bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic promotion of breast cancer cells death by targeting molecular chaperone GRP78 and heat shock protein 70
Authors: Li Minjing , Wang Jiao , Jing Jian , Hua Hui , Luo Ting , Xu Li , Wang Ranran , Liu Dongbo , Jiang Yangfu 
Published: November 2008

AbstractHeat shock protein 70 (HSP70) is frequently overexpressed in a variety of human malignancies and protects cancer cells against apoptosis in response to various stresses. The bioflavonoid quercetin inhibits HSP70 expression and induces cancer cells apoptosis. In the present study, we have investigated the effects of HSP70 down‐regulation on the unfolded protein response (UPR) and addressed a novel strategy to enhance the proapoptotic effect of quercetin by suppressing GRP78 induction simultaneously. Treatment of human breast cancer cells with quercetin down‐regulates HSP70 expression, but up‐regulates GRP78 expression in a dose‐dependent manner. Down‐regulation of HSP70 by small interfering RNA also leads to induction of GRP78. Moreover, our studies reveal that HSP70 knockdown or quercetin induces other typical components of the UPR, including CHOP expression, eIF2α and JNK phosphorylation, caspases activation and XBP‐1 splicing. Abrogating the induction of pro‐survival chaperone GRP78 by small interfering RNA sensitizes breast cancer cells to quercetin. Colony survival assays demonstrate that treatment of breast cancer cells with green tea (−)‐epigallocatechin gallate (EGCG), which binds to the ATP‐binding domain of GRP78 and blocks its protective function, synergistically promoted quercetin‐induced cell death. These studies reveal that HSP70 down‐regulation leads to the induction of UPR. The pro‐survival GRP78 induction contributes to quercetin resistance. Abrogation of GRP78 induction or inhibition of GRP78 activity increases the effectiveness of quercetin. These findings indicate that combinational administration of flavonoids capable of suppressing HSP70 and GRP78 such as quercetin and EGCG might represent a novel approach for cancer therapy or chemoprevention.
Possible application of flow cytometry for evaluation of the structure and functional status of WASP in peripheral blood mononuclear cells
Authors: Nakajima Masaru , Yamada Masafumi , Yamaguchi Koji , Sakiyama Yukio , Oda Atsushi , Nelson David L. , Yawaka Yasutaka , Ariga Tadashi 
Published: November 2008

AbstractThe Wiskott‐Aldrich syndrome protein (WASP), which is defective in Wiskott‐Aldrich syndrome (WAS) patients, is an intracellular protein expressed in non‐erythroid hematopoietic cells. Previously, we have established methods to detect intracellular WASP expression in peripheral blood mononuclear cells (PBMNCs) using flow cytometric analysis (FCM‐WASP) and have revealed that WAS patients showed absent or very low level intracellular WASP expression in lymphocytes and monocytes, while a significant amount of WASP was detected in those of normal individuals. We applied these methods for diagnostic screening of WAS patients and WAS carriers, as well as to the evaluation of mixed chimera in WAS patients who had previously undergone hematopoietic stem cell transplantation. During these procedures, we have noticed that lymphocytes from normal control individuals showed dual positive peaks, while their monocytes invariably showed a single sharp WASP‐positive peak. To investigate the basis of the dual positive peaks (WASPlow‐bright and WASPhigh‐bright), we characterized the constituent linage lymphocytes of these two WASP‐positive populations. As a result, we found each WASPlow/high population comprised different linage PBMNCs. Furthermore, we propose that the difference between the two WASP‐positive peaks did not result from any difference in WASP expression in the cells, but rather from a difference in the structural and functional status of the WASP protein in the cells. It has been shown that WASP may exist in two forms; an activated or inactivated form. Thus, the structural and functional WASP status or configuration could be evaluated by flow cytometric analysis.
Frequency of the major histocompatibility complex Mamu‐A*01 allele in a closed breeding colony of rhesus monkey (Macaca mulatta) from Brazil
Authors: Andrade Márcia Cristina Ribeiro , Leite José Paulo Gagliardi , Cabello Pedro Hernan 
Published: November 2008

AbstractBackground  Rhesus monkeys are relevant models for human diseases. The simian immunodeficiency virus (SIV) infection is an useful macaque model for assessing human immunodeficiency virus (HIV) vaccine strategies. Susceptibility and resistance to viruses have been associated with particular major histocompatibility complex (MHC) molecules. Several epitopes in the HIV structural and non‐structural protein restricted by distinct MHC class I haplotypes are important targets for human cytotoxic T lymphocytes, which mediate protection against SIVmac infection. Mamu‐A*01, for example, is a MHC class I molecule of rhesus monkeys that presents a peptide from SIV gag protein.Methods Our study determined the frequency of Mamu‐A*01 in a closed colony of rhesus monkeys from Brazil by polymerase chain reaction.Results A high frequency of the allele was found in the study colony.Conclusion This colony provides a significant source of A*01‐positive animals to investigators.
ORIGINAL ARTICLE: Pathomorphologic and Immunohistochemical Study on the Devastation of Rat Embryos by Antiphospholipid Antibody Positive Serum
Authors: Halperin Reuvit , Elhayany Asher , Ben‐Hur Herzel , Gurevich Pavel , Kaganovsky Ella , Zusman Itzhak , Shinnar Nili , Hadas Eran 
Published: November 2008

Problem  While relying on previous publications, our aim was to examine the morphologic changes, induced in early rat embryos by intra‐uterine exposure to the low‐molecular weight fraction of boiled human serum containing antiphospholipid antibodies (APLA) that had been obtained from women with antiphospholipid syndrome (APS).Method of study   Human APLA‐positive sera were pooled, boiled, centrifuged and separated by ultrafiltration. The molecular weight fraction lower than 30 kDa was used for the experiments. One hundred and fifty microlitres was injected into one uterine horn of 12 pregnant rats, 5 or 6 days after fertilization, while similarly prepared normal human serum or saline were injected into the contralateral horn. The rats were subsequently sacrificed. Serial sections, obtained from all uterine horns, were stained histologically and immunohistochemically. Normal embryos developed in the control uterine horns, while embryos in the experimental horns were destroyed rapidly.Results  Signs of apoptosis appeared 2 hr following the injection, and 4 hr later all the embryonic cells were apoptotically destroyed. There was only partial damage to cytotrophoblasts and intermediate trophoblasts.Conclusion  These findings support the existence of a novel factor in the APLA‐positive serum, causing a detrimental effect to the conceptus, without any relation to the antiphospholipid antibodies.
ORIGINAL ARTICLE: Localization of Toll‐Like Receptors on Epididymal Epithelial Cells and Spermatozoa
Authors: Palladino Michael A. , Savarese Michael A , Chapman Jessica L. , Dughi Mary‐Katherine , Plaska Daniel 
Published: November 2008

Problem  Toll‐like receptors (TLRs) are a family of innate immunity receptors that are essential for detecting invading pathogens. Objectives of this study were to identify epididymal cell types expressing TLRs and to determine if TLRs are present on spermatozoa.Method of study  Immunohistochemical analysis of paraffin‐embedded sections from regions of the rat epididymis was used to identify epididymal cell types expressing TLRs. Immunoblot analysis and immunofluorescence were used to detect TLRs on spermatozoa.Results  TLRs 1–9 and 11 are abundantly expressed by the epididymal epithelium in most regions of the duct with the exception of clear cells of the cauda which do not express TLRs 5–7 or 11. TLRs were detected on epididymal spermatozoa and several TLRs showed regional distributions patterns suggesting modification during epididymal transit.Conclusion  The abundance of TLR family members in the epididymal epithelium and on spermatozoa provides strong evidence that TLRs play important roles in innate immunity of the male reproductive tract.
U.S. Hegemony, China, and the U.S. Current Account Deficit
Authors: Davis Carmel 
Published: November 2008

The U.S. runs a large current account deficit, much of which is with China. I argue that this is the action of a liberal hegemon supporting and integrating a potential challenger and so preserving its hegemony. The U.S. current account deficit supports China in two ways. First, it increases demand for Chinese exports. The Chinese economy has grown faster than it would have if the U.S. had not had a current account deficit with China. Second, and more speculatively, this accelerated U.S. demand for Chinese exports has helped China integrate its large population of un‐ and underemployed labor and so reduced political instability in the context of rapid economic growth. It has benefited U.S. hegemony in two political ways. First, it has accelerated the rate at which China has integrated into the U.S.‐led liberal trading order created in the mid‐1940s and so enhances U.S. hegemony: China is the plausible peer competitor whose economic size might allow it to challenge the existing liberal trading order or even challenge the U.S. militarily; increasing integration makes it much more costly for China to challenge the U.S. and the liberal trading order. The cost for China to challenge the order reduces U.S. costs to preserve its position as hegemon and the congenial environment it created for itself in the second‐half of the twentieth century. Second, and more speculatively, a China that is domestically tranquil poses less of a threat to its neighbors and so further reduces U.S. costs to preserve its position.I first discuss the U.S. as a liberal hegemon. I then consider China and its economic and political challenges. I conclude by discussing how China benefits from the U.S. acting as a hegemon and how U.S. hegemony preserves itself by addressing these Chinese issues.
Simple Tests for Rapid Detection of Canine Parvovirus Antigen and Canine Parvovirus-Specific Antibodies
Authors: Marulappa Shashidhara Y. , Kapil Sanjay 
Published: November 2008

ABSTRACT
Canine parvovirus (CPV) is the number one viral cause of enteritis, morbidity, and mortality in 8-week-old young puppies. We have developed twin assays (slide agglutination test [SAT] for CPV antigen and slide inhibition test [SIT] for CPV antibody) that are sensitive, specific, cost-effective, generic for all genotypes of CPV, and provide instant results for CPV antigen detection in feces and antibody quantification in serum. We found these assays to be useful for routine applications in kennels with large numbers of puppies at risk. The results of these assays are available in 1 min and do not require any special instrumentation. SAT-SIT technology will find applications in rapid screening of samples for other hemagglutinating emerging viruses of animals and humans (influenza virus and severe acute respiratory syndrome coronavirus).
Evaluation of the Vitros ECiQ Immunodiagnostic System for Detection of Anti-
Toxoplasma
Immunoglobulin G and Immunoglobulin M Antibodies for Confirmatory Testing for Acute
Toxoplasma gondii
Infection in Pregnant Women
Authors: Kasper David C. , Prusa Andrea R. , Hayde Michael , Gerstl Nicole , Pollak Arnold , Herkner Kurt R. , Reiter-Reisacher Rosmarie 
Published: November 2008

ABSTRACT

Infection with
Toxoplasma gondii
is often asymptomatic and, when acquired during pregnancy, may lead to connatal toxoplasmosis in the offspring. The newly introduced Vitros anti-
Toxoplasma
immunoglobulin G (IgG) and IgM assays, designed for the Vitros ECiQ immunodiagnostic system, a fully automated system based on chemiluminescence, were evaluated as a screening method for the serological detection of acute and chronic
Toxoplasma
infections in the sera of 719 pregnant women. The combination of the Vitros IgG and IgM assays demonstrated a sensitivity and a specificity of 100% for the successful detection of all acute
T. gondii
infections by comparison with the Sabin-Feldman dye test as the reference test. The Vitros IgG assay parameter revealed a sensitivity of 95.0%, a specificity of 100.0%, a positive predictive value of 100.0%, a negative predictive value of 86.2%, and an overall agreement of 96.2% by comparison with the dye test. Comparison of the Vitros
Toxoplasma
IgM assay with the immunosorbent agglutination assay yielded values of 77.1%, 99.0%, 97.7%, 88.5%, and 91.1%, respectively. Subsequent receiver operating characteristic curve analysis for the accurate detection of
Toxoplasma
IgM in acute (
n
= 90) and chronic (
n
= 461) infections demonstrated high sensitivity (92.2%) and specificity (81.6%). The combination of a
Toxoplasma
-specific IgG assay with specific IgM antibody detection has improved the diagnosis of
T. gondii
infection by decreasing follow-up testing. Nonetheless, positive
Toxoplasma
IgM test results during pregnancy necessitate confirmatory testing by a reference laboratory to ensure fast and, above all, accurate test results.
Stepwise Diagnosis of
Trichomonas vaginalis
Infection in Adolescent Women
Authors: Pattullo Lucia , Griffeth Sarah , Ding Lili , Mortensen Joel , Reed Jennifer , Kahn Jessica , Huppert Jill 
Published: November 2008

ABSTRACT

The objective of this study was to examine the effects of clinical factors and of the type and timing of a secondary test in improving the sensitivity of
Trichomonas vaginalis
detection in young women over that of a wet mount alone. For this purpose, sexually active adolescent women (
n
= 345) were recruited from a hospital teen clinic or emergency department. Following an interview and a pelvic exam, four primary
T. vaginalis
tests (wet mount, culture, a rapid test, and a nucleic acid amplification test [NAAT]) were performed on vaginal swabs. If the wet-mount result was negative, two secondary tests (culture and a rapid test) were performed on the used wet-mount swab and saline. A positive result by any of the four primary tests was considered a true
T. vaginalis
-positive result. The prevalence of
T. vaginalis
was 18.8% overall and 8.8% in the 307 wet-mount-negative women. There was 100% concordance between primary and secondary rapid tests. Secondary culture was 80% sensitive compared to primary culture. The likelihood of a positive rapid test increased with increasing time between specimen collection and testing. A wet mount followed by a rapid test was the most sensitive strategy using two tests (86.4%; confidence interval [CI], 75.3 to 93.4%). Limiting secondary testing to those with multiple partners resulted in a lower sensitivity (73.9%; CI, 61.5 to 84%) that was not significantly better than that of the wet mount alone (58.5%; CI, 45.6 to 70.6%). We conclude that a rapid test can be delayed or performed on a used swab with no loss of sensitivity. Until a NAAT for
T. vaginalis
is commercially available, a stepwise approach using an additional rapid test for wet-mount-negative women is recommended for adolescent women regardless of clinical factors.
Modulation of Macrophage Infiltration and Inflammatory Activity by the Phosphatase SHP-1 in Virus-Induced Demyelinating Disease
Authors: Christophi George P. , Hudson Chad A. , Panos Michael , Gruber Ross C. , Massa Paul T. 
Published: November 2008

ABSTRACTThe protein tyrosine phosphatase SHP-1 is a crucial negative regulator of cytokine signaling and inflammatory gene expression, both in the immune system and in the central nervous system (CNS). Mice genetically lacking SHP-1 (me/me) display severe inflammatory demyelinating disease following inoculation with the Theiler's murine encephalomyelitis virus (TMEV) compared to infected wild-type mice. Therefore, it became essential to investigate the mechanisms of TMEV-induced inflammation in the CNS of SHP-1-deficient mice. Herein, we show that the expression of several genes relevant to inflammatory demyelination in the CNS of infectedme/memice is elevated compared to that in wild-type mice. Furthermore, SHP-1 deficiency led to an abundant and exclusive increase in the infiltration of high-level-CD45-expressing (CD45hi) CD11b+Ly-6Chimacrophages into the CNS ofme/memice, in concert with the development of paralysis. Histological analyses of spinal cords revealed the localization of these macrophages to extensive inflammatory demyelinating lesions in infected SHP-1-deficient mice. Sorted populations of CNS-infiltrating macrophages from infectedme/memice showed increased amounts of viral RNA and an enhanced inflammatory profile compared to wild-type macrophages. Importantly, the application of clodronate liposomes effectively depleted splenic and CNS-infiltrating macrophages and significantly delayed the onset of TMEV-induced paralysis. Furthermore, macrophage depletion resulted in lower viral loads and lower levels of inflammatory gene expression and demyelination in the spinal cords ofme/memice. Finally,me/memacrophages were more responsive than wild-type macrophages to chemoattractive stimuli secreted byme/meglial cells, indicating a mechanism for the increased numbers of infiltrating macrophages seen in the CNS ofme/memice. Taken together, these findings demonstrate that infiltrating macrophages in SHP-1-deficient mice play a crucial role in promoting viral replication by providing abundant viral targets and contribute to increased proinflammatory gene expression relevant to the effector mechanisms of macrophage-mediated demyelination.
Continuous Viral Escape and Selection by Autologous Neutralizing Antibodies in Drug-Naïve Human Immunodeficiency Virus Controllers
Authors: Mahalanabis Madhumita , Jayaraman Pushpa , Miura Toshiyuki , Pereyra Florencia , Chester E. Michael , Richardson Barbra , Walker Bruce , Haigwood Nancy L. 
Published: November 2008

ABSTRACT

We assessed differences in the character and specificity of autologous neutralizing antibodies (ANAbs) against individual viral variants of the quasispecies in a cohort of drug-naïve subjects with long-term controlled human immunodeficiency virus type 1 (HIV-1) infection and moderate levels of broad heterologous neutralizing antibodies (HNAb). Functional plasma virus showed continuous
env
evolution despite a short time frame and low levels of viral replication. Neutralization-sensitive variants dominated in subjects with intermittent viral blips, while neutralization-resistant variants predominated in elite controllers. By sequence analysis of this panel of autologous variants with various sensitivities to neutralization, we identified more than 30 residues in envelope proteins (Env) associated with resistance or sensitivity to ANAbs. The appearance of new sensitive variants is consistent with a model of continuous selection and turnover. Strong ANAb responses directed against autologous Env variants are present in long-term chronically infected individuals, suggesting a role for these responses in contributing to the durable control of HIV replication.
Intracellular Signaling Mechanisms and Activities of Human Herpesvirus 8 Interleukin-6
Authors: Chen Daming , Sandford Gordon , Nicholas John 
Published: November 2008

ABSTRACT
Human herpesvirus 8 (HHV-8)-encoded viral interleukin-6 (vIL-6) has been implicated as a key factor in virus-associated neoplasia because of its proproliferative and survival effects and also in view of its angiogenic properties. A major difference between vIL-6 and human IL-6 (hIL-6) is that vIL-6, uniquely, is largely retained and can signal intracellularly. While vIL-6 is generally considered to be a lytic gene, several reports have noted its low-level expression in latently infected primary effusion lymphoma (PEL) cultures, in the absence of other lytic gene expression. Thus, intracellular autocrine signal transduction by the viral cytokine may be of particular relevance to the growth and survival of latently infected cells and to pathogenesis. Here we report that most intracellular vIL-6 is located in the endoplasmic reticulum (ER), signals via the gp130 signal transducer in this compartment, and does so independently of the gp80 α-subunit of the IL-6 receptor, required for hIL-6 signal transduction. Signaling and biological assays incorporating ER-retained vIL-6 and hIL-6 confirmed vIL-6 activity, specifically, in this compartment. Knockdown of vIL-6 expression in PEL cells led to markedly reduced cell growth in normal culture, independently of extracellular cytokines. This could be reversed by reintroduction via virus vector of exclusively ER-retained vIL-6. These data indicate that in virus biology vIL-6 may act to support the growth and survival of cells latently infected with HHV-8 in an autocrine manner via intracrine signaling and that these activities may contribute to the maintenance of latently infected cells and to virus-induced neoplasia.
Analysis of Epstein-Barr Virus Glycoprotein B Functional Domains via Linker Insertion Mutagenesis
Authors: Reimer Jessica J. , Backovic Marija , Deshpande Charuhas G. , Jardetzky Theodore , Longnecker Richard 
Published: November 2008

ABSTRACT
Epstein-Barr Virus (EBV) glycoprotein B (gB) is essential for viral fusion events with epithelial and B cells. This glycoprotein has been studied extensively in other herpesvirus family members, but functional domains outside of the cytoplasmic tail have not been characterized in EBV gB. In this study, a total of 28 linker insertion mutations were generated throughout the length of gB. In general, the linker insertions did not disrupt intracellular expression and variably altered cell surface expression. Oligomerization was disrupted by insertions located between residues 561 and 620, indicating the location of a potential site of oligomer contacts between EBV gB monomers. In addition, a novel N-glycosylated form of wild-type gB was identified under nonreducing Western blot conditions that likely represents a mature form of the protein. Fusion activity was abolished in all but three variants containing mutations in the N-terminal region (gB30), within the ectodomain (gB421), and in the intracellular C-terminal domain (gB832) of the protein. Fusion activity with variants gB421 and gB832 was comparable to that of the wild type with epithelial and B cells, and only these two mutants, but not gB30, were able to complement gB-null virus and subsequently function in virus entry. The mutant gB30 exhibited a low level of fusion activity with B cells and was unable to complement gB-null virus. The mutations generated here indicate important structural domains, as well as regions important for function in fusion, within EBV gB.