bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Domains of Glycoprotein D Required To Block Apoptosis Induced by Herpes Simplex Virus 1 Are Largely Distinct from Those Involved in Cell-Cell Fusion and Binding to Nectin1
Authors: Zhou Guoying , Avitabile Elisa , Campadelli-Fiume Gabriella , Roizman Bernard 
Published: February 2003

ABSTRACT

Glycoprotein D (gD) interacts with two alternative protein receptors, nectin1 and HveA, to mediate herpes simplex virus (HSV) entry into cells. Fusion of the envelope with the plasma membrane requires, in addition to gD, glycoproteins gB, gH, and gL. Coexpression of the four glycoproteins (gD, gB, gH, and gL) promotes cell-cell fusion. gD delivered in
trans
is also capable of blocking the apoptosis induced by gD deletion viruses grown either in noncomplementing cells (gD
−/−
) or in complementing cells (gD
−/+
). While ectopic expression of cation-independent mannose-6 phosphate receptor blocks apoptosis induced by both stocks, other requirements differ. Thus, apoptosis induced by gD
−/−
virus is blocked by full-length gD (or two gD fragments reconstituting a full-length molecule), whereas ectopic expression of the gD ectodomain is sufficient to block apoptosis induced by gD
−/+
virus. In this report we took advantage of a set of gD insertion-deletion mutants to map the domains of gD required to block apoptosis by gD
−/−
and gD
−/+
viruses and those involved in cell-cell fusion. The mutations that resulted in failure to block apoptosis were the same for gD
−/−
and gD
−/+
viruses and were located in three sites, one within the immunoglobulin-type core region (residues 125, 126, and 151), one in the upstream connector region (residues 34 and 43), and one in the C-terminal portion of the ectodomain (residue 277). A mutant that carried amino acid substitutions at the three glycosylation sites failed to block apoptosis but behaved like wild-type gD in all other assays. The mutations that inhibited polykaryocyte formation were located in the upstream connector region (residues 34 and 43), at the α1 helix (residue 77), in the immunoglobulin core and downstream regions (residue 151 and 187), and at the α3 helix (residues 243 and 246). Binding of soluble nectin1-Fc to cells expressing the mutant gDs was generally affected by the same mutations that affected fusion, with one notable exception (Δ277-310), which affected fusion without hampering nectin1 binding. This deletion likely identifies a region of gD involved in fusion activity at a post-nectin1-binding step. We conclude that whereas mutations that affected all functions (e.g., upstream connector region and residue 151) may be detrimental to overall gD structure, the mutations that affect specific activities identify domains of gD involved in the interactions with entry receptors and fusogenic glycoproteins and with cellular proteins required to block apoptosis. The evidence that glycosylation of gD is required for blocking apoptosis supports the conclusion that the interacting protein is the mannose-6 phosphate receptor.
Human Papillomavirus Types 16, 31, and 58 Use Different Endocytosis Pathways To Enter Cells
Authors: Bousarghin Latifa , Touzé Antoine , Sizaret Pierre-Yves , Coursaget Pierre 
Published: February 2003

ABSTRACT
The early steps of the intracellular trafficking of human papillomavirus type 16 (HPV-16), -31, and -58 pseudovirions were studied by investigating the effects of drugs acting at defined points of endocytosis pathways on virus-like particle-mediated pseudoinfection by overexpression of a dominant-negative form of the Eps15 protein to inhibit clathrin-mediated endocytosis and by electron microscopy. The results obtained suggested the involvement of clathrin-mediated endocytosis in HPV-16 and HPV-58 entry and caveola-mediated endocytosis in HPV-31 entry.
Malignant Transformation of Epstein-Barr Virus-Negative Akata Cells by Introduction of the BARF1 Gene Carried by Epstein-Barr Virus
Authors: Sheng Wang , Decaussin Gisèle , Ligout Audrey , Takada Kenzo , Ooka Tadamasa 
Published: February 2003

ABSTRACT
Spontaneous loss of the Epstein-Barr virus (EBV) genome in the BL cell line Akata led to loss of tumorigenicity in SCID mice, suggesting an important oncogenic activity of EBV in B cells. We previously showed that introduction of the BARF1 gene into the human B-cell line Louckes induced a malignant transformation in newborn rats (M. X. Wei, J. C. Moulin, G. Decaussin, F. Berger, and T. Ooka, Cancer Res. 54:1843-1848, 1994). Since 1 to 2% of Akata cells expressed lytic antigens and expressed the BARF1 gene, we investigated whether introduction of the BARF1 gene into EBV-negative Akata cells can induce malignant transformation. Here we show that BARF1-transfected, EBV-negative Akata cells activated Bcl2 expression and induced tumor formation when they were injected into SCID mice. In addition, when EBV-positive Akata cells expressing a low level of BARF1 protein were injected into SCID mice, the expression of BARF1, as well as several lytic proteins, such as EA-D, ZEBRA, and a 135-kDa DNA binding protein, increased in tumor cells while no latent LMP1 and late gp220-320 expression was observed in tumor cells. These observations suggest that the BARF1 gene may be involved in the conferral of tumorigenicity by EBV.
The Type B Leukemogenic Virus Truncated Superantigen Is Dispensable for T-Cell Lymphomagenesis
Authors: Mustafa Farah , Bhadra Sanchita , Johnston Dennis , Lozano Mary , Dudley Jaquelin P. 
Published: February 2003

ABSTRACTType B leukemogenic virus (TBLV) is a variant of mouse mammary tumor virus (MMTV) that causes T-cell lymphomas in mice. We have constructed a TBLV-MMTV hybrid, pHYB-TBLV, in which 756 bp of the C3H MMTV long terminal repeat (LTR) was replaced with 438 bp of the TBLV LTR. Intraperitoneal injection of pHYB-TBLV transfectants consistently resulted in T-cell lymphomas in 50% of injected weanling BALB/c mice with an average latency period of 5.7 (± 1.5) months. Transfectants of pHYB-TBLV containing a double-frameshift mutation in the truncated superantigen gene (sag) induced T-cell lymphomas with similar incidences, latency periods, and phenotypes, suggesting thatcis-acting elements in the TBLV LTR determine disease specificity.
Effects of Dipeptide Insertions between Codons 69 and 70 of Human Immunodeficiency Virus Type 1 Reverse Transcriptase on Primer Unblocking, Deoxynucleoside Triphosphate Inhibition, and DNA Chain Elongation
Authors: Meyer Peter R. , Lennerstrand Johan , Matsuura Suzanne E. , Larder Brendan A. , Scott Walter A. 
Published: February 2003

ABSTRACT
Finger insertion mutations of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) (T69S mutations followed by various dipeptide insertions) have a multinucleoside resistance phenotype that can be explained by decreased sensitivity to deoxynucleoside triphosphate (dNTP) inhibition of the nucleotide-dependent unblocking activity of RT. We show that RTs with SG or AG (but not SS) insertions have three- to fourfold-increased unblocking activity and that all three finger insertion mutations have threefold-decreased sensitivity to dNTP inhibition. The additional presence of M41L and T215Y mutations increased unblocking activity for all three insertions, greatly reduced the sensitivity to dNTP inhibition, and resulted in defects in in vitro DNA chain elongation. The DNA chain elongation defects were partially repaired by additional mutations at positions 210, 211, and 214. These results suggest that structural communication between the regions of RT defined by these mutations plays a role in the multinucleoside resistance phenotype.
Role of the Virus Nucleoprotein in the Regulation of Lymphocytic Choriomeningitis Virus Transcription and RNA Replication
Authors: Pinschewer Daniel D. , Perez Mar , de la Torre Juan Carlos 
Published: February 2003

ABSTRACT

The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) has a bisegmented negative-strand RNA genome. Each segment carries two viral genes in opposite orientation and separated by an intergenic region (IGR). The RNA-dependent RNA polymerase (RdRp) L of LCMV produces subgenomic mRNA and full-length genomic and antigenomic RNA species in two different processes termed transcription and replication, respectively. It is widely accepted that intracellular nucleoprotein (NP) levels regulate these two processes. Intracellular NP levels increase during the course of the infection, resulting in the unfolding of secondary RNA structures within the IGR. Structure-dependent transcription termination at the IGR is thereby attenuated, promoting replication of genome and antigenome RNA species. To test this hypothesis, we established a helper-virus-free minigenome (MG) system where intracellular synthesis of an S segment analogue from a plasmid is driven by RNA polymerase I. Cotransfection with two additional plasmids expressing the minimal viral
trans
-acting factors L and NP under control of RNA polymerase II allowed for RNA synthesis mediated by the intracellularly reconstituted LCMV polymerase. Both processes, transcription and replication, were strictly dependent on NP. However, both were equally enhanced by incrementally increasing amounts of NP up to levels in the range of those in LCMV-infected cells. Our data are consistent with a central role for NP in transcription and replication of the LCMV genome, but they do not support the participation of NP levels in balancing the two processes.
Text and Context in the Study of Religion
Authors: Burris John 
Published: February 2003

AbstractRussell McCutcheon's Manufacturing Religion and David Chidester's Savage Systems give us two potentially complementary ways of imagining pivotal issues pertaining to the study of religion and its history. McCutcheon's predominant concern is to show that many of the classical theorists who have helped shape a field of religion have failed to locate themselves and their work adequately within their own subjective contexts, thus unconsciously advancing arguments that treat religion as, in McCutcheon's words, a "sui generis" phenomenon. By contrast, Chidester's study is more concerned with establishing the wider historical context of the field of religion, rather than with isolating particular texts and their authors and pointing out tacit assumptions inhering in the way they develop the concept "religion". While differing greatly in emphasis, both of these approaches are necessary in establishing the study of religion as a credible academic discipline. This article uses these two studies to place textual (McCutcheon) and contextual (Chidester) approaches to the study of religion and its history in relationship to one another. It argues that the contextual approach has been a minority tradition and that more attention now needs to be paid to history itself rather than to the analysis of prominent texts in reconstructing the history and parameters of the discipline.
Randomized, Multicenter, Phase II Trial of Two Multicomponent Regimens in Androgen-Independent Prostate Cancer
Authors: Millikan Randall , Thall Peter F. , Lee Sang-Joon , Jones Donnah , Cannon M.W. , Kuebler J. Phillip , Wade James , Logothetis Christopher J. 
Published: February 2003

Purpose: Several multicomponent regimens have been reported to be useful in advanced androgen-independent prostate cancer. We used a randomized phase II design to evaluate and compare two such regimens. Patients were accrued primarily in the community setting. Patients and Methods: Patients with progressive, androgen-independent prostate cancer were randomly assigned to one of two treatments: either ketoconazole/doxorubicin alternating with vinblastine/estramustine (KA/VE) or paclitaxel, estramustine, and oral etoposide (TEE). Patients were prospectively stratified on the basis of disease volume. The primary end points were response and overall survival time. Results: A total of 75 patients were registered; 71 are included in the analysis. By the criterion of an 80% prostate-specific antigen reduction maintained for at least 8 weeks, 11 (30%) of 37 patients in the TEE arm responded, whereas 11 (32%) of 34 assigned to KA/VE responded. Median survival was 16.9 months (95% confidence interval [CI], 10.5 to 21.2 months) in the TEE arm and 23.4 months (95% CI, 12.9 to 30.6 months) for patients treated with KA/VE. Many patients (24%) failed to complete at least 6 weeks of therapy, including five (8%) treatment-related early deaths. Conclusion: Each of these regimens produced clinically significant responses, and the observed median survival (18.9 months for all 71 patients) compares favorably with previously published results, especially in the community setting. Nonetheless, it is apparent that these first-generation regimens must be applied judiciously, and thus we view efforts at better patient selection and the development of more tolerable therapies as higher priorities than carrying either of these regimens to phase III evaluation in the cooperative group setting.
Lung Cancer Risk Reduction After Smoking Cessation: Observations From a Prospective Cohort of Women
Authors: Ebbert J.O. , Yang P. , Vachon C.M. , Vierkant R.A. , Cerhan J.R. , Folsom A.R. , Sellers T.A. 
Published: February 2003

Purpose: We conducted this study because the duration of excess lung cancer risk among former smokers has been inconsistently reported, doubt has been raised regarding the population impact of smoking cessation, and differential risk reduction by histologic cell type after smoking cessation needs to be confirmed. Methods: The Iowa Women’s Health Study is a prospective cohort study of 41,836 Iowa women aged 55 to 69 years. In 1986, mailed questionnaires were used to collect detailed smoking history. Age-adjusted lung cancer incidence through 1999 was analyzed according to years of smoking abstinence. Relative risks were estimated using Cox regression analysis. Results: There were 37,078 women in the analytic cohort. Compared with the never smokers, former smokers had an elevated lung cancer risk (relative risk, 6.6; 95% confidence interval, 5.0 to 8.7) up to 30 years after smoking cessation for all former smokers. However, a beneficial effect of smoking cessation was observed among recent and distant former smokers. The risk of adenocarcinoma remained elevated up to 30 years for both former heavier and former lighter smokers. Conclusion: The risk for lung cancer is increased for both current and former smokers compared with never smokers and declines for former smokers with increasing duration of abstinence. The decline in excess lung cancer risk among former smokers is prolonged compared with other studies, especially for adenocarcinoma and for heavy smokers, suggesting that more emphasis should be placed on smoking prevention and lung cancer chemoprevention.
Impact of Smoking on Cancer Stage at Diagnosis
Authors: Kobrinsky Nathan L. , Klug Marilyn G. , Hokanson Peggy Jo , Sjolander Diane E. , Burd Larry 
Published: February 2003

Background: Studies evaluating the relationship between smoking and cancer spread are limited. Methods: We studied the relationship between cancer stage at diagnosis (local, regional, or metastatic) and smoking history (current, previous, or nonsmoker). For lung cancer, patterns of spread were also studied. Results: In a tumor registry for eastern North Dakota, northwestern Minnesota, and northern South Dakota, 11,716 cases were identified from 1986 to 2001. Current smokers (relative risk [RR], 2.11; 95% confidence interval, 1.93 to 2.32; P < .001) and previous smokers (RR, 1.56; 95% confidence interval, 1.42 to 1.72; P < .001) had an increased risk of metastatic disease at diagnosis. Current smokers (RR, 1.39; 95% confidence interval, 1.29 to 1.51; P < .001), but not previous smokers, also had an increased risk of regional disease. An increase in metastatic disease was most evident for prostate cancer (RR, 1.53; P = .003). An increase in regional disease was most evident for head and neck (RR, 3.53; P < .001), prostate (RR, 1.83; P = .030), and breast cancer (RR, 1.22; P = .005). Compared with previous smokers, current smokers with metastatic lung cancer were more likely to have involvement of the brain (33.6% v 23.0%; P = .004), bone marrow, adrenal gland, and pericardium (24.7% v 15.9%; P = .004). Conclusion: Previous or current smoking is a risk factor for increased cancer stage in a wide range of malignancies. Further study is required to determine whether this association is causal.
Intensive Induction Chemotherapy With CBOP/BEP in Patients With Poor Prognosis Germ Cell Tumors
Authors: Christian J.A. , Huddart R.A. , Norman A. , Mason M. , Fossa S. , Aass N. , Nicholl E.J. , Dearnaley D.P. , Horwich A. 
Published: February 2003

Purpose: Despite a high cure rate in patients with testicular cancer, there remain patients in the poor prognosis group who have a less favorable outcome. Intensive induction chemotherapy using a regimen consisting of carboplatin, bleomycin, vincristine, and cisplatin, followed by bleomycin, etoposide, and cisplatin (CBOP/BEP), developed at the Royal Marsden Hospital, is designed to overcome the rapid proliferation seen in germ cell tumors. This study assesses the outcome of patients with poor-prognosis nonseminomatous germ cell tumors (NSGCT) treated with CBOP/BEP. Patients and Methods: Patients with NSGCT from three centers, classified as poor prognosis according to International Germ Cell Classification Consensus Group criteria, were treated with CBOP/BEP regimen during the period from 1989 to 2000. Data on treatment toxicity, relapse-free survival (RFS), and overall survival (OS) were collected prospectively on a hospital database. Results: Fifty-four male patients with poor prognosis NSGCT were treated with CBOP/BEP. The RFS at 3 and 5 years for all patients was 83.2% (95% confidence interval [CI], 68.8% to 91.3%). After a median follow-up of 4 years, the OS of the 54 patients was 91.5% (95% CI, 78.6% to 96.8%) at 3 years and 87.6% (95% CI, 71.3% to 94.9%) at 5 years. Three-year OS in patients with a primary mediastinal germ cell tumor was 77.1% (95% CI, 34.5% to 93.9%) compared with 95.4% (95% CI, 82.8% to 98.8%) in patients with a testicular primary tumor (P = .24). Conclusion: The results reported here compare favorably with the historical results of alternative regimens used in the management of poor-prognosis NSGCT. We suggest a phase III trial to confirm our findings.
Genetic Tumor Markers With Prognostic Impact in Dukes’ Stages B and C Colorectal Cancer Patients
Authors: Diep Chieu B. , Thorstensen Lin , Meling Gunn Iren , Skovlund Eva , Rognum Torleiv O. , Lothe Ragnhild A. 
Published: February 2003

Purpose: To examine several genetic changes in primary colorectal carcinomas (CRCs) from patients with 10 years of follow-up and associate the findings with clinicopathologic variables. Material and Methods: DNA from 220 CRCs were analyzed for allelic imbalances at 12 loci on chromosome arms 1p, 14q, 17p, 18q, and 20q, and the microsatellite instability (MSI) status was determined. The clinical significance of the tumor protein 53 (TP53) mutations was re-evaluated. Results: Patients with tumors containing 17p or 18q deletions had shorter survival than those without these alterations (P = .021, P = .008, respectively). This was also significant for the Dukes’ B group (P = .025, P = .010, respectively). Furthermore, patients with tumors showing losses of both chromosome arms revealed an even poorer disease outcome than those with either 17p or 18q loss. Patients with low increase in 20q copy number in their tumors had longer survival compared with those without changes (P = .009) or those with a high increase of copy number (P = .037). This was also evident for the Dukes’ C group (P = .018, P = .030, respectively). MSI was seemingly a beneficial marker for survival (P = .071). A significant association between mutations affecting the L3 zinc-binding domain of TP53 and survival was confirmed in this cohort after 10 years of follow-up, and also was found to apply for patients in the Dukes’ B group. Several associations were found among genetic and pathologic data. Conclusion: The present study indicates that 17p, 18q, and 20q genotypes, and TP53 mutation status add information in the subclassification of Dukes’ B and C patients and may have impact on the choice of treatment.
Treatment of Children With Nonmetastatic Paratesticular Rhabdomyosarcoma: Results of the Malignant Mesenchymal Tumors Studies (MMT 84 and MMT 89) of the International Society of Pediatric Oncology
Authors: Stewart Richard J. , Martelli Hélène , Oberlin Odile , Rey Annie , Bouvet Nathalie , Spicer Richard D. , Godzinski Jan , Stevens Michael C.G. 
Published: February 2003

Purpose: To report the results of the Malignant Mesenchymal Tumors studies (MMT 84 and 89) of the International Society of Pediatric Oncology (SIOP) in males with nonmetastatic paratesticular rhabdomyosarcoma. Patients and Methods: From 1984 to 1994, 96 males were treated in SIOP protocols. Radical inguinal orchidectomy was recommended, but initial retroperitoneal lymph node dissection was not performed. Disease was staged according to the SIOP tumor-node-metastasis staging system. Treatment was stratified by stage. In the MMT 89 study, males with completely resected tumors at diagnosis received less chemotherapy (vincristine and dactinomycin) than patients in the MMT 84 study (ifosfamide, vincristine, and dactinomycin). Results: Median age at diagnosis was 65 months. Thirty-one tumors were larger than 5 cm, and 13 males were older than 10 years with a tumor larger than 5 cm. At a median follow-up of 7 years, 87 patients were alive; 79 were in first complete remission and eight were in second complete remission. Relapse occurred in 16 patients (17%). At 5 years, the overall survival (OS) rate was 92%, with an event-free survival (EFS) rate of 82%. OS and EFS were significantly worse for males with tumors greater than 5 cm and for males older than 10 years at diagnosis. Conclusion: Males with paratesticular RMS have an excellent prognosis except for a selected group of patients older than 10 years or with tumor greater than 5 cm. Intensified chemotherapy incorporating alkylating agents for this subgroup may be preferred to the use of systematic lymphadenectomy to improve survival while minimizing the burden of therapy.