bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of gp120 Binding Sites on CXCR4 by Using CD4-Independent Human Immunodeficiency Virus Type 2 Env Proteins
Authors: Lin George , Baribaud Frédéric , Romano Josephine , Doms Robert W. , Hoxie James A. 
Published: December 2002

ABSTRACTHuman immunodeficiency virus (HIV) and simian (SIV) immunodeficiency virus entry is mediated by binding of the viral envelope glycoprotein (Env) to CD4 and chemokine receptors, CCR5 and/or CXCR4. CD4 induces extensive conformational changes that expose and/or induce formation of a chemokine receptor binding site on gp120. CD4-independent Env's of HIV type 1 (HIV-1), HIV-2, and SIV have been identified that exhibit exposed chemokine receptor binding sites and can bind directly to CCR5 or CXCR4 in the absence of CD4. While many studies have examined determinants for gp120-CCR5 binding, analysis of gp120-CXCR4 binding has been hindered by the apparently lower affinity of this interaction for X4-tropic HIV-1 isolates. We show here that gp120 proteins from two CD4-independent HIV-2 Env's, VCP and ROD/B, bind directly to CXCR4 with an apparently high affinity. By use of CXCR4 N-terminal deletion constructs, CXCR4-CXCR2 chimeras, and human-rat CXCR4 chimeras, binding determinants were shown to reside in the amino (N) terminus, extracellular loop 2 (ECL2), and ECL3. Alanine-scanning mutagenesis of charged residues, tyrosines, and phenylalanines in extracellular CXCR4 domains implicated multiple amino acids in the N terminus (E14/E15, D20, Y21, and D22), ECL2 (D187, R188, F189, Y190, and D193), and ECL3 (D262, E268, E277, and E282) in binding, although minor differences were noted between VCP and ROD/B. However, mutations in CXCR4 that markedly reduced binding did not necessarily hinder cell-cell fusion by VCP or ROD/B, especially in the presence of CD4. These gp120 proteins will be useful in dissecting determinants for CXCR4 binding and Env triggering and in evaluating pharmacologic inhibitors of the gp120-CXCR4 interaction.
The Multimerization of Hantavirus Nucleocapsid Protein Depends on Type-Specific Epitopes
Authors: Yoshimatsu Kumiko , Lee Byoung-Hee , Araki Koichi , Morimatsu Masami , Ogino Michiko , Ebihara Hideki , Arikawa Jiro 
Published: December 2002

ABSTRACT
Multimerization of the Hantaan virus nucleocapsid protein (NP) in Hantaan virus-infected Vero E6 cells was observed in a competitive enzyme-linked immunosorbent assay (ELISA). Recombinant and truncated NPs of Hantaan, Seoul, and Dobrava viruses lacking the N-terminal 49 amino acids were also detected as multimers. Although truncated NPs of Hantaan virus lacking the N-terminal 154 amino acids existed as a monomer, those of Seoul and Dobrava formed multimers. The multimerized truncated NP antigens of Seoul and Dobrava viruses could detect serotype-specific antibodies, whereas the monomeric truncated NP antigen of Hantaan virus lacking the N-terminal 154 amino acids could not, suggesting that a hantavirus serotype-specific epitope on the NP results in multimerization. The NP-NP interaction was also detected by using a yeast two-hybrid assay. Two regions, amino acids 100 to 125 (region 1) and amino acids 404 to 429 (region 2), were essential for the NP-NP interaction in yeast. The NP of Seoul virus in which the tryptophan at amino acid number 119 was replaced by alanine (W119A mutation) did not multimerize in the yeast two-hybrid assay, indicating that tryptophan 119 in region 1 is important for the NP-NP interaction in yeast. However, W119A mutants expressed in mammalian cells were detected as the multimer by using competitive ELISA. Similarly, the truncated NP of Seoul virus expressing amino acids 155 to 429 showed a homologous interaction in a competitive ELISA but not in the yeast two-hybrid assay, indicating that the C-terminal region is important for the multimerization detected by competitive ELISA. Combined, the results indicate that several steps and regions are involved in multimerization of hantavirus NP.
Identification of Immunodominant Epitopes Derived from the Respiratory Syncytial Virus Fusion Protein That Are Recognized by Human CD4 T Cells
Authors: van Bleek Grada M. , Poelen Martien C. , van der Most Robbert , Brugghe Humphrey F. , Timmermans Hans A. M. , Boog Claire J. , Hoogerhout Peter , Otten Henny G. , van Els Cécile A. C. M. 
Published: December 2002

ABSTRACTMemory CD4 T-cell responses against respiratory syncytial virus (RSV) were evaluated in peripheral blood mononuclear cells of healthy blood donors with gamma interferon enzyme-linked immunospot (Elispot) assays. RSV-specific responses were detected in every donor at levels varying between 0.05 and 0.3% of CD4 T cells. For all donors tested, a considerable component of the CD4 T-cell response was directed against the fusion (F) protein of RSV. We characterized a set of 31 immunodominant antigenic peptides targeted by CD4 T cells in the context of the most prevalent HLA class II molecules within the Caucasian population. Most antigenic peptides were HLA-DR restricted, whereas two dominant DQ peptides were also identified. The antigenic peptides identified were located across the entire sequence of the F protein. Several peptides were presented by more than one major histocompatibility complex class II molecule. Furthermore, most donors recognized several F peptides. Detailed knowledge about immunodominant antigenic peptides will facilitate the ability to monitor CD4 T-cell responses in patients and the measurement of correlates of protection in vaccinated subjects.
EBNA3A Association with RBP-Jκ Down-Regulates c-mycand Epstein-Barr Virus-Transformed Lymphoblast Growth
Authors: Cooper Andrew , Johannsen Eric , Maruo Seiji , Cahir-McFarland Ellen , Illanes Diego , Davidson David , Kieff Elliott 
Published: December 2002

ABSTRACTEpstein-Barr virus nuclear antigen protein 3A (EBNA3A) is one of four EBNAs (EBNA-2, EBNALP, EBNA3A, and EBNA3C) through the cellular DNA sequence-specific transcription factor RBP-Jκ/CBF-1/CSL and are essential for conversion of primary B lymphocytes to lymphoblastoid cell lines (LCLs). In the present study, we investigated the effects of EBNA3A on EBNA2 activation of transcription in the IB4 LCL by conditionally overexpressing EBNA3A three- to fivefold. EBNA3A overexpression increased EBNA3A association with RBP-Jκ, did not change EBNA3C association with RBP-Jκ or EBNA or LMP1 expression, decreased EBNA2 association with RBP-Jκ, decreased c-mycexpression, and caused G0/G1growth arrest with prolonged viability. Expression of the fusion protein MycERTM in cells with conditional EBNA3A overexpression restored cell cycle progression and caused apoptosis. In contrast, MycER in the same cells without EBNA3A overexpression enhanced cell proliferation and did not increase apoptosis. These data indicate that EBNA3A overexpression inhibits protection from c-myc-induced apoptosis. In assays of EBNA2- and RBP-Jκ-dependent transcription, EBNA3A amino acids 1 to 386 were sufficient for repression equivalent to that by wild-type EBNA3A, amino acids 1 to 124 were unimportant, amino acids 1 to 277 were insufficient, and a triple alanine substitution within the EBNA3A core RBP-Jκ binding domain was a null mutation. In reverse genetic experiments with IB4 LCLs, the effects of conditional EBNA3A overexpression on c-mycexpression and proliferation did not require amino acids 524 to 944 but did require amino acids 278 to 524 as well as wild-type sequence in the core RBP-Jκ binding domain. The dependence of EBNA3A effects on the core RBP-Jκ interaction domain and on the more C-terminal amino acids (amino acids 278 to 524) required for efficient RBP-Jκ association strongly implicates RBP-Jκ in c-mycpromoter regulation.
Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder
Authors: Lawson Deborah C. , Turic Darko , Langley Kate , Pay Helen M. , Govan Catherine F. , Norton Nadine , Hamshere Marian L. , Owen Michael J. , O'Donovan Michael C. , Thapar Anita 
Published: December 2002

AbstractAttention deficit hyperactivity disorder (ADHD) is a highly heritable disorder. Although the causes of ADHD are unknown, dopaminergic, serotonergic and nor‐adrenergic pathways have been strongly implicated. Monoamine Oxidase A (MAOA) is involved in the degradation of all three of these neurotransmitters and therefore has been suggested as a strong candidate gene for ADHD. Animal and human studies have implicated MAOA and 5‐HT in impulsive and aggressive behavior. We therefore additionally postulated that MAOA might be associated with a subtype of ADHD where aggressive and impulsive features are especially prominent. We have tested this hypothesis by genotyping two polymorphisms (the 30‐bp VNTR in the promoter and the Fnu4HI 941T→G) in MAOA that are associated with altered MAOA function. Our sample consisted of 171 British Caucasian children 6–16 years of age fulfilling DSM‐III R, DSM‐IV or ICD‐10 criteria for ADHD/Hyperkinetic Disorder. Using case control analysis and then the TDT, no association was found between these two MAOA polymorphisms and ADHD. Case control analysis of the VNTR showed an association with a subgroup of children with comorbid conduct problems (OR = 2.0, 95% CI = 1.09, 3.5), and TDT analysis indicated a statistical trend toward association. Our findings highlight the importance of phenotype definition and the need for the MAOA VNTR to be further examined. © 2003 Wiley‐Liss, Inc.
Polymorphisms of dopamine receptors and tardive dyskinesia among Chinese patients with schizophrenia
Authors: Chong Siow‐Ann , Tan Ene‐Choo , Tan Chay Hoon , Mythily  , Chan Yiong Huak 
Published: December 2002

AbstractThe putative role of dopamine in the pathophysiology of tardive dyskinesia (TD) makes the genes coding for dopamine receptors the appropriate candidates for study. We investigate the association of the polymorphism of the Ser311Cys and Ser9Gly of the dopamine D2 (DRD2) and D3 receptor (DRD3) genes respectively with TD in Chinese patients with schizophrenia. In a case‐control study, 117 Chinese patients with TD were compared to 200 patients without TD. Patients were diagnosed to have schizophrenia according to DSM‐IV criteria. Dyskinesia was assessed by the Abnormal Involuntary Movement Scale (AIMS), whereas extrapyramidal side‐effects (EPSE) were assessed by the Simpson‐Angus Rating Scale. Genotype groups were comparable in age, gender, duration of illness, daily neuroleptic and benzodiazepine dose as well as the mean scores for EPSE. We failed to find an association between the polymorphism of the DRD2 gene with TD but found an increased risk of developing TD among those with D3 serine/serine genotype. Our results did not indicate that the D2 genotype has a role in the pathophysiology of TD in Chinese patients with schizophrenia. The association of TD with the serine/serine genotype of the DRD3 may be an epiphenomenon of patients with a subtype of schizophrenia who had more exposure to neuroleptics. © 2003 Wiley‐Liss, Inc.
Genetic linkage and association between chromosome 1q and working memory function in schizophrenia
Authors: Gasperoni Timothy L. , Ekelund Jesper , Huttunen Matti , Palmer Christina G.S. , Tuulio‐Henriksson Annamari , Lönnqvist Jouko , Kaprio Jaakko , Peltonen Leena , Cannon Tyrone D. 
Published: December 2002

AbstractSchizophrenia is substantially heritable, but specific susceptibility genes remain to be identified. Progress in this endeavor has been hindered by non‐Mendelian transmission patterns, probable genetic heterogeneity, and an inability to detect premorbid and nonpenetrant carriers of predisposing genes. To circumvent these complexities, this study employed quantitative measures of liability, or “endophenotypes,” within a sample of twins discordant for schizophrenia, drawn from the relatively genetically isolated population of Finland. A region on the distal portion of chromosome 1 has shown evidence for linkage to schizophrenia in two prior studies using Finnish patient samples. To elucidate further the nature and location of this potential susceptibility gene, linkage and association analyses were carried out across the chromosome 1 region of interest using quantitative neuropsychological measures of liability. Analyses with a composite measure of liability yielded suggestive evidence for linkage at marker D1S2833 (P = 0.04). Follow‐up analyses of the individual trait measures showed that the Visual Span subtest of the Wechsler Memory Scale (WMS), an indicator of spatial working memory function, was uniquely sensitive to marker D1S2833 (P = 0.007). Association analysis confirmed that allelic variation in D1S2833 is associated with variation in spatial working memory performance as measured by the Visual Span subtest (P = 0.003), the significance of which was confirmed in an analysis of 10,000 Monte Carlo permutations. These data support the utility of this approach and provide evidence for a gene affecting spatial working memory function in schizophrenia patients and their unaffected co‐twins. © 2002 Wiley‐Liss, Inc.
Generalized Cognitive Impairment in Male Adolescents With Schizotypal Personality Disorder
Authors: Weiser M. , Noy S. , Kaplan Z. , Reichenberg A. , Yazvitsky R. , Nahon D. , Grotto Itamar , Knobler H.Y. 
Published: December 2002

AbstractSchizotypal Personality Disorder (SPD) shares common genetic and biological substrates with schizophrenia, and patients with SPD have been reported to suffer both from specific cognitive impairments, and from a generalized cognitive dysfunction, similar to those found in schizophrenia. The aim of this cross‐sectional, population‐based study was to assess general cognitive functioning in adolescents with SPD. The Israeli Draft Board systematically assesses cognitive functioning and administers psychiatric screening in all 16–17‐year‐old males in the population. Of 341,511 males assessed, the cognitive test scores of adolescents with SPD (N = 326) were retrieved, and compared to the scores of adolescents diagnosed as suffering from schizophrenia (N = 901), and adolescents with no neurological or psychiatric diagnosis (controls, N = 293,820). Male adolescents with SPD or with schizophrenia scored lower on all measures compared to healthy individuals (effect sizes ranging from 0.6–0.88, all P < 0.001). The SPD patients scored significantly higher than the schizophrenia patients on the sub‐tests of similarities and Ravens Progressive Matrices, tests that reflect abstract reasoning. On the sub‐tests of arithmetic and instruction comprehension, tests that rely on concentration, SPD and schizophrenia patients' scores did not differ significantly from each other. These results might be interpreted to imply that a generalized cognitive impairment, in the presence of schizotypal personality traits and in the absence of psychosis, might be conceptualized as being the core of the schizotaxia syndrome. The greater impairment in abstract reasoning in the schizophrenia patients might be correlated with the psychotic symptoms that differentiate schizophrenia from SPD. © 2003 Wiley‐Liss, Inc.
Synthesis and characterization of polyacrylamide‐grafted chitosan hydrogel microspheres for the controlled release of indomethacin
Authors: Kumbar Sangamesh G. , Soppimath Kumaresh S. , Aminabhavi Tejraj M. 
Published: December 2002

AbstractMicrospheres of polyacrylamide‐grafted‐chitosan crosslinked with glutaraldehyde were prepared and used to encapsulate indomethacin, a nonsteroidal anti‐inflammatory drug. The microspheres were produced by the water/oil emulsion technique and encapsulation of indomethacin was carried out before crosslinking of the matrix. The extent of crosslinking was analyzed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Microspheres were characterized for drug‐entrapment efficiency, particle size, and water transport into the polymeric matrix as well as for drug‐release kinetics. Scanning electron microscopy confirmed the spherical nature and surface morphology of the particles with a mean particle size of 525 μm. Dynamic swelling experiments suggested that, with an increase in crosslinking, the transport mechanism changed from Fickian to non‐Fickian. The release of indomethacin depends upon the crosslinking of the network and also on the amount of drug loading. This was further supported by the calculation of drug‐diffusion coefficients using the initial time approximation. The drug release in all the formulations followed a non‐Fickian trend and the diffusion was relaxation‐controlled. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1525–1536, 2003
Conducting polyaniline nanofiber networks prepared by the doping induction of camphor sulfonic acid
Authors: He Chang , Tan Yiwei , Li Yongfang 
Published: December 2002

AbstractBranched nanofibers of conducting polyaniline (PANI) buried in the crystals of camphor sulfonic acid (CSA) were prepared from an m‐cresol solution of PANI and excessive CSA. After the excessive CSA was dissolved through ultrasonication in deionized water, networks of PANI nanofibers with spherical nodes, nanoparticles, leaf‐vein‐shaped nanofibers, and so forth were obtained according to the strength of the ultrasonic treatment. The X‐ray diffraction patterns of the CSA‐doped PANI showed high crystallinity. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 1537–1540, 2003
Flow cytometric‐based isolation of nucleated erythroid cells during maturation: An approach to cell surface antigen studies
Authors: Fornas Oscar , Domingo Joan Carles , Marin Pedro , Petriz Jordi 
Published: December 2002

AbstractNucleated red blood cells (NRBCs) are involved in normal physiologic processes, as well as in several malignancies. They are usually counted manually under the microscope. However, blood sample manipulation may be a source of variability and manual counting is imprecise, time‐consuming, and subjective. To improve identification of CD45‐negative cells, we used a flow cytometry technique that avoids the addition of lysing reagents and stains viable cell nuclei. We applied this method for counting and isolating NRBC subpopulations in whole blood samples, using DNA/RNA viable staining to discriminate nonnucleated erythroid cells and debris. NRBC counts gave 197.95 cells per mm3 in mobilized peripheral blood samples (1.00%, n = 20), 3,897.59 cells per mm3 in leukapheresis products (3.08%, n = 20), and 765.21 cells per mm3 in cord blood samples (6.09%, n = 20). Normal bone marrow counts were 5,449.42 cells per mm3 (11.76%, n = 20). Scatter profiles showed three distinct populations, from early to late‐stage erythroblasts, consisting of erythroblasts, orthochromatic erythroblasts, and ejected nuclei, as confirmed by Wright‐Giemsa staining. In addition, flow cytometry immunophenotyping showed that glycophorin A was expressed dimly on NRBCs during maturation. These findings point to the feasibility of live NRBCs studies, which offer great potential for a wide range of disciplines. Cytometry (Clin. Cytometry) 50:305–312, 2002. © 2002 Wiley‐Liss, Inc.
9‐Aminoacridine: An efficient reagent to improve human and plant chromosome banding patterns and to standardize chromosome image analysis
Authors: Muravenko Olga V. , Amosova Alexandra V. , Samatadze Tatiana E. , Popov Konstantin V. , Poletaev Andrei I. , Zelenin Alexander V. 
Published: December 2002

AbstractBackgroundSuccessful automated chromosome analysis requires the development of new techniques to increase and standardize chromosome length and improve banding patterns.MethodsHuman and plant cells were pretreated with the DNA intercalator 9‐aminoacridine (9‐AMA), and chromosomes were stained with GTG and aceto‐orcein banding techniques and investigated by an image analysis system.ResultsThe human optimal chromosome spreads with the 850 G‐band resolution level, suitable for image analysis, were obtained by 9‐AMA pretreatment for 1 h at a final concentration of 0.5–1 μg/ml, as compared with 600–700 bands after ethidium bromide treatment and about 400 bands without pretreatment. The best results for plant chromosomes were obtained after pretreatment with 1–2 μg/ml of 9‐AMA for 12–24 h. The chromosomes elongated approximately 1.5‐fold, and the resolution of chromosome banding patterns increased, reaching approximately 140 bands per haploid set in the case of camomile.Conclusions9‐AMA is an efficient reagent for the standardization and increasing the resolution of chromosome banding patterns in human and plant chromosomes. It is extremely important for chromosome investigation in small plants. Cytometry Part A 51A:52–57, 2003. © 2002 Wiley‐Liss, Inc.
Acute toxicity of all‐trans‐retinoic acid loaded poly(L‐lactide)/poly(ethylene glycol)‐poly(L‐lactide) microspheres in mice
Authors: Choi Yongdoo , Lee Chulkyu , Kim Sang Yoon , Kim Sun Hee , Moon Hyun Tae , Park Tae Gwan , Byun Youngro 
Published: December 2002

AbstractPreviously, poly(L‐lactide) microspheres containing retinoic acid (RA) had been prepared for parenteral administration in order to overcome “acute retinoic acid resistance.” In this study, acute toxicities of RA‐loaded microspheres were investigated in mice after the microspheres were injected intramuscularly. The maximum dose of RA in the microspheres was determined by considering both the injection volume and dispersion of microspheres in the vehicle media, and the dose levels were determined to be 0, 90, 180, and 360 mg RA/kg. Mice were carefully observed for any clinical signs for 14 days, and gross observation of the organs was performed at 14 days. When a dose of 90 mg RA/kg was administered, no severe toxicities were observed; however, with the administration of 180 and 360 mg RA/kg, abnormal appearances of organs, such as discolor, atrophy, hemorrhage, etc., were observed. There were no mortalities or bone fractures observed at any of the doses. In our previous study of cancer treatment using the RA‐loaded microspheres, the growth of head and neck carcinoma in athymic nude mice was successfully inhibited at the dose of 100 mg RA/kg. It was concluded that a dose of approximately 90 mg RA/kg of the RA‐loaded microspheres would be most desirable for cancer therapy. Drug Dev. Res. 57:134–139, 2002. © 2002 Wiley‐Liss, Inc.
Changing the environment in eating disorders: working with carers/families to improve motivation and facilitate change
Authors: Treasure Janet , Gavan Kay , Todd Gill , Schmidt Ulrike 
Published: December 2002

AbstractThe aim of this paper is to consider the needs of carers of people with adult anorexia nervosa both from a theoretical and practical basis. Families have been successfully involved in the management of adolescent anorexia nervosa but it is uncertain how best to work with the families of people who have a more chronic course of illness. The management of severe, persistent, eating disorders has benefited from the application of theory derived from models of health behaviour. These theory‐driven approaches can also be applied to work with carers. We argue that illness perception theory can also have potential utility in understanding the needs and difficulties faced by carers. In this paper we briefly review these theoretical models and consider how they can be applied to carers of people with chronic anorexia nervosa. Finally we discuss how these theory driven approaches can guide the development of interventions for use with carers. Copyright © 2002 John Wiley & Sons, Ltd and Eating Disorders Association.