bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Unintended Impact of Welfare Reform on the Medicaid Enrollment of Eligible Immigrants
Authors: Kandula Namratha R. , Grogan Colleen M. , Rathouz Paul J. , Lauderdale Diane S. 
Published: August 2004

Background. During welfare reform, Congress passed legislation barring legal immigrants who entered the United States after August 1996 from Medicaid for five years after immigration. This legislation intended to bar only new immigrants (post‐1996 immigrants) from Medicaid. However it may have also deterred the enrollment of legal immigrants who immigrated before 1996 (pre‐1996 immigrants) and who should have remained Medicaid eligible.Objectives. To compare the Medicaid enrollment of U.S.‐born citizens to pre‐1996 immigrants, before and after welfare reform, and to determine if variation in state Medicaid policies toward post‐1996 immigrants modified the effects of welfare reform on pre‐1996 immigrants.Data Source/Study Design. Secondary database analysis of cross‐sectional data from 1994–2001 of the U.S. Census Bureau, Annual Demographic Survey of March Supplement of the Current Population Survey.Subjects. Low‐income, U.S.‐born adults (N=116,307) and low‐income pre‐1996 immigrants (N=24,367) before and after welfare reform.Measures. Self‐reported Medicaid enrollment.Results. Before welfare reform, pre‐1996 immigrants were less likely to enroll in Medicaid than the U.S.‐born (OR=0.55; 95 percent CI, 0.51–0.59). After welfare reform, pre‐1996 immigrants were even less likely to enroll in Medicaid. The proportion of immigrants in Medicaid dropped 3 percentage points after 1996; for the U.S.‐born it dropped 1.6 percentage points (p=0.012). Except for California, state variation in Medicaid policy toward post‐1996 immigrants did modify the effect of welfare reform on pre‐1996 immigrants.Conclusions. Federal laws limiting the Medicaid eligibility of specific subgroups of immigrants appear to have had unintended consequences on Medicaid enrollment in the larger, still eligible immigrant community. Inclusive state policies may overcome this effect.
Subsidies and the Demand for Individual Health Insurance in California
Authors: Susan Marquis M. , Buntin Melinda Beeuwkes , Escarce José J. , Kapur Kanika , Yegian Jill M. 
Published: August 2004

Objective. To estimate the effect of changes in premiums for individual insurance on decisions to purchase individual insurance and how this price response varies among subgroups of the population.Data Source. Survey responses from the Current Population Survey (http://www.bls.census.gov/cps/cpsmain.htm), the Survey of Income and Program Participation (http://www.sipp.census.gov/sipp), the National Health Interview Survey (http://www.cdc.gov/nchs/nhis.htm), and data about premiums and plans offered in the individual insurance market in California, 1996–2001.Study Design. A logit model was used to estimate the decisions to purchase individual insurance by families without access to group insurance. This was modeled as a function of premiums, controlling for family characteristics and other characteristics of the market. A multinomial model was used to estimate the choice between group coverage, individual coverage, and remaining uninsured for workers offered group coverage as a function of premiums for individual insurance and out‐of‐pocket costs of group coverage.Principal Findings. The elasticity of demand for individual insurance by those without access to group insurance is about −.2 to −.4, as has been found in earlier studies. However, there are substantial differences in price responses among subgroups with low‐income, young, and self‐employed families showing the greatest response. Among workers offered group insurance, a decrease in individual premiums has very small effects on the choice to purchase individual coverage versus group coverage.Conclusions. Subsidy programs may make insurance more affordable for some families, but even sizeable subsidies are unlikely to solve the problem of the uninsured. We do not find evidence that subsidies to individual insurance will produce an unraveling of the employer‐based health insurance system.
Genome Size and Structure Determine Efficiency of Postinternalization Steps and Gene Transfer of Capsid-Modified Adenovirus Vectors in a Cell-Type-Specific Manner
Authors: Shayakhmetov Dmitry M. , Li Zong-Yi , Gaggar Anuj , Gharwan Helen , Ternovoi Vladimir , Sandig Volker , Lieber André 
Published: August 2004

ABSTRACTAdenovirus serotype 5 (Ad5) vectors containing Ad B-group fibers have become increasingly popular as gene transfer vectors because they efficiently transduce human cell types that are relatively refractory to Ad5 infection. So far, most B-group fiber-containing vectors have been first-generation vectors, deleted of E1 and/or E3 genes. Transduction with these vectors, however, results in viral gene expression and is associated with cytotoxicity and immune responses against transduced cells. To circumvent these problems, we developed fiber-chimeric Ad vectors devoid of all viral genes that were produced either by the homologous recombination of first-generation vectors or by using the Cre/lox-based helper virus system. In this study we compared early steps of infection between first-generation (35-kb genome) and Ad vectors devoid of all viral genes with genome sizes of 28 kb and 12.6 kb. All vectors possessed an Ad35-derived fiber knob domain, which uses CD46 as a primary attachment receptor. Using immortalized human hematopoietic cell lines and primary human CD34-positive hematopoietic cells, we found that the Ad genome size did not affect the efficiency of virus attachment to and internalization into cells. Furthermore, independently of the genome length and structure, all vectors migrated to the nucleus through late endosomal and lysosomal cellular compartments. However, the vector containing the short 12.6-kb genome was unable to efficiently escape from endosomes and deliver its DNA into the nucleus. Moreover, compared to other vectors, these Ad particles were less stable and had an abnormal capsid protein composition, including a lack of capsid-stabilizing protein IX. Our data indicate that the size and structure of the packaged viral genomes can affect the integrity of Ad particles, which in turn results in lower infectivity of Ad vectors.
Human Cytomegalovirus UL131-128 Genes Are Indispensable for Virus Growth in Endothelial Cells and Virus Transfer to Leukocytes
Authors: Hahn Gabriele , Revello Maria Grazia , Patrone Marco , Percivalle Elena , Campanini Giulia , Sarasini Antonella , Wagner Markus , Gallina Andrea , Milanesi Gabriele , Koszinowski Ulrich , Baldanti Fausto , Gerna Giuseppe 
Published: August 2004

ABSTRACT

Human cytomegalovirus (HCMV), a ubiquitous human pathogen, is the leading cause of birth defects and morbidity in immunocompromised patients and a potential trigger for vascular disease. HCMV replicates in vascular endothelial cells and drives leukocyte-mediated viral dissemination through close endothelium- leukocyte interaction. However, the genetic basis of HCMV growth in endothelial cells and transfer to leukocytes is unknown. We show here that the UL131-128 gene locus of HCMV is indispensable for both productive infection of endothelial cells and transmission to leukocytes. The experimental evidence for this is based on both the loss-of-function phenotype in knockout mutants and natural variants and the gain-of-function phenotype by
trans
-complementation with individual UL131, UL130, and UL128 genes. Our findings suggest that a common mechanism of virus transfer may be involved in both endothelial cell tropism and leukocyte transfer and shed light on a crucial step in the pathogenesis of HCMV infection.
Transcriptional Activation by the Kaposi's Sarcoma-Associated Herpesvirus Latency-Associated Nuclear Antigen Is Facilitated by an N-Terminal Chromatin-Binding Motif
Authors: Wong Lai-Yee , Matchett Gerald A. , Wilson Angus C. 
Published: August 2004

ABSTRACT
In immunocompromised patients, infection with Kaposi's sarcoma-associated herpesvirus (KSHV) can give rise to Kaposi's sarcoma and several lymphoproliferative disorders. In these tumors, KSHV establishes a latent infection in many of the rapidly proliferating and morphologically abnormal cells. Only a few viral gene products are expressed by the latent virus, and one of the best characterized is the latency-associated nuclear antigen (LANA), a nuclear protein required for the maintenance of viral episomal DNA in the dividing host cell. LANA can also activate or repress an assortment of cellular and viral promoters and may contribute to pathogenesis by allowing the proliferation and survival of host cells. Here we show that activation of the human E2F1 and cyclin-dependent kinase-2 (CDK2) promoters requires elements from both the N- and C-terminal regions of LANA. Deletion of the first 22 amino acids, which are necessary for episome tethering, does not affect nuclear localization but significantly reduces transactivation. Within the deleted peptide, we have identified a short sequence, termed the chromatin-binding motif (CBM), that binds tightly to interphase and mitotic chromatin. A second chromatin-binding activity resides in the C terminus but is not sufficient for optimal transactivation. Alanine substitutions within the CBM reveal a close correlation between the transactivation and chromatin binding activities, implying a mechanistic link. In contrast to promoter activation, we find that the 223 amino acids of the LANA C terminus are sufficient to inhibit p53-mediated activation of the human BAX promoter, indicating that the CBM is not required for all transcription-related functions.
Re-Evaluating Natural Resistance to Herpes Simplex Virus Type 1
Authors: Halford William P. , Balliet John W. , Gebhardt Bryan M. 
Published: August 2004

ABSTRACTIt is often stated that individuals of a species can differ significantly in their innate resistance to infection with herpes simplex virus type 1 (HSV-1). Three decades ago Lopez reported that C57BL/6 mice could survive a 5,000-fold-higher inoculum of HSV-1 given intraperitoneally than mice of the A or BALB/c strain (Nature258:152-153, 1975). Susceptible strains of mice died of encephalitis-like symptoms, suggesting that viral spread to the central nervous system was the cause of death. Although Lopez's study documented that C57BL/6 mice were resistant to the development of HSV-1 encephalitis and mortality, the resistance of C57BL/6 mice to other steps of the HSV-1 infection process was not assessed. The results of the present study extend these observations to clarify the difference between resistance to (i) HSV-1 pathogenesis, (ii) HSV-1 replication, (iii) HSV-1 spread, and (iv) the establishment of latent HSV-1 infection. Although C57BL/6 mice are more resistant to HSV-1 pathogenesis than BALB/c mice, the results of the present study establish that HSV-1 enters, replicates, spreads, and establishes latent infections with virtually identical efficiencies in C57BL/6 and BALB/c mice. These observations raise questions about the validity of the inference that differences in natural resistance are relevant in explaining what differentiates humans with recurrent herpetic disease from the vast majority of asymptomatic carriers of HSV-1 and HSV-2.
Kinetics of Virus-Specific CD8+T Cells and the Control of Human Immunodeficiency Virus Infection
Authors: Davenport Miles P. , Ribeiro Ruy M. , Perelson Alan S. 
Published: August 2004

ABSTRACTSeveral primate models indicate that cytotoxic T lymphocyte-inducing vaccines may be unable to prevent human immunodeficiency virus infection but may have a long-term benefit in controlling viral replication and delaying disease progression. Here we show that analysis of the kinetics of antigen-specific CD8+T-cell expansion suggests a delay in activation following infection that allows unimpeded early viral replication. Viral kinetics do not differ between controls and vaccinees during this delay phase. An increase in virus-specific CD8+T-cell numbers around day 10 postinfection coincides with a slowing in viral replication in vaccinees and reduces peak viral loads by around 1 log. However, this response is too little too late to prevent establishment of persistent infection.
Helper-Dependent Adenoviral Vector-Mediated Delivery of Woodchuck-Specific Genes for Alpha Interferon (IFN-α) and IFN-γ: IFN-α but Not IFN-γ Reduces Woodchuck Hepatitis Virus Replication in Chronic Infection In Vivo
Authors: Fiedler Melanie , Rödicker Florian , Salucci Valentina , Lu Mengji , Aurisicchio Luigi , Dahmen Uta , Jun Li , Dirsch Olaf , Pützer Brigitte M. , Palombo Fabio , Roggendorf Michael 
Published: August 2004

ABSTRACTAlpha interferon (IFN-α) and IFN-γ are able to suppress hepadnavirus replication. The intrahepatic expression of high levels of IFN may enhance the antiviral activity. We investigated the effects of woodchuck-specific IFN-α (wIFN-α) and IFN-γ(wIFN-γ) on woodchuck hepatitis virus (WHV) replication in vivo by helper-dependent adenoviral (HD-Ad) vector-mediated gene transfer. The expression of biologically active IFNs was demonstrated in vitro after transduction of woodchuck cells with HD-Ad vectors encoding wIFN-α (HD-AdwIFN-α) or wIFN-γ (HD-AdwIFN-γ). The transduction efficacy of the HD-Ad vector in woodchuck liver in vivo was tested with a vector expressing green fluorescence protein (GFP). Immunohistochemical staining of liver samples on day 5 after injection showed expression of GFP in a high percentage of liver cells surrounding the central vein. The transduction of livers of WHV carriers in vivo with HD-AdwIFN-α or HD-AdwIFN-γ induced levels of biologically active IFN, which could be measured in the sera of these animals. Expression of wIFN-α in the liver reduced intrahepatic WHV replication and WHV DNA in sera of about 1 log step in two of two woodchucks. Transduction with HD-AdwIFN-γ, however, reduced WHV replicative intermediates only slightly in two of three animals, which was not accompanied with significant changes in the WHV DNA in sera. We demonstrated for the first time the successful HD-Ad vector-mediated transfer of genes for IFN-α and IFN-γ in vivo and timely limited reduction of WHV replication by wIFN-α, but not by wIFN-γ.
Bidirectional Increase in Permeability of Nuclear Envelope upon Poliovirus Infection and Accompanying Alterations of Nuclear Pores
Authors: Belov George A. , Lidsky Peter V. , Mikitas Olga V. , Egger Denise , Lukyanov Konstantin A. , Bienz Kurt , Agol Vadim I. 
Published: August 2004

ABSTRACT

Poliovirus and some other picornaviruses trigger relocation of certain nuclear proteins into the cytoplasm. Here, by using a protein changing its fluorescence color with time and containing a nuclear localization signal (NLS), we demonstrate that the poliovirus-triggered relocation is largely due to the exit of presynthesized nuclear protein into the cytoplasm. The leakiness of the nuclear envelope was also documented by the inability of nuclei from digitonin-permeabilized, virus-infected (but not mock-infected) cells to retain an NLS-containing derivative of green fluorescent protein (GFP). The cytoplasm-to-nucleus traffic was also facilitated during infection, as evidenced by experiments with GAPDH (glyceraldehyde-3-phosphate dehydrogenase), cyclin B1, and an NLS-lacking derivative of GFP, which are predominantly cytoplasmic in uninfected cells. Electron microscopy demonstrated that a bar-like barrier structure in the channel of the nuclear pores, seen in uninfected cells, was missing in the infected cells, giving the impression of fully open pores. Transient expression of poliovirus 2A protease also resulted in relocation of the nuclear proteins. Lysates from poliovirus-infected or 2A-expressing cells induced efflux of 3×EGFP-NLS from the nuclei of permeabilized uninfected cells. This activity was inhibited by the elastase inhibitors elastatinal and
N
-(methoxysuccinyl)-
l
-alanyl-
l
-alanyl-
l
-prolyl-
l
-valine chloromethylketone (drugs known also to be inhibitors of poliovirus protease 2A), a caspase inhibitor zVAD(OMe), fmk, and some other protease inhibitors. These data suggest that 2A elicited nuclear efflux, possibly in cooperation with a zVAD(OMe).fmk-sensitive protease. However, poliovirus infection facilitated nuclear protein efflux also in cells deficient in caspase-3 and caspase-9, suggesting that the efflux may occur without the involvement of these enzymes. The biological relevance of nucleocytoplasmic traffic alterations in infected cells is discussed.
During Lytic Infection Herpes Simplex Virus Type 1 Is Associated with Histones Bearing Modifications That Correlate with Active Transcription
Authors: Kent J. R. , Zeng P.-Y. , Atanasiu D. , Gardner J. , Fraser N. W. , Berger S. L. 
Published: August 2004

ABSTRACT
Herpes simplex virus type 1 (HSV-1) is a large (150-kb) double-stranded DNA virus that forms latent infections in neuronal cells of the human peripheral nervous system. Previous work determined that the HSV-1 genome is found in an ordered nucleosomal structure during latent infection. However, during lytic infection, it was unclear whether viral DNA was in a chromatin state. We examined HSV-1 during lytic infection using micrococcal nuclease digestion and chromatin immunoprecipitation. The HSV-1 genome is at least partially nucleosomal, although apparently not in a regular repeating structure. Analysis of histones associated with HSV-1, within both the promoter and the transcribed regions, revealed covalent amino tail modifications similar to those associated with active host mammalian genes. Certain of the modifications were detected in the temporal order expected of the immediate-early, early, and late gene classes. These data suggest that productive infection may be accompanied by acquisition of a permissive chromatin state.
A Naturally Occurring Variation in the Proline-Rich Region Does Not Attenuate Human Immunodeficiency Virus Type 1 Nef Function
Authors: Rücker Elke , Münch Jan , Wildum Steffen , Brenner Matthias , Eisemann Jutta , Margolis Leonid , Kirchhoff Frank 
Published: August 2004

ABSTRACT
We analyzed human immunodeficiency virus type 1 (HIV-1) Nef variants to further evaluate the functional relevance of the R71T substitution previously proposed to attenuate viral replication (Fackler et al., Curr. Biol. 11:1294-1299, 2001). Our results demonstrate that this variation in the proline-rich region does not significantly affect the functional activity of Nef or HIV-1 infectivity or replication.
Newly Synthesized Hepatitis C Virus Replicon RNA Is Protected from Nuclease Activity by a Protease-Sensitive Factor(s)
Authors: Yang Guang , Pevear Daniel C. , Collett Marc S. , Chunduru Srinivas , Young Dorothy C. , Benetatos Christopher , Jordan Robert 
Published: August 2004

ABSTRACT
Biochemical characterization of hepatitis C virus (HCV) replication using purified, membrane-associated replication complexes is hampered by the presence of endogenous nuclease activity that copurifies with the replication complex. In this study, pulse-chase analyses were used to demonstrate that newly synthesized replicon RNA was protected from nuclease activity by a factor(s) that was sensitive to 0.5% NP-40 or protease treatment. Nuclease susceptibility was not related to disruption of lipid membranes, since NP-40 did not significantly affect the buoyant density of HCV replication complexes or protease susceptibility of HCV NS3 and NS5A proteins. These results suggest that a protease-sensitive factor(s) protects newly synthesized RNA from nuclease degradation.
Detection of JC Virus-Specific Cytotoxic T Lymphocytes in Healthy Individuals
Authors: Du Pasquier R. A. , Schmitz J. E. , Jean-Jacques J. , Zheng Y. , Gordon J. , Khalili K. , Letvin N. L. , Koralnik I. J. 
Published: August 2004

ABSTRACTThe polyomavirus JC (JCV) infects 85% of healthy individuals, and its reactivation in a limited number of immunosuppressed people causes progressive multifocal leukoencephalopathy (PML), a severe demyelinating disease of the central nervous system. We hypothesized that JCV-specific cytotoxic T lymphocytes (CTLs) might control JCV replication in healthy individuals, blocking the evolution of PML. Using51Cr release and tetramer staining assays, we show that 8 of 11 HLA-A*0201+healthy subjects (73%) harbor detectable JCV-specific CD8+CTLs that recognize one or two epitopes of JCV VP1 protein, the HLA-A*0201-restricted VP1p36and VP1p100epitopes. We determined that the frequency of JCV VP1 epitope-specific CTLs varied from less than 1/100,000 to 1/2,494 peripheral blood mononuclear cells. More individuals had JCV VP1-specific than cytomegalovirus-specific CTLs (8 of 11 subjects [73%] versus 2 of 10 subjects [20%], respectively). These results show that a CD8+-T-cell response against JCV is commonly found in immunocompetent people and suggest that these cells might protect against the development of PML.
Effect of the Addition of Oligosaccharides on the Biological Activities and Antigenicity of Influenza A/H3N2 Virus Hemagglutinin
Authors: Abe Yasuhiro , Takashita Emi , Sugawara Kanetsu , Matsuzaki Yoko , Muraki Yasushi , Hongo Seiji 
Published: August 2004

ABSTRACT
Influenza A/H3N2 viruses have developed an increased number of glycosylation sites on the globular head of the hemagglutinin (HA) protein since their appearance in 1968. Here, the effect of addition of oligosaccharide chains to the HA of A/H3N2 viruses on its biological activities was investigated. We constructed seven mutant HAs of A/Aichi/2/68 virus with one to six glycosylation sites on the globular head, as found in natural isolates, by site-directed mutagenesis and analyzed their intracellular transport, receptor binding, and cell fusion activities. The glycosylation sites of mutant HAs correspond to representative A/H3N2 isolates (A/Victoria/3/75, A/Memphis/6/86, or A/Sydney/5/97). The results showed that all the mutant HAs were transported to the cell surface as efficiently as wild-type HA. Although mutant HAs containing three to six glycosylation sites decreased receptor binding activity, their cell fusion activity was not affected. The reactivity of mutant HAs having four to six glycosylation sites with human sera collected in 1976 was much lower than that of wild-type HA. Thus, the addition of new oligosaccharides to the globular head of the HA of A/H3N2 viruses may have provided the virus with an ability to evade antibody pressures by changing antigenicity without an unacceptable defect in biological activity.