bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mycobacterium tuberculosisPathogenesis and Molecular Determinants of Virulence
Authors: Smith Issar 
Published: July 2003

SUMMARYTuberculosis (TB), one of the oldest known human diseases. is still is one of the major causes of mortality, since two million people die each year from this malady. TB has many manifestations, affecting bone, the central nervous system, and many other organ systems, but it is primarily a pulmonary disease that is initiated by the deposition ofMycobacterium tuberculosis, contained in aerosol droplets, onto lung alveolar surfaces. From this point, the progression of the disease can have several outcomes, determined largely by the response of the host immune system. The efficacy of this response is affected by intrinsic factors such as the genetics of the immune system as well as extrinsic factors,e.g., insults to the immune system and the nutritional and physiological state of the host. In addition, the pathogen may play a role in disease progression since some M. tuberculosis strains are reportedly more virulent than others, as defined by increased transmissibility as well as being associated with higher morbidity and mortality in infected individuals. Despite the widespread use of an attenuated live vaccine and several antibiotics, there is more TB than ever before, requiring new vaccines and drugs and more specific and rapid diagnostics. Researchers are utilizing information obtained from the complete sequence of the M. tuberculosis genome and from new genetic and physiological methods to identify targets in M. tuberculosis that will aid in the development of these sorely needed antitubercular agents.
Mycotoxins
Authors: Bennett J. W. , Klich M. 
Published: July 2003

SUMMARYMycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. Because of their pharmacological activity, some mycotoxins or mycotoxin derivatives have found use as antibiotics, growth promotants, and other kinds of drugs; still others have been implicated as chemical warfare agents. This review focuses on the most important ones associated with human and veterinary diseases, including aflatoxin, citrinin, ergot akaloids, fumonisins, ochratoxin A, patulin, trichothecenes, and zearalenone.
Borna Disease Virus Infection, a Human Mental-Health Risk
Authors: Bode Liv , Ludwig Hans 
Published: July 2003

SUMMARY
This article focuses on human Borna disease virus (BDV) infections, most notably on the development of valid diagnostic systems, which have arisen as a major research issue in the past decade. The significance of a novel modular triple enzyme-linked immunosorbent assay that is capable of specifically measuring anti-BDV antibodies as well as major structural proteins N (p40) and P (p24) in the blood, either as free antigens in the plasma or as antibody-bound circulating immune complexes (CICs), is explained. The impact of CICs and plasma antigen, which indicate periods of antigenemia in the course of BDV infection, along with other infection markers that are still in use is discussed. The review further provides new insight into possible links of BDV to human diseases, summarizing cross-sectional and longitudinal data which correlate acute depression with the presence and amount of antigen and CICs. Moreover, BDV prevalence in healthy people is reevaluated, suggesting that this was previously underestimated. Antiviral efficacy of amantadine, in vivo and in vitro, is outlined as well, with emphasis on wild-type (human and equine) versus laboratory strains. Finally, the pros and cons of the association of BDV with human disease, as detailed in the literature, are critically discussed and related to our data and concepts. This article supports existing correlative evidence for a pathogenic role of BDV infection in particular human mental disorders, in analogy to what has been proven for a variety of animal species.
Virus-Neutralizing Activity Mediated by the Fab Fragment of a Hemagglutinin-Specific Antibody Is Sufficient for the Resolution of Influenza Virus Infection in SCID Mice
Authors: Mozdzanowska Krystyna , Feng Jingqi , Gerhard Walter 
Published: July 2003

ABSTRACTAntibodies (Abs) contribute to the control of influenza virus infection in vivo by reducing progeny virus yield from infected cells (yield reduction [YR]) and by inhibiting progeny virus from spreading the infection to new host cells (virus neutralization [VN]). Previous studies showed that the infection could be resolved in severe combined immunodeficiency (SCID) mice by treatment with hemagglutinin (HA)-specific monoclonal antibodies (MAbs) that exhibit both VN and YR activities but not by MAbs that exhibited only YR activity. To determine whether virus clearance requires both activities, we measured the therapeutic activity of an HA-specific MAb (VN and YR) and its Fab fragment (VN) by intranasal (i.n.) administration to infected SCID mice. Immunoglobulin G (IgG) and Fab cleared the infection with i.n. 50% effective doses (ED50s) of 16 and 90 pmol, respectively. To resolve an established infection solely by VN activity, Fab must be present in the respiratory tract at an effective threshold concentration until all infected cells have died and production of virus has ceased. Because IgG and Fab had different half-lives in the respiratory tract (22 and 8 h, respectively) and assuming that both operated mainly or solely by VN, it could be estimated that clearance was achieved 24 h after Ab treatment when both reagents were present in the respiratory tract at ∼10 pmol. This dose was ∼200 times larger than the respiratory tract-associated Ab dose resulting from administration of the intraperitoneal ED50(270 pmol) of IgG. This indicated that our procedure of i.n. administration of Ab did not make optimal use of the Ab's therapeutic activity.
Chimeric Human Papillomavirus Type 16 (HPV-16) L1 Particles Presenting the Common Neutralizing Epitope for the L2 Minor Capsid Protein of HPV-6 and HPV-16
Authors: Varsani Arvind , Williamson Anna-Lise , de Villiers Debbie , Becker Inga , Christensen Neil D. , Rybicki Edward P. 
Published: July 2003

ABSTRACT

Both the
Human papillomavirus
(HPV) major (L1) and minor (L2) capsid proteins have been well investigated as potential vaccine candidates. The L1 protein first oligomerizes into pentamers, and these capsomers assemble into virus-like particles (VLPs) that are highly immunogenic. Here we examine the potential of using HPV type 16 (HPV-16) L1 subunits to display a well-characterized HPV-16 L2 epitope (LVEETSFIDAGAP), which is a common-neutralizing epitope for HPV types 6 and 16, in various regions of the L1 structure. The L2 sequence was introduced by PCR (by replacing 13 codons) into sequences coding for L1 surface loops D-E (ChiΔC-L2), E-F (ChiΔA-L2), and an internal loop C-D (ChiΔH-L2); into the h4 helix (ChiΔF-L2); and between h4 and β-J structural regions (ChiΔE-L2). The chimeric protein product was characterized using a panel of monoclonal antibodies (MAbs) that bind to conformational and linear epitopes, as well as a polyclonal antiserum raised to the L2 epitope. All five chimeras reacted with the L2 serum. ChiΔA-L2, ChiΔE-L2, and ChiΔF-L2 reacted with all the L1 antibodies, ChiΔC-L2 did not bind H16:V5 and H16:E70, and ChiΔH-L2 did not bind any conformation-dependent MAb. The chimeric particles elicited high-titer anti-L1 immune responses in BALB/c mice. Of the five chimeras tested only ChiΔH-L2 did not elicit an L2 response, while ChiΔF-L2 elicited the highest L2 response. This study provides support for the use of PV particles as vectors to deliver various epitopes in a number of locations internal to the L1 protein and for the potential of using chimeric PV particles as multivalent vaccines. Moreover, it contributes to knowledge of the structure of HPV-16 L1 VLPs and their derivatives.
Equine Infectious Anemia Virus Utilizes Host Vesicular Protein Sorting Machinery during Particle Release
Authors: Tanzi Giancarlo O. , Piefer Andrew J. , Bates Paul 
Published: July 2003

ABSTRACT
A final step in retrovirus assembly, particle release from the cell, is modulated by a small motif in the Gag protein known as a late domain. Recently, human immunodeficiency virus type 1 (HIV-1) and Moloney murine leukemia virus (M-MuLV) were shown to require components of the cellular vacuolar protein sorting (VPS) machinery for efficient viral release. HIV-1 interacts with the VPS pathway via an association of HIV-1 Gag with TSG101, a component of the cellular complexes involved in VPS. Equine infectious anemia virus (EIAV) is unique among enveloped viruses studied to date because it utilizes a novel motif, YPDL in Gag, as a late domain. Our analysis of EIAV assembly demonstrates that EIAV Gag release is blocked by inhibition of the VPS pathway. However, in contrast to HIV-1, EIAV Gag release is insensitive to TSG101 depletion and EIAV particles do not contain significant levels of TSG101. Finally, we demonstrate that fusing EIAV Gag directly with another cellular component of the VPS machinery, VPS28, can restore efficient release of an EIAV Gag late-domain mutant. These results provide evidence that retroviruses can interact with the cellular VPS machinery in several different ways to accomplish particle release.
Herpes Simplex Virus Glycoproteins gD and gE/gI Serve Essential but Redundant Functions during Acquisition of the Virion Envelope in the Cytoplasm
Authors: Farnsworth Aaron , Goldsmith Kimberly , Johnson David C. 
Published: July 2003

ABSTRACT

The late stages of assembly of herpes simplex virus (HSV) and other herpesviruses are not well understood. Acquisition of the final virion envelope apparently involves interactions between viral nucleocapsids coated with tegument proteins and the cytoplasmic domains of membrane glycoproteins. This promotes budding of virus particles into cytoplasmic vesicles derived from the
trans
-Golgi network or endosomes. The identities of viral membrane glycoproteins and tegument proteins involved in these processes are not well known. Here, we report that HSV mutants lacking two viral glycoproteins, gD and gE, accumulated large numbers of unenveloped nucleocapsids in the cytoplasm. These aggregated capsids were immersed in an electron-dense layer that appeared to be tegument. Few or no enveloped virions were observed. More subtle defects were observed with an HSV unable to express gD and gI. A triple mutant lacking gD, gE, and gI exhibited more severe defects in envelopment. We concluded that HSV gD and the gE/gI heterodimeric complex act in a redundant fashion to anchor the virion envelope onto tegument-coated capsids. In the absence of either one of these HSV glycoproteins, envelopment proceeds; however, without both gD and gE, or gE/gI, there is profound inhibition of cytoplasmic envelopment.
NF-κB Inhibits Gammaherpesvirus Lytic Replication
Authors: Brown Helen J. , Song Moon Jung , Deng Hongyu , Wu Ting-Ting , Cheng Genhong , Sun Ren 
Published: July 2003

ABSTRACT
Nasopharyngeal carcinoma, Kaposi's sarcoma, and B-cell lymphomas are human malignancies associated with gammaherpesvirus infections. Members of this virus family are characterized by their ability to establish latent infections in lymphocytes. The latent viral genome expresses very few gene products. The infected cells are therefore poorly recognized by the host immune system, allowing the virus to persist for long periods of time. We sought to identify the cell-specific factors that allow these viruses to redirect their life cycle from productive replication to latency. We find that the cellular transcription factor NF-κB can regulate this process. Epithelial cells and fibroblasts support active (lytic) gammaherpesvirus replication and have low NF-κB activity. However, overexpression of NF-κB in these cells inhibits the replication of the gammaherpesvirus murine herpesvirus 68 (MHV68). In addition, overexpression of NF-κB inhibits the activation of lytic promoters from MHV68 and human gammaherpesviruses Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV). In lymphocytes latently infected with KSHV or EBV, the level of NF-κB activity is high, and treatment of these cells with an NF-κB inhibitor leads to lytic protein synthesis consistent with virus reactivation. These results suggest that high levels of NF-κB can inhibit gammaherpesvirus lytic replication and may therefore contribute to the establishment and maintenance of viral latency in lymphocytes. They also suggest that NF-κB may be a novel target for the disruption of virus latency and therefore the treatment of gammaherpesvirus-related malignancies.
The Gammaherpesvirus Chemokine Binding Protein Binds to the N Terminus of CXCL8
Authors: Webb Louise M. C. , Clark-Lewis Ian , Alcami Antonio 
Published: July 2003

ABSTRACTViruses encode proteins that disrupt chemokine responses. The murine gammaherpesvirus 68 geneM3encodes a chemokine binding protein (vCKBP-3) which has no sequence similarity to chemokine receptors but inhibits chemokine receptor binding and activity. We have used a panel of CXCL8 analogs to identify the structural requirements for CXCL8 to bind to vCKBP-3 in a scintillation proximity assay. Our data suggest that vCKBP-3 acts by mimicking the binding of chemokine receptors to CXCL8.
E4orf3 Is Necessary for Enhanced S-Phase Replication of Cell Cycle-Restricted Subgroup C Adenoviruses
Authors: Shepard Robin N. , Ornelles David A. 
Published: July 2003

ABSTRACT

E1B-55K-mutant or E4orf6-mutant adenoviruses replicate more effectively after infecting cells in S phase than after infecting cells in G
1
. Enhanced S-phase replication of the E4orf6-mutant viruses requires the E4orf3 gene. This report demonstrates that the E4orf3 gene is also required for enhanced S-phase replication of the E1B-55K-mutant virus.
Acquiring and Applying Contextualised Tacit Knowledge
Authors: Richards Debbie , Busch Peter 
Published: July 2003

The acquisition and application of knowledge, in particular tacit knowledge (TK), are seen as decisive competitive factors in the knowledge society of the twenty-first century. Despite much talk about the importance of knowledge transfer, little research shows how to identify and measure TK, less research addresses how to transfer TK between individuals and even fewer of these approaches offer any technology that can assist with transfer. This paper does not address the issues of identification and measurement of TK. The purpose of this paper is two-fold: describe a knowledge acquisition and representation technique, known as Ripple Down Rules (RDR), which can be used to capture knowledge, explicit and tacit, in context from those already identified as experts and to describe a set-theoretical technique, known as formal concept analysis (FCA) to assist transfer of the RDR knowledge to another human. Unlike most knowledge acquisition approaches, the RDR knowledge acquisition technique does not rely on the expert to specify what they know. Instead, knowledge becomes codified by the RDR system while the domain expert exercises his or her expertise. The approach does not capture all organisational knowledge, but the knowledge that is captured will be a mixture of different types of knowledge, including formal and codified knowledge that can be learnt from a book and practice-based knowledge that is passed on while on the job. The knowledge captured using RDR may be transferred to another individual through the use of FCA to retrospectively and automatically develop knowledge models that the user can explore. This work offers a possible solution to three knowledge management challenges: capture, utilisation and preservation of knowledge within an organisation.
Checkmark Fetal Heart Rate Pattern Associated with Severe Fetal Hypoxia
Authors: Kashiwagi Satoshi , Miyakoshi Kei , Ishimoto Hitoshi , Tanaka Mamoru , Yoshimura Yasunori 
Published: July 2003

A 31-year-old nulliparous woman developed vaginal bleeding after spontaneous rupture of the membranes at 40 weeks of gestation. Fetal heart rate monitoring showed checkmark and sinusoidal patterns. A 3,281 g male neonate was delivered by emergency cesarean section, with Apgar scores of 1 and 3 at 1 and 5 min, respectively. The neonate exhibited severe acidosis with arterial blood gas pH of 6.96, and was diagnosed to have severe hypoxic-ischemic encephalopathy. An umbilical artery branch was noted in the membrane near the cervical os and found to be torn, representing hemorrhagic vasa previa. Severe fetal hypoxia resulting from hemorrhagic vasa previa might be associated with checkmark fetal heart rate pattern.
Pre-Eclampsia: Maternal Risk Factors and Perinatal Outcome
Authors: Al-Mulhim Abdul-Aziz , Abu-Heija Adel , Al-Jamma Fathia , El-Harith El-Harith A. 
Published: July 2003

<i>Objective:</i> The aim of this study was to throw light on the incidence of pre-eclampsia (PE) in women attending for care and delivery at a hospital in Saudi Arabia, and analyze the maternal risk factors and outcome of mothers and neonates in pregnancies complicated by PE. <i>Methods:</i> This retrospective study involved almost all women (n = 27,787) who delivered at King Fahad Hospital of the University in a 10-year period (1992–2001). The maternal records were reviewed for age, parity, gestational age, mode of delivery, antenatal care, onset of PE, severity of proteinuria, and the frequency of antenatal and intrapartum complications. The neonatal records were reviewed for perinatal outcome including birth weight, frequency of stillbirths, and neonatal deaths. <i>Results:</i> Among the study cohort of maternities, 685 women, i.e. 2.47%, were diagnosed as having PE among whom a high proportion (42.0%) were nulliparous women. Similarly, PE was encountered at a high percentage (40.0%) in women at the extreme of their reproductive age (< 20 and >40 years), and more women with PE delivered prematurely (30.2%) as compared to healthy controls (13.5%). Spontaneous vaginal deliveries were less frequent in women with PE (69.2%) as compared with healthy controls (86.2%). Instrumental deliveries, with spontaneous labor, amounted to 15.9% in women with PE, but they comprised only 2.9% in healthy women. The deliveries were more likely to be induced (22.8%) or be performed by cesarean section (14.9%) in women with PE than in healthy controls (6.8% and 9.6%). Placental abruption was the most common maternal complication (12.6%) in women with PE, followed by oligouria (7.9%), coagulopathy (6.0%), and renal failure (4.1%). The perinatal outcome of maternities with PE shows that stillbirths (2.34%) and early neonatal deaths (1.02%) comprised an overall mortality rate of 33.6 per 1,000. More stillbirths and neonatal deaths showed a tendency to be associated with the severe form of PE (diastolic BP ≧120), as compared with the mild form (diastolic BP 90–110). Stillbirths and neonatal deaths appear to be associated with women who had no or irregular antenatal care and whose proteinuria amounted to or exceeded 3 g per 24 h, when delivery occurred at 28th gestational week or less, and when the birth-weight of the neonates was between 500 and 1,000 g. <i>Conclusion:</i> We document a hospital-based incidence rate of PE of 2.47%, with a high proportion of PE cases occurring among nulliparous women and those at the extreme ends of the reproductive age. More maternal and neonatal complications were encountered in women with PE when the PE was severe, when the pregnancy had to be terminated early, when there was no regular antenatal care, the birth-weight was low, or the proteinuria was severe.
Silver-Coated Textiles Reduce <i>Staphylococcus aureus </i>Colonization in Patients with Atopic Eczema
Authors: Gauger Anke , Mempel Martin , Schekatz Annika , Schäfer Torsten , Ring Johannes , Abeck Dietrich 
Published: July 2003

<i>Background:</i> In atopic eczema (AE), skin colonization with <i>Staphylococcus aureus</i> is known to play a major triggering and possibly pathophysiological role. <i>Methods:</i> In this open-labeled controlled side-to-side comparative trial, affected sites (flexures of both elbows) in 15 patients diagnosed as having generalized or localized AE were evaluated regarding <i>S. aureus</i> colonization and clinical severity of AE over a 2-week period. Flexures of the elbows were covered with silver-coated textiles on one arm and cotton on the other for 7 days followed by a 7-day control period. <i>Results:</i> A highly significant decrease in <i>S. aureus</i> colonization could be seen on the site covered by the silver-coated textile already 2 days after initiation lasting until the end of the treatment. Seven days after cessation, <i>S. aureus</i> density remained significantly lower compared to baseline. In addition, significantly lower numbers of <i>S. aureus</i> were observed on the silver-coated textile site in comparison to cotton at the end of treatment as well as at the time point of control. Clinical improvement correlated with the reduction of <i>S. aureus</i> colonization. <i>Conclusion:</i> A superior improvement achieved by silver-coated compared to cotton textiles paralleled a potent anti-<i>S.-aureus</i> effect.
Occlusive Treatment of Chronic Hand Dermatitis with Pimecrolimus Cream 1% Results in Low Systemic Exposure, Is Well Tolerated, Safe, and Effective
Authors: Thaçi Diamant , Steinmeyer Katrin , Ebelin Marie-Eve , Scott Graham , Kaufmann Roland 
Published: July 2003

<i>Background:</i> Pimecrolimus cream 1% (Elidel<sup>®</sup>, SDZ ASM 981) is a novel, non-steroid inflammatory cytokine inhibitor, effective in the treatment of atopic dermatitis. Here, we evaluate the treatment of chronic hand dermatitis with pimecrolimus cream 1%. <i>Objectives:</i> To determine pimecrolimus blood concentrations, and evaluate the safety, tolerability and efficacy following application of pimecrolimus cream 1% to subjects with chronic hand dermatitis. <i>Method:</i> In this open-label, multiple-topical-dose, non-controlled, pharmacokinetic study, pimecrolimus cream 1% was applied twice daily to dorsal and palmar areas (affected and unaffected) of both hands. Evening applications (except day 8) were immediately followed by overnight occlusion (≧6 h). Full pharmacokinetic profile (days 1, 8 and 22), trough concentrations (days 3 and 15), physical examinations, laboratory measurements and adverse events were recorded. Efficacy was assessed via Investigators’ Global Assessment (IGA), total key signs and symptoms and the subject’s overall self-assessment. <i>Results:</i> Twelve patients completed the study. The majority of pimecrolimus blood concentrations (73.6%) remained below the limit of quantitation (0.1 ng/ml). The maximum concentration observed was 0.91 ng/ml and the maximum area under the concentration-time curve from 0–12 h post dose was 7.6 ng·h/ml. Treatment was well tolerated locally and systemically. No serious adverse events occurred; 4/13 subjects showed a total of 6 adverse events at the application site: burning (n = 4), and pruritus (n = 2). No clinically relevant or drug-related changes were observed. Clear efficacy of the treatment was shown by all 3 assessment methods. Disease state at day 22 had improved in 11 (85%) subjects compared with baseline (IGA). <i>Conclusion:</i> Twice daily topical treatment of moderate to severe chronic hand dermatitis with pimecrolimus cream 1% results in low pimecrolimus blood levels, is well tolerated, safe, and effective.
Cerebral Involvement as the Initial Manifestation of Chronic Lymphocytic Leukaemia
Authors: Kaiser Ulrich 
Published: July 2003

A 53-year-old man presented with focal jacksonian seizures that were due to cerebral tumour manifestations. Stereotactic biopsy revealed infiltration by lymphocytes compatible with the diagnosis of chronic lymphocytic leukaemia (CLL). Simultaneously, Binet stage II CLL with bone marrow infiltration was diagnosed. Cranial radiotherapy with 36 Gy was performed. One year after diagnosis, the patient is in stable disease. Cerebral involvement is rare but may occur in early CLL. Cranial radiotherapy may lead to lasting remission. In case of spinal fluid involvement intrathecal chemotherapy is recommended.