilepsies of mesial temporal lobe origin.

Methods: From July 1996 to March 2000, three European centers selected 21 patients with mesial temporal lobe epilepsy (MTLE) for a temporal lobectomy. The preoperative investigations included video‐EEG with foramen ovale electrodes, magnetic resonance imaging, neuropsychological testing, and the ESI‐55 quality‐of‐life questionnaire. In place of a cortectomy, radiosurgical treatment was performed by using the Leksell Gamma Knife (LGK) at a dose of 24 ± 1 Gy at the margin. The target included the anterior parahippocampal cortex and the basal and lateral part of the amygdala and anterior hippocampus (head and body). One patient (a heavy smoker) died of a myocardial infarction. Twenty patients were available for prospective evaluation. A minimum 2‐year follow‐up period included clinical, neuropsychological, and radiologic evaluations.

Results: At each 6‐month follow‐up evaluation, the frequency of seizures was significantly smaller than that at the previous visit. The median seizure frequency of 6.16 the month before treatment was reduced to 0.33 at 2 years after treatment. At 2 years, 65% of the patients (13 of 20) were seizure free. Five patients had transient side effects, including depression, headache, nausea, vomiting, and imbalance. There was no permanent neurological deficit reported except nine visual field deficits. No neuropsychological deterioration was observed 2 years after treatment. The quality of life was significantly better than that before surgery.

Conclusions: The safety and efficacy of the radiosurgical treatment of MTLEs appears good in this group of patient over short‐to‐middle term. Delay of the seizure cessation was the major disadvantage of GKS. A longer follow‐up period is required for confirmation of these results.
Cognitive, Psychosocial, and Family Function One Year after Pediatric Epilepsy Surgery
Authors: Smith Mary Lou , Elliott Irene M. , Lach Lucyna
Published: May 2004

Summary: Purpose:Assumptions regarding the benefits of seizure control after pediatric epilepsy surgery for cognitive, psychosocial, and family function were explored in a prospective study of 51 children with intractable epilepsy.

Methods:Thirty children who underwent surgery were studied before and 1 year after surgery, and a comparison group of 21 children with medically refractory seizures was examined at comparable times.

Results:One year after surgery, 57% of the surgical group was seizure free. Seizure status after surgery did not predict change over time in any of the areas measured. Cognitive and psychosocial status did not change over time in either group, and the strongest predictor of individual change in psychosocial status in the surgical group was baseline level of function. Within the surgical group, a trend toward an increase in independence promotion was noted in the family, but the children's satisfaction with the family declined.

Conclusions:These findings challenge the assumption that elimination of seizures will result in improved cognitive, psychosocial, and family functioning, at least within the first year after surgery.
The Pathology of Rasmussen Syndrome: Stages of Cortical Involvement and Neuropathological Studies in 45 Hemispherectomies
Authors: Pardo Carlos A. , Vining Eileen P. G. , Guo Liping , Skolasky Richard L. , Carson Benjamin S. , Freeman John M.
Published: May 2004

Summary:  Purpose: Rasmussen syndrome (RS) is a rare form of epilepsy characterized by progressive destruction of a single hemisphere. To characterize the profile of cortical involvement in RS, we studied the pathological changes in the cerebral cortex of 45 hemispherectomies performed at Johns Hopkins Hospital between 1985 and 2002.

Methods: The patterns of pathologic changes and stages of cortical abnormalities were studied by histology and immunocy to chemistry methods. The burden of pathology (BP) was quantified in all brain regions of each of the 45 hemispheres.

Results: Our study demonstrated significant heterogeneity in the stages of cortical pathology and the multifocal nature of the disease. These stages varied from early inflammation defined by infiltration of T lymphocytes and neuroglial reactions, to more severe stages with extensive neuronal cell death and cavitation of the cerebral cortex. A greater BP was significantly associated with an early age at onset (p = 0.01) and longer duration of disease (p ≤ 0.001). The BP was similar in all brain regions except the occipital lobe, where the BP was significantly lower (p = 0.032).

Conclusions: The multifocal distribution of pathologic changes, as well as the heterogeneity in the stages of cortical damage in each patient, is consistent with an ongoing and progressive immune‐mediated process of neuronal damage that involves neuroglial and lymphocytic responses, resembling other autoimmune CNS disorders such as multiple sclerosis.
Genetic Architecture of Idiopathic Generalized Epilepsy: Clinical Genetic Analysis of 55 Multiplex Families
Authors: Marini Carla , Scheffer Ingrid E. , Crossland Kathryn M. , Grinton Bronwyn E. , Phillips Fiona L. , McMahon Jacinta M. , Turner Samantha J. , Dean Joanne T. , Kivity Sara , Mazarib Aziz , Neufeld Miriam Y. , Korczyn Amos D. , Harkin Louise A. , Dibbens Leanne M. , Wallace Robyn H. , Mulley John C. , Berkovic Samuel F.
Published: May 2004

Summary:  Purpose: In families with idiopathic generalized epilepsy (IGE), multiple IGE subsyndromes may occur. We performed a genetic study of IGE families to clarify the genetic relation of the IGE subsyndromes and to improve understanding of the mode(s) of inheritance.

Methods: Clinical and genealogic data were obtained on probands with IGE and family members with a history of seizures. Families were grouped according to the probands' IGE subsyndrome: childhood absence epilepsy (CAE), juvenile absence epilepsy (JAE), juvenile myoclonic epilepsy (JME), and IGE with tonic–clonic seizures only (IGE‐TCS). The subsyndromes in the relatives were analyzed. Mutations in genes encoding α1 and γ2 γ‐aminobutyric acid (GABA)‐receptor subunits, α1 and β1 sodium channel subunits, and the chloride channel CLC‐2 were sought.

Results: Fifty‐five families were studied. 122 (13%) of 937 first‐ and second‐degree relatives had seizures. Phenotypic concordance within families of CAE and JME probands was 28 and 27%, respectively. JAE and IGE‐TCS families had a much lower concordance (10 and 13%), and in the JAE group, 31% of relatives had CAE. JME was rare among affected relatives of CAE and JAE probands and vice versa. Mothers were more frequently affected than fathers. No GABA‐receptor or sodium or chloride channel gene mutations were identified.

Conclusions: The clinical genetic analysis of this set of families suggests that CAE and JAE share a close genetic relation, whereas JME is a more distinct entity. Febrile seizures and epilepsy with unclassified tonic–clonic seizures were frequent in affected relatives of all IGE individuals, perhaps representing a nonspecific susceptibility to seizures. A maternal effect also was seen. Our findings are consistent with an oligogenic model of inheritance.
The Relative Impact of Anxiety, Depression, and Clinical Seizure Features on Health‐related Quality of Life in Epilepsy
Authors: Johnson Erica K. , Jones Jana E. , Seidenberg Michael , Hermann Bruce P.
Published: May 2004

Summary:  Purpose: To determine the independent effects of depression and anxiety on health‐related quality of life (HRQOL) in epilepsy as well as the relative explanatory power of psychiatric comorbidity compared with demographic and clinical epilepsy variables (e.g., seizure frequency, severity, and chronicity).

Methods: Subjects (n = 87) with temporal lobe epilepsy completed self‐report measures of depression, anxiety, HRQOL, and seizure severity. Information was derived regarding subjects' seizure frequency, duration, and treatment. HRQOL status (QOLIE‐89) was examined in relation to self‐reported symptoms of anxiety and depression, clinical seizure features, and demographic characteristics.

Results: Depression and anxiety were independently associated with reduced HRQOL. Psychiatric comorbidity explained more variance in HRQOL than did combined groups of clinical seizure or demographic variables. Although weaker in explanatory power than psychiatric comorbidity, several epilepsy factors were nonetheless significantly related to HRQOL, including seizure frequency, severity, and chronicity.

Conclusions: Interictal anxiety and depression exert independent adverse effects on HRQOL. In addition, frequent, severe, and chronic seizures reduce HRQOL, but appear less powerful predictors of HRQOL than interictal psychiatric symptoms. Recognition and treatment of comorbid depression and anxiety is an important consideration in improving quality of life in epilepsy.
Intracranial EEG in Temporal Lobe Epilepsy: Location of Seizure Onset Relates to Degree of Hippocampal Pathology
Authors: Vossler David G. , Kraemer Diana L. , Haltiner Alan M. , Rostad Steven W. , Kjos Bent O. , Davis Bradley J. , Morgan John D. , Caylor Lisa M.
Published: May 2004

Summary:  Purpose: To determine whether the specific location of electrographic seizure onset in the temporal lobe is related to hippocampal pathology in temporal lobe epilepsy (TLE).

Methods: Consecutive presurgical patients with scalp EEG‐video evidence of TLE and no or mild hippocampal atrophy (HA) on magnetic resonance imaging (MRI) were prospectively studied by using depth and subdural strip electrode recordings to identify the site of the initial ictal discharge (IID). Thirty‐four patients had either no or mild HA (HA– group). Four additional patients with moderate or marked HA (HA+ group) who required depth and strip electrodes served as a comparison group. Hippocampal pathology was assessed by MRI volumetrics and histopathologic grade of sclerosis (HS).

Results: Thirty‐eight patients were investigated. In the HA– group, 10 patients had lobar ictal EEG onsets in the hippocampus (HF), medial paleocortex (MPC), and lateral neocortex (LNC); eight cases had regional IIDs in both HF and MPC; 12 persons had IIDs completely outside the HF; three cases lacked depth electrodes, and only one case (3%) had an IID confined to the HF. By contrast, three (75%) of four HA+ cases had IIDs confined to the HF (p = 0.002). Similarly, in 12 patients with low‐grade HS, IIDs confined to the HF area were seen significantly less often than in six cases with high‐grade HS (p = 0.025).

Conclusions: In this study of a large number of patients with no to mild and a smaller group with moderate to marked HA and HS, the location of seizure onset in the temporal lobe was related to the degree of hippocampal pathology. Absence of HA and low‐grade HS was each associated with IIDs in both the hippocampus and medial (with or without lateral) temporal cortex, or only the MPC or LNC. Marked HA and high‐grade HS both were associated with IIDs restricted to the HF.
Antimyoclonic Effect of Levetiracetam in 13 Patients with Unverricht–Lundborg Disease: Clinical Observations
Authors: Magaudda Adriana , Gelisse Philippe , Genton Pierre
Published: May 2004

Summary: Purpose:Disabling myoclonus is the main symptom in long‐standing Unverricht–Lundborg disease (ULD), and levetiracetam (LEV) appears to be an effective anticonvulsant with promising short‐term antimyoclonic properties.

Methods:LEV was prescribed to 13 patients with ULD. We retrospectively analyzed the efficacy of LEV on seizure frequency and on myoclonus, by using a simplified myoclonus rating score, and compared the patients' status before LEV and at the last follow‐up. They were two women and 11 men, aged 14 to 52 years (mean, 36.5 years), with a disease duration of 4 to 40 years (mean, 24.3 years). LEV was given at 2,000 to 4,000 mg/d for 0.5 to 26 months (mean, 13.8 months).

Results:One patient stopped LEV within 2 weeks because of side effects and lack of efficacy. None of the other 12 patients reported side effects. The average myoclonus score significantly changed from 3.1 to 2.4 (p = 0.01), but only eight had a measurable improvement.

Conclusions:The best effects were noted in the younger patients. In patients previously treated with high‐dose piracetam (PIR), discontinuation of PIR was not always well tolerated, and a combination of PIR at lower doses and LEV appeared to be a practical solution. LEV should probably be considered as a major treatment option early in the course of ULD.
Vasoconstriction as the Etiology of Hypercalcemia‐induced Seizures
Authors: Chen Tsung‐Hua , Huang Chih‐Cheng , Chang Yung‐Yee , Chen Ying‐Fa , Chen Wei‐Hsi , Lai Shung‐Lon
Published: May 2004

Summary:  Purpose: Reversible cerebral vasoconstriction has been hypothesized to be the etiology of seizures due to hypercalcemia, but angiographic studies documenting vasoconstriction have not previously been available.

Methods: We present a 43‐year‐old woman who had frequent seizures that later evolved to status epilepticus with marked hypercalcemia at the time of the seizures.

Results: Magnetic resonance imaging (MRI) of the patient's brain revealed high signal changes in T2‐weighted imaging, fluorescence‐attenuated inversion recovery (FLAIR), and diffusion‐weighted imaging (DWI) over the bilateral occipital and thalamic areas. Cerebral angiography showed blood vessels narrowing, disappearing altogether over the right posterior cerebral artery (PCA) branch, which is compatible with vasoconstriction. Vasoconstriction caused the MRI high signal in the occipital area, which was associated with subsequent periodic lateralized epileptic discharges. The patient's clinical condition improved with management of seizures and hypercalcemia. A second brain MRI 2 weeks later revealed complete resolution of the high‐signal lesions. Follow‐up cerebral angiography study also showed total recovery of vasoconstriction.

Conclusions: The sequence of events suggests the hypothesis that reversible cerebral vasoconstriction may play a role in hypercalcemia‐induced seizures.
Valproate Reduced Synaptic Activity Increase Induced by 4‐Aminopyridine at the Hippocampal CA3‐CA1 Synapse
Authors: Martín and Eduardo D. , Pozo Miguel A.
Published: May 2004

Summary:  Purpose: We investigated the effects of valproate (VPA) on excitatory synaptic transmission changes induced by 4‐aminopyridine (4‐AP) to determine whether the antiepileptic effects shown by VPA can be ascribed to a modulation of spontaneous excitatory postsynaptic currents (sEPSCs) in the CA3‐CA1 synapse.

Methods: Rat hippocampal slices were prepared and maintained in vitro with standard methods. Whole‐cell current and voltage‐clamp recordings were obtained from CA1 pyramidal neurons by using the “blind” patch‐clamp technique in an immersion recording chamber. Increase in the spontaneous excitatory synaptic activity was induced by addition of 4‐AP to the medium.

Results: Perfusion with VPA significantly counteracted the increase of frequency and amplitude of the sEPSCs induced by application of 4‐AP and suppressed the epileptiform activity.

Conclusions: We conclude that VPA decreases the 4‐AP–induced enhancement of excitatory synaptic activity at the CA3‐CA1 synapse, and that this reduction of excitation input to CA1 contributes to the anticonvulsant effects of VPA.
Does Glucocorticoid Administration Prevent Late Seizures after Head Injury?
Authors: Watson Nathaniel F. , Barber Jason K. , Doherty Michael J. , Miller John W. , Temkin Nancy R.
Published: May 2004

Summary:  Purpose: Preventing posttraumatic epilepsy has been a difficult challenge. In this study we evaluated the association between glucocorticoid administration after traumatic brain injury (TBI) and posttraumatic seizures.

Methods: We examined a seizure‐prevention trial database of 404 patients with severe TBI for exposure to glucocorticoids in the early (<1 week) posttraumatic period. After controlling for seizure risk, we compared the odds of developing first and second late posttraumatic seizures between those that received glucocorticoids and those that did not.

Results: Patients dosed with glucocorticoids within 1 day of their TBI were more likely to develop first late seizures than were those without [p = 0.04; hazard ratio = 1.74; 95% confidence interval (CI), 1.01–2.98]; whereas those receiving glucocorticoids ≥2 days after their injury had no similar association (p = 0.66; hazard ratio = 0.77; 95% CI, 0.23–2.56; p = 0.10 among the three groups). Receiving glucocorticoids within 1 day, or ≥2 days after TBI was not associated with second late seizure development.

Conclusions: Glucocorticoid treatment after TBI is not associated with decreased late posttraumatic seizures, and early treatment is associated with increased seizure activity.
Does Hyperventilation Elicit Epileptic Seizures?
Authors: Holmes Mark D. , Dewaraja Asanka S. , Vanhatalo Sampsa
Published: May 2004

Summary:  Purpose: Voluntary hyperventilation has been advocated for many decades as an “activating” procedure to provoke clinical seizures and epileptiform discharges in subjects with suspected epilepsy who undergo standard EEG recordings. This study was undertaken to determine the effects of hyperventilation in patients with proven epilepsy.

Methods: We examined the records of 433 consecutive patients with proven epilepsy, as documented by long‐term video‐EEG studies. The patients underwent 5 min of voluntary hyperventilation during standard EEG recordings. All EEGs were interpreted by board‐certified electroencephalographers. The patients ranged in age from 10 to 64 years; 384 (88.7%) had localization‐related and 48 (11.3%) generalized epilepsy syndromes.

Results: Hyperventilation was associated with a clinical seizure in two (0.46%) of the subjects (partial seizures in both cases). Interictal epileptiform discharges were interpreted as showing in increase in frequency during hyperventilation in 19 (4.4%) patients, when compared with the baseline EEG.

Conclusions: Voluntary hyperventilation in patients with unequivocal epilepsy is rarely associated with either clinical seizures or an increase in frequency of epileptiform discharges.
Prolonged Infusion of Tetrodotoxin Does Not Block Mossy Fiber Sprouting in Pilocarpine‐treated Rats
Authors: Buckmaster Paul S.
Published: May 2004

Summary:  Purpose: Mossy fiber sprouting is a common abnormality found in patients and models of temporal lobe epilepsy. The role of mossy fiber sprouting in epileptogenesis is unclear, and its blockade would be useful experimentally and perhaps therapeutically. Results from previous attempts to block mossy fiber sprouting have been disappointing or controversial. In some brain regions, prolonged application of the sodium channel blocker tetrodotoxin prevents axon sprouting and posttrauma epileptogenesis. The present study tested the hypothesis that prolonged, focal infusion of tetrodotoxin would block mossy fiber sprouting after an epileptogenic treatment.

Methods: Adult rats were treated with pilocarpine to induce status epilepticus. Several hours to 3 days after pilocarpine treatment, a pump with a cannula directed toward the dentate gyrus was implanted to deliver 10 μM tetrodotoxin or vehicle alone at 0.25 μl/h. This method blocks local EEG activity in the hippocampus (Galvan et al. J Neurosci 2000; 20:2904–16). After 28 days of continuous infusion, rats were perfused with fixative, and their hippocampi analyzed anatomically with stereologic techniques.

Results: Tetrodotoxin infusion was verified immunocytochemically in tetrodotoxin‐treated but not vehicle‐treated hippocampi. Tetrodotoxin‐infused and vehicle‐infused hippocampi displayed similar levels of hilar neuron loss. The Timm stain revealed mossy fiber sprouting regardless of whether hippocampi were treated with tetrodotoxin infusion, vehicle infusion, or neither.

Conclusions: Prolonged infusion of tetrodotoxin did not block mossy fiber sprouting. This finding suggests that sodium channel–mediated neuronal activity is not necessary for mossy fiber sprouting after an epileptogenic treatment.
Mechanisms of species coexistence: a field test of theoretical models using intertidal snails
Authors: Rochette Rémy , Grand Tamara C.
Published: May 2004

Competitor coexistence is often facilitated by spatial segregation. Traditionally, spatial segregation is predicted to occur when species differ in the habitat in which they are either superior at competing for resources or less susceptible to predation. However, predictions from a behavioural model demonstrate that spatial segregation and coexistence can also occur in the absence of such interspecific trade‐offs in competitive ability and vulnerability to predation. Unlike other models of competitor coexistence this model predicts that when species rank both habitat productivity and ‘riskinesses’ similarly, but differ slightly in their habitat‐specific vulnerabilities to predators, they will tend to segregate across habitats, with the species experiencing the higher ratio of mortality risk across the habitats occurring primarily in the safer habitat. Here, we investigate the hypothesis that intraspecific trade‐offs between resource availability and mortality risk can lead to spatial segregation of competing species by (1) documenting the spatial (i.e. intertidal) distribution of two marine snails,Littorina sitkanaandL. subrotundataand (2) performing field experiments to quantify growth and mortality rates of each species at ‘low’ and ‘high’ intertidal heights. Our results indicate that both species agree on the rankings of habitat riskiness and productivity, experiencing higher predation and higher growth in low‐ than in high‐intertidal habitats. However,L. sitkanaandL. subrotundataexperienced differences in their habitat‐specific mortality risks and growth rates. Despite both species being similarly at risk of predation in high‐intertidal habitats (where mortality was lower),L. subrotundatawas subject to significantly higher mortality thanL. sitkanaat the low‐intertidal height. In contrast, growth rate differences between habitats were greater forL. sitkanathan forL. subrotundata. Whereas both species grew at the same rate at the high‐intertidal level (where growth was lower),L. sitkanaindividuals grew more rapidly thanL. subrotundatasnails at the low‐intertidal level. As predicted by the behavioural model, the species that experienced the higher ratio of mortality across habitats (i.e.L. subrotundata) occurred exclusively in the safer, high‐intertidal habitat. Taken together, these results provide support for the hypothesis that spatial segregation, and potentially competitor coexistence, can occur in the absence of interspecific trade‐offs in resource acquisition ability or vulnerability to predation.
The intrinsic mean time to extinction: a unifying approach to analysing persistence and viability of populations
Authors: Grimm Volker , Wissel Christian
Published: May 2004

Analysing the persistence and viability of small populations is a key issue in extinction theory and population viability analysis. However, there is still no consensus on how to quantify persistence and viability. We present an approach to evaluate any simulation model concerned with extinction. The approach is devised from general Markov models of stochastic population dynamics. From these models, we distil insights into the general mathematical structure of the risk of extinction by time t, P0(t). From this mathematical structure, we devise a simple but effective protocol – the ln(1−P0)‐plot – which is applicable for situations including environmental noise or catastrophes. This plot delivers two quantities which are fundamental to the assessment of persistence and viability: the intrinsic mean time to extinction, Tm, and the probability c1of the population reaching the established phase. The established phase is characterized by typical fluctuations of the population's state variable which can be described by quasi‐stationary probability distributions. The risk of extinction in the established phase is constant and given by 1/Tm. We show that Tmis the basic currency for the assessment of persistence and viability because Tmis independent of initial conditions and allows the risk of extinction to be calculated for any time horizon. For situations where initial conditions are important, additionally c1has to be considered.
Comparison of discriminant function and classification tree analyses for age classification of marmots
Authors: Karels Tim J. , Bryant Andrew A. , Hik David S.
Published: May 2004

We evaluated the predictive power of two classification techniques, one parametric – discriminant function analysis (DFA) and the other non‐parametric – classification and regression tree analysis (CART), in order to provide a non‐subjective quantitative method of determining age class in Vancouver Island marmots (Marmota vancouverensis) and hoary marmots (Marmota caligata). For both techniques we used morphological measurements of known‐age male and female marmots from two independent population studies to build and test predictive models of age class. Both techniques had high predictive power (69–86%) for both sexes and both species. Overall, the two methods performed identically with 81% correct classification. DFA was marginally better at discriminating among older more challenging age classes compared to CART. However, in our test samples, cases with missing values in any of the discriminant variables were deleted and hence unclassified by DFA, whereas CART used values from closely correlated variables to substitute for the missing values. Therefore, overall, CART performed better (CART 81% vs DFA 76%) because of its ability to classify incomplete cases. Correct classification rates were approximately 10% higher for hoary marmots than for Vancouver Island marmots, a result that could be attributed to different sets of morphological measurements. Zygomatic arch breadth measured in hoary marmots was the most important predictor of age class in both sexes using both classification techniques. We recommend that CART analysis be performed on data‐sets with incomplete records and used as a variable screening tool prior to DFA on more complete data‐sets.
When is a correlation between non‐independent variables “spurious”?
Authors: Brett Michael T.
Published: May 2004

Correlations which are artifacts of various types of data transformations can be said to be spurious. This study considers four common types of analyses where the X and Y variables are not independent; these include regressions of the form X/Z vs Y/Z, X×Z vs Y×Z, X vs Y/X, and X+Y vs Y. These analyses were carried out using a series of Monte Carlo simulations while varying sample size and sample variability. The impact of disparities in variability between the shared and non‐shared terms and measurement error for the shared term on the magnitude of the spurious correlations was also considered. The accuracy of equations previously derived to predict the magnitude of spurious correlations was also assessed. These results show the risk of producing spurious correlations when analyzing non‐independent variables is very large. Spurious correlations occurred in all cases assessed, the mean spurious coefficient of determination (r2) frequently exceeded 0.50, and in some cases the 90% confidence interval for these simulations included all large r2 values. The magnitude of spurious correlations was sensitive to differences in the variability of the shared and non‐shared terms, with large spurious correlations obtained when the variability for the shared term was larger. Sample size had only a modest impact on the magnitude of spurious correlations. When measurement error for the shared variable was smaller than one half the coefficient of variation for that variable, which is generally the case, the measurement error did not generate large spurious correlations. The equations available to predict expected spurious correlations provided accurate predictions for the case of X×Z vs Y×Z, variable predictions for the case of X vs Y/X, and poor predictions for most cases of X/Z vs Y/Z, and X+Y vs Y.