bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Immunodeficiency Virus Type 2 Gag Interacts Specifically with PRP4, a Serine-Threonine Kinase, and Inhibits Phosphorylation of Splicing Factor SF2
Authors: Bennett Erin M. , Lever Andrew M. L. , Allen Jane F. 
Published: September 2004

ABSTRACT
Using a yeast two-hybrid screen of a T-cell cDNA library to identify cellular proteins that bind to the human immunodeficiency virus type 2 (HIV-2) Gag polyprotein, we identified PRP4, a serine-threonine protein kinase. Specific interaction of PRP4 and HIV-2 Gag was confirmed in in vitro and in vivo assays. The interacting region of HIV-2 Gag is located in the conserved matrix and capsid domains, while both the RS (arginine-serine-rich) domain and the KS (kinase) domain of PRP4 are able to bind to HIV-2 Gag. PRP4 is not incorporated into virus particles. HIV-2 Gag is able to inhibit PRP4-mediated phosphorylation of the splicing factor SF2. This is also observed with Gag from simian immunodeficiency virus, a closely related virus, but not with Gag from human T-cell lymphotropic virus type 1. Our results provide evidence for a novel interaction between Gag and a cellular protein kinase involved in the control of constitutive splicing in two closely related retroviruses. We hypothesize that as Gag accumulates in the cell, down regulation of splicing occurs through reduced phosphorylation of SF2. At late stages of infection, this interaction may replace the function of the early viral regulatory protein Rev.
Coxsackievirus B4-Induced Cytokine Production in Pancreatic Cells Is Mediated through Toll-Like Receptor 4
Authors: Triantafilou Kathy , Triantafilou Martha 
Published: September 2004

ABSTRACT

Coxsackievirus B4 (CBV4), a member of the
Picornavirus
genus, has long been implicated in the development of insulin-dependent diabetes mellitus (IDDM) caused by virus-induced pancreatic cell damage. The progressive destruction of pancreatic β cells is responsible for the development of IDDM. It has recently been suggested that CBV4 infection can induce the production of proinflammatory cytokines, and these cytokines seem to be involved in the damage to the insulin-producing cells. In this study we investigated whether toll-like receptors (TLRs) are responsible for triggering the proinflammatory cytokine production in human pancreatic cells in response to CBV4. Here we demonstrate that CBV4 triggers cytokine production through a TLR4-dependent pathway. This interaction seems to be independent of virus attachment and cell entry.
Small Molecules Blocking the Entry of Severe Acute Respiratory Syndrome Coronavirus into Host Cells
Authors: Yi Ling , Li Zhengquan , Yuan Kehu , Qu Xiuxia , Chen Jian , Wang Guangwen , Zhang Hong , Luo Hongpeng , Zhu Lili , Jiang Pengfei , Chen Lirong , Shen Yan , Luo Min , Zuo Guoying , Hu Jianhe , Duan Deliang , Nie Yuchun , Shi Xuanling , Wang Wei , Han Yang , Li Taisheng , Liu Yuqing , Ding Mingxiao , Deng Hongkui , Xu Xiaojie 
Published: September 2004

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV) is the pathogen of SARS, which caused a global panic in 2003. We describe here the screening of Chinese herbal medicine-based, novel small molecules that bind avidly with the surface spike protein of SARS-CoV and thus can interfere with the entry of the virus to its host cells. We achieved this by using a two-step screening method consisting of frontal affinity chromatography-mass spectrometry coupled with a viral infection assay based on a human immunodeficiency virus (HIV)-luc/SARS pseudotyped virus. Two small molecules, tetra-
O
-galloyl-β-
d
-glucose (TGG) and luteolin, were identified, whose anti-SARS-CoV activities were confirmed by using a wild-type SARS-CoV infection system. TGG exhibits prominent anti-SARS-CoV activity with a 50% effective concentration of 4.5 μM and a selective index of 240.0. The two-step screening method described here yielded several small molecules that can be used for developing new classes of anti-SARS-CoV drugs and is potentially useful for the high-throughput screening of drugs inhibiting the entry of HIV, hepatitis C virus, and other insidious viruses into their host cells.
A Lentiviral cDNA Library Employing Lambda Recombination Used To Clone an Inhibitor of Human Immunodeficiency Virus Type 1-Induced Cell Death
Authors: Kawano Yuji , Yoshida Takeshi , Hieda Kuniko , Aoki Jun , Miyoshi Hiroyuki , Koyanagi Yoshio 
Published: September 2004

ABSTRACT

Expression cloning technology of cDNAs is a suitable tool for identifying novel functional properties of genes. Here, we generated a lentiviral cDNA library-expressing system for human T cells based on a site-specific recombination system of phage lambda for transferring cDNA libraries with a minimum loss of its complexity. The library-transduced CD4
+
T cells were challenged with wild-type human immunodeficiency virus type 1 (HIV-1), and the cells that acquired resistance to HIV-1-induced cytopathic effect (CPE) were selected. From these cells, CD14 was isolated and proved to inhibit the entry of HIV-1 and the HIV-1-induced CPE. This cloning system allows rapid identification of genes encoding novel properties in human T cells and probably other mammalian cells.
Enhanced Apoptosis of Peripheral CD5-Negative B Lymphocytes from Chronically Hepatitis C Virus-Infected Patients: Reversal after Antiviral Treatment
Authors: Toubi Elias , Kessel Aharon , Peri Regina , Shmuel Zehava , Bamberger Ellen , Sabo Edmond , Zuckerman Eli 
Published: September 2004

ABSTRACT

Whereas enhanced peripheral T-cell apoptosis and its association with autoimmunity have recently been reported, the apoptotic status of peripheral B cells in chronic hepatitis C virus (HCV) infection remains ambiguous. We therefore sought to investigate the sensitivity of peripheral B cells to apoptosis and to assess the possible benefits of antiviral treatment in mitigating these effects. Spontaneous apoptosis, the extent of apoptosis rescue, and NF-κB expression in peripheral B cells were studied in patients with chronic HCV infections (group 1), in sustained responders after antiviral treatment (group 2), and in healthy controls (group 3). For group 1, spontaneous B-cell apoptosis was increased (26% ± 4.6%) and apoptosis rescue was altered (39%) compared to group 3 (18% ± 5% and 50%, respectively;
P
= 0.001). In contrast, apoptosis and apoptosis rescue were similar for groups 2 and 3. Enhanced B-cell apoptosis was associated with decreased NF-κB expression and was found only in CD5-negative (CD5
neg
) B cells, whereas CD5
pos
cells were apoptosis resistant. Chronic HCV infection is associated with enhanced peripheral B-cell apoptosis and decreased apoptosis rescue. Successful antiviral treatment reverses these abnormalities to the levels seen in healthy individuals. The relative resistance of the CD5
pos
B-cell subpopulation to apoptosis may play a role in HCV-related autoimmunity and lymphoproliferation.
Targeting c-Mpl for Revival of Human Immunodeficiency Virus Type 1-Induced Hematopoietic Inhibition When CD34+Progenitor Cells Are Re-Engrafted into a Fresh Stromal Microenvironment In Vivo
Authors: Koka Prasad S. , Kitchen Christina M. R. , Reddy Srinivasa T. 
Published: September 2004

ABSTRACTThe inhibition of multilineage hematopoiesis which occurs in the severe combined immunodeficiency mouse with transplanted human fetal thymus and liver tissues (SCID-hu Thy/Liv) due to human immunodeficiency virus type 1 (HIV-1) infection is also accompanied by a severe loss of c-Mpl expression on these progenitor cells. Inhibition of colony-forming activity (CFA) of the CD34+progenitor cells is partially revived to about 40% of mock-infected Thy/Liv implants, following reconstitution of the CD34+cells that were exposed to HIV-1 infection, in a new Thy/Liv stromal microenvironment of irradiated secondary SCID-hu recipients at 3 weeks post-re-engraftment. In addition, in these reconstituted animals, the proportion of c-Mpl+CD34+cells relative to c-Mpl−CD34+cells increased by about 25%, to 35% of mock-infected implants, suggesting a reacquirement of c-Mpl phenotype by the c-Mpl−CD34+cells. These results suggest a correlation between c-Mpl expression and multilineage CFA of the human CD34+progenitor cells that have experienced the effects of HIV-1 infection. Treatment of the secondary-recipient animals with the c-Mpl ligand, thrombopoietin (Tpo), further increased c-Mpl expression and CFA of re-engrafted CD34+cells previously exposed to virus in the primary implants to about 50 to 70% over that of those re-engrafted CD34+cells derived from implants of untreated animals. Blocking of c-Mpl with anti-c-Mpl monoclonal antibody in vivo by injecting the SCID-hu animals resulted in the reduction or loss of CFA. Thus, inhibition, absence, or loss of c-Mpl expression as in the c-Mpl−CD34+subset of cells is the likely cause of CFA inhibition. Further, CFA of the CD34+cells segregates with their c-Mpl expression. Therefore, c-Mpl may play a role in hematopoietic inhibition during HIV-1 infection, and control of its expression levels may aid in hematopoietic recovery and thereby reduce the incidence of cytopenias occurring in infected individuals.
Visualization by Live-Cell Microscopy of Disruption of ND10 during Herpes Simplex Virus Type 1 Infection
Authors: Everett Roger D. , Zafiropoulos Alexandros 
Published: September 2004

ABSTRACT
ND10 structures are disrupted during herpes simplex virus type 1 (HSV-1) infection by viral regulatory protein ICP0. The significance of this effect remains controversial, partly because of a report that high-level expression of the major ND10 promyelocytic leukemia (PML) protein precludes ND10 disruption yet does not inhibit HSV-1 infection. Here we demonstrate dramatic reorganization of ND10 during HSV-1 infection by live-cell microscopy, even in the presence of overexpressed PML.
Thogoto Virus Lacking Interferon-Antagonistic Protein ML Is Strongly Attenuated in Newborn
Mx1
-Positive but Not
Mx1
-Negative Mice
Authors: Pichlmair Andreas , Buse Johanna , Jennings Stephanie , Haller Otto , Kochs Georg , Staeheli Peter 
Published: September 2004

ABSTRACT

The Thogoto virus ML protein suppresses interferon synthesis in infected cells. Nevertheless, a virus mutant lacking ML remained highly pathogenic in standard laboratory mice. It was strongly attenuated, however, in mice carrying the interferon-responsive
Mx1
gene found in wild mice, demonstrating that enhanced interferon synthesis is protective only if appropriate antiviral effector molecules are present. Our study shows that the virulence-enhancing effects of some viral interferon antagonists may escape detection in conventional animal models.
Modulation by Morphine of Viral Set Point in Rhesus Macaques Infected with Simian Immunodeficiency Virus and Simian-Human Immunodeficiency Virus
Authors: Kumar Rakesh , Torres Cynthia , Yamamura Yasuhiro , Rodriguez Idia , Martinez Melween , Staprans Silvija , Donahoe Robert M. , Kraiselburd Edmundo , Stephens Edward B. , Kumar Anil 
Published: September 2004

ABSTRACT

Six rhesus macaques were adapted to morphine dependence by injecting three doses of morphine (5 mg/kg of body weight) for a total of 20 weeks. These animals along with six control macaques were infected intravenously with mixture of simian-human immunodeficiency virus KU-1B (SHIV
KU-1B
), SHIV
89.6P
, and simian immunodeficiency virus 17E-Fr. Levels of circulating CD4
+
T cells and viral loads in the plasma and the cerebrospinal fluid were monitored in these macaques for a period of 12 weeks. Both morphine and control groups showed precipitous loss of CD4
+
T cells. However this loss was more prominent in the morphine group at week 2 (
P
= 0.04). Again both morphine and control groups showed comparable peak plasma viral load at week 2, but the viral set points were higher in the morphine group than that in the control group. Likewise, the extent of virus replication in the cerebral compartment was more pronounced in the morphine group. These results provide a definitive evidence for a positive correlation between morphine and levels of viral replication.
Efficient Replication of Severe Acute Respiratory Syndrome Coronavirus in Mouse Cells Is Limited by Murine Angiotensin-Converting Enzyme 2
Authors: Li Wenhui , Greenough Thomas C. , Moore Michael J. , Vasilieva Natalya , Somasundaran Mohan , Sullivan John L. , Farzan Michael , Choe Hyeryun 
Published: September 2004

ABSTRACT
Replication of viruses in species other than their natural hosts is frequently limited by entry and postentry barriers. The coronavirus that causes severe acute respiratory syndrome (SARS-CoV) utilizes the receptor angiotensin-converting enzyme 2 (ACE2) to infect cells. Here we compare human, mouse, and rat ACE2 molecules for their ability to serve as receptors for SARS-CoV. We found that, compared to human ACE2, murine ACE2 less efficiently bound the S1 domain of SARS-CoV and supported less-efficient S protein-mediated infection. Rat ACE2 was even less efficient, at near background levels for both activities. Murine 3T3 cells expressing human ACE2 supported SARS-CoV replication, whereas replication was less than 10% as efficient in the same cells expressing murine ACE2. These data imply that a mouse transgenically expressing human ACE2 may be a useful animal model of SARS.
Expression of thyroid transcription factor 1 in primary brain tumours
Authors: Zamecnik J , Chanova M , Kodet R 
Published: September 2004

Background:Thyroid transcription factor 1 (TTF-1) is expressed in a proportion of carcinomas derived from follicular thyroid cells and respiratory epithelium. Immunohistochemical detection of this protein was shown previously to be a helpful aid in tumour diagnosis, specifically in deciding whether a tumour is primary to the lung/thyroid gland or metastatic. Recently, TTF-1 expression was also observed in certain areas of postnatal brain.Aim/Method:To investigate the expression of TTF-1 protein in a spectrum of 73 primary brain tumours including astrocytomas, glioblastomas, ependymomas, oligodendrogliomas, medulloblastomas, and gangliogliomas of different sites.Results:All the tumours were negative for TTF-1 except for two ependymomas of the third ventricle.Conclusions:The expression of TTF-1 in brain tumours appears to be site specific rather than associated with tumour dedifferentiation. The presented expression of TTF-1 protein in certain primary brain tumours should be taken into consideration when interpreting the immunohistochemical staining of brain tumours of uncertain primary site.
The prognostic value of progesterone receptor status in meningiomas
Authors: Roser F , Nakamura M , Bellinzona M , Rosahl S K , Ostertag H , Samii M 
Published: September 2004

Background:Meningiomas are known to recur frequently, and their longterm management remains controversial. Previous studies indicate that progesterone and its receptors can play a role in the recurrence of meningiomas, but the correlation between the presence of these receptors and patients’ outcome is unclear.Aim:To conduct a retrospective analysis to investigate the prognostic relevance of progesterone receptor (PR) expression in meningiomas.Methods:Five hundred and eighty eight meningiomas operated on over a period of 10 years were examined immunohistochemically to determine the PR status using monoclonal antibodies. Several factors including recurrence (mean follow up of 65 month), sex, tumour tissue consistency, location, vascularity, and en plaque appearance were analysed.Results:PR status showed comparable values for men and women. World Health Organisation (WHO) grade II and III tumours had significantly fewer receptors than benign meningiomas. There was no significant correlation between PR status and recurrence rates in WHO grade I totally removed meningiomas. However, a combination of PR status and proliferation indices was shown to predict recurrence reliably.Conclusions:Together with routine histological evaluation, PR status can help to describe the biological behaviour of meningiomas. Only a combination of clinical and biological features can describe the behaviour of meningiomas, predict their recurrence, and help to devise more effective follow up strategies.
THE HOMEOPATHIC PREPARATION TRAUMEEL® S COMPARED WITH NSAIDS FOR SYMPTOMATIC TREATMENT OF EPICONDYLITIS
Authors: Birnesser Heinz , Oberbaum Menachem , Klein Peter , Weiser Michael 
Published: September 2004

Objective: To compare the homeopathic remedy Traumeel® S with standard NSAID therapy for effects on symptomatic relief in patients with diagnosed epicondylitis. Methods: An observational, non-randomized study over 2 weeks in 184 patients with diagnosed epicondylitis from 38 primary care centers in Germany. At the start of the study, patients were given initial injections of either Traumeel® S or NSAID (unspecified; mainly diclofenac). Traumeel® S patients might have other Traumeel® S injections and other treatments were allowed, e.g. oral analgesics (in the NSAID group only) or physiotherapy. Treatments were evaluated on clinically relevant variables: three pain variables (local pressure pain, pain with movements, pain at rest) and two mobility variables (change in extensional joint mobility and change in torsional joint mobility). Results: Both treatments significantly improved scores on all five variables with no significant differences in time to onset of action. Traumeel® S was equivalent to NSAIDs on all evaluated variables and was significantly superior to NSAID therapy on the variables pain at rest (p<0.01), torsional joint mobility (p<0.01), and extensional joint mobility (p<0.05). Patients' verdicts on the global outcome reflected the results, with the terms "very good" or "good", given by 71.0% of patients in the Traumeel® S group versus 44.2% of patients receiving NSAIDs. Tolerability was good in all groups. Conclusion: Traumeel® S represents an appealing and well-tolerated alternative to NSAIDs for symptomatic treatment of epicondylitis.
VALIDATION OF THE USE OF A SKIN-MOUNTED DEVICE TO MEASURE OUT-OF-PLANE ROTATIONS OF THE SPINE FOR A ROWING ACTIVITY
Authors: Bull Anthony M. J. , Holt Peter J. , Wragg Paul , McGregor Alison H. 
Published: September 2004

Objective: To assess the accuracy of a skin-mounted device to measure lumbar spinal rotations in rowers. Methods: Nine subjects were each imaged in 12 extremes of lateral flexion and rotation in an open MR scanner, and the movement between external MR markers fixed to the skin, and the underlying vertebral bodies was quantified. Results: The average error in measuring the changes in the lateral flexion and rotation between the MR markers and the underlying vertebral bodies was ±5.0° (95% CI 3.5–6.4°, S.E. 0.7°) for lateral flexion and 4.4° (95% CI 3.2–5.6°, S.E 0.6°) for lateral rotation (nine subjects). Conclusions: This study has demonstrated the accuracy of using an externally mounted device to measure out-of-plane rotations for the extremes of motion achieved during a rowing activity, allowing this system to be used to quantify deviations in rowing technique. The method could be applied to other repetitive activities of the spine.
Birnennamen Aus Hemşin: Vorarbeiten zur Feststellung und Beschreibung der Birnenarten und ihrer regionalen Namen im östlichen Schwarzmeergebiet
Authors: Bläsing Uwe 
Published: September 2004

AbstractThe article discusses a number of dialectal names for pears, which I collected in the Hamshen area of the Eastern Pontic range in Turkey. This study is the first attempt to give the etymology of these terms and to also describe the kind of pears meant by the respective names. As it is to be expected for Hamshen, which in former times was almost exclusively inhabited by an Armenian population, a great many of the pear names have a direct Armenian background. Others are of Pontic Greek origin, and a third group is represented by typical Turkish formations. The investigation showed that it was not possible to elucidate these names without considering the aspects of areal lingustics and cultural relationships. Irrespective of the language we can often observe several common patterns and motives in the formation of these terms. Thus, in addition to the 32 terms collected in Hamshen, many names taken from other languages of the area had to be included into the discussion.
A novel celecoxib derivative, OSU03012, induces cytotoxicity in primary CLL cells and transformed B-cell lymphoma cell line via a caspase- and Bcl-2–independent mechanism
Authors: Johnson Amy J. , Smith Lisa L. , Zhu Jiuxiang , Heerema Nyla A. , Jefferson Sara , Mone Andrew , Grever Michael , Chen Ching-Shih , Byrd John C. 
Published: September 2004

AbstractChronic lymphocytic leukemia (CLL) is an incurable adult leukemia characterized by disrupted apoptosis. OSU03012 is a bioavailable third-generation celecoxib derivative devoid of cyclooxygenase-2 inhibitory activity that potently induces apoptosis in prostate cancer cell lines and is being developed as an anticancer therapy in the National Cancer Institute (NCI) Rapid Access to Intervention Development (RAID) program. We assessed the ability of OSU03012 to induce apoptosis in primary CLL cells and the mechanism by which this occurs. The LC50 (lethal concentration 50%) of OSU03012 at 24 hours was 7.1 μM, and this decreased to 5.5 μM at 72 hours. Additionally, we have demonstrated that OSU03012 mediates apoptosis by activation of the intrinsic, mitochondrial pathway of apoptosis but also activates alternative cell death pathways that are caspase independent. The early activation of both caspase-dependent and -independent pathways of apoptosis is novel to OSU03012 and suggests it has great potential promise for the treatment of CLL. Moreover, unlike the great majority of therapeutic agents used to treat leukemia or other forms of cancer, OSU03012 induces cell death entirely independent of bcl-2 expression. Overall, these data provide justification for further preclinical development of OSU03012 as a potential therapeutic agent for CLL.
Leukotriene B4 plays a pivotal role in CD40-dependent activation of chronic B lymphocytic leukemia cells
Authors: Runarsson Gudmundur , Liu Anquan , Mahshid Yilmaz , Feltenmark Stina , Pettersson Annika , Klein Eva , Björkholm Magnus , Claesson Hans-Erik 
Published: September 2004

AbstractBiosynthesis of leukotrienes (LTs) occurs in human myeloid cells and B lymphocytes. However, the function of leukotrienes in B lymphocytes is unclear. Here, we report that B-cell chronic lymphocytic leukemia (B-CLL) cells produce leukotriene B4, and that specific leukotriene biosynthesis inhibitors counteracted CD40-dependent activation of B-CLL cells. Studies on the expression of the high-affinity receptor for LTB4 (BLT1) by flow cytometry analysis showed that the receptor was expressed, to a varying degree, in all investigated B-CLL clones. At a concentration of 100 nM, the drugs BWA4C (a specific 5-lipoxygenase inhibitor) and MK-886 (a specific 5-lipoxygenase activating protein inhibitor) markedly inhibited CD40-induced DNA synthesis (45% and 38%, respectively) and CD40-induced expression of CD23, CD54, and CD150. Addition of exogenous LTB4 (150 nM) almost completely reversed the effect of the inhibitors on DNA synthesis and antigen expression. Taken together, the results of the present study suggest that leukotriene biosynthesis inhibitors may have a therapeutic role in B-CLL.