bluuebunny/crossref_metadata_2025_split huggingface dataset:
HEALTH TECHNOLOGY ASSESSMENT IN THE AREA OF PREVENTION
Authors: Mousiama Tereza , Ioakimidou Souzana , Largatzi Evagelia , Kaitelidou Daphne , Liaropoulus Lycurgus 
Published: December 2002

Objective: To explore the impact of health technology assessment (HTA) on health policy and practice in Greece through selected screening case studies in the prevention area. The three cases studied were mammography screening, PSA screening, and routine ultrasonography in normal pregnancy.Methods: Official policy recommendations or reports, a literature review of Greek published research as well as gray literature from various sources, and interviews with specialists and medical associations were performed, and their impact on health policy formulation was examined.Results: The implementation of the screening tests does not take the form of structured mass screening programs. Almost all physicians (urologists-pathologists, gynecologists) apply PSA and routine ultrasonography in normal pregnancy respectively with the purpose of either prevention or diagnosis. Mammography is applied generally for prevention or diagnosis, but there are some mass screening programs at a local level. In addition, the results show no evidence that the efficacy and the cost-effectiveness of the three screening programs have been a matter of serious concern and investigation for the purposes of policy formulation in Greece.Conclusion: The results point to a need for the implementation of HTA methods on mass screening preventive programs in which real value and cost remain unclear and whose use is based on empirical and personal assessments.
A METHOD FOR RESEARCH PROGRAMMING IN THE FIELD OF EVIDENCE-BASED MEDICINE
Authors: de Vet Henrica C. W. , Kroese Mariëlle E. A. L. , Scholten Rob J. P. M. , Bouter Lex M. 
Published: December 2002

Objective: This paper presents the method we used in programming research on the efficacy of therapeutic interventions for nine chronic benign pain disorders.Methods: We started with an inventory to identify commonly applied interventions. For these interventions we searched the literature to identify gaps in evidence. First, we searched for recent reviews, of which we assessed the methodologic quality. If only reviews of poor or moderate quality were found, a new systematic review was recommended. When we found no recent reviews, we searched for randomized controlled trials (RCTs). If there was insufficient or inconsistent evidence, the performance of a new RCT was advised. This structured procedure resulted in a list with topics for which new systematic reviews were recommended and topics for which new RCTs were needed. These lists were the starting points for priority setting by four Centers for Pain Management and Research. All members of the centers were asked to state the priority of each topic. The resulting hierarchy of topics for their own center was discussed in a meeting in each center, giving participants the opportunity to elucidate their views and considerations.Results: The final result was a robust priority list for the need of research (systematic reviews and RCTs) on chronic benign pain syndromes.Discussion: The strength and weaknesses of this approach are discussed. This method of priority setting is by no means restricted to treatments for chronic pain; it is also a useful approach for programming research to enable evidence-based medicine in other fields of interest.
THE MAN WHO WAS WALTER
Authors: Pattinson John Patrick 
Published: December 2002

His tall upright figure and quick penetrating glance indicate the man of energy and decision, and those who are most intimately acquainted with him know best that these qualities are combined with a large measure of kindliness and breadth of view, and a readiness to be of use to such as are brought into contact with him in official capacity and in private life. (Biograph 158)IT IS MY PURPOSE to demonstrate that the above paragraph, published in 1880, is a description of the man who wrote My Secret Life, the man who called himself Walter. I shall be very little concerned with literary or psychological analysis. I intend simply to present the process of research which led me to conclude, beyond reasonable doubt, that I have discovered the identity of the author, then to summarize such biographical information as I have been able to obtain from contemporary sources or archival records, and to comment, where necessary, on the correspondences or differences between Walter’s narrative and the real man’s outer life.
L‐Arginine and Antineutrophil Serum Enable Venular Control of Capillary Perfusion in Hypercholesterolemic Rats
Authors: NELLORE KAVITHA , HARRIS NORMAN R. 
Published: December 2002

ABSTRACTObjective: The purpose of this study was to investigate and counteract dysfunctional control of capillary flow in hypercholesterolemia. Capillary flow is controlled by arteriolar tone, which in turn is influenced by mediators released from closely paired venules in a mechanism that involves nitric oxide (NO). However, venular control of capillary flow is altered with hypercholesterolemia.Methods: Rats were given a normal or high‐cholesterol diet before measurements of mesenteric capillary red blood cell velocity. The arteriolar pathway leading to the capillary was videotaped to measure the percent of the surrounding area (within 15 µm) that was occupied by a venule (% pairing).Results: Venule‐paired arterioles were significantly smaller in hypercholesterolemia compared with normocholesterolemia, corresponding to slower capillary flow. A positive correlation between capillary velocity and % pairing observed in normocholesterolemia was not observed during NO synthase inhibition or in hypercholesterolemic rats. However, positive correlations between the two parameters were found in hypercholesterolemia when the rats were given drinking water supplementation of L‐arginine or an injection of antineutrophil serum, both of which tended to improve velocity in capillaries branching from venulepaired arteriolar pathways.Conclusions: Dysfunctional venular control of capillary perfusion in hypercholesterolemia may be a consequence of a neutrophil‐mediated deficiency of NO.
Mutations in the Cytoplasmic Domain of a Paramyxovirus Fusion Glycoprotein Rescue Syncytium Formation and Eliminate the Hemagglutinin-Neuraminidase Protein Requirement for Membrane Fusion
Authors: Seth Shaguna , Vincent Annelet , Compans R. W. 
Published: December 2002

ABSTRACT
SER virus is closely related to the paramyxovirus simian virus 5 (SV5) but is defective in syncytium formation. The SER virus F protein has a long cytoplasmic tail (CT) domain that has been shown to inhibit membrane fusion, and this inhibitory effect could be eliminated by truncation of the C-terminal sequence (S. Tong, M. Li, A. Vincent, R. W. Compans, E. Fritsch, R. Beier, C. Klenk, M. Ohuchi, and H.-D. Klenk, Virology 301:322-333, 2002). To study the sequence requirements for regulation of fusion, codons for SER virus F protein residues spanning amino acids 535 to 542 and 548 were mutated singly to alanines, and the two leucine residues at positions 539 and 548 were mutated doubly to alanines. We found that leu-539 and leu-548 in the CT domain played a critical role in the inhibition of fusion, as mutation of the two leucines singly to alanines partially rescued fusion, and the double mutation L539, 548A completely rescued syncytium formation. Mutation of charged residues to alanines had little effect on the suppression of fusion activity, whereas the mutation of serine residues to alanines enhanced fusion activity significantly. The L539, 548A mutant also showed extensive syncytium formation when expressed without the SER virus HN protein. By constructing a chimeric SV5-SER virus F CT protein, we also found that the inhibitory effect of the long CT of the SER virus F protein could be partially transferred to the SV5 F protein. These results demonstrate that an elongated CT of a paramyxovirus F protein interferes with membrane fusion in a sequence-dependent manner.
ZEB Negatively Regulates the Lytic-Switch BZLF1 Gene Promoter of Epstein-Barr Virus
Authors: Kraus Richard J. , Perrigoue Jacqueline G. , Mertz Janet E. 
Published: December 2002

ABSTRACTEpstein-Barr virus (EBV) is a human herpesvirus capable of establishing a latent state in B lymphocytes. The product of the immediate-early BZLF1 gene, Zta, is a transcriptional transactivator essential for viral DNA amplification and virion production. Previously, we identified a negativecis-acting element within the BZLF1 promoter termed ZV. ZV contains the sequence 5′-CAGGTA-3′ located at nucleotides −17 to −12 relative to the transcription initiation site. It sequence specifically binds a cellular factor, ZVR. Based on sequence binding specificity, we postulated that ZVR may be zinc finger E-box binding factor (ZEB) or a related zinc finger/homeodomain family member. We show here by immunoshift assays that ZVR and human ZEB specifically cross-react with an antibody to δEF1, the chicken homolog of ZEB. Competition electrophoretic mobility shift assays confirmed that ZEB binds to the ZV element with the same binding specificity as ZVR. Overexpression of ZEB in either B-lymphocytic DG75 cells or mammary epithelial MCF-7 cells repressed Zta-induced activation of the BZLF1 promoter four- to fivefold via the ZV site. Thus, we conclude that the previously identified cellular repressor ZVR is, in fact, ZEB. We also present evidence that other cellular factors likely affect the transcriptional activity of ZEB. Lastly, we identify a ZEB-binding site within the promoter of the lytic BRLF1 gene of EBV. We postulate that ZEB likely plays an important role in regulating the life cycle of EBV.
Second-Generation Rabies Virus-Based Vaccine Vectors Expressing Human Immunodeficiency Virus Type 1 Gag Have Greatly Reduced Pathogenicity but Are Highly Immunogenic
Authors: McGettigan James P. , Pomerantz Roger J. , Siler Catherine A. , McKenna Philip M. , Foley Heather D. , Dietzschold B. , Schnell Matthias J. 
Published: December 2002

ABSTRACT

Rabies virus (RV) vaccine strain-based vectors show great promise as vaccines against other viral diseases such as human immunodeficiency virus type 1 (HIV-1) infection and hepatitis C, but a low residual pathogenicity remains a concern for their use. Here we describe several highly attenuated second-generation RV-based vaccine vehicles expressing HIV-1 Gag. For this approach, we modified the previously described RV vaccine vector SPBN by replacing the arginine at position 333 (R333) within the RV glycoprotein (G) with glutamic acid (E333), deleting 43 amino acids of the RV G cytoplasmic domain (CD), or combining the R333 exchange and the CD deletion. In addition, we constructed a new RV vector that expresses HIV-1 Gag from an RV transcription unit upstream of the RV phosphoprotein gene (BNSP-Gag) instead of upstream of the G gene. As expected and as demonstrated for SPBN-Gag, all vaccine vehicles were apathogenic after peripheral administration. However, the new, second-generation vaccine vectors containing modifications in the RV G were also apathogenic after intracranial infection with 10
5
infectious particles, and BNSP-Gag produced a 50%-reduced mortality in mice. Of note, the observed attenuation of pathogenicity did not result in either the attenuation of the humoral response against the RV G or the previously observed robust cellular response against HIV-1 Gag. These findings demonstrate that very safe and highly effective RV-based vaccines can be constructed and further emphasize their potential utility as efficacious antiviral vaccines.
An Internally Located RNA Hairpin Enhances Replication of
Tomato Bushy Stunt Virus
RNAs
Authors: Ray Debashish , White K. Andrew 
Published: December 2002

ABSTRACT

Defective interfering (DI) RNAs of
Tomato bushy stunt virus
(TBSV), a plus-sense RNA virus, comprise four conserved noncontiguous regions (I through IV) derived from the viral genome. Region III, a 70-nucleotide-long sequence corresponding to a genomic segment located 378 nucleotides upstream of the 3′ terminus of the genome, has been found to enhance DI RNA accumulation by approximately 10-fold in an orientation-independent manner (D. Ray and K. A. White, Virology 256:162-171, 1999). In this study, a more detailed structure-function analysis of region III was conducted. RNA secondary-structure analyses indicated that region III contains stem-loop structures in both plus and minus strands. Through deletion analyses of a DI RNA, a primary determinant of region III activity was mapped to the 5′-proximal 35-nucleotide segment. Compensatory-type mutational analyses showed that a stem-loop structure in the minus strand of this subregion was required for enhanced DI RNA replication. The same stem-loop structure was also found to function in a position-independent manner in a DI RNA (albeit at reduced levels) and to be important for efficient accumulation within the context of the TBSV genome. Taken together, these observations suggest that the 5′-proximal segment of region III is a modular RNA replication element that functions primarily through the formation of an RNA hairpin structure in the minus strand.
The RNA Replication Enhancer Element of Tombusviruses Contains Two Interchangeable Hairpins That Are Functional during Plus-Strand Synthesis
Authors: Panavas T. , Nagy P. D. 
Published: December 2002

ABSTRACT

Replication of the RNA genomes of tombusviruses, which are small plus-sense RNA viruses of plants, may be regulated by
cis
-acting elements, including promoters and replication enhancers that are present in the RNA templates. Using a partially purified RNA-dependent RNA polymerase (RdRp) preparation (P. D. Nagy and J. Pogany, Virology 276:279-288, 2000), we demonstrate that the minus-strand templates of tombusviruses contain a replication enhancer, which can upregulate RNA synthesis initiating from the minimal plus-strand initiation promoter by 10- to 20-fold in an in vitro assay. Dissection of the sequence of the replication enhancer element revealed that the two stem-loop structures present within the ∼80-nucleotide-long enhancer region have interchangeable roles in upregulating RNA synthesis. The single-stranded sequence located between the two stem-loops also plays an important role in stimulation of RNA synthesis. We also demonstrate that one of the two hairpins, both of which are similar to the hairpin of the minus-strand initiation promoter, can function as a promoter in vitro in the presence of short cytidylate-containing initiation sites. Overall, the in vitro data presented are consistent with previous in vivo results (D. Ray and K. A. White, Virology 256:162-171, 1999) and they firmly establish the presence of a replication enhancer on the minus-stranded RNA of tombusviruses.
Mutations in Human Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase Causing Increased Receptor Binding Activity and Resistance to the Transition State Sialic Acid Analog 4-GU-DANA (Zanamivir)
Authors: Murrell Matthew , Porotto Matteo , Weber Thomas , Greengard Olga , Moscona Anne 
Published: December 2002

ABSTRACT
Entry and fusion of human parainfluenza virus type 3 (HPF3) require the interaction of the viral hemagglutinin-neuraminidase (HN) glycoprotein with its sialic acid receptor. 4-GU-DANA, a potent inhibitor of influenza virus neuraminidase, inhibits not only HPF3 neuraminidase but also the receptor binding activity of HPF3 HN and thus its ability to promote attachment and fusion. We previously generated a 4-GU-DANA-resistant HPF3 virus variant (ZM1) with a markedly fusogenic plaque morphology that harbored two HN gene mutations resulting in amino acid alterations. The present study using cells that express the individual mutations of ZM1 HN shows that one of these mutations is responsible for the increases in receptor binding and neuraminidase activities as well as the diminished sensitivity of both activities to the inhibitory effect of 4-GU-DANA. To examine the hypothesis that increased receptor binding avidity underlies 4-GU-DANA resistance, parallel studies were carried out on the high-affinity HN variant virus C22 and cells expressing the C22 variant HN. This variant also exhibited reduced sensitivity to 4-GU-DANA in terms of receptor binding and infectivity but without concomitant changes in the neuraminidase activity of HN. Another high-affinity HN variant, C0, was not resistant in terms of infectivity; however, a small increase in the receptor binding activity of C0 HN and a partial resistance of this activity to 4-GU-DANA were revealed by sensitive methods that we developed. In each virus variant, one mutation in HN accounted for both increased receptor binding avidity and 4-GU-DANA resistance; the higher affinity for the receptor overcomes the inhibitory effect of 4-GU-DANA. Thus, in contrast to influenza viruses for which 4-GU-DANA escape variants include hemagglutinin mutants with decreased receptor binding avidity that promotes virion release, for HPF3, HN mutants with increased receptor binding avidity are those that can escape the growth inhibitory effect of 4-GU-DANA.
Role of Protein Kinase C βII in Influenza Virus Entry via Late Endosomes
Authors: Sieczkarski Sara B. , Brown H. Alex , Whittaker Gary R. 
Published: December 2002

ABSTRACT
Many viruses take advantage of receptor-mediated endocytosis in order to enter target cells. We have utilized influenza virus and Semliki Forest virus (SFV) to define a role for protein kinase C βII (PKCβII) in endocytic trafficking. We show that specific PKC inhibitors prevent influenza virus infection, suggesting a role for classical isoforms of PKC. We also examined virus entry in cells overexpressing dominant-negative forms of PKCα and -β. Cells expressing a phosphorylation-deficient form of PKCβII (T500V), but not an equivalent mutant form of PKCα, inhibited successful influenza virus entry—with the virus accumulating in late endosomes. SFV, however, believed to enter cells from the early endosome, was unaffected by PKCβII T500V expression. We also examined the trafficking of two cellular ligands, transferrin and epidermal growth factor (EGF). PKCβII T500V expression specifically blocked EGF receptor trafficking and degradation, without affecting transferrin receptor recycling. As with influenza virus, in PKCβII kinase-dead cells, EGF receptor was trapped in a late endosome compartment. Our findings suggest that PKCβII is an important regulator of a late endosomal sorting event needed for influenza virus entry and infection.
Ribavirin Causes Error Catastrophe during Hantaan Virus Replication
Authors: Severson William E. , Schmaljohn Connie S. , Javadian Ali , Jonsson Colleen B. 
Published: December 2002

ABSTRACT
Except for ribavirin, no other antiviral drugs for treating hantaviral diseases have been identified. It is well established that ribavirin will inhibit the production of infectious Hantaan virus (HTNV); however, its mechanism of action is unknown. To characterize the inhibitory effect of ribavirin on HTNV, the levels of viral RNAs, proteins, and infectious particles were measured for 3 days posttreatment of HTNV-infected Vero E6 cells. HTNV-infected cells treated with ribavirin showed a slight reduction in the levels of cRNA, viral RNA, and mRNA populations on the first day postinfection. The amount of cRNA and viral RNA increased to that observed for untreated HTNV-infected cells on day 2, whereas mRNA levels were more greatly reduced on days 2 and 3. Despite the finding of S-segment mRNA, albeit low, three of the viral proteins—nucleocapsid (N) protein and glycoproteins G1 and G2—could not be detected by immunohistochemistry in ribavirin-treated cells. To test the hypothesis that these effects were caused by incorporation of ribavirin into nascent RNA and a resultant “error catastrophe” was occurring, we cloned and sequenced the S-segment cRNA/mRNA from ribavirin-treated or untreated cells from day 3. We found a high mutation frequency (9.5/1,000 nucleotides) in viral RNA synthesized in the presence of ribavirin. Hence, the transcripts produced in the presence of the drug were not functional. These results suggest that ribavirin's mechanism of action lies in challenging the fidelity of the hantavirus polymerase, which causes error catastrophe.
Partial Molecular Characterization of Two Simian Immunodeficiency Viruses (SIV) from African Colobids: SIVwrc from Western Red Colobus (
Piliocolobus badius
) and SIVolc from Olive Colobus (
Procolobus verus
)
Authors: Courgnaud Valerie , Formenty Pierre , Akoua-Koffi Chantal , Noe Ronald , Boesch Christophe , Delaporte Eric , Peeters Martine 
Published: December 2002

ABSTRACT

In order to study primate lentivirus evolution in the
Colobinae
subfamily, in which only one simian immunodeficiency virus (SIV) has been described to date, we screened additional species from the three different genera of African colobus monkeys for SIV infection. Blood was obtained from 13 West African colobids, and HIV cross-reactive antibodies were observed in 5 of 10
Piliocolobus badius
, 1 of 2
Procolobus verus,
and 0 of 1
Colobus polykomos
specimens. Phylogenetic analyses of partial
pol
sequences revealed that the new SIVs were more closely related to each other than to the other SIVs and especially did not cluster with the previously described SIVcol from
Colobus guereza
. This study presents evidence that the three genera of African colobus monkeys are naturally infected with an SIV and indicates also that there was no coevolution between virus and hosts at the level of the
Colobinae
subfamily.
Differential Cytokine Responses following Marek's Disease Virus Infection of Chickens Differing in Resistance to Marek's Disease
Authors: Kaiser Pete , Underwood Greg , Davison Fred 
Published: December 2002

ABSTRACTThe production of cytokine mRNAs, in addition to viral DNA, was quantified by real-time quantitative reverse transcription-PCR (RT-PCR) (cytokines) or PCR (virus) in splenocytes during the course of Marek's disease virus (MDV) infection in four inbred chicken lines: two resistant (lines 61and N) and two susceptible (lines 72and P). Virus loads were only different after 10 days postinfection (dpi), increasing in susceptible lines and decreasing in resistant lines. Gamma interferon (IFN-γ) mRNA was expressed by splenocytes from all infected birds between 3 and 10 dpi, associated with increasing MDV loads. For other cytokines, differences between lines were only seen for interleukin-6 (IL-6) and IL-18, with splenocytes from susceptible birds expressing high levels of both transcripts during the cytolytic phase of infection, whereas splenocytes from resistant birds expressed neither transcript. These results indicate that these two cytokines could play a crucial role in driving immune responses, which in resistant lines maintain MDV latency but in susceptible lines result in lymphomas.