bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spontaneous elimination of serum hepatitis C virus (HCV) RNA in chronic HCV carriers: A population‐based cohort study
Authors: Watanabe Hisayoshi , Saito Takafumi , Shinzawa Haruhide , Okumoto Kazuo , Hattori Etsuko , Adachi Tohru , Takeda Tadashi , Sugahara Kazuhiko , Ito Jun‐itsu , Saito Koji , Togashi Hitoshi , Suzuki Ryosuke , Hayashi Masahiro , Miyamura Tatsuo , Matsuura Yoshiharu , Kawata Sumio 
Published: July 2003

AbstractThe natural course of hepatitis C virus (HCV) infection has not been fully elucidated. To investigate whether HCV is spontaneously eliminated in chronic carriers, a long‐term population‐based cohort study was conducted on 435 chronic HCV carriers. Individual characteristics, serum HCV RNA, and liver function tests were analyzed, and ultra sonography (US) was performed in all subjects. Subjects were followed up for 7.2 ± 2.4 years (mean ± SD). Serum HCV RNA was spontaneously eliminated in 16/435 (3.7%) individuals during this period; thus, the incidence of spontaneous elimination of serum HCV RNA was 0.5%/year/person. Multivariate analysis revealed that both a low value of ZTT and no US finding of chronic liver disease were associated with spontaneous viral elimination in HCV carriers. Three of these 16 individuals had chronic hepatitis, and 13 of them had normal ALT levels. When the neutralization of binding (NOB) assay that evaluates inhibition of the HCV envelope‐2 protein binding to human cells was examined using sera from these 16 individuals, the NOB antibody was detected in only 3 cases with chronic hepatitis. These results suggest that serum HCV RNA is spontaneously eliminated in chronic HCV carriers in a population, and that the development of NOB antibody is associated with a natural resolution of chronic hepatitis in the minority of them. J. Med. Virol. 71:56–61, 2003. © 2003 Wiley‐Liss, Inc.
Viral agents of acute gastroenteritis in German children: Prevalence and molecular diversity
Authors: Oh Djin‐Ye , Gaedicke Gerhard , Schreier Eckart 
Published: July 2003

AbstractAcute gastroenteritis is a major source of morbidity and mortality among young children in developed and developing countries. Enteropathogenic viruses are regarded as particularly relevant causative agents. Between February 2001 and January 2002, fecal specimens were obtained from German children admitted to hospital with acute gastroenteritis and examined for rotaviruses, Noroviruses, enteric adenoviruses, and astroviruses using (RT‐)PCR methods. Of the 59% (129/217) samples positive for ≥1 viral agent, 79% (102/129) carried rotavirus, whereas Norovirus was detected in 35% (45/129), enteric adenovirus in 14% (18/129), and astrovirus in 4% (5/129). Thirty‐eight specimens contained at least two enteropathogenic viruses, with the majority of coinfections attributable to rotavirus/Norovirus dual infections. Sequence analysis revealed a cocirculation of G1, G3, G4, and G9 type rotavirus with G1 being the most common and G9 the second most common rotavirus G‐type. Emergence of G9 rotaviruses in Germany may have implications for future vaccine development. A variety of Norovirus genotypes, most belonging to GGII, were found. Apart from subgenus F, adenovirus related genetically to subgenera A–C were detected. All astroviruses belonged to genotype 1. This is the first study concerning German children admitted to hospital that assesses the relative importance of these viruses by nested (RT‐) PCR methods. J. Med. Virol. 71:82–93, 2003. © 2003 Wiley‐Liss, Inc.
Herpes simplex virus DNA in corneal transplants: Prospective study of 38 recipients
Authors: Robert Pierre‐Yves , Adenis Jean‐Paul , Denis François , Alain Sophie , Ranger‐Rogez Sylvie 
Published: July 2003

AbstractHerpes simplex virus (HSV) infection of the eye can induce epithelial and stromal keratitis and may also lead to postoperative endothelial failure in keratoplasty. Clinical symptoms and/or virus culture of corneal scrapings most frequently provide the basis for diagnosis of ocular HSV infection, and although HSV DNA has been shown to be present in the cornea, its role in success or failure of corneal grafts remains unclear. In this study, a PCR assay was used to detect HSV DNA in corneal buttons of 38 corneal graft recipients and in donor scleral remnants, retaining one‐half of each sample for subsequent viral isolation. Recipients were followed up clinically for a period of 6 months after keratoplasty. All recipients but three were found to be HSV seropositive. Eight recipient corneal buttons contained detectable HSV DNA (7 HSV‐1, 1 HSV‐2, the latter case confirmed by viral culture). Two donor corneas were found positive for HSV‐1 DNA, with negative cultures, and endothelial graft failure occurred in one of the matching recipients after 4 months. One recipient with no history of herpes contracted herpetic keratitis 4 months after keratoplasty, even though the corneal button and donor scleral remnants contained no detectable HSV DNA. The study confirms previous observations of HSV DNA in the corneal tissue of HSV seropositive patients apparently unrelated to any clinical manifestation of herpes infection. However, as demonstrated by culture, HSV remains infectious and may therefore induce donor‐to‐host infection in corneal recipients. J. Med. Virol. 71:69–74, 2003. © 2003 Wiley‐Liss, Inc.
Human herpesvirus 6 infection of human epidermal cell line: Pathogenesis of skin manifestations
Authors: Yoshikawa Tetsushi , Goshima Fumi , Akimoto Shiho , Ozaki Takao , Iwasaki Takuya , Kurata Takeshi , Asano Yoshizo , Nishiyama Yukihiro 
Published: July 2003

AbstractIn order to elucidate the pathogenesis of variant B human herpesvirus 6 (HHV‐6) infection in skin tissues, an A431 cell line was inoculated with variant B HHV‐6. HHV‐6 causes abortive infection in the A431 cells, because neither late antigen (OHV‐3 antigen) nor progeny virus is produced. Maximum levels of HHV‐6 antigen (IEA/ex3 antigen)‐positive cells (36.4%) were observed 48 hr after viral infection. Cocultivation of HHV‐6‐infected cord blood mononuclear cells with A431 cells was necessary for the establishment of a sufficient level of viral infection. Cell‐to‐cell contact between the infected cord blood mononuclear cells and A431 cells was crucial for increasing infection efficiency. To determine the biological effect of HHV‐6 infection, flow cytometric analysis was carried out in HHV‐6‐ and mock‐infected A431 cells. Although no alteration was observed in VCAM‐1 and ELAM‐1 expression, that of HLA‐ABC, HLA‐DR, and ICAM‐1 was upregulated after infection with HHV‐6. J. Med. Virol. 71:62–68, 2003. © 2003 Wiley‐Liss, Inc.
Patterns of circulating hepatitis B virus serum nucleic acids during lamivudine therapy
Authors: Zhang Wei , Hacker Hans Jörg , Tokus Mehmet , Bock Thomas , Schröder Claus H. 
Published: July 2003

AbstractWe examined whether lamivudine treatment, in addition to the rapid decline of HBV serum DNA described in a large number of laboratories, causes changes in composition and amount of discernable circulating viral DNA and RNA. Nucleic acids were extracted from serial serum samples of a patient infected chronically and treated with lamivudine for 14 weeks. Three sequence segments of the HBV genome synthesized successively during replication, X, C, and X‐preC, were analyzed by competitive PCR and RT/PCR. In addition, RNA was examined for differential polyadenylation. Before treatment, identical DNA copy numbers (109/ml) were found in all three segments. C segment DNA displayed the expected rapid decline. X‐preC, a target contiguous only on plus‐strand DNA behaved similarly. In contrast, the X segment DNA copy numbers showed a less pronounced decrease remaining at higher values (107/ml) than the C and X‐preC segment (both about 2 × 105/ml) at the end of therapy. X segment RNA displayed a persisting copy number of about 107/ml, while C and X‐preC RNA decreased to about 105 copies/ml. Polyadenylated HBV RNA, full‐length and truncated, persisted initially at 105 but decreased to 104 to 103 copies/ml at the end of treatment. The major conclusions are the actual numbers of virus particles during lamivudine therapy can only be assessed via X segment DNA, since it is reverse transcribed first, and Lamivudine induced coexistence of DNA and RNA for the C and X segment at similar levels indicates drug‐arrested intermediates of reverse transcribed HBV DNA minus‐strand. Packaged RNA lacks a poly(A) tail whereas polyadenylated RNA is likely not packaged. J. Med. Virol. 71:24–30, 2003. © 2003 Wiley‐Liss, Inc.
Genotyping of herpes simplex virus type 1 strains isolated from ocular materials of patients with herpetic keratitis
Authors: Umene Kenichi , Inoue Tomoyuki , Inoue Yoshitsugu , Shimomura Yoshikazu 
Published: July 2003

AbstractHerpes simplex virus type 1 (HSV‐1) is the etiological agent of herpetic keratitis. The epithelial form (“epithelial keratitis”) is attributed mainly to destruction of the epithelium through active viral replication within the epithelium. The stromal form (“stromal keratitis”) is associated with immune reactions within the stroma and is the common cause of human blindness. In the present study, 29 HSV‐1 strains isolated from human ocular materials of herpetic keratitis were classified into 14 genotypes on the basis of DNA polymorphisms. Twenty‐one of 29 (72%) strains from eyes examined in the present study were of genotypes that were shown previously to be present in strains from non‐ocular lesions (including genital herpes). Five of nine (56%) strains from eyes related to stromal keratitis were of the F1 genotype, while four of twenty (20%) strains from eyes not related to stromal keratitis were of the F1 genotype. Thus, the proportion of F1 genotype was assumed to be larger in the group of strains related to stromal keratitis than in that not so related, suggesting an association of the F1 genotype with stromal keratitis. A connection of F1 genotype with recurrence was proposed previously; hence, F1 genotype seems to be associated to both stromal keratitis and the recurrence, thereby supporting the relationship between stromal keratitis and recurrence. J. Med. Virol. 71:75–81, 2003. © 2003 Wiley‐Liss, Inc.
Ground state solutions of non‐linear singular Schrödinger equations with lack of compactness
Authors: Mihǎilescu Mihai , Rǎdulescu Vicenţiu 
Published: July 2003

AbstractWe study a class of time‐independent non‐linear Schrödinger‐type equations on the whole space with a repulsive singular potential in the divergence operator and we establish the existence of non‐trivial standing wave solutions for this problem in an appropriate weighted Sobolev space. Such equations have been derived as models of several physical phenomena. Our proofs rely essentially on critical point theory tools combined with the Caffarelli–Kohn–Nirenberg inequality. Copyright © 2003 John Wiley & Sons, Ltd.
On a quadrature algorithm for the piecewise linear wavelet collocation applied to boundary integral equations
Authors: Rathsfeld Andreas , Schneider Reinhold 
Published: July 2003

AbstractIn this paper, we consider a piecewise linear collocation method for the solution of a pseudo‐differential equation of order r=0, −1 over a closed and smooth boundary manifold. The trial space is the space of all continuous and piecewise linear functions defined over a uniform triangular grid and the collocation points are the grid points. For the wavelet basis in the trial space we choose the three‐point hierarchical basis together with a slight modification near the boundary points of the global patches of parametrization. We choose linear combinations of Dirac delta functionals as wavelet basis in the space of test functionals. For the corresponding wavelet algorithm, we show that the parametrization can be approximated by low‐order piecewise polynomial interpolation and that the integrals in the stiffness matrix can be computed by quadrature, where the quadrature rules are composite rules of simple low‐order quadratures. The whole algorithm for the assembling of the matrix requires no more than O(N [logN]3) arithmetic operations, and the error of the collocation approximation, including the compression, the approximative parametrization, and the quadratures, is less than O(N−(2−r)/2). Note that, in contrast to well‐known algorithms by Petersdorff, Schwab, and Schneider, only a finite degree of smoothness is required. In contrast to an algorithm of Ehrich and Rathsfeld, no multiplicative splitting of the kernel function is required. Beside the usual mapping properties of the integral operator in low order Sobolev spaces, estimates of Calderón–Zygmund type are the only assumptions on the kernel function. Copyright © 2003 John Wiley & Sons, Ltd.
Monocyte Chemoattractant Protein‐1 (CCL2) in Inflammatory Disease and Adaptive Immunity: Therapeutic Opportunities and Controversies
Authors: DALY CHRISTINE , ROLLINS BARRETT J. 
Published: July 2003

ABSTRACTMonocyte chemoattractant protein (MCP)‐1 (CCL2) specifically attracts monocytes and memory T cells. Its expression occurs in a variety of diseases characterized by mononuclear cell infiltration, and there is substantial biological and genetic evidence for its essential role in atherosclerosis and multiple sclerosis. Despite intensive screening, there are as yet no small‐molecule antagonists of the receptor of MCP‐1/CCL2, CCR2. However, biological agents, including antibodies and inhibitory peptides, have been developed and may be useful for these indications. Recent evidence from genetically modified mice indicates that MCP‐1 and CCR2 have unanticipated effects on T helper (Th) cell development. However, unlike the identical phenotypes of MCP‐1/CCL2−/− and CCR2−/− mice in inflammatory diseases, the phenotypes of these mice are disparate in adaptive immunity: MCP‐1 stimulates Th2 polarization, whereas CCR2 activation stimulates Th1 polarization. This presents both a challenge and an opportunity for targeting the MCP‐1/CCL2/CCR2 axis in disease.
Chemokines in Lymphocyte Trafficking and Intestinal Immunity
Authors: KUNKEL ERIC J. , CAMPBELL DANIEL J. , BUTCHER EUGENE C. 
Published: July 2003

ABSTRACTLymphocyte migration through gut‐associated lymphoid tissues (GALT) and into intestinal effector sites is critical to intestinal immune system function and homeostasis. Chemokines contribute to lymphocyte trafficking by triggering integrin activation and firm arrest in the vasculature and mediating chemotactic localization within tissues. Several chemokines have been identified that are expressed in the GALT and/or the intestines themselves (TECK/CCL25, MEC/CCL28, and MIP‐3α/CCL20) and play a role in intestinal lymphocyte localization, including unification of intestinal and other mucosa‐associated effector sites; segmental specialization of the intestines; and subset selective localization to the intestines. This review examines the role of these chemokines (and their receptors CCR9, CCR10, and CCR6, respectively) in lymphocyte homing to the GALT, in the induction and differentiation of intestinal effector and memory lymphocytes, and in the homeostatic and inflammatory localization of lymphocytes to the intestines.
Shaping Up Adaptive Immunity: The Impact of CCR7 and CXCR5 on Lymphocyte Trafficking
Authors: MÜLLER GERD , LIPP MARTIN 
Published: July 2003

ABSTRACTThe effective onset of adaptive immune responses requires that naïve antigen‐specific lymphocytes, being inherently rare throughout the body, rapidly encounter foreign antigens. This problem has been elegantly solved in evolution by inventing secondary lymphoid tissues as intersections in the migratory pathway of antigen‐presenting dendritic cells and antigen‐specific lymphocytes. Chemokines play a central role in guiding cell movements in the course of immune responses and in lymphoid system homeostasis. In particular, the chemokine receptors CCR7 and CXCR5 are key molecules for the entry of lymphocytes and dendritic cells into secondary lymphoid organs and their homing to T‐cell and B‐cell zones therein. CCR7 and CXCR5 are differentially expressed on the cell surface of lymphocytes and dendritic cells depending on the stage of cellular differentiation and activation, thus allowing these cells to change their homing capacity and prospective traffic routes.
Role of Chemokines in Angiogenesis: CXCL12/SDF‐1 and CXCR4 Interaction, a Key Regulator of Endothelial Cell Responses
Authors: SALCEDO ROSALBA , OPPENHEIM JOOST J. 
Published: July 2003

ABSTRACTChemokines are small proteins that act as cell attractants via the activation of G protein‐coupled receptors. Chemokines play an important role in several pathophysiological processes such as inflammation and immunity. Many proinflammatory chemokines also support the development of vascular blood supply at the site of inflammation. Similarly, tumor‐generated chemokines can contribute to tumor growth by promoting angiogenesis. Recently, significant advances have been made in understanding the contribution of chemokines to the angiogenesis process. This review will discuss first the evidence supporting the direct contribution of different chemokine subfamily members, including CC, CXC, and CX3C chemokines, as positive or negative regulators of the angiogenesis process based on the expression of their cognate receptors on endothelial cells. Additionally, the relationship between classic angiogenic factors and chemokine receptor expression on endothelial cells, and the implications of chemokine production by cancer cells will be analyzed with particular emphasis on the CXCL12/stromal‐cell derived factor‐1 interaction with CXCR4.
L‐Selectin: An Emerging Player in Chemokine Function
Authors: KHAN ADIL I. , KUBES PAUL 
Published: July 2003

ABSTRACTThe emigration of leukocytes across the blood‐endothelium barrier and their subsequent transmigration through the interstitium is a complex process that is vital for maintaining the efficiency of the body's innate and adaptive immunity. The chemokines, a family of low‐molecular‐weight chemoattractant cytokines, are well recognized to be key players in this process. However, recent investigations have highlighted an important role played by the selectin family of adhesion molecules in enhancing chemokine functions. This review summarizes the in vitro and in vivo studies that support this growing notion. It discusses chemotaxis in the context of the phosphoinositide 3‐kinase and p38 mitogen‐activated protein kinase pathways, and their relation to several chemoattractants (i.e., interleukin‐8, leukotriene‐B4, formyl‐methionyl‐leucyl‐phenylalanine, keratinocyte‐derived cytokine, and macrophage inflammatory protein‐2), the possible role played by L‐selectin, and finally how chemotaxis can be altered in different inflammatory settings, such as lipopolysaccharide‐mediated endotoxemia or chronic vasculitis.
Lack of pharmacokinetic interaction between retigabine and phenobarbitone at steady‐state in healthy subjects
Authors: Ferron Geraldine M. , Patat Alain , Parks Virginia , Rolan Paul , Troy Steven M. 
Published: July 2003

Aims  To evaluate potential pharmacokinetic interactions between phenobarbitone and retigabine, a new antiepileptic drug.
Methods
Fifteen healthy men received 200 mg of retigabine on day 1. On days 4–32, phenobarbitone 90 mg was administered at 22.00 h. On days 26–32, increasing doses of retigabine were given to achieve a final dose of 200 mg every 8 h on day 32. The pharmacokinetics of retigabine were determined on days 1 and 32, and those for phenobarbitone on days 25 and 31.Results  After administration of a single 200 mg dose, retigabine was rapidly absorbed and eliminated with a mean terminal half‐life of 6.7 h, a mean AUC of 3936 ng ml−1 h and a mean apparent clearance of 0.76 l h−1 kg−1. Similar exposure to the partially active acetylated metabolite (AWD21‐360) of retigabine was observed. After administration of phenobarbitone dosed to steady‐state, the pharmacokinetics of retigabine at steady‐state were similar (AUC of 4433 ng ml−1 h and t1/2 of 8.5 h) to those of retigabine alone. The AUC of phenobarbitone was 298 mg l−1 h when administered alone and 311 mg ml−1 h after retigabine administration. The geometric mean ratios and 90% confidence intervals of the AUC were 1.11 (0.97, 1.28) for retigabine, 1.01 (0.88, 1.06) for AWD21‐360 and 1.04 (0.96, 1.11) for phenobarbitone. Individual and combined treatments were generally well tolerated. One subject was withdrawn from the study on day 10 due to severe abdominal pain. Headache was the most commonly reported adverse event. No clinically relevant changes were observed in the electrocardiograms, vital signs or laboratory measurements.Conclusions  There was no pharmacokinetic interaction between retigabine and phenobarbitone in healthy subjects. No dosage adjustment is likely to be necessary when retigabine and phenobarbitone are coadministered to patients.
Effects of fluticasone vs. fluticasone/salmeterol on airway calibre and airway hyperresponsiveness in mild persistent asthma
Authors: Currie Graeme P. , Stenback Suvi , Lipworth Brian J. 
Published: July 2003

Aims  Inhaled corticosteroids alone or in combination with long acting β2‐agonists are indicated for use in mild persistent asthmatics. We set out to evaluate effects on airway hyperresponsiveness (AHR) and airway calibre using hydrofluoroalkane fluticasone/salmeterol (FP/SM) vs. double the dose of fluticasone alone (FP).Methods  Fourteen mild persistent asthmatics completed a randomized double‐blind crossover study with 1‐week run‐in and washout periods prior to treatments. Subjects received 3 weeks of FP 250 µg or FP 125 µg/SM 25 µg as 1 puff twice daily. Methacholine PD20 and lung function were measured after both baseline and treatment periods.Results  There were no significant differences in baseline values prior to randomized treatments. Compared with pooled baseline, FP/SM and FP conferred improvements (P < 0.05) on methacholine PD20: 2.5 (95% confidence interval 1.7, 3.2) and 1.6 (0.8–2.3) doubling dose improvements, respectively; between FP/SM vs. FP there was a 0.9 (0.4, 1.4) doubling dose difference (P < 0.05). For forced expiratory volume in 1 s (FEV1), forced mid‐expiratory flow (FEF25−75) and morning peak expiratory flow (PEF), FP/SM but not FP conferred improvements (P < 0.05) compared with pooled baseline, with FP/SM being greater than FP (P < 0.05): differences in FEV1 of 7.2% (3.8, 10.6) predicted, FEF25−75 of 11.2% (6.3, 16.1) predicted, and morning PEF of 17 L min−1(1–32).Conclusions  FP/SM conferred improvements on AHR and airway calibre, while twice the dose of FP improved only AHR in patients with mild asthma. The differential effects of FP/SM and FP suggest separate but complementary actions of the two moieties on airway inflammation and smooth muscle stabilization. This may explain the beneficial effects of combination inhalers on exacerbations.