bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of EDTA treatment upon the protein subunit composition and mechanical properties of mammalian single skeletal muscle fibers
Authors: Moss RL , Giulian GG , Greaser ML 
Published: May 2004

Considerable interest has been focused on the role of myosin light chain LC(2) in the contraction of vertebrate striated muscle. A study was undertaken to further our investigations (Moss, R.L., G.G. Giulian, and M.L. Greaser, 1981, J. Biol. Chem., 257:8588-8591) of the effects of LC(2) removal upon contraction in skinned fibers from rabbit psoas muscles. Isometric tension and maximum velocity of shortening, V(max), were measured in fiber segments prior to LC(2) removal. The segments were then bathed at 30 degrees C for up to 240 min in a buffer solution containing 20 mM EDTA in order to extract up to 60 percent of the LC(2). Troponin C (TnC) was also partially removed by this procedure. Mechanical measurements were done following the EDTA extraction and the readditions of first TnC and then LC(2) to the segments. The protein subunit compositions of the same fiber segments were determined following each of these procedures by SDS PAGE of small pieces of the fiber.
V(max) was found to decrease as the LC(2) content of the fiber segments was reduced by increasing the duration of extraction. EDTA treatment also resulted in substantial reductions in tension due mainly to the loss of TnC, though smaller reductions due to the extraction of LC(2) were also observed. Reversal of the order of recombination of LC(2) and TnC indicated that the reduction in V(max) following EDTA treatment was a specific effect of LC(2) removal. These results strongly suggest that LC(2) may have roles in determining the kinetics and extent of interaction between myosin and actin.
In vivo and in vitro processing of seed reserve protein in the endoplasmic reticulum: evidence for two glycosylation steps
Authors: Bollini R , Vitale A , Chrispeels MJ 
Published: May 2004

Cotyledons of the common bean (Phaseolus vulgaris L.) synthesize large amounts of the reserve protein phaseolin. The polypeptides are synthesized on membrane-bound polysomes, pass through the endoplasmic reticulum (ER) and accumulate in protein bodies. For a study of the biosynthesis and processing of phaseolin, developing cotyledons were labeled with radioactive amino acids, glucosamine and mannose, and isolated fractions (polysomal RNA, polysomes, and rough ER) were used for in vitro protein synthesis. Newly synthesized phaseolin present in the ER of developing cotyledons can be fractioned into four glycopolypeptides by SDS PAGE. In vitro synthesis with polysomal RNA results in the formation of two polypeptides by polysome run-off shows that glycosylation is a co-translational event. The two unglycosylated polypeptides formed by polysome run-off are slightly smaller than the two polypeptides formed by in vitro translation of isolated RNA, indicating that a signal peptide may be present on these polypeptides.
Run-off synthesis with rough ER produces a pattern of four polypeptides similar to the one obtained by in vivo labeling. The two abundant glycopolypeptides formed by polysome run-off. This result indicates the existence of a second glycosylation event for the abundant polypeptides. Inhibition of glycosylation by Triton X-100 during chain-completion with rough ER was used to show that these two glycosylation steps normally occur sequentially. Both glycosylation steps are inhibited by tunicamycin. Analysis of carhohydrate to protein ratios of the different polypeptides and of trypsin digests of polypeptides labeled with [(3)H]glucosamine confirmed the conclusion that some glycosylated polypeptides contain two oligosaccharide chains, while others contain only one. An analysis of tryptic peptide maps shows that each of the unglycosylated polypeptides is the precursor for one glycosylated polypeptide with one oligosaccharide chain and one with two oligosaccharide chains.
Lionel Penrose, F.R.S. (1898–1972) and eugenics. Part two
Authors: Watt D.C. 
Published: May 2004

The method of improving the human genetic constitution divides into positive and negative eugenics. Positive eugenics is the policy of encouraging and promoting the procreation of those with socially desirable faculties and abilities. Negative eugenics on the other hand is designed to limit the procreation of those with a poor, disadvantageous genetic constitution which may be transmitted to their offspring. Policy proposals to achieve the aims of positive eugenics included family allowances, grants towards the education of children of able families, counselling, physical and psychological testing, medical examination to facilitate ssortative marriage of desirable parents and banking sperm of outstanding men for insemination of comparable women. These were all vigorously advocated. Fisher stated in a review of an article by Leonard Darwin that
Galton's work in fact left no room for doubt that if the methods of the stockyard were applicable to mankind the human race could be improved in any desired direction, within a short historical period, to an extent exceeding existing differences between widely different races.
Despite continued vigorous approbation the practical outcome of positive eugenics proposals seems very little in terms, for instance, of government enquiries, formal scientific trials or earnest attempts at practical application.
Efficacy and Tolerability of the New Antiepileptic Drugs, II: Treatment of Refractory Epilepsy: Report of the TTA and QSS Subcommittees of the American Academy of Neurology and the American Epilepsy Society
Authors: French Jacqueline A. , Kanner Andres M. , Bautista Jocelyn , Abou‐Khalil Bassel , Browne Thomas , Harden Cynthia L. , Theodore William H. , Bazil Carl , Stern John , Schachter Steven C. , Bergen Donna , Hirtz Deborah , Montouris Georgia D. , Nespeca Mark , Gidal Barry , Marks William J. , Turk William R. , Fischer James H. , Bourgeois Blaise , Wilner Andrew , Faught R. Edward , Sachdeo Rajesh C. , Beydoun Ahmad , Glauser Tracy A. 
Published: May 2004

Summary:  Purpose: To assess the evidence demonstrating efficacy, tolerability, and safety of seven new antiepileptic drugs (AEDs) [gabapentin (GBP), lamotrigine (LTG), topiramate (TPM), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), and zonisamide (ZNS)] in the treatment of children and adults with refractory partial and generalized epilepsies. Methods: A 23‐member committee, including general neurologists, pediatric neurologists, epileptologists, and doctors in pharmacy, evaluated the available evidence based on a structured literature review including MEDLINE, Current Contents, and Cochrane Library for relevant articles from 1987 to March 2003. Results: All of the new AEDs were found to be appropriate for adjunctive treatment of refractory partial seizures in adults. GBP can be effective for the treatment of mixed seizure disorders, and GBP, LTG, OXC, and TPM for the treatment of refractory partial seizures in children. Limited evidence suggests that LTG and TPM also are effective for adjunctive treatment of idiopathic generalized epilepsy in adults and children, as well as treatment of the Lennox–Gastaut syndrome. Conclusions: The choice of AED depends on seizure and/or syndrome type, patient age, concomitant medications, and AED tolerability, safety, and efficacy. The results of this evidence‐based assessment provide guidelines for the prescription of AEDs for patients with refractory epilepsy and identify those seizure types and syndromes for which more evidence is necessary.
Parietal Lobe Epilepsy: The Semiology, Yield of Diagnostic Workup, and Surgical Outcome
Authors: Kim Dong Wook , Lee Sang Kun , Yun Chang‐Ho , Kim Kwang‐Ki , Lee Dong Soo , Chung Chun‐Kee , Chang Kee‐Hyun 
Published: May 2004

Summary:  Purpose: To characterize the clinical features, the prognostic value, and diagnostic sensitivities of various presurgical evaluations and the surgical outcomes in parietal lobe epilepsy (PLE), we describe 40 patients who were diagnosed as having PLE, including 27 surgically treated patients. Methods: The diagnosis was established by means of a standard presurgical evaluation, including magnetic resonance imaging (MRI), fluorodeoxyglucose–positron emission tomography (FDG‐PET), ictal single‐photon emission tomography (SPECT), and scalp video‐electroencephalography (EEG) monitoring, with additional intracranial EEG monitoring in selected cases. Results: Among the 40 patients, 27 experienced at least one type of aura. The most common auras were somatosensory (13 patients), followed by affective, vertiginous, and visual auras. The patients had diverse manifestations. Eighteen patients showed simple motor seizure, followed by automotor seizure, and dialeptic seizure. Two patients manifested generalized tonic–clonic seizures only, and 19 patients experienced more than one type of seizure. The surgical outcome was favorable in 22 of 26 patients including 14 who were seizure free. Patients with localized MRI abnormality had a higher probability to be seizure free, with marginal significance (p = 0.062), whereas other diagnostic modalities failed to predict the surgical outcome. In the seizure‐free group, localization sensitivity was 64.3% by MRI, 50% by PET, 45.5% by ictal SPECT, and 35.7% by ictal EEG. The concordance rate of the various diagnostic modalities was higher in the seizure‐free group than in the non–seizure‐free group, although it did not reach statistical significance. Conclusions: Seizures, in the case of PLE, can manifest themselves in a wider variety of ways than was previously thought. Surgical outcome was favorable in most of the patients. MRI abnormality and concordance of different diagnostic modalities were associated with high seizure‐free rate.
Accidents in Patients with Epilepsy: Types, Circumstances, and Complications: A European Cohort Study
Authors: Van Den Broek Mariska , Beghi Ettore ,   RESt‐1 Group
Published: May 2004

Summary: Purpose:To investigate the risk of accidents in a cohort of patients with epilepsy and in matched nonepilepsy controls, by type, circumstances, and complications.Methods:A total of 951 children and adults with idiopathic, cryptogenic, or remote symptomatic epilepsy and 904 matched controls seen in secondary and tertiary centers in eight European countries (England, Estonia, Germany, Italy, the Netherlands, Portugal, Russia, and Slovenia) were followed up prospectively for 17,484 and 17,206 person‐months and asked to report any accident requiring medical attention, its site, and complications. Risk assessment was done by using actuarial methods, relative risks (RRs), and 95% confidence intervals (CIs).Results:During the study period, 199 (21%) patients and 123 (14%) controls reported an accident (p < 0.0001); 24% were seizure related. The cumulative probability of accidents at 12 and 24 months was 17 and 27% in the cases and 12 and 17% in the controls. The risk was highest for concussions (RR, 2.6; 95% CI, 1.2–5.8), abrasions (RR, 2.1; 95% CI, 1.1–4.0), and wounds (RR, 1.9; CI, 1.2–3.1). Domestic accidents prevailed in both groups, followed by street and work accidents, and were more common among cases. Compared with controls, patients with epilepsy reported more hospitalization, complications, and medical action. Disease characteristics associated with an increased risk of accidents included generalized epilepsy (concussions), active epilepsy, and at least monthly seizures (abrasions). Most risks decreased, becoming nonsignificant after excluding seizure‐related events.Conclusions:Patients with epilepsy are at higher risk of accidents and their complications. However, the risk was substantially lower after exclusion of seizure‐related events.
fMRI of Brain Activation in a Genetic Rat Model of Absence Seizures
Authors: Tenney Jeffrey R. , Duong Timothy Q. , King Jean A. , Ferris Craig F. 
Published: May 2004

Summary: Purpose: EEG‐triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike‐and‐wave discharges (SWDs) in an epileptic rat strain under awake conditions.Methods: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*‐weighted echo planar imaging at 4.7 Tesla. fMRI of the blood‐oxygenation‐level–dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images.Results: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area.Conclusions: We have shown that EEG‐triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG‐triggered fMRI in a genetic rat model of absence seizure.
Severity of Histopathologic Abnormalities and In Vivo Epileptogenicity in the In Utero Radiation Model of Rats Is Dose Dependent
Authors: Kellinghaus Christoph , Kunieda Takeharu , Ying Zhong , Pan Andrew , Lüders Hans O. , Najm Imad M. 
Published: May 2004

Summary:  Purpose: Malformations of cortical development (MCDs) are a frequent cause of refractory epilepsy in humans. The in utero radiation model in rats shares many clinical and histopathologic characteristics with human MCDs. Previous studies reported the presence of clinical seizures in radiated rats, but also suggested a dose‐dependent differential effect. Methods: Time‐pregnant Sprague–Dawley rats were irradiated on embryonic day E17 with 100 cGy (low dose), 145 cGy (medium dose), 175 cGy (high dose), or were left untreated. Their adult litters were implanted with bifrontal epidural and hippocampal depth electrodes and underwent long‐term video‐EEG monitoring. After 2 weeks of monitoring, the animals were killed and their brains processed for histological studies. Results: Spikes were most frequently found in the rats that were subjected to low‐ and medium‐dose radiation at E17 and were less frequently seen in the animals that were subjected to high‐dose radiation. No interictal spikes were found in any of the control animals. Seizures were recorded in three of five animals of the medium‐dose group. Histological studies showed a dose‐dependent decrease in cortical thickness as well as an increase of cortical and hippocampal disorganization. Conclusions: In vivo epileptogenicity in radiated animals was present only in mild or moderate MCD. No in vivo epileptogenicity was seen in severe radiation‐induced MCD.
Evaluation of GABA System and Cell Damage in Parahippocampus of Patients with Temporal Lobe Epilepsy Showing Antiepileptic Effects after Subacute Electrical Stimulation
Authors: Cuéllar‐Herrera Manola , Velasco Marcos , Velasco Francisco , Velasco Ana Luisa , Jiménez Fiacro , Orozco Sandra , Briones Magdalena , Rocha Luisa 
Published: May 2004

Summary:  Purpose: The γ‐aminobutyric acid (GABA) system and neuronal loss were evaluated in the parahippocampal cortex (PHC) of patients with intractable mesial temporal lobe epilepsy (MTLE) who received subacute electrical stimulation and showed antiepileptic effects. Methods: GABA tissue content, GABAA and benzodiazepine (BZD) receptor levels, as well as neuronal density were determined in PHC of five patients (ESAE group) with an MTLE history of 14.8 ± 2.5 years and seizure frequency of 11 ± 2.9 per month, two (40%) of them with mesial sclerosis. This group demonstrated antiepileptic effects after subacute electrical stimulation (130 Hz, 450 μs, 200–400 μA), applied continuously during 16 to 20 days in PHC. Values were compared with those obtained from patients with severe MTLE (history of 21.7 ± 2.8 years and seizure frequency of 28.2 ± 14 per month) in whom electrical stimulation did not induce antiepileptic effects (ESWAE group, n = 4), patients with MTLE in whom no electrical stimulation was applied (MTLE group, n = 4), and autopsy material acquired from subjects without epilepsy (n = 4 obtained from three subjects). Results: The ESAE group demonstrated high GABA tissue levels (219%), as well as a significantly higher cell count (58.5%) when compared with the MTLE group. The ESWAE group showed enhanced BZD‐receptor levels (38%), whereas their values for GABA tissue levels and GABAA receptor were similar to those obtained from the MTLE group. Conclusions: It is suggested that subacute electrical stimulation of PHC is more effective in patients with less severe epilepsy, an effect associated with a high GABA tissue content and a low rate of cell loss.
Pharmacodynamic Analysis of the Anticonvulsant Effects of Tiagabine and Lamotrigine in Combination in the Rat
Authors: Jonker Daniël M. , Voskuyl Rob A. , Danhof Meindert 
Published: May 2004

Summary:  Purpose: The pharmacodynamic interaction between the antiepileptic drugs (AEDs) tiagabine (TGB) and lamotrigine (LTG) was characterized on basis of the anticonvulsant effect in the cortical stimulation model in the rat. Methods: The study was conducted according to a partial crossover design, in which both drugs were infused intravenously to achieve linear increases in the plasma concentration in the absence and presence of a steady‐state concentration of the second drug. The anticonvulsant effect was quantified by counts of four specific ictal signs (eye closure, forelimb clonus, forelimb extension, and head jerk). A potential pharmacokinetic interaction was accounted for by determination of total plasma concentrations of both drugs. Results: When given separately, both TGB and LTG suppressed all ictal signs in a concentration‐dependent manner, with the exception of eye closure, which was not suppressed by LTG. The interaction between both drugs was estimated by response surface analysis by using the difference between the observed effect and the additive effect to identify synergistic drug concentrations. This analysis showed that the pharmacodynamic interaction between TGB and LTG is synergistic for the ictal signs of eye closure and head jerk. In contrast, the interaction was additive for the ictal signs of forelimb clonus and forelimb tonus. Conclusions: This study demonstrates the usefulness of ictal‐component analysis for studying the pharmacodynamic interaction between AEDs. Quantification of both the nature and the magnitude of the interaction between TGB and LTG led to the identification of two ictal signs that were synergistically suppressed. This approach offers a theoretical basis to identify and optimize drug combinations that are useful to treat refractory epilepsy.
EEG and MEG Source Analysis of Single and Averaged Interictal Spikes Reveals Intrinsic Epileptogenicity in Focal Cortical Dysplasia
Authors: Bast Thomas , Oezkan Oezdin , Rona Sabine , Stippich Christoph , Seitz Angelika , Rupp Andre , Fauser Susanne , Zentner Josef , Rating Dietz , Scherg Michael 
Published: May 2004

Summary:  Purpose: Simultaneous interictal EEG and magnetoencephalography (MEG) recordings were used for noninvasive analysis of epileptogenicity in focal cortical dysplasia (FCD). The results of two different approach methods (multiple source analysis of averaged spikes and single dipole peak localization of single spikes) were compared with pre‐ and postoperative anatomic magnetic resonance imaging (MRI). Patients: We studied nine children and adolescents (age, 3.5–15.9 years) with localization‐related epilepsy and FCD diagnosis based on MRI. Five patients underwent epilepsy surgery, two of them after long‐term recording with subdural grid electrodes, and one after intraoperative electrocorticography. Methods: The 122‐channel whole‐head MEGs and 33‐channel EEGs were recorded simultaneously for 25 to 40 min. Interictal spikes were identified visually and used as templates to search for similar spatiotemporal spike patterns throughout the recording. With the BESA program, similar spikes (r > 0.85) were detected, averaged, high‐pass filtered (5 Hz) to enhance spike onset, and subjected to multiple spatiotemporal source analysis with a multishell spherical head model. Peak activity from single spikes was modeled by single dipoles for the same subset of spikes. Source localization was visualized by superposition on T1‐weighted MRI and compared with the lesion identified in T1‐ and T2‐weighted MRI. In the five cases undergoing epilepsy surgery, the results were correlated with invasive recordings, postoperative MRI, and outcome. Results: In all cases, the analysis of averaged spikes showed a localization of onset‐ and peak‐related sources within the visible lesion for both EEG and MEG. Of the single spikes, 128 (45%; total 284) were localizable at the peak in MEG, and 170 (60%) in EEG. Of these, 91% localized within the lesion with MEG, and 93.5% with EEG. In three of five patients operated on, the resected area included the onset zones of averaged EEG and MEG spike activity. These patients had excellent postoperative outcome, whereas the others did not become seizure free. Conclusions: Consistent MEG and EEG spike localization in the lesional zone confirmed the hypothesis of intrinsic epileptogenicity in FCD.
Expression and Cellular Distribution of Multidrug Resistance–related Proteins in the Hippocampus of Patients with Mesial Temporal Lobe Epilepsy
Authors: Aronica Eleonora , Gorter Jan A. , Ramkema Marja , Redeker Sandra , Özbas‐Gerçeker Filiz , Van Vliet Edwin A. , Scheffer George L. , Scheper Rik J. , Van Der Valk Paul , Baayen Johannes C. , Troost Dirk 
Published: May 2004

Summary: Purpose:This study investigated the cellular distribution of different multidrug resistance (MDR)‐related proteins such as P‐glycoprotein (P‐gp), the multidrug resistance–associated proteins (MRP) 1 and 2, and the major vault protein (MVP) in normal and sclerotic hippocampus of patients with medically refractory mesial temporal lobe epilepsy (MTLE).Methods:Single‐ and double‐label immunocytochemistry was used on brain sections of control hippocampus and of hippocampus of refractory MTLE patients.Results:In TLE cases with hippocampal sclerosis (HS), all four MDR proteins examined that had low or no expression in control tissue were upregulated, albeit with different cellular distribution patterns. P‐gp immunoreactivity (IR) was observed in astrocytes in regions with diffuse reactive gliosis. In 75% of HS cases, strong P‐gp IR was detected in blood vessels, with prominent endothelial labeling. Reactive astrocytes displayed low MRP1 IR. However, glial MRP1 expression was noted in glial endfoot processes around blood vessels. Neuronal MRP1 expression was observed in hypertrophic hilar neurons and in a few residual neurons of the CA1 region. Hippocampal MRP2 expression was observed in the large majority of HS cases in blood vessels. Hypertrophic hilar neurons and blood vessels within the sclerotic hippocampus expressed major vault protein (MVP).Conclusions:These findings indicate that MDR proteins are upregulated in concert in the hippocampus of patients with refractory MTLE, supporting their role in the mechanisms underlying drug resistance. The specific cell‐distribution patterns within the sclerotic hippocampus suggest different cellular functions, not necessarily linked only to clinical drug resistance.