bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Hepatitis B Virus Polymerase by Entecavir
Authors: Langley David R. , Walsh Ann W. , Baldick Carl J. , Eggers Betsy J. , Rose Ronald E. , Levine Steven M. , Kapur A. Jayne , Colonno Richard J. , Tenney Daniel J. 
Published: February 2007

ABSTRACTEntecavir (ETV; Baraclude) is a novel deoxyguanosine analog with activity against hepatitis B virus (HBV). ETV differs from the other nucleoside/tide reverse transcriptase inhibitors approved for HBV therapy, lamivudine (LVD) and adefovir (ADV), in several ways: ETV is >100-fold more potent against HBV in culture and, at concentrations below 1 μM, displays no significant activity against human immunodeficiency virus (HIV). Additionally, while LVD and ADV are obligate DNA chain terminators, ETV halts HBV DNA elongation after incorporating a few additional bases. Three-dimensional homology models of the catalytic center of the HBV reverse transcriptase (RT)-DNA-deoxynucleoside triphosphate (dNTP) complex, based on the HIV RT-DNA structure, were used with in vitro enzyme kinetic studies to examine the mechanism of action of ETV against HBV RT. A novel hydrophobic pocket in the rear of the RT dNTP binding site that accommodates the exocyclic alkene moiety of ETV was predicted, establishing a basis for the superior potency observed experimentally. HBV DNA chain termination by ETV was accomplished through disfavored energy requirements as well as steric constraints during subsequent nucleotide addition. Validation of the model was accomplished through modeling of LVD resistance substitutions, which caused an eightfold decrease in ETV susceptibility and were predicted to reduce, but not eliminate, the ETV-binding pocket, in agreement with experimental observations. ADV resistance changes did not affect the ETV docking model, also agreeing with experimental results. Overall, these studies explain the potency, mechanism, and cross-resistance profile of ETV against HBV and account for the successful treatment of naive and LVD- or ADV-experienced chronic HBV patients.
CTCF-Dependent Chromatin Boundary Element between the Latency-Associated Transcript and ICP0 Promoters in the Herpes Simplex Virus Type 1 Genome
Authors: Chen Qi , Lin Lan , Smith Sheryl , Huang Jing , Berger Shelley L. , Zhou Jumin 
Published: February 2007

ABSTRACT

Cells latently infected with herpes simplex virus (HSV) contain nucleosomal DNA similar to that of host cell chromatin. Recent studies have demonstrated that histones in the latency-associated transcript (LAT) promoter and intron regions contain histone modifications permissive for transcription. However, those histones associated with the lytic-specific
ICP0
gene, which lies only 5 kb away, contain modifications typical of silenced chromatin. How this active chromatin is kept separate from the repressed chromatin in the nearby
ICP0
region remains crucial to the understanding of the HSV lytic cycle. In this study, we show that the LAT intron region contains an insulator. Specifically, we show that an 800-bp region from the LAT intron can block enhancers in both tissue culture cells and
Drosophila melanogaster
embryos. Importantly, the 800-bp HSV insulator protects a LAT transgene from positional effects in
Drosophila
eye tissue. The 800-bp region contains nine copies of 16-bp repeats. In vitro electrophoretic mobility shift assay revealed that CTCF interacts with the CTCCC sequence within the repeats. In vivo chromatin immunoprecipitation assay demonstrated that CTCF interacts with these repeats in latently infected trigeminal ganglion neurons. The deletion of these repeats impaired insulator activity in human K562 cells and
Drosophila
embryos. Finally, double-spaced RNA knockdown of CTCF disrupts enhancer-blocking activity of the LAT insulator in transfected
Drosophila
S3 cells. These results strongly support the hypothesis that the 800-bp DNA in the LAT intron region works as a chromatin boundary during latency to separate active chromatin associated with the LAT promoter region from repressed chromatin in the ICP0 gene.
A Mutation in Alpha Helix 3 of CA Renders Human Immunodeficiency Virus Type 1 Cyclosporin A Resistant and Dependent: Rescue by a Second-Site Substitution in a Distal Region of CA
Authors: Yang Ruifeng , Aiken Christopher 
Published: February 2007

ABSTRACT
The replication of many isolates of human immunodeficiency virus type 1 (HIV-1) is enhanced by binding of the host cell protein cyclophilin A (CypA) to the viral capsid protein (CA). The immunosuppressive drug cyclosporine A (CsA) and its nonimmunosuppressive analogs bind with high affinity to CypA and inhibit HIV-1 replication. Previous studies have identified two mutations, A92E and G94D, in the CypA-binding loop of CA that confer the ability of HIV-1 to replicate in the presence of CsA. Interestingly, CsA stimulates the replication of HIV-1 mutants containing either the A92E or G94D substitution in some human cell lines. Here, we show that substitution of alanine for threonine at position 54 of CA (T54A) also confers HIV-1 resistance to and dependence on CsA. Like the previously identified CsA-resistant/dependent mutants, infection by the T54A mutant was stimulated by CsA in a target cell-specific manner. RNA interference-mediated reduction of CypA expression enhanced the permissiveness of HeLa cells to infection by the T54A mutant. A suppressor mutation, encoding a substitution of threonine for alanine at position 105 of CA (A105T), was identified through adaptation of the T54A mutant virus for growth in CEM cells. A105T rescued the impaired single-cycle infectivity and replication defects of both T54A and A92E mutants. These results indicate that CA determinants outside the CypA-binding loop can modulate the dependence of HIV-1 infection on CypA.
Cubital tunnel syndrome
Authors: Cutts Steven 
Published: February 2007

Abstract
Cubital tunnel syndrome is the second most common peripheral nerve entrapment syndrome in the human body. It is the cause of considerable pain and disability for patients. When appropriately diagnosed, this condition may be treated by both conservative and operative means. In this review, the current thinking on this important and common condition is discussed The recent literature on cubital tunnel syndrome was reviewed, and key papers on upper limb and hand surgery were discussed with colleagues.
The rGel/BLyS fusion toxin specifically targets malignant B cells expressing the BLyS receptors BAFF-R, TACI, and BCMA
Authors: Lyu Mi-Ae , Cheung Lawrence H. , Hittelman Walter N. , Marks John W. , Aguiar Ricardo C.T. , Rosenblum Michael G. 
Published: February 2007

Abstract
B lymphocyte stimulator (BLyS) is crucial for B-cell survival, and the biological effects of BLyS are mediated by three cell surface receptors designated B cell–activating factor receptor (BAFF-R), transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B-cell maturation antibody (BCMA). Increased expression of BLyS and its receptors has been identified in numerous B-cell malignancies. We generated a fusion toxin designated rGel/BLyS for receptor-mediated delivery of the recombinant gelonin (rGel) toxin to neoplastic B cells, and we characterized its activity against various B-cell tumor lines. Three mantle cell lymphoma (MCL) cell lines (JeKo-1, Mino, and SP53) and two diffuse large B-cell lymphoma (DLBCL) cell lines (SUDHL-6 and OCI-Ly3) expressing all three distinct BLyS receptors were found to be the most sensitive to the fusion toxin (IC50 = 2–5 pmol/L and 0.001–5 nmol/L for MCL and DLBCL, respectively). The rGel/BLyS fusion toxin showed specific binding to cells expressing BLyS receptors and rapid internalization of the rGel component into target cells. The cytotoxic effects of rGel/BLyS were inhibited by pretreatment with free BLyS or with soluble BAFF-R, TACI, and BCMA decoy receptors. This suggests that the cytotoxic effects of the fusion toxin are mediated through BLyS receptors. The rGel/BLyS fusion toxin inhibited MCL cell growth through induction of apoptosis associated with caspase-3 activation and poly (ADP-ribose) polymerase cleavage. Our results suggest that BLyS has the potential to serve as an excellent targeting ligand for the specific delivery of cytotoxic molecules to neoplastic B cells expressing the BLyS receptors, and that the rGel/BLyS fusion toxin may be an excellent candidate for the treatment of B-cell malignancies especially MCL and DLBCL. [Mol Cancer Ther 2007;6(2):460–70]
Autonomous Underwater Vehicle Measurements of Surface Wave Decay and Directional Spectra in the Marginal Sea Ice Zone*
Authors: Hayes Daniel R. , Jenkins Adrian , McPhail Stephen 
Published: February 2007

AbstractIn March 2003 several autonomous underwater vehicle (AUV) missions were carried out under sea ice in the western Bellingshausen Sea. Data from the upward-looking acoustic Doppler current profiler (ADCP) on the “Autosub” AUV indicate a strongly oscillating horizontal velocity of the ice due to ocean swell. Swell period, height, direction, and directional spread have been computed every 800 m from the ice edge to 10 km inward for three missions. Exponential, period-dependent attenuation of waves propagating through sea ice was observed. Mean period increased with distance from the ice edge. The wave field refracted during propagation. The directional wave spread does not seem to relate to distance from the ice edge, although higher frequencies tended to be more spread. If suitably deployed, an ordinary ADCP may be used with this technique to study both scalar and directional properties of waves in open or ice-covered water.
An Exchange Window for the Injection of Antarctic Intermediate Water into the South Pacific
Authors: Iudicone Daniele , Rodgers Keith B. , Schopp Richard , Madec Gurvan 
Published: February 2007

Abstract
Antarctic Intermediate Water (AAIW) occupies the intermediate horizon of most of the world oceans. Formed in the Southern Ocean, it is characterized by a relative salinity minimum. With a new, denser in situ National Oceanographic Data Center dataset, the authors have reanalyzed the export characteristics of AAIW from the Southern Ocean into the South Pacific Ocean. These new data show that part of the AAIW is exported from the subpolar frontal region by the large-scale circulation through an exchange window of 10° width situated east of 90°W in the southeast corner of the Pacific basin. This suggests the origin of this water to be in the Antarctic Circumpolar Current. A set of numerical modeling experiments has been used to reproduce these observed features and to demonstrate that the dynamics of the exchange window is controlled by the basin-scale meridional pressure gradient. The exchange of AAIW between the Southern and Pacific Oceans must therefore be understood in the context of the large basin-scale dynamical balance rather than simply local effects.
Outcome of Conservative Management of Athletic Chronic Groin Injury Diagnosed as Pubic Bone Stress Injury
Authors: Verrall Geoffrey M. , Slavotinek John P. , Fon Gerald T. , Barnes Peter G. 
Published: February 2007

Background Little data exist on the results of treatment for sports-related chronic groin injury. Hypothesis Sports-related chronic groin injury treated with a conservative (rest) program results in a satisfactory outcome. Study Design Case series; Level of evidence, 4. Methods Professional Australian male football players, at the end of the playing season, had their groin injury diagnosed using specific clinical and magnetic resonance imaging (MRI) criteria. Those assessed as having a non-hip-related cause for their chronic groin injury were treated principally by 12 weeks of complete rest from active weightbearing activities. Response to treatment was assessed at different stages of rehabilitation by recording the number of athletes who had returned to playing football and the number of athletes without symptoms. Results Twenty-seven athletes were considered to have chronic groin injury. Clinical and MRI (pubic bone marrow edema N = 26 [96%]), hyperintense line N = 25 [93%]) criteria suggested a pubic bone stress injury as diagnosis for the chronic groin injury. Eighty-nine percent of athletes returned to sport in the subsequent playing season, with 100% having returned by the second playing season after diagnosis. Forty-one percent of the athletes were without symptoms at the commencement of the following playing season, rising to 67% by the end of that playing season. Conclusions Conservative management of athletic chronic groin injury resulted in an excellent outcome when assessed by the return to sport criterion. However, the results were only satisfactory if the criterion of ongoing symptoms after treatment was used. More research is needed to compare the efficacy of all treatments that are used in this troublesome condition.
Arthroscopic Repair of Type II Superior Labral Anterior Posterior Lesions with and without Acromioplasty
Authors: Coleman Struan H. , Cohen David B. , Drakos Mark C. , Allen Answorth A. , Williams Riley J. , O'Brien Stephen J. , Altchek David W. , Warren Russell F. 
Published: February 2007

Background The treatment of type II superior labral anterior posterior (SLAP) lesions remains controversial. Many surgeons are reluctant to combine a SLAP repair with an acromioplasty for fear of postoperative shoulder stiffness and a poor clinical outcome. Hypothesis A SLAP repair and an acromioplasty done concomitantly may yield acceptable outcomes. Study Design Case series; Level of evidence, 4. Methods We compared the clinical results of 50 patients who had either an isolated type II SLAP repair (SLAP group, 34 patients) or a combined type II SLAP repair and acromioplasty (combined group, 16 patients). Patients were excluded for full-thickness rotator cuff tears or instability. All patients were evaluated with the L'Insalata Functional Shoulder Rating Questionnaire, with the American Shoulder and Elbow Surgeons (ASES) questionnaire, and by subjective evaluation. Results At an average of 3.4 years postoperatively, the L'Insalata and ASES scores were similar for the 2 groups: 87.1 and 85.8 for the SLAP group and 85.1 and 86.5 for the combined group, respectively (P > .05). Subjectively, only 65% of the patients in the SLAP group reported a “good” or “excellent” satisfaction with the surgery, compared with an 81% “good” or “excellent” satisfaction rating among the patients in the combined group. Seven patients (21%) in the SLAP group had postoperative clinical impingement, compared with no patients (0%) in the combined group (P < .03). Conclusions According to our data, these 2 procedures done concomitantly may yield acceptable outcomes. Our findings indicated that a combined type II SLAP repair and acromioplasty had no negative effect clinically and, furthermore, appeared to prevent residual clinical impingement.
Interobserver Agreement in the Classification of Rotator Cuff Tears
Authors:   Multicenter Orthopaedic Outcomes Network-Shoulder (MOON Shoulder Group), Kuhn John E. , Dunn Warren R. , Ma Benjamin , Wright Rick W. , Jones Grant , Spencer Edwin E. , Wolf Brian , Safran Marc , Spindler Kurt P. , McCarty Eric , Kelly Brian , Holloway Brian 
Published: February 2007

Background Six classification systems have been proposed for describing rotator cuff tears designed to help understand their natural history and make treatment decisions. Purpose To assess the interobserver variation for these classification systems and identify the method with the best interob-server agreement. Study Design Cohort study (diagnosis); Level of evidence, 2. Methods Six rotator cuff tear classification systems were identified in a literature search. The components of these systems included partial-thickness rotator cuff tears and classification by size, shape, configuration, number of tendons involved, and by extent, topography, and nature of the biceps. Twelve fellowship-trained orthopaedic surgeons who each perform at least 30 rotator cuff repairs per year reviewed arthroscopy videos from 30 patients with a random assortment of rotator cuff tears and classified them by the 6 classification systems. Interobserver variation was determined by a kappa analysis. Results Interobserver agreement was high when distinguishing between full-thickness and partial-thickness tears (0.95, [UNKNOWN]=0.85). The investigators agreed on the side (articular vs bursal) of involvement for partial-thickness tears (observed agreement 0.92, [UNKNOWN]= 0.85) but could not agree when classifying the depth of the partial-thickness tear (observed agreement 0.49, [UNKNOWN]= 0.19). The best agreement for full-thickness tears was seen when the tear was classified by topography (degree of retraction) in the frontal plane (observed agreement 0.70, [UNKNOWN]= 0.54). Conclusion With the exception of distinguishing partial-thickness from full-thickness rotator cuff tears and identifying the side (articular vs bursal) of involvement with partial-thickness tears, currently described rotator cuff classification systems have little interobserver agreement among experienced shoulder surgeons. Researchers should consider describing full-thickness rotator cuff tears by topography (degree of retraction) in the frontal plane.
Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFα-dependent and Fc-receptor–independent way
Authors: Jarius Sven , Eichhorn Peter , Albert Michael H. , Wagenpfeil Stefan , Wick Manfred , Belohradsky Bernd H. , Hohlfeld Reinhard , Jenne Dieter E. , Voltz Raymond 
Published: February 2007

AbstractIntravenous immunoglobulin (IVIg) preparations are increasingly used for therapy of several neuroimmunologic diseases. IVIg therapy is considered safe, although serious side effects like aseptic meningitis, cerebral vasospasm, or ischemic encephalopathy have been reported. These side effects are frequently associated with neutrophilic pleocytosis in the cerebrospinal fluid (CSF), suggesting a neutrophil-mediated mechanism. To elucidate the potential role of neutrophil activation, we analyzed IVIg preparations from 5 different commercial sources for the presence of antineutrophil cytoplasmic antibody (ANCA)–like immunoglobulins against ethanol-fixed peripheral-blood neutrophils, purified human antigens, and a panel of human and nonhuman tissues. All IVIg batches tested (n = 13) contained atypical ANCAs (IgG titer up to 1:2048, IgA up to 1:512). Moreover, all preparations were capable of inducing hydrogen peroxide production in TNFα-primed human neutrophils, with a significant correlation (P < .005) between atypical ANCA titers in IVIg preparations and neutrophil activation. Fc-mediated binding and activation was ruled out by the use of IVIg-F(ab′)2 fragments. Our findings strongly suggest that in vivo activation of TNFα-primed neutrophils by atypical ANCAs of IVIg may contribute to the side effects of IVIg therapy and for the first time demonstrate that the activation of neutrophil granulocytes by IVIg occurs in an Fc receptor (FcR)–independent, hence antigen-dependent, way.
Mapping helper T-cell epitopes on platelet membrane glycoprotein IIIa in chronic autoimmune thrombocytopenic purpura
Authors: Sukati Hosea , Watson Henry G. , Urbaniak Stanislaw J. , Barker Robert N. 
Published: February 2007

Abstract
Chronic autoimmune thrombocytopenic purpura (AITP) is associated with autoantibodies specific for platelet membrane components, often including glycoprotein GPIIIa. T helper (Th) cells reactive with GPIIIa, which are capable of driving the autoantibody response, are activated in AITP, and the aim here was to map the epitopes that they recognize. Peripheral blood mononuclear cells (PBMCs) were obtained from 31 patients with AITP and 30 control donors and stimulated with a panel of 86 overlapping synthetic 15-mer peptides spanning the complete sequence of GPIIIa. One or more peptides elicited recall proliferation by PBMCs from 28 of the patients, and, typically, multiple sequences were stimulatory. In contrast, responses in healthy control donors were rare (chi-square test = 115.967; P ≤ .001). It was confirmed that the proliferating PBMCs from patients were cells of the CD3+CD4+ helper phenotype that were MHC class II restricted. Despite variation between different cases of AITP, particular sequences were commonly recognized with PBMCs from 24 patients (77%) responding to 1 or more of the 4 most dominant peptides. Mapping such dominant autoreactive helper epitopes is the first step in the development of new approaches to the treatment of AITP, based on the use of peptides to tolerize Th cells specific for platelet glycoproteins.
Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511
Authors: Wetzler Meir , Sanford Ben L. , Kurtzberg Joanne , DeOliveira Divino , Frankel Stanley R. , Powell Bayard L. , Kolitz Jonathan E. , Bloomfield Clara D. , Larson Richard A. 
Published: February 2007

Abstract
CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.
Statins synergistically potentiate 7-hydroxystaurosporine (UCN-01) lethality in human leukemia and myeloma cells by disrupting Ras farnesylation and activation
Authors: Dai Yun , Khanna Payal , Chen Shuang , Pei Xin-Yan , Dent Paul , Grant Steven 
Published: February 2007

AbstractInteractions between UCN-01 and HMG-CoA reductase inhibitors (ie, statins) have been examined in human leukemia and myeloma cells. Exposure of U937 and U266 cells to minimally toxic concentrations of UCN-01 and various statins (eg, lovastatin, simvastatin, or fluvastatin) dramatically increased mitochondrial dysfunction, caspase activation, and apoptosis. Comparable effects were observed in other leukemia and myeloma cell lines as well as in primary acute myeloid leukemia (AML) blasts but not in normal hematopoietic cells. Potentiation of UCN-01 lethality by lovastatin was associated with disruption of Ras prenylation and activation. These events were significantly attenuated by farnesyl pyrophosphate (FPP) but not by geranylgeranyl pyrophosphate (GGPP), implicating perturbations in farnesylation rather than geranylgeranylation in synergistic interactions. Coexposure to statins and UCN-01 resulted in inactivation of ERK1/2 and Akt, accompanied by JNK activation. U266 cells ectopically expressing JNK1-APF, a dominant negative JNK1 mutant, displayed significantly reduced susceptibility to lovastatin/UCN-01–mediated lethality. Moreover, transfection of U266 cells with constitutively activated H-Ras (Q61L) attenuated ERK1/2 inactivation and dramatically diminished the lethality of this regimen. Collectively, these findings indicate that HMG-CoA reductase inhibitors act through a Ras farnesylation-associated mechanism to induce signaling perturbations, particularly prevention of Ras and ERK1/2 activation, in UCN-01–treated cells, resulting in the synergistic induction of cell death.