bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Comparison of Epilepsy Patients in a Traditional Ambulatory Clinic and a Telemedicine Clinic
Authors: Rasmusson Karen A. , Hartshorn Jeanette C. 
Published: April 2005

Summary:  Purpose: This article compares a traditional ambulatory clinic in an academic medical center with a telemedicine clinic. The telemedicine clinic is a joint project of the UTMB Telehealth Center and the Epilepsy Foundation of Southeast Texas, with partial funding for clinical operations provided by the Texas Department of Health. Methods: Data were collected on all the patients (n = 155) in both clinics for 3 months in 2004. In addition to demographic information, outcome data (number of seizures, hospitalizations, and emergency room visits) were gathered. Medication compliance also was collected by using self‐report and medication levels. Results: Outcome variables were subjected to t test and χ2 analysis. No significant differences were found in any of the demographic data or outcome measures between the two groups. Conclusions: Telemedicine is an acceptable alternative to in‐person clinics for the provision of care to adults with epilepsy. Because telemedicine programs are designed to bring medical care closer to where patients live, these clinics provide an excellent alternative to provide consistent care in rural and geographically isolated areas. Additional studies are needed to investigate the potential costs associated with telemedicine as well as the potential for cost savings over time as patients are more able to access care and therefore may be more likely to seek the needed routine care and follow‐up.
Lack of Association between the C3435T Polymorphism in the Human Multidrug Resistance (MDR1) Gene and Response to Antiepileptic Drug Treatment
Authors: Sills Graeme J. , Mohanraj Rajiv , Butler Elaine , McCrindle Sheila , Collier Lindsay , Wilson Elaine A. , Brodie Martin J. 
Published: April 2005

Summary:  Purpose: P‐glycoprotein (P‐gp) has been implicated in the causation of refractory epilepsy. The expression and efflux efficiency of P‐gp is influenced by a polymorphism (C3435T) in the encoding gene (MDR1). Recent evidence suggests that the homozygous C‐variant, which is associated with higher expression and increased activity of P‐gp, is more common in patients with pharmacoresistant epilepsy. We have investigated the prevalence of this polymorphism in a series of patients attending a specialist epilepsy clinic. Methods: DNA samples were obtained from 400 patients, irrespective of seizure type or drug treatment. Genotype of the C3435T polymorphism was determined by traditional polymerase chain reaction (PCR) followed by restriction digest. Classification of response to treatment was determined in a blinded fashion by an independent physician. Results were expressed as genotype and allele frequencies per response group and compared by logistic regression analysis. Results: In total, 170 patients were classified as responders, with ≥12 months seizure freedom on current treatment. The remaining 230 patients were classified as nonresponders. Comparison of responders and nonresponders revealed no significant difference in allele frequency (C vs. T; odds ratio, 1.03; 95% CI, 0.78–1.37; p = 0.83) or genotype frequency (CC vs TT; odds ratio, 1.07; 95% CI, 0.60–1.91; p = 0.81). Subanalyses of individual seizure types were similarly unremarkable. Conclusions: This study failed to corroborate a previously reported association between the C3435T polymorphism in the human MDR1 gene and pharmacoresistant epilepsy. Whether the C3435T polymorphism can act as a marker for the natural history of treated epilepsy remains to be determined.
Is Variation in the GABA(B) Receptor 1 Gene Associated with Temporal Lobe Epilepsy?
Authors: Tan Nigel C.K. , Heron Sarah E. , Scheffer Ingrid E. , Berkovic Samuel F. , Mulley John C. 
Published: April 2005

Summary:  Purpose:γ‐Aminobutyric acid (GABA)‐receptor genes are prime candidates for a role in seizure susceptibility. An association between the c.1465G→A variant in the GABA(B) receptor 1 gene (GABBR1) and susceptibility to temporal lobe epilepsy (TLE) has been reported in an Italian cohort. We sought to replicate this association in an independent Australian cohort. Methods: The 234 patients with TLE and 164 healthy controls were genotyped for the c.1465G→A variant, by using inclusion criteria identical to those of the first study. Results: The c.1465G→A variant was found in one TLE patient and one control subject. Genotype and allele frequencies did not differ between groups. Conclusions: We did not replicate the reported associations between the c.1465G→A variant and susceptibility to TLE. We suggest that the initial positive association may be due to undetected population stratification; the importance of genomic control is emphasized. Population‐specific effects also may play a role, and we highlight the need to demonstrate an in vitro functional effect to give biologic meaning to any proposed association.
Adding Video Recording Increases the Diagnostic Yield of Routine Electroencephalograms in Children with Frequent Paroxysmal Events
Authors: Watemberg Nathan , Tziperman Barak , Dabby Ron , Hasan Mariana , Zehavi Liora , Lerman‐Sagie Tally 
Published: April 2005

Summary: Purpose:To report on the usefulness of adding video recording to routine EEG studies of infants and children with frequent paroxysmal events.Methods:We analyzed the efficacy of this diagnostic means during a 4‐year period. The decision whether to add video recording was made by the pediatric EEG interpreter at the time of the study. Studies were planned to last between 20 and 30 min, and, if needed, were extended by the EEG interpreter. For most studies, video recording was added from the beginning of EEG recording. In a minority of cases, the addition of video was implemented during the first part of the EEG test, as clinical events became obvious. In these cases, a new study (file) was begun. The success rate was analyzed according to the indications for the EEG study: paroxysmal eye movements, tremor, suspected seizures, myoclonus, staring episodes, suspected stereotypias and tics, absence epilepsy follow‐up, cyanotic episodes, and suspected psychogenic nonepileptic events.Results:Video recording was added to 137 of 666 routine studies. Mean patient age was 4.8 years. The nature of the event was determined in 61 (45%) of the EEG studies. Twenty‐eight percent were hospitalized patients. The average study duration was 26 min. This diagnostic means was particularly useful for paroxysmal eye movements, staring spells, myoclonic jerks, stereotypias, and psychogenic nonepileptic events. About 46% of 116 patients for whom cognitive data were available were mentally retarded. EEG with added video recording was successfully performed in all 116 cases and provided useful information in 29 (55%) of these 53 patients.Conclusions:Adding video recording to routine EEG was helpful in 45% of cases referred for frequent paroxysmal events. This technique proved useful for hospitalized children as well as for outpatients. Moreover, it was successfully applied in cognitively impaired patients. Infants and children with paroxysmal eye movements, staring spells, myoclonic jerks, stereotypias, and pseudoseizures especially benefited from this diagnostic means. Because of its low cost and the little discomfort imposed on the patient and his or her family, this technique should be considered as a first diagnostic step in children with frequent paroxysmal events.
Visually Self‐induced Seizures Sensitive to Round Objects
Authors: Brockmann Knut , Huppke Peter , Karenfort Michael , Gärtner Jutta , Höger Christoph 
Published: April 2005

Summary: Purpose:To describe a previously unreported type of self‐induced pattern‐sensitive seizures in a child.Methods:Evaluation of clinical and EEG features.Results:An 18‐month‐old boy was initially seen with series of short focal tonic seizures self‐induced by gazing intermittently at round objects. Self‐induction of these seizures had an obvious relieving effect on the child. Covering the round object foiled further seizures but resulted in a tantrum. Later in the course, an increasing variety of patterns proved to be capable of inducing seizures, which occurred with increasing frequency and severity, including secondarily generalized tonic–clonic seizures. Interictal EEG revealed multifocal sharp‐and‐slow‐waves. Ictal EEG showed no abnormalities during short focal seizures and rapidly generalizing epileptic discharges during a secondarily generalized seizure. No photosensitivity was noted. Motor and mental development of the boy stagnated over a period of 2 years. Behavioral therapy as well as medical treatment, consisting of various combinations of antiepileptic drugs (AEDs) together with a selective serotonin‐reuptake inhibitor, were of merely transient benefit. Only combined pharmacotherapy, including valproate, sulthiame, and clobazam, resulted in seizure control at age 3 years 9 months.Conclusions:Visual capture of geometric patterns other than stripes or gratings may trigger focal seizures with secondary generalization. Synchronization of cortical neurons responsible for pattern recognition may account for epileptogenesis in this child.
Mitogen-Activated Protein Kinases Regulate LSF Occupancy at the Human Immunodeficiency Virus Type 1 Promoter
Authors: Ylisastigui Loyda , Kaur Rupinderjeet , Johnson Holly , Volker Janet , He Guocheng , Hansen Ulla , Margolis David 
Published: April 2005

ABSTRACT

Human immunodeficiency virus type 1 (HIV-1) establishes a persistent, nonproductive state within a small population of memory CD4
+
cells. The transcription factor LSF binds to sequences within the HIV-1 long terminal repeat (LTR) initiation region and recruits a second factor, YY1, to the LTR. These factors then cooperatively recruit histone deacetylase 1 to the LTR, resulting in inhibition of transcription. This appears to be one mechanism contributing to HIV persistence within resting CD4
+
T cells. We sought to further detail LSF binding to the HIV-1 LTR and factors that regulate LSF occupancy. We find that LSF binds the LTR as a tetramer and that binding is regulated by phosphorylation mediated by mitogen-activated protein kinases (MAPKs). In vitro, phosphorylation of LSF by Erk decreases binding to the LTR, while binding is increased by p38 phosphorylation. LSF occupancy at LTR chromatin is increased by the p38 agonist anisomycin and decreased by specific p38 inhibition. p38 inhibition also results in increased acetylation of histone H4 at the LTR nucleosome adjacent to the LSF binding site. p38 inhibition also blocked the ability of YY1 to inhibit activation of the integrated HIV promoter. Finally, HIV was recovered from the resting CD4
+
T cells of aviremic, HIV-infected donors upon treatment of these cells with specific inhibitor of p38. These data suggest that the MAPK pathway regulates LSF binding to the LTR and thereby one aspect of the regulation of HIV expression. This mechanism could be exploited as a novel therapeutic target to disrupt latent HIV infection.
Virus-Specific CD4+and CD8+Cytotoxic T-Cell Responses and Long-Term T-Cell Memory in Individuals Vaccinated against Polio
Authors: Wahid Rahnuma , Cannon Martin J. , Chow Marie 
Published: April 2005

ABSTRACTThe presence of poliovirus (PV)-specific CD4+T cells in individuals vaccinated against polio has been shown, but CD8+T-cell responses have not been described. Here, we functionally characterize the CD4+T-cell response and show for the first time that dendritic cells and macrophages can stimulate PV-specific CD8+T-cell responses in vitro from vaccinees. Both CD4+T and CD8+T cells secrete gamma interferon in response to PV antigens and are cytotoxic via the perforin/granzyme B-mediated pathway. Furthermore, the T cells also recognize and kill Sabin 1 vaccine-infected targets. The macrophage-stimulated CD4+T and CD8+T cells most likely represent memory T cells that persist for long periods in vaccinated individuals. Thus, immunity to PV vaccination involves not only an effective neutralizing antibody titer but also long-term CD4+and CD8+cytotoxic T-cell responses.
Constitutive Activation of the Transcription Factor NF-κB Results in Impaired Borna Disease Virus Replication
Authors: Bourteele Soizic , Oesterle Katja , Pleschka Stephan , Unterstab Gunhild , Ehrhardt Christina , Wolff Thorsten , Ludwig Stephan , Planz Oliver 
Published: April 2005

ABSTRACTThe inducible transcription factor NF-κB is commonly activated upon RNA virus infection and is a key player in the induction and regulation of the innate immune response. Borna disease virus (BDV) is a neurotropic negative-strand RNA virus, which replicates in the nucleus of the infected cell and causes a persistent infection that can lead to severe neurological disorders. To investigate the activation and function of NF-κB in BDV-infected cells, we stably transfected the highly susceptible neuronal guinea pig cell line CRL with a constitutively active (IKK EE) or dominant-negative (IKK KD) regulator of the IKK/NF-κB signaling pathway. While BDV titers were not affected in cells with impaired NF-κB signaling, the expression of an activated mutant of IκB kinase (IKK) resulted in a strong reduction in the intracellular viral titer in CRL cells. Electrophoretic mobility shift assays and luciferase reporter gene assays revealed that neither NF-κB nor interferon regulatory factors (IRFs) were activated upon acute BDV infection of wild-type or vector-transfected CRL cells. However, when IKK EE-transfected cells were used as target cells for BDV infection, DNA binding to an IRF3/7-responsive DNA element was detectable. Since IRF3/7 is a key player in the antiviral interferon response, our data indicate that enhanced NF-κB activity in the presence of BDV leads to the induction of antiviral pathways resulting in reduced virus titers. Consistent with this observation, the anti-BDV activity of NF-κB preferentially spread to areas of the brains of infected rats where activated NF-κB was not detectable.
Myxoma Virus M141R Expresses a Viral CD200 (vOX-2) That Is Responsible for Down-Regulation of Macrophage and T-Cell Activation In Vivo
Authors: Cameron Cheryl M. , Barrett John W. , Liu Liying , Lucas Alexandra R. , McFadden Grant 
Published: April 2005

ABSTRACTM141R is a myxoma virus gene that encodes a cell surface protein with significant amino acid similarity to the family of cellular CD200 (OX-2) proteins implicated in the regulation of myeloid lineage cell activation. The creation of an M141R deletion mutant myxoma virus strain (vMyx141KO) and its subsequent infection of European rabbits demonstrated that M141R is required for the full development of a lethal infection in vivo but is not required for efficient virus replication in susceptible cell lines in vitro. Minor secondary sites of infection were detected in the majority of rabbits infected with the M141R deletion mutant, demonstrating that the M141R protein is not required for the dissemination of virus within the host. When compared to wild-type myxoma virus-infected rabbits, vMyx141KO-infected rabbits showed higher activation levels of both monocytes/macrophages and lymphocytes in situ through assessments of inducible nitric oxide synthase-positive and CD25+infiltrating cells in infected and lymphoid tissues. Purified peripheral blood mononuclear cells from vMyx141KO-infected rabbits demonstrated an increased ability to express gamma interferon upon activation by phorbol myristate acetate plus ionomycin compared to cells purified from wild-type myxoma virus-infected rabbits. We concluded that the M141R protein is a bona fide CD200-like immunomodulator protein which is required for the full pathogenesis of myxoma virus in the European rabbit and that its loss from the virus results in increased activation levels of macrophages in infected lesions and draining lymph nodes as well as an increased activation level of circulating T lymphocytes during infection. We propose a model whereby M141R transmits inhibitory signals to tissue macrophages, and possibly resident CD200R+dendritic cells, that reduce their ability to antigenically prime lymphocytes and possibly provides anergic signals to T cells directly.
Receptor-Independent Spread of a Highly Neurotropic Murine Coronavirus JHMV Strain from Initially Infected Microglial Cells in Mixed Neural Cultures
Authors: Nakagaki Keiko , Nakagaki Kazuhide , Taguchi Fumihiro 
Published: April 2005

ABSTRACTAlthough neurovirulent mouse hepatitis virus (MHV) strain JHMV multiplies in a variety of brain cells, expression of its receptor carcinoembryonic antigen cell adhesion molecule 1 (CEACAM 1) (MHVR) is restricted only in microglia. The present study was undertaken to clarify the mechanism of an extensive JHMV infection in the brain by using neural cells isolated from mouse brain. In contrast to wild-type (wt) JHMV, a soluble-receptor-resistant mutant (srr7) infects and spreads solely in an MHVR-dependent fashion (F. Taguchi and S. Matsuyama, J. Virol. 76:950-958, 2002). In mixed neural cell cultures, srr7 infected a limited number of cells and infection did not spread, although wt JHMV induced syncytia in most of the cells. srr7-infected cells were positive for GS-lectin, a microglia marker. Fluorescence-activated cell sorter analysis showed that about 80% of the brain cells stained with anti-MHVR antibody (CC1) were also positive for GS-lectin. Pretreatment of those cells with CC1 prevented virus attachment to the cell surface and also blocked virus infection. These results show that microglia express functional MHVR that mediates JHMV infection. As expected, in microglial cell-enriched cultures, both srr7and wt JHMV produced syncytia in a majority of cells. Treatment with CC1 of mixed neural cell cultures and microglia cultures previously infected with wt virus failed to block the spread of infection, indicating that wt infection spreads in an MHVR-independent fashion. Thus, the present study indicates that microglial cells are the major population of the initial target for MHV infection and that the wt spreads from initially infected microglia to a variety of cells in an MHVR-independent fashion.
The B30.2(SPRY) Domain of the Retroviral Restriction Factor TRIM5α Exhibits Lineage-Specific Length and Sequence Variation in Primates
Authors: Song Byeongwoon , Gold Bert , O'hUigin Colm , Javanbakht Hassan , Li Xing , Stremlau Matthew , Winkler Cheryl , Dean Michael , Sodroski Joseph 
Published: April 2005

ABSTRACT

Tripartite motif (TRIM) proteins are composed of RING, B-box 2, and coiled coil domains. Some TRIM proteins, such as TRIM5α, also possess a carboxy-terminal B30.2(SPRY) domain and localize to cytoplasmic bodies. TRIM5α has recently been shown to mediate innate intracellular resistance to retroviruses, an activity dependent on the integrity of the B30.2 domain, in particular primate species. An examination of the sequences of several TRIM proteins related to TRIM5 revealed the existence of four variable regions (v1, v2, v3, and v4) in the B30.2 domain. Species-specific variation in TRIM5α was analyzed by amplifying, cloning, and sequencing nonhuman primate
TRIM5
orthologs. Lineage-specific expansion and sequential duplication occurred in the TRIM5α B30.2 v1 region in Old World primates and in v3 in New World monkeys. We observed substitution patterns indicative of selection bordering these particular B30.2 domain variable elements. These results suggest that occasional, complex changes were incorporated into the TRIM5α B30.2 domain at discrete time points during the evolution of primates. Some of these time points correspond to periods during which primates were exposed to retroviral infections, based on the appearance of particular endogenous retroviruses in primate genomes. The results are consistent with a role for TRIM5α in innate immunity against retroviruses.
Infectious Bronchitis Virus 3a Protein Localizes to a Novel Domain of the Smooth Endoplasmic Reticulum
Authors: Pendleton Amanda R. , Machamer Carolyn E. 
Published: April 2005

ABSTRACTAll coronaviruses possess small open reading frames (ORFs) between structural genes that have been hypothesized to play important roles in pathogenesis. Infectious bronchitis virus (IBV) ORF 3a is one such gene. It is highly conserved among group 3 coronaviruses, suggesting that it has an important function in infection. IBV 3a protein is expressed in infected cells but is not detected in virions. Sequence analysis predicted that IBV 3a was a membrane protein; however, only a fraction behaved like an integral membrane protein. Microscopy and immunoprecipitation studies demonstrated that IBV 3a localized to the cytoplasm in a diffuse pattern as well as in sharp puncta in both infected and transfected cells. These puncta did not overlap cellular organelles or other punctate structures. Confocal microscopy demonstrated that IBV 3a puncta lined up along smooth endoplasmic reticulum (ER) tubules and, in a significant number of instances, were partially surrounded by these tubules. Our results suggest that IBV 3a is partially targeted to a novel domain of the smooth ER.
Relocalization of the Mre11-Rad50-Nbs1 Complex by the Adenovirus E4 ORF3 Protein Is Required for Viral Replication
Authors: Evans Jared D. , Hearing Patrick 
Published: April 2005

ABSTRACT
Adenovirus replication is controlled by the relocalization or modification of nuclear protein complexes, including promyelocytic leukemia protein (PML) nuclear domains and the Mre11-Rad50-Nbs1 (MRN) DNA damage machinery. In this study, we demonstrated that the E4 ORF3 protein effects the relocalization of both PML and MRN proteins to similar structures within the nucleus at early times after infection. These proteins colocalize with E4 ORF3. Through the analysis of specific viral mutants, we found a direct correlation between MRN reorganization at early times after infection and the establishment of viral DNA replication domains. Further, the reorganization of MRN components may be uncoupled from the ability of E4 ORF3 to rearrange PML. At later stages of infection, components of the MRN complex disperse within the nucleus, Nbs1 is found within viral replication centers, Rad50 remains localized with E4 ORF3, and Mre11 is degraded. The importance of viral regulation of the MRN complex is underscored by the complementation of E4 mutant viruses in cells that lack Mre11 or Nbs1 activity. These results illustrate the importance of nuclear organization in virus growth and suggest that E4 ORF3 regulates activities in both PML nuclear bodies and the MRN complex to stimulate the viral replication program.