bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electronically measured adherence to immunosuppressive medications and kidney function after deceased donor kidney transplantation
Authors: Israni Ajay K. , Weng Francis L. , Cen Ye‐Ying , Joffe Marshall , Kamoun Malek , Feldman Harold I. 
Published: October 2010

Israni AK, Weng FL, Cen Y‐Y, Joffe M, Kamoun M, Feldman HI. Electronically measured adherence to immunosuppressive medications and kidney function after deceased donor kidney transplantation.  Clin Transplant 2011: 25: E124–E131. © 2010 John Wiley & Sons A/S.Abstract:  Background: Non‐adherence with immunosuppressive medications can result in allograft rejection and eventually allograft loss.Methods: In a racially diverse population, we utilized microelectronic cap monitors to determine the association of adherence with a single immunosuppressive medication and kidney allograft outcomes post‐transplantation. This prospective cohort study enrolled 243 patients from eight transplant centers to provide adherence and kidney allograft outcomes data. To determine the association of adherence with change in estimated glomerular filtration rate (eGFR), we fit mixed effects models with the outcome being change in eGFR over time. We also fit Cox proportional hazards models to determine the association of adherence with time to persistent 25% and 50% decline in eGFR.Results: The distribution of adherence post‐transplant was as follows: 164 (68%), 49 (20%), and 30 (12%) had >85–100%, 50–85%, and <50% adherence, respectively. Seventy‐nine (33%) and 36 (15%) of the subjects experienced a persistent 25% decline in eGFR or allograft loss and 50% decline in eGFR or allograft loss during follow‐up. Adherence was not associated with acute rejection or 25% decline or 50% decline in eGFR. In the adjusted and unadjusted model, adherence and black race were not associated with change in eGFR over time.Conclusions: Non‐adherence with a single immunosuppressive medication was not associated with kidney allograft outcomes.
Rapidly progressive hepatic alveolar echinococcosis in an ABO‐incompatible renal transplant recipient
Authors: Geyer M. , Wilpert J. , Wiech T. , Theilacker C. , Stubanus M. , Kramer‐Zucker A. , Fischer K.‐G. , Drognitz O. , Frydrychowicz A. , Kern W. , Walz G. , Pisarski P. 
Published: October 2010

M. Geyer, J. Wilpert, T. Wiech, C. Theilacker, M. Stubanus, A. Kramer‐Zucker, K.‐G. Fischer, O. Drognitz, A. Frydrychowicz, W. Kern, G. Walz, P. Pisarski. Rapidly progressive hepatic alveolar echinococcosis in an ABO‐incompatible renal transplant recipient. Transpl Infect Dis 2011: 13: 278–284. All rights reservedAbstract: We report on the case of an ABO‐incompatible renal re‐transplant recipient maintained on an intensified immunosuppressive regimen for recurrent cellular rejection episodes and transplant glomerulopathy who presented with rapidly growing hepatic tumors, radiologically suggestive of hemangiosarcoma. Upon resection and pathological work‐up, the lesions revealed alveolar echinococcosis, a rare but potentially life‐threatening parasitosis. Usually infection with Echinococcus multilocularis remains asymptomatic for extended periods of time and can go unrecognized for years. In the case presented, we observed an atypically rapid growth pattern of E. multilocularis that might have been due to the extent of the immunosuppressive regimen, which included repetitive anti‐CD20 treatments. Retrospectively performed serological studies with enzyme‐linked immunosorbent assays known to provide high sensitivity and specificity for the detection of echinococcosis in the general population, yielded ambiguous results in our immunocompromised host, which could be, in part, explained by B‐cell depletion and its effects on antibody production and indirect actions on cellular immunity. In conclusion, this is the first report to our knowledge of hepatic alveolar echinococcosis in a renal transplant recipient. This case documents an altered clinical course of the parasitosis and the challenge of serological diagnostic tools under an intensified regimen of immunosuppressive agents, including rituximab.
5‐α‐Reductase inhibitors for prostate cancer chemoprevention: an updated Cochrane systematic review
Authors: Wilt Timothy J. , MacDonald Roderick , Hagerty Karen , Schellhammer Paul , Tacklind James , Somerfield Mark R. , Kramer Barnett S. 
Published: October 2010

OBJECTIVE

To estimate the benefits and harms of 5‐α‐reductase inhibitors (5‐α‐RIs) in preventing prostate cancer.

MATERIALS AND METHODS

We searched MEDLINE and the Cochrane Collaboration Library through June 2010 to identify randomized trials.
We included articles if they examined 5‐α‐RI vs control, were ≥1 year in duration and provided clinical outcomes.
Our primary outcome was prostate cancer period‐prevalence ‘for‐cause’.

RESULTS

Eight studies met inclusion criteria but only the Prostate Cancer Prevention Trial and the Reduction by Dutasteride of Prostate Cancer Events were designed to assess the impact of 5‐α‐RIs on prostate cancer period‐prevalence. The mean age of enrolees was 64 years, 92% were White, and mean PSA level was 3.1 ng/mL. For‐cause prostate cancers comprised 54% of all cancers detected in placebo‐controlled studies.
Compared with placebo, 5‐α‐RI resulted in a 25% relative risk (RR) reduction in prostate cancers detected for‐cause [RR 0.75, 95% confidence interval (CI) 0.67–0.83; 1.4% absolute risk reduction (3.5% vs 4.9%)]. One BPH trial reported that the risk of prostate cancers detected for‐cause was significantly reduced with dutasteride and combined dutasteride plus tamsulosin compared with tamsulosin monotherapy.
Six trials vs placebo assessed prostate cancers detected overall. There was a 26% RR reduction favouring 5‐α‐RI [RR 0.74, 95% CI 0.55–1.00; 2.9% absolute risk reduction (6.3% vs 9.2%)]. There were reductions across categories of age, race and family history of prostate cancer.
One placebo‐controlled trial of men that investigators considered at greater risk for prostate cancer (based on age, elevated PSA level and having a previous suspicion of prostate cancer leading to a prostate biopsy) reported that dutasteride did not reduce prostate cancers detected for‐cause based on needle‐biopsy but did reduce risk of overall incident prostate cancer detected by biopsy by 23%[RR 0.77, 95% CI 0.70–0.85; absolute reduction 16.1% vs 20.8%]. There were reductions across age, family history of prostate cancer, PSA level, and prostate volume subgroups.
Incidences of erectile dysfunction, ejaculate volume, decreased libido, and gynaecomastia were greater with 5‐α‐RI vs placebo.

CONCLUSIONS

5‐α‐RIs reduce the risk of being diagnosed with prostate cancer among men who are screened regularly for prostate cancer.
Information is inadequate to assess the effect of 5‐α‐RIs on prostate cancer or all‐cause mortality.
5‐α‐RIs increase sexual and erectile dysfunction.
Pictures in Wittgenstein's Later Philosophy
Authors: Egan David 
Published: October 2010

AbstractThe word “picture” occurs pervasively in Wittgenstein's later philosophy. Not only does Wittgenstein often use literal pictures or the notion of mental pictures in his investigations, but he also frequently uses “picture” to speak about a way of conceiving of a matter (e.g. “A picture held us captive” at Philosophical Investigations§115). I argue that “picture” used in this conceptual sense is not a shorthand for an assumption or a set of propositions but is rather an expression of conceptual bedrock on the model of an organising myth. This reading builds primarily on work by Gordon Baker and Stanley Cavell.
Presence of Host ICAM-1 in Laboratory and Clinical Strains of Human Immunodeficiency Virus Type 1 Increases Virus Infectivity and CD4+-T-Cell Depletion in Human Lymphoid Tissue, a Major Site of Replication In Vivo
Authors: Bounou Salim , Leclerc Jacques E. , Tremblay Michel J. 
Published: October 2010

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) incorporates several host proteins. Earlier studies have indicated that such foreign constituents can modulate the virus life cycle, although the potential roles that these proteins might play in the viral pathology in vivo remain unclear. In an attempt to shed light on this issue, we first exposed explants of human lymphoid tissue to isogenic viruses except for the presence or absence of host-derived ICAM-1. Incorporation of ICAM-1 alone increased HIV-1 infectivity for human tonsillar tissue cultured ex vivo. This observation was made for viruses bearing distinct coreceptor utilization profiles. Conversion of LFA-1 to a high-affinity-high-avidity state for ICAM-1 further augmented the susceptibility of human tonsillar histocultures to infection by ICAM-1-bearing virions. A more massive depletion of CD4+T lymphocytes was seen with X4 ICAM-1/POS viruses than with isogenic ICAM-1/NEG virions. Exposure of X4 and R5 primary isolates of HIV-1 to a blocking anti-ICAM-1 antibody resulted in a decrease of virus infection. Finally, X4 and R5 virions derived from a natural human lymphoid tissue microenvironment incorporated high levels of ICAM-1. Altogether, these results indicate that the incorporation of host ICAM-1 can significantly modulate the biology of HIV-1 in a cellular milieu recognized as the major site of replication in vivo and suggest that host proteins found in HIV-1 particles may participate in the pathogenesis of this disease.
The Late-Domain-Containing Protein p6 Is the Predominant Phosphoprotein of Human Immunodeficiency Virus Type 1 Particles
Authors: Müller Barbara , Patschinsky Tilo , Kräusslich Hans-Georg 
Published: October 2010

ABSTRACT

The Gag-derived protein p6 of human immunodeficiency virus type 1 (HIV-1) plays a crucial role in the release of virions from the membranes of infected cells. It is presumed that p6 and functionally related proteins from other viruses act as adapters, recruiting cellular factors to the budding site. This interaction is mediated by so-called late domains within the viral proteins. Previous studies had suggested that virus release from the plasma membrane shares elements with the cellular endocytosis machinery. Since protein phosphorylation is known to be a regulatory mechanism in these processes, we have investigated the phosphorylation of HIV-1 structural proteins. Here we show that p6 is the major phosphoprotein of HIV-1 particles. After metabolic labeling of infected cells with [
ortho-
32
P]phosphate, we found that phosphorylated p6 from infected cells and from virus particles consisted of several forms, suggesting differential phosphorylation at multiple sites. Apparently, phosphorylation occurred shortly before or after the release of p6 from Gag and involved only a minor fraction of the total virion-associated p6 molecules. Phosphoamino acid analysis indicated phosphorylation at Ser and Thr, as well as a trace of Tyr phosphorylation, supporting the conclusion that multiple phosphorylation events do occur. In vitro experiments using purified virus revealed that endogenous or exogenously added p6 was efficiently phosphorylated by virion-associated cellular kinase(s). Inhibition experiments suggested that a cyclin-dependent kinase or a related kinase, most likely ERK2, was involved in p6 phosphorylation by virion-associated enzymes.
Conserved Region CR2 of Epstein-Barr Virus Nuclear Antigen Leader Protein Is a Multifunctional Domain That Mediates Self-Association as well as Nuclear Localization and Nuclear Matrix Association
Authors: Tanaka Michiko , Yokoyama Akihiko , Igarashi Mie , Matsuda Go , Kato Kentaro , Kanamori Mikiko , Hirai Kanji , Kawaguchi Yasushi , Yamanashi Yuji 
Published: October 2010

ABSTRACT

Self-association of viral proteins is important for many of their functions, including enzymatic, transcriptional, and transformational activities. Epstein-Barr virus (EBV) nuclear antigen leader protein (EBNA-LP) contains various numbers of W1W2 repeats and a unique carboxyl-terminal Y1Y2 domain. It was reported that EBNA-LP associates with a variety of cellular proteins and plays a critical role in EBV-induced transformation. We report here that EBNA-LP self-associates in vivo and the domain responsible for the homotypic association is a multifunctional domain mediating nuclear localization, nuclear matrix association, and EBNA-2-dependent coactivator function of the protein. Our conclusions are based on the following observations. (i) EBNA-LP interacts with itself or its derivatives in the yeast two-hybrid system. (ii) A purified chimeric protein consisting of glutathione
S
-transferase fused to EBNA-LP specifically formed complexes with EBNA-LP transiently expressed in COS-7 cells. (iii) When Flag epitope-tagged EBNA-LP with either one or two W1W2 repeats and EBNA-LP containing four W1W2 repeats were coexpressed in COS-7 cells, the latter was specifically coimmunoprecipitated with the former. (iv) Mutational analyses of EBNA-LP with deletion mutants revealed that the region between codons 19 and 39 (relative to the first amino acid residue of the W2 domain) is essential for self-association of the protein. The mapped region almost completely overlaps with CR2 and CR3, regions conserved among a subset of primate γ-herpesviruses and critical for EBNA-2-dependent coactivator function. Amino acid substitutions in CR2 alone abolished the ability of the protein to self-interact. This laboratory previously reported that CR2 is also responsible for nuclear localization and nuclear matrix association (A. Yokoyama, Y. Kawaguchi, I. Kitabayashi, M. Ohki, and K. Hirai, Virology 279:401–413, 2001). (v) Sucrose gradient sedimentation showed that amino acid substitutions in CR2 reduced the ability of the protein to form protein complexes in B cells. These results suggest that self-association of EBNA-LP may be important for its various functions and interactions of the protein with multiple cellular proteins.
Adeno-Associated Virus Type 2 Rep78 Inhibition of PKA and PRKX: Fine Mapping and Analysis of Mechanism
Authors: Schmidt Michael , Chiorini John A. , Afione Sandra , Kotin Robert 
Published: October 2010

ABSTRACT

Hormones and neurotransmitters utilize cyclic AMP (cAMP) as a second messenger in signal transduction pathways to regulate cell growth and division, differentiation, gene expression, and metabolism. Adeno-associated virus type 2 (AAV-2) nonstructural protein Rep78 inhibits members of the cAMP signal transduction pathway, the protein kinases PKA and PRKX. We mapped the kinase binding and inhibition domain of Rep78 for PRKX to amino acids (aa) 526 to 561 and that for PKA to aa 526 to 621. These polypeptides were as potent as full-length Rep78 in kinase inhibition, which suggests that the kinase-inhibitory domain is entirely contained in these Rep peptides. Steady-state kinetic analysis of Rep78-mediated inhibition of PKA and PRKX showed that Rep78 appears to increase the
K

m

value of the peptide kinase substrate, while the maximal velocity of the reaction was unaffected. This indicates that Rep78 acts as a competitive inhibitor with respect to the peptide kinase substrate. We detected homology between a cellular pseudosubstrate inhibitor of PKA, the protein kinase inhibitor PKI, and the PRKX and PKA inhibition domains of Rep78. Due to this homology and the competitive inhibition mechanism of Rep78, we propose that Rep78 inhibits PKA and PRKX kinase activity by pseudosubstrate inhibition.
Thermostability of Reovirus Disassembly Intermediates (ISVPs) Correlates with Genetic, Biochemical, and Thermodynamic Properties of Major Surface Protein μ1
Authors: Middleton Jason K. , Severson Tonya F. , Chandran Kartik , Gillian Anne Lynn , Yin John , Nibert Max L. 
Published: October 2010

ABSTRACT
Kinetic analyses of infectivity loss during thermal inactivation of reovirus particles revealed substantial differences between virions and infectious subvirion particles (ISVPs), as well as between the ISVPs of reoviruses type 1 Lang (T1L) and type 3 Dearing (T3D). The difference in thermal inactivation of T1L and T3D ISVPs was attributed to the major surface protein μ1 by genetic analyses with reassortant viruses and recoated cores. Irreversible conformational changes in ISVP-bound μ1 were shown to accompany thermal inactivation. The thermal inactivation of ISVPs approximated first-order kinetics over a range of temperatures, permitting the use of Arrhenius plots to estimate activation enthalpies and entropies that account for the different behaviors of T1L and T3D. An effect similar to enthalpy-entropy compensation was additionally noted for the ISVPs of these two isolates. Kinetic analyses with other ISVP-like particles, including ISVPs of a previously reported thermostable mutant, provided further insights into the role of μ1 as a determinant of thermostability. Intact virions, which contain ς3 bound to μ1 as their major surface proteins, exhibited greater thermostability than ISVPs and underwent thermal inactivation with kinetics that deviated from first order, suggesting a role for ς3 in both these properties. The distinct inactivation behaviors of ISVPs are consistent with their role as an essential intermediate in reovirus entry.
Replication of Subgenomic Hepatitis A Virus RNAs Expressing Firefly Luciferase Is Enhanced by Mutations Associated with Adaptation of Virus to Growth in Cultured Cells
Authors: Yi MinKyung , Lemon Stanley M. 
Published: October 2010

ABSTRACT

Replication of hepatitis A virus (HAV) in cultured cells is inefficient and difficult to study due to its protracted and generally noncytopathic cycle. To gain a better understanding of the mechanisms involved, we constructed a subgenomic HAV replicon by replacing most of the P1 capsid-coding sequence from an infectious cDNA copy of the cell culture-adapted HM175/18f virus genome with sequence encoding firefly luciferase. Replication of this RNA in transfected Huh-7 cells (derived from a human hepatocellular carcinoma) led to increased expression of luciferase relative to that in cells transfected with similar RNA transcripts containing a lethal premature termination mutation in 3D
pol
(RNA polymerase). However, replication could not be confirmed in either FrhK4 cells or BSC-1 cells, cells that are typically used for propagation of HAV. Replication was substantially slower than that observed with replicons derived from other picornaviruses, as the basal luciferase activity produced by translation of input RNA did not begin to increase until 24 to 48 h after transfection. Replication of the RNA was reversibly inhibited by guanidine. The inclusion of VP4 sequence downstream of the viral internal ribosomal entry site had no effect on the basal level of luciferase or subsequent increases in luciferase related to its amplification. Thus, in this system this sequence does not contribute to viral translation or replication, as suggested previously. Amplification of the replicon RNA was profoundly enhanced by the inclusion of P2 (but not 5′ noncoding sequence or P3) segment mutations associated with adaptation of wild-type virus to growth in cell culture. These results provide a simple reporter system for monitoring the translation and replication of HAV RNA and show that critical mutations that enhance the growth of virus in cultured cells do so by promoting replication of viral RNA in the absence of encapsidation, packaging, and cellular export of the viral genome.
Binding of Hepatitis C Virus-Like Particles Derived from Infectious Clone H77C to Defined Human Cell Lines
Authors: Wellnitz Sabine , Klumpp Bettina , Barth Heidi , Ito Susumu , Depla Erik , Dubuisson Jean , Blum Hubert E. , Baumert Thomas F. 
Published: October 2010

ABSTRACT
Hepatitis C virus (HCV) is a leading cause of chronic hepatitis in the world. The study of viral entry and infection has been hampered by the inability to efficiently propagate the virus in cultured cells and the lack of a small-animal model. Recent studies have shown that in insect cells, the HCV structural proteins assemble into HCV-like particles (HCV-LPs) with morphological, biophysical, and antigenic properties similar to those of putative virions isolated from HCV-infected humans. In this study, we used HCV-LPs derived from infectious clone H77C as a tool to examine virus-cell interactions. The binding of partially purified particles to human cell lines was analyzed by fluorescence-activated cell sorting with defined monoclonal antibodies to envelope glycoprotein E2. HCV-LPs demonstrated dose-dependent and saturable binding to defined human lymphoma and hepatoma cell lines but not to mouse cell lines. Binding could be inhibited by monoclonal anti-E2 antibodies, indicating that the HCV-LP-cell interaction was mediated by envelope glycoprotein E2. Binding appeared to be CD81 independent and did not correlate with low-density lipoprotein receptor expression. Heat denaturation of HCV-LPs drastically reduced binding, indicating that the interaction of HCV-LPs with target cells was dependent on the proper conformation of the particles. In conclusion, our data demonstrate that insect cell-derived HCV-LPs bind specifically to defined human cell lines. Since the envelope proteins of HCV-LPs are presumably presented in a virion-like conformation, the binding of HCV-LPs to target cells may allow the study of virus-host cell interactions, including the isolation of HCV receptor candidates and antibody-mediated neutralization of binding.
A Gene Capable of Blocking Apoptosis Can Substitute for the Herpes Simplex Virus Type 1 Latency-Associated Transcript Gene and Restore Wild-Type Reactivation Levels
Authors: Perng Guey-Chuen , Maguen Barak , Jin Ling , Mott Kevin R. , Osorio Nelson , Slanina Susan M. , Yukht Ada , Ghiasi Homayon , Nesburn Anthony B. , Inman Melissa , Henderson Gail , Jones Clinton , Wechsler Steven L. 
Published: October 2010

ABSTRACT

After ocular herpes simplex virus type 1 (HSV-1) infection, the virus travels up axons and establishes a lifelong latent infection in neurons of the trigeminal ganglia. LAT (latency-associated transcript), the only known viral gene abundantly transcribed during HSV-1 neuronal latency, is required for high levels of reactivation. The LAT function responsible for this reactivation phenotype is not known. Recently, we showed that LAT can block programmed cell death (apoptosis) in neurons of the trigeminal ganglion in vivo and in tissue culture cells in vitro (G.-C. Perng et al., Science 287:1500–1503, 2000; M. Inman et al., J. Virol. 75:3636–3646, 2001). Consequently, we proposed that this antiapoptosis function may be a key to the mechanism by which LAT enhances reactivation. To study this further, we constructed a recombinant HSV-1 virus in which the HSV-1 LAT gene was replaced by an alternate antiapoptosis gene. We used the bovine herpes virus 1 (BHV-1) latency-related (LR) gene, which was previously shown to have antiapoptosis activity, for this purpose. The resulting chimeric virus, designated CJLAT, contains two complete copies of the BHV-1 LR gene (one in each viral long repeat) in place of the normal two copies of the HSV-1 LAT, on an otherwise wild-type HSV-1 strain McKrae genomic background. We report here that in both rabbits and mice reactivation of CJLAT was significantly greater than the LAT null mutant dLAT2903 (
P
< 0.0004 and
P
= 0.001, respectively) and was at least as efficient as wild-type McKrae. This strongly suggests that a BHV-1 LR gene function was able to efficiently substitute for an HSV-1 LAT gene function involved in reactivation. Although replication of CJLAT in rabbits and mice was similar to that of wild-type McKrae, CJLAT killed more mice during acute infection and caused more corneal scarring in latently infected rabbits. This suggested that the BHV-1 LR gene and the HSV-1 LAT gene are not functionally identical. However, LR and LAT both have antiapoptosis activity. These studies therefore strongly support the hypothesis that replacing LAT with an antiapoptosis gene restores the wild-type reactivation phenotype to a LAT null mutant of HSV-1 McKrae.