bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of nicotine on proliferation, cell cycle, and differentiation in immortalized and malignant oral keratinocytes
Authors: Lee Hwa‐Jeong , Guo Han‐Young , Lee Sun‐Kyung , Jeon Byung‐Hun , Jun Chang‐Duk , Lee Suk‐Keun , Park Myung‐Hee , Kim Eun‐Cheol 
Published: July 2005

Background:  Numerous epidemiological studies have reported that tobacco smoking is a major risk factor for oral cancer, but relatively little is known about the effect of nicotine, a major product of cigarette smoking, on immortalized oral keratinocytes and cancer cells.Methods:  We investigated the effects of nicotine on the growth and differentiation of immortalized human oral keratinocytes (IHOK), primary oral cancer cells (HN4), metastatic oral cancer cells (HN12), and human skin keratinocytes (HaCaT), in the monolayer and in the three‐dimensional (3D) raft cultures using the MTT assay, Western blotting, and cell cycle analysis.Results:  Nicotine inhibited the proliferation of immortalized and malignant keratinocytes in dose‐ and time‐dependent manners as determined by MTT assay. The 3D organotypic culture showed that nicotine at high concentration (300 μM) inhibits epithelial maturation, surface keratinization, and decreased epithelial thickness. Flow cytometry showed that nicotine inhibited cell cycle progression by inducing G0/G1 arrest of HaCaT, IHOK, HN4, and HN12 cells without causing apoptosis. Nicotine treatment increased p21 expression in immortalized cells (HaCaT, IHOK) and oral cancer cells (HN4, HN12), but decreased pRb and p53 expression in oral cancer cells. Moreover, after high‐dose nicotine treatment, the involucrin expression increased markedly in immortalized cells, but not in oral cancer cells.Conclusions:  We demonstrated that nicotine inhibits growth through cell cycle arrest at G0/G1 phase probably by increasing the expression of p21WAF1/CIP1. Nicotine also affects epithelial differentiation in immortalized and malignant oral keratinocytes. Malignant oral keratinocytes appear to be more resistant to the effects of nicotine on epithelial growth and differentiation as compared to the immortalized cells.
A systematic heuristic approach for feature selection for melanoma discrimination using clinical images
Authors: Chang Ying , Stanley R. Joe , Moss Randy H. , Van Stoecker William 
Published: July 2005

Background: Numerous features are derived from the asymmetry, border irregularity, color variegation, and diameter of the skin lesion in dermatology for diagnosing malignant melanoma. Feature selection for the development of automated skin lesion discrimination systems is an important consideration.Methods: In this research, a systematic heuristic approach is investigated for feature selection and lesion classification. The approach integrates statistical‐, correlation‐, histogram‐, and expert system‐based components. Using statistical and correlation measures, interrelationships among features are determined. Expert system analysis is performed to identify redundant features. The feature selection process is applied to 19 shape and color features for a clinical image data set containing 355 malignant melanomas, 125 basal cell carcinomas, 177 dysplastic nevi, 199 nevocellular nevi, 139 seborrheic keratoses, and 45 vascular lesions.Results: Experimental results show reduced lesion classification error rates based on condensing the shape and color feature set from 19 features to 13 features using the feature selection process. Specifically, average test lesion classification error rates for discriminating malignant melanoma from non‐melanoma lesions were reduced from 26.6% for 19 features to 23.2% for 13 features over five randomly generated training and test sets.Conclusions: The experimental results show that the systematic heuristic approach for feature reduction can be successfully applied to achieve improved lesion discrimination. The feature reduction technique facilitates the elimination of redundant information that may inhibit lesion classification performance. The clinical application of this result is that automated skin lesion classification algorithm development can be fostered with systematic feature selection techniques.
High resolution B‐scan ultrasound of hypertrophic scars
Authors: Bessonart María Nélida , Macedo Néstor , Carmona Carlos 
Published: July 2005

Background: Ultrasonography has provided the means for objective and non‐invasive monitoring of the dynamics of some skin diseases. The pathologic scars (keloids and hypertrophic scars) that have an increased content of collagen, and have been not analyzed by high‐frequency ultrasound so far. The purpose of the present study was to determine the ecographic features of these scars with a view in developing a reliable method for assessing the effectiveness of different therapeutic approaches.Methods: Six pathological scars from five patients were examined by a 20 MHz B‐Scanner and compared with healthy skin of the same region. Densitometry analysis was performed with the aid of a dedicated software.Results: All the pathologic scars studied showed an easily identified echo‐poor image clearly demarcated from the surrounding not involved tissue. When they were analyzed by densitometry, the lesions had highly significant reduced densitometric values (7.6±4.7) compared with regional healthy skin (31.79±10.8).Conclusion: The high‐frequency ultrasonography is a suitable objective and non‐invasive method for discriminating healthy from pathologic skin in hypertrophic scars and keloids.
Regional and seasonal variations in facial sebum secretions: a proposal for the definition of combination skin type
Authors: Youn Sang Woong , Na Jung Im , Choi Sun Young , Huh Chang Hun , Park Kyoung Chan 
Published: July 2005

Background/aims: Facial sebum secretions are known to change under various circumstances. Facial skin types have been categorized as oily, normal, dry, and combination types. However, these have been evaluated subjectively by individuals to date, and no objective accepted standard measurement method exists. The combination skin type is most common, but its definition is vaguer than the definitions of the other skin types.Methods: We measured facial sebum secretions with Sebumeter®. Sebum secretions were measured at five sites of the face seasonally for a year, in the same volunteers. Using the data obtained we developed a set of rules to define the combination skin type.Results: Regional differences in sebum secretion were confirmed. Sebum secretions on forehead, nose, and chin were higher than on both cheeks. Summer was found to be the highest sebum‐secreting season, and seasonal variations were found in the T‐ and U‐zones. A mismatch of skin type in the T‐ and U‐zones in more than two seasons appears to be close to subjective ratings of what is described as the ‘combination’ skin type.Conclusion: We showed that the face shows definitive regional and seasonal variations in sebum secretion. To define the combination skin type, seasonal variations in sebum secretion should be considered in addition to regional variations.
Castanospermine, a Potent Inhibitor of Dengue Virus Infection In Vitro and In Vivo
Authors: Whitby Kevin , Pierson Theodore C. , Geiss Brian , Lane Kelly , Engle Michael , Zhou Yi , Doms Robert W. , Diamond Michael S. 
Published: July 2005

ABSTRACTPrevious studies have suggested that α-glucosidase inhibitors such as castanospermine and deoxynojirimycin inhibit dengue virus type 1 infection by disrupting the folding of the structural proteins prM and E, a step crucial to viral secretion. We extend these studies by evaluating the inhibitory activity of castanospermine against a panel of clinically important flaviviruses including all four serotypes of dengue virus, yellow fever virus, and West Nile virus. Using in vitro assays we demonstrated that infections by all serotypes of dengue virus were inhibited by castanospermine. In contrast, yellow fever virus and West Nile virus were partially and almost completely resistant to the effects of the drug, respectively. Castanospermine inhibited dengue virus infection at the level of secretion and infectivity of viral particles. Importantly, castanospermine prevented mortality in a mouse model of dengue virus infection, with doses of 10, 50, and 250 mg/kg of body weight per day being highly effective at promoting survival (P≤ 0.0001). Correspondingly, castanospermine had no adverse or protective effect on West Nile virus mortality in an analogous mouse model. Overall, our data suggest that castanospermine has a strong antiviral effect on dengue virus infection and warrants further development as a possible treatment in humans.
Mycobacterial Codon Optimization Enhances Antigen Expression and Virus-Specific Immune Responses in RecombinantMycobacterium bovisBacille Calmette-Guérin Expressing Human Immunodeficiency Virus Type 1 Gag
Authors: Kanekiyo Masaru , Matsuo Kazuhiro , Hamatake Makiko , Hamano Takaichi , Ohsu Takeaki , Matsumoto Sohkichi , Yamada Takeshi , Yamazaki Shudo , Hasegawa Atsuhiko , Yamamoto Naoki , Honda Mitsuo 
Published: July 2005

ABSTRACTAlthough its potential for vaccine development is already known, the introduction of recombinant human immunodeficiency virus (HIV) genes toMycobacterium bovisbacille Calmette-Guérin (BCG) has thus far elicited only limited responses. In order to improve the expression levels, we optimized the codon usage of the HIV type 1 (HIV-1) p24 antigen gene ofgag(p24gag) and established a codon-optimized recombinant BCG (rBCG)-p24 Gag which expressed a 40-fold-higher level of p24 Gag than did that of nonoptimized rBCG-p24 Gag. Inoculation of mice with the codon-optimized rBCG-p24 Gag elicited effective immunity, as evidenced by virus-specific lymphocyte proliferation, gamma interferon ELISPOT cell induction, and antibody production. In contrast, inoculation of animals with the nonoptimized rBCG-p24 Gag induced only low levels of immune responses. Furthermore, a dose as small as 0.01 mg of the codon-optimized rBCG per animal proved capable of eliciting immune responses, suggesting that even low doses of a codon-optimized rBCG-based vaccine could effectively elicit HIV-1-specific immune responses.
Detailed Mapping of the Nuclear Export Signal in the Rous Sarcoma Virus Gag Protein
Authors: Scheifele Lisa Z. , Ryan Eileen P. , Parent Leslie J. 
Published: July 2005

ABSTRACT

The Rous sarcoma virus (RSV) Gag polyprotein undergoes transient nuclear trafficking as an intrinsic part of the virus assembly pathway. Nuclear export of Gag is crucial for the efficient production of viral particles and is accomplished through the action of a leptomycin B (LMB)-dependent nuclear export signal (NES) in the p10 domain (L. Z. Scheifele, R. A. Garbitt, J. D. Rhoads, and L. J. Parent, Proc. Natl. Acad. Sci. USA
99:
3944-3949, 2002). We have now mapped the nuclear export activity to the C-terminal portion of the p10 sequence and identified the four hydrophobic amino acids within this region that comprise a leucine-rich NES. Alteration of these hydrophobic residues resulted in the accumulation of Gag proteins within the nucleus and a budding defect greater than that obtained with LMB treatment of cells expressing the wild-type Gag protein (Scheifele et al., Proc. Natl. Acad. Sci. USA
99:
3944-3949, 2002). In addition, export of Gag from the nucleus was found to be a rate-limiting step in virus-like particle production. Consistent with a role for the NES sequence in viral replication, this cluster of hydrophobic residues in p10 is conserved across a wide range of avian retroviruses. Furthermore, naturally occurring substitutions within this region in related viruses maintained nuclear export activity and remained sensitive to the activity of LMB. Using gain-of-function approaches, we found that the hydrophobic motif in p10 was sufficient to promote the nuclear export of a heterologous protein and was positionally independent within the Gag polyprotein. Finally, the export pathway was further defined by the ability of specific nucleoporin inhibitors to prevent the egress of Gag from the nucleus, thereby identifying additional cellular mediators of RSV replication.
A Somatic Knockout of CBF1 in a Human B-Cell Line Reveals that Induction of CD21 and CCR7 by EBNA-2 Is Strictly CBF1 Dependent and that Downregulation of Immunoglobulin M Is Partially CBF1 Independent
Authors: Maier Sabine , Santak Maja , Mantik Anja , Grabusic Kristina , Kremmer Elisabeth , Hammerschmidt Wolfgang , Kempkes Bettina 
Published: July 2005

ABSTRACTCBF1 is a cellular highly conserved DNA binding factor that is ubiquitously expressed in all tissues and acts as a repressor of cellular genes. In Epstein-Barr virus growth-transformed B-cell lines, CBF1 serves as a central DNA adaptor molecule for several viral proteins, including the viral transactivator Epstein-Barr virus nuclear antigen 2 (EBNA-2). EBNA-2 binds to CBF1 and thereby gains access to regulatory regions of target genes and activates transcription. We have inactivated the CBF1 gene by homologous recombination in the human B-cell line DG75 and characterized changes in cellular gene expression patterns upon loss of CBF1 and activation of EBNA-2. CBF1-negative DG75 cells were viable and proliferated at wild-type rates. Loss of CBF1 was not sufficient to release repression of the previously described EBNA-2 target genes CD21 or CCR7, whereas induction of both target genes by EBNA-2 required CBF1. In contrast, repression of immunoglobulin M by EBNA-2 was mainly CBF1 independent. CBF1-negative DG75 B cells thus provide an excellent tool to dissect CBF1-dependent and -independent functions exerted by the EBNA-2 protein in future studies.
Interaction of Bovine Papillomavirus E2 Protein with Brd4 Stabilizes Its Association with Chromatin
Authors: McPhillips Maria G. , Ozato Keiko , McBride Alison A. 
Published: July 2005

ABSTRACT
The bovine papillomavirus E2 protein maintains and segregates the viral extrachromosomal genomes by tethering them to cellular mitotic chromosomes. E2 interacts with a cellular bromodomain protein, Brd4, to mediate the segregation of viral genomes into daughter cells. Brd4 binds acetylated histones and has been observed to diffusely coat mitotic chromosomes in several cell types. In this study, we show that in mitotic C127 cells, Brd4 diffusely coated the condensed chromosomes. However, in the presence of the E2 protein, E2 and Brd4 colocalized in punctate dots that were randomly distributed over the chromosomes. A similar pattern of E2 and Brd4 colocalization on mitotic chromosomes was observed in CV-1 cells, whereas only a faint chromosomal coating of Brd4 was detected in the absence of the E2 protein. Therefore, the viral E2 protein relocalizes and/or stabilizes the association of Brd4 with chromosomes in mitotic cells. The colocalization of E2 and Brd4 was also observed in interphase cells, indicating that this protein-protein interaction persists throughout the cell cycle. The interaction of E2 with Brd4 greatly stabilized the association of Brd4 with interphase chromatin. In both mitotic and interphase cells, this stabilization required a transcriptionally competent transactivation domain, but not the DNA binding function of the E2 protein. Thus, the E2 protein modulates the chromatin association of Brd4 during both interphase and mitosis. This study demonstrates that the segregation of papillomavirus genomes is not simply due to the passive hitchhiking of the E2/genome complex with a convenient cellular chromosomal protein.
AIP1/Alix Is a Binding Partner of Sendai Virus C Protein and Facilitates Virus Budding
Authors: Sakaguchi Takemasa , Kato Atsushi , Sugahara Fumihiro , Shimazu Yukie , Inoue Makoto , Kiyotani Katsuhiro , Nagai Yoshiyuki , Yoshida Tetsuya 
Published: July 2005

ABSTRACT
The C protein, an accessory protein of Sendai virus (SeV), has anti-interferon capacity and suppresses viral RNA synthesis. In addition, it is thought that the C protein is involved in virus budding because of the low efficiency of release of progeny virions from C-knockout virus-infected cells and because of the requirement of the C protein for efficient release of virus-like particles. Here, we identified AIP1/Alix, a host protein involved in apoptosis and endosomal membrane trafficking, as an interacting partner of the C protein using a yeast two-hybrid system. The amino terminus of AIP1/Alix and the carboxyl terminus of the C protein are important for the interaction in mammalian cells. Mutant C proteins unable to bind AIP1/Alix failed to accelerate the release of virus-like particles from cells. Furthermore, overexpression of AIP1/Alix enhanced SeV budding from infected cells in a C-protein-dependent manner, while the release of nucleocapsid-free empty virions was also enhanced. Finally, AIP1/Alix depletion by small interfering RNA resulted in suppression of SeV budding. The results of this study suggest that AIP1/Alix plays a role in efficient SeV budding and that the SeV C protein facilitates virus budding through interaction with AIP1/Alix.
Human Tripartite Motif 5α Domains Responsible for Retrovirus Restriction Activity and Specificity
Authors: Perez-Caballero David , Hatziioannou Theodora , Yang Annie , Cowan Simone , Bieniasz Paul D. 
Published: July 2005

ABSTRACT
The tripartite motif 5α protein (TRIM5α) is one of several factors expressed by mammalian cells that inhibit retrovirus replication. Human TRIM5α (huTRIM5α) inhibits infection by N-tropic murine leukemia virus (N-MLV) but is inactive against human immunodeficiency virus type 1 (HIV-1). However, we show that replacement of a small segment in the carboxy-terminal B30.2/SPRY domain of huTRIM5α with its rhesus macaque counterpart (rhTRIM5α) endows it with the ability to potently inhibit HIV-1 infection. The B30.2/SPRY domain and an additional domain in huTRIM5α, comprising the amino-terminal RING and B-box components of the TRIM motif, are required for N-MLV restriction activity, while the intervening coiled-coil domain is necessary and sufficient for huTRIM5α multimerization. Truncated huTRIM5α proteins that lack either or both the N-terminal RING/B-Box or the C-terminal B30.2/SPRY domain form heteromultimers with full-length huTRIM5α and are dominant inhibitors of its N-MLV restricting activity, suggesting that homomultimerization of intact huTRIM5α monomers is necessary for N-MLV restriction. However, localization in large cytoplasmic bodies is not required for inhibition of N-MLV by huTRIM5α or for inhibition of HIV-1 by chimeric or rhTRIM5α.
The Replicative Fitness of Primary Human Immunodeficiency Virus Type 1 (HIV-1) Group M, HIV-1 Group O, and HIV-2 Isolates
Authors: Ariën Kevin K. , Abraha Awet , Quiñones-Mateu Miguel E. , Kestens Luc , Vanham Guido , Arts Eric J. 
Published: July 2005

ABSTRACTThe main (M) group of human immunodeficiency virus type 1 (HIV-1) is responsible for the global AIDS epidemic while HIV-1 group O (outlier) and HIV type 2 are endemic only in west and central Africa. The failure of HIV-2 and especially HIV-1 group O to spread following the initial zoonotic jumps is not well understood. This study was designed to examine the relative replicative capacities between these human lentiviruses. A pairwise competition experiment was performed with peripheral blood mononuclear cells with eight HIV-2 isolates, 6 group O viruses, and 15 group M viruses of subtype A (2 viruses), B (5 viruses), C (4 viruses), D (2 viruses) and CRF01_AE (2 viruses). HIV-1 group M isolates of any subtype were typically 100-fold-more fit than group O or HIV-2 strains when competed in peripheral blood mononuclear cells from various humans. This order in replicative fitness was also observed when virus pairs were added to human dendritic cells and then cocultured with primary, quiescent T cells, which is the model for HIV-1 transmission. These results suggest that reduced replicative and transmission fitness may be contributing to the low prevalence and limited geographical spread of HIV-2 and group O HIV-1 in the human population.
Molecular Epidemiology of Simian Immunodeficiency Virus SIVsm in U.S. Primate Centers Unravels the Origin of SIVmac and SIVstm
Authors: Apetrei Cristian , Kaur Amitinder , Lerche Nicholas W. , Metzger Michael , Pandrea Ivona , Hardcastle Johnny , Falkenstein Shelley , Bohm Rudolf , Koehler Jeffrey , Traina-Dorge Vicki , Williams Tessa , Staprans Silvija , Plauche Gail , Veazey Ronald S. , McClure Harold , Lackner Andrew A. , Gormus Bobby , Robertson David L. , Marx Preston A. 
Published: July 2005

ABSTRACT

Retrospective molecular epidemiology was performed on samples from four sooty mangabey (SM) colonies in the United States to characterize simian immunodeficiency virus SIVsm diversity in SMs and to trace virus circulation among different primate centers (PCs) over the past 30 years. The following SIVsm sequences were collected from different monkeys: 55 SIVsm isolates from the Tulane PC sampled between 1984 and 2004, 10 SIVsm isolates from the Yerkes PC sampled in 2002, 7 SIVsm isolates from the New Iberia PC sampled between 1979 and 1986, and 8 SIVsm isolates from the California PC sampled between 1975 and 1977. PCR and sequencing were done to characterize the
gag
,
pol
, and
env
gp36 genes. Phylogenetic analyses were correlated with the epidemiological data. Our analysis identified nine different divergent phylogenetic lineages that cocirculated in these four SM colonies in the Unites States in the past 30 years. Lineages 1 to 5 have been identified previously. Two of the newly identified SIVsm lineages found in SMs are ancestral to SIVmac251/SIVmac239/SIVmne and SIVstm. We further identified the origin of these two macaque viruses in SMs from the California National Primate Research Center. The diversity of SIVsm isolates in PCs in the United States mirrors that of human immunodeficiency virus type 1 (HIV-1) group M subtypes and offers a model for the molecular epidemiology of HIV and a new approach to vaccine testing. The cocirculation of divergent SIVsm strains in PCs resulted in founder effects, superinfections, and recombinations. This large array of SIVsm strains showing the same magnitude of diversity as HIV-1 group M subtypes should be extremely useful for modeling the efficacy of vaccination strategies under the real-world conditions of HIV-1 diversity. The genetic variability of SIVsm strains among PCs may influence the diagnosis and monitoring of SIVsm infection and, consequently, may bias the results of pathogenesis studies.
Changes in Human Immunodeficiency Virus Type 1 Fitness and Genetic Diversity during Disease Progression
Authors: Troyer Ryan M. , Collins Kalonji R. , Abraha Awet , Fraundorf Erika , Moore Dawn M. , Krizan Randall W. , Toossi Zahra , Colebunders Robert L. , Jensen Mark A. , Mullins James I. , Vanham Guido , Arts Eric J. 
Published: July 2005

ABSTRACT

This study examined the relationship between ex vivo human immunodeficiency virus type 1 (HIV-1) fitness and viral genetic diversity during the course of HIV-1 disease. Primary HIV-1 isolates from 10 patients at different time points were competed against control HIV-1 strains in peripheral blood mononuclear cell (PBMC) cultures to determine relative fitness values. Patient HIV-1 isolates sequentially gained fitness during disease at a significant rate that directly correlated with viral load and HIV-1
env
C2V3 diversity. A loss in both fitness and viral diversity was observed upon the initiation of antiretroviral therapy. A possible relationship between genotype and phenotype (virus replication efficiency) is supported by the parallel increases in ex vivo fitness and viral diversity during disease, of which the correlation is largely based on specific V3 sequences. Syncytium-inducing, CXCR4-tropic HIV-1 isolates did have higher relative fitness values than non-syncytium-inducing, CCR5-tropic HIV-1 isolates, as determined by dual virus competitions in PBMC, but increases in fitness during disease were not solely powered by a gradual switch in coreceptor usage. These data provide in vivo evidence that increasing HIV-1 replication efficiency may be related to a concomitant increase in HIV-1 diversity, which in turn may be a determining factor in disease progression.