bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and inhibitor development in previously treated patients with haemophilia A switched to a B domain‐deleted recombinant factor VIII
Authors: Gringeri Alessandro , Tagliaferri Annarita , Tagariello Giuseppe , Morfini Massimo , Santagostino Elena , Mannucci Piermannuccio ,   the ReFacto–AICE Study Group
Published: July 2004

SummaryThere have been recent reports of unexpected poor efficacy of a B‐domain‐deleted recombinant factor VIII (BDD‐rFVIII) in haemophiliacs, and inhibitor development in previously treated patients (PTPs) switched to BDD‐rFVIII. The results of a 6‐month prospective study of 25 PTPs and of a retrospective survey of 94 PTPs, all switched to BDD‐rFVIII, were used to evaluate efficacy and inhibitor development. The prospective study showed that 89% of 362 bleeds were controlled by one to two infusions, reproducing the efficacy profiles of other recombinant products (rFVIIIs). One patient, previously treated with plasma‐derived FVIII only, developed a high titre inhibitor (30 BU) after 5 days of exposure. The retrospective survey, carried out in the total Italian PTP population switched to BDD‐rFVIII, involved 19 PTPs at higher inhibitor risk due to previous exposure of ≤ 50 days and 75 PTPs at lower inhibitor risk due to previous exposure of >50 days. One patient developed an inhibitor: he was a high‐risk, severe PTP previously exposed to another rFVIII for 3 days only. Among the entire low‐risk population of severe Italian PTPs switched to BDD‐rFVIII (25 in the prospective study, 49 in the retrospective cohort) only one developed an inhibitor (1·3%). These data indirectly support the views that BDD‐rFVIII is equivalent to other rFVIIIs in term of efficacy and inhibitor development.
Intraindividual consistency of the activated protein C resistance phenotype
Authors: Tosetto Alberto , Simioni Monica , Madeo Domenico , Rodeghiero Francesco 
Published: July 2004

SummaryResistance to activated protein C (APC) has been demonstrated to be a risk factor for venous thromboembolism, but it is not known whether this phenotype is consistent over time. We reinvestigated 2580 subjects from the Vicenza Thrombophilia and Atherosclerosis (VITA) Project to evaluate the prevalence of a consistent APC resistance phenotype in the population. Among the 433 subjects with an APC resistance at first visit, the phenotype was confirmed in all the 74 factor V (FV) Leiden carriers and in 124 of 359 FV Leiden negative subjects (34%). The prevalence of a confirmed phenotype, not associated with FV Leiden, was 4·8% in our population. In a subgroup of subjects previously investigated for heritability of the APC resistance, we confirmed the APC resistance phenotype in seven of 39 (17·9%) subjects with an APC resistant sibling but only in 20 of 408 (4·9%) subjects without a sibling with the same phenotype (P = 0·005). Among the 124 FV Leiden negative subjects with a persistent APC resistance phenotype, 40 (32%) had a plasma factor VIII coagulant activity level above 150 IU/dl and eight (6·4%) were carriers of the G20210A prothrombin allele. APC resistance not due to FV Leiden is a frequent and consistent phenotype in the general population, with a possibly strong genetic influence.
Meiotic segregation of translocations during male gametogenesis
Authors: Morel Frédéric , Douet‐Guilbert Nathalie , Le Bris Marie‐Josée , Herry Angèle , Amice Véronique , Amice Jean , De Braekeleer Marc 
Published: July 2004

SummaryBalanced reciprocal and Robertsonian translocations are the most common structural chromosomal abnormalities in humans. Generally, they are without consequence for the carrier, but for various degrees of oligoasthenoteratozoospermia in men. As these carriers can produce a significant percentage of gametes with an unbalanced combination of the parental rearrangement, there is a more or less significant risk, according to cases, of chromosomal imbalances for their offspring. Therefore, techniques were developed to study the meiotic segregation of these translocations in males. Direct investigation of human sperm chromosomes became possible by karyotyping spermatozoa after penetration of zona‐free hamster oocytes and, more recently, using fluorescent in situ hybridization (FISH). This paper reviews the results obtained using these techniques in Robertsonian and reciprocal translocations. The studies on spermatozoa from translocation carriers help the comprehension of the mechanisms of the meiotic segregation. They should be integrated in the genetic exploration of the infertile men, in order to give them a personalized risk assessment of unbalanced spermatozoa, specially as a correlation was found recently between the percentage of abnormal spermatozoa and that of abnormal embryos.
Glial Aromatization Decreases Neural Injury in the Zebra Finch (Taeniopygia guttata): Influence on Apoptosis
Authors: Wynne R. D. , Saldanha C. J. 
Published: July 2004

AbstractEmerging evidence suggests a neuroprotective role for oestrogens following damage to the vertebrate brain. Aromatase (oestrogen synthase) is rapidly transcribed and translated in glial cells around areas of neural damage in several vertebrates. However, the potential neuroprotection afforded by locally up‐regulated glial aromatase immediately surrounding the injury remains to be tested. Towards this end, individual birds sustained penetrating mechanical injuries via a needle that contained either vehicle or the aromatase inhibitor fadrozole into contralateral hemispheres. Seventy‐two hours later, the size of neural injury (as assessed by the extent of necrotic tissue) and the number of apoptotic cells around the injuries were evaluated. The size of injury in the hemisphere injected with fadrozole was significantly larger than the injury caused by vehicle injection. Furthermore, a greater number of apoptotic nuclei were found around the fadrozole‐associated lesion relative to vehicle. Finally, constitutively expressed, neuronal aromatase close to the injury site did not differ between hemispheres. We conclude that local inhibition of glial aromatase immediately around the site of injury plays a neuroprotective role in the songbird brain and this protection involves apoptotic pathways. Local up‐regulation of glial aromatase may play a pivotal role in the limitation of secondary damage and/or the acceleration of restorative processes following injury to the vertebrate brain.
Glial Limitans Elasticity Subjacent to the Supraoptic Nucleus
Authors: Salm A. K. , Hawrylak N. 
Published: July 2004

AbstractTwo previous studies from our laboratory have indicated that the ventral glial limitans subjacent to the hypothalamic supraoptic nucleus (SON‐VGL) undergoes a reversible thinning upon chronic activation of the magnocellular neuroendocrine cells (MNCs) of the supraoptic nucleus (SON). Numerous other studies have shown that MNC somata hypertrophy with activation. One aim of the current study was to understand better how SON‐VGL thinning occurs. A second aim was to quantify overall changes of the MNC somata region due to cellular hypertrophy to compare relative changes in dimensions. Here, we undertook a light microscopic stereological investigation of the SON and the subjacent SON‐VGL of Nissl stained material under basal and activated conditions. Astrocyte numbers in the underlying SON‐VGL remained stable across hydration state as did the overall volume of the SON‐VGL and dendritic zone reference area. How these data are consistent with our earlier observations of SON‐VGL thinning was resolved by the finding of a highly significant, 30% increase in the mediolateral dimension of the SON‐VGL in dehydrated rats. These observations fit well with previous work from our laboratory that demonstrates a reorientation of SON‐VGL astrocytes, from vertical to horizontal, which occurs in the activated SON‐VGL. We found a significant, approximately 54%, increase in the overall volume of the MNC region of the SON. No significant rostrocaudal lengthening of the SON was detected, although a trend was evident. All the observed changes reversed with rehydration. These data indicate that elasticity of the SON‐VGL acts to accommodate the volume expansion of the MNCs and enables the SON‐VGL to continue as an interface between the underlying cerebrospinal fluid in the subarachnoid space and the expanded SON above.
Patient characteristics and quality of life among a sample of Australian chronic pain clinic attendees
Authors: Kerr S. , Fairbrother G. , Crawford M. , Hogg M. , Fairbrother D. , Khor K.E. 
Published: July 2004

Abstract Background : Multidisciplinary chronic pain management programs have proliferated widely in recent decades. The clinical characteristics of patients attending these clinics are becoming the subject of increased research. Recent European data suggests that patients attending these clinics report very low quality of life.Aims:  The present study profiles an Australian popu­lation in terms of demographics, clinical characteristics and quality of life, as measured by the Short Form 36 Quality of Life Questionnaire (SF‐36).Methods:  Data were collected prospectively from consecutive patients presenting to a multidisciplinary chronic pain clinic at a major Sydney metropolitan teaching ­hospital. Cross‐sectional analysis of demographic and clin­ical characteristics and quality of life were then undertaken.Results:  Descriptive analysis of demographics and clin­ical characteristics suggest a patient population group reporting significant pain severity and reduced quality of life. The comparison of SF‐36 domain scores between clinic patients and Australian norm values indicates a greatly reduced score on all SF‐36 domains for clinic patients. Pain clinic patients reported the most profound effect upon quality of life in the role physical, physical function and social function domains of the SF‐36. Stepwise multiple regression indicated impaired coping ability and depressive disability as the most significant correlates of low quality of life.Conclusion:  Patients who attend chronic pain clinics are likely to report low quality of life with an inability to cope. These findings suggest that future intervention research should explore the impacts of behavioural and self‐management interventions. Psychological distress and ability to cope could be used as indices of improvement. (Intern Med J 2004; 34: 403−409)
Repetitive strain injuries: has the Australian epidemic burnt out?
Authors: Awerbuch M. 
Published: July 2004

Abstract In the 1980s Australia experienced an epidemic of medically certified claims for non‐specific arm symptoms described as repetitive strain injury. Although a number of factors were mooted as causal of the epidemic, no single factor emerged as a compelling putative candidate. The present paper discusses the results of research which was published only after the epidemic had waned. It provides possible insights into the rise and fall of repetitive strain injury. (Intern Med J 2004; 34: 416−419)
Justice and Union Participation: An Extension and Test of Mobilization Theory
Authors: Johnson Nancy Brown , Jarley Paul 
Published: July 2004

AbstractHeeding John Kelly's call to reorient the field of industrial relations towards the study of injustice, we employ mobilization, social exchange and organizational justice theories to specify and test a model of union participation. Using individual‐level survey data from public‐sector union members to test our model, we find that differences in worker perceptions of workplace injustice and union justice explain slightly more variation in members’ union participation than more traditional measures of job satisfaction and union instrumentality perceptions. The implications of our analysis for researchers and union practitioners are also discussed.
How chronic inflammation can affect the brain and support the development of Alzheimer's disease in old age: the role of microglia and astrocytes
Authors: Blasko Imrich , Stampfer‐Kountchev Michaela , Robatscher Peter , Veerhuis Robert , Eikelenboom Piet , Grubeck‐Loebenstein Beatrix 
Published: July 2004

SummaryA huge amount of evidence has implicated amyloid beta (Aβ) peptides and other derivatives of the amyloid precursor protein (βAPP) as central to the pathogenesis of Alzheimer's disease (AD). It is also widely recognized that age is the most important risk factor for AD and that the innate immune system plays a role in the development of neurodegeneration. Little is known, however, about the molecular mechanisms that underlie age‐related changes of innate immunity and how they affect brain pathology. Aging is characteristically accompanied by a shift within innate immunity towards a pro‐inflammatory status. Pro‐inflammatory mediators such as tumour necrosis factor‐α or interleukin‐1β can then in combination with interferon‐γ be toxic on neurons and affect the metabolism of βAPP such that increased concentrations of amyloidogenic peptides are produced by neuronal cells as well as by astrocytes. A disturbed balance between the production and the degradation of Aβ can trigger chronic inflammatory processes in microglial cells and astrocytes and thus initiate a vicious circle. This leads to a perpetuation of the disease.
Stress responses and innate immunity: aging as a contributory factor
Authors: Butcher Stephen K. , Lord Janet M. 
Published: July 2004

SummaryEvolutionary pressure has selected individuals with traits that allow them to survive to reproduction, without consideration of the consequences for the post‐child rearing years and old age. In the 21st century, society is populated increasingly by the elderly and with the falling birth rate and improved health care this trend is set to continue for the foreseeable future. To minimize the potential burden on health services one would hope that ‘growing old gracefully’ should also mean ‘growing old healthily’. However, for too many the aging process is accompanied by increasing physical and mental frailty producing an elevated risk of physical and psychological stress in old age. Stress is a potent modulator of immune function, which in youth can be compensated for by the presence of an optimal immune response. In the elderly the immune response is blunted as a result of the decline in several components of the immune system (immune senescence) and a shifting to a chronic pro‐inflammatory status (the so‐called ‘inflamm‐aging’ effect). We discuss here what is known of the effects of both stress and aging upon the innate immune system, focusing in particular upon the age‐related alterations in the hypopituitary–adrenal axis. We propose a double hit model for age and stress in which the age‐related increase in the cortisol/sulphated dehydroepiandrosterone ratio synergizes with elevated cortisol during stress to reduce immunity in the elderly significantly.
NK and NKT cell functions in immunosenescence
Authors: Mocchegiani Eugenio , Malavolta Marco 
Published: July 2004

SummaryImmunosenescence is defined as the state of dysregulated immune function that contributes to the increased susceptibility to infection, cancer and autoimmune diseases observed in old organisms, including humans. However, dysregulations in the immune functions are normally counterbalanced by continuous adaptation of the body to the deteriorations that occur over time. These adaptive changes are likely to occur in healthy human centenarians. Both innate (natural) and adaptive (acquired) immune responses decline with advancing age. Natural killer (NK) and natural killer T (NKT) cells represent the best model to describe innate and adaptive immune response in aging. NK and NKT cell cytotoxicity decreases in aging as well as interferon‐γ (IFN‐γ) production by both activated cell types. Their innate and acquired immune responses are preserved in very old age. However, NKT cells bearing T‐cell receptor (TCR) γδ also display an increased cytotoxicity and IFN‐γ production in very old age. This fact suggests that NKT cells bearing TCRγδ are more involved in maintaining innate and adaptive immune response in aging leading to successful aging. The role played by the neuroendocrine–immune network and by nutritional factors, such as zinc, in maintaining NK and NKT cell functions in aging is discussed.
ALL THINGS CONSIDERED, TAXES DRIVE THE JANUARY EFFECT
Authors: Chen Honghui , Singal Vijay 
Published: July 2004

AbstractThe multitude of explanations for the January effect leaves the reader confused about its primary cause(s): is it tax‐loss selling, window dressing, information, bid‐ask bounce, or a combination of these causes? The confusion arises, in part, because evidence has generally been presented in support of a particular hypothesis though the same evidence may be consistent with another hypothesis. Furthermore, prior work does not adequately control for the bid‐ask bounce. In this article we try to disentangle different explanations of the January effect and identify its primary cause. We find that tax‐related selling is the most important cause, overshadowing other explanations.
TRADING COSTS AND QUOTE CLUSTERING ON THE NYSE AND NASDAQ AFTER DECIMALIZATION
Authors: Chung Kee H. , Van Ness Bonnie F. , Van Ness Robert A. 
Published: July 2004

AbstractWe examine execution costs and quote clustering on the New York Stock Exchange (NYSE) and NASDAQ using 517 matching pairs of stocks after decimalization. We find that the mean spread of NASDAQ stocks is greater than the mean spread of NYSE stocks when spreads are equally weighted across stocks, and the difference is greater for smaller stocks. In contrast, the mean NASDAQ spread is narrower than the mean NYSE spread when spreads are volume weighted, and the difference is statistically significant for large stocks. Both NYSE and NASDAQ stocks exhibit high degrees of quote clustering on nickels and dimes, and quote clustering has a significant effect on spreads in both markets.
Adaptive Mutations Producing Efficient Replication of Genotype 1a Hepatitis C Virus RNA in Normal Huh7 Cells
Authors: Yi MinKyung , Lemon Stanley M. 
Published: July 2004

ABSTRACT
Despite recent successes in generating subgenomic RNA replicons derived from genotype 1b strains of hepatitis C virus (HCV) that replicate efficiently in cultured cells, it has proven difficult to generate efficiently replicating RNAs from any other genotype of HCV. This includes genotype 1a, even though it is closely related to genotype 1b. We show here that an important restriction to replication of the genotype 1a H77c strain RNA in normal Huh7 cells resides within the amino-terminal 75 residues of the NS3 protease. We identified adaptive mutations located within this NS3 domain and within NS4A, in close proximity to the essential protease cofactor sequence, that act cooperative to substantially enhance the replication of this genotype 1a RNA in Huh7 cells. These and additional adaptive mutations, identified through a series of iterative transfections and the selection of G418-resistant cell clones, form two groups associating with distinct nonstructural protein domains: the NS3/4A protease and NS5A. A combination of mutations from both groups led to robust replication of otherwise unmodified H77c genomic RNA that was readily detectable by northern analysis within 4 days of transfection into Huh7 cells. We speculate that these adaptive mutations favorably influence assembly of the replicase complex with host cell-specific proteins, or alternatively promote interactions of NS3/4A and/or NS5A with cellular proteins involved in host cell antiviral defenses.
Superinfection Exclusion in Duck Hepatitis B Virus Infection Is Mediated by the Large Surface Antigen
Authors: Walters Kathie-Anne , Joyce Michael A. , Addison William R. , Fischer Karl P. , Tyrrell D. Lorne J. 
Published: July 2004

ABSTRACT
Superinfection exclusion is the phenomenon whereby a virus prevents the subsequent infection of an already infected host cell. The Pekin duck hepatitis B virus (DHBV) model was used to investigate superinfection exclusion in hepadnavirus infections. Superinfection exclusion was shown to occur both in vivo and in vitro with a genetically marked DHBV, DHBV-ClaI, which was unable to establish an infection in either DHBV-infected ducklings or DHBV-infected primary duck hepatocytes (PDHs). In addition, exclusion occurred in vivo even when the second virus had a replicative advantage. Superinfection exclusion appears to be restricted to DHBV, as adenovirus, herpes simplex virus type 1, and vesicular stomatitis virus were all capable of efficiently infecting DHBV-infected PDHs. Exclusion was dependent on gene expression by the original infecting virus, since UV-irradiated DHBV was unable to mediate the exclusion of DHBV-ClaI. Using recombinant adenoviruses expressing DHBV proteins, we determined that the large surface antigen mediated exclusion. The large surface antigen is known to cause down-regulation of a DHBV receptor, carboxypeptidase D (CPD). Receptor down-regulation is a mechanism of superinfection exclusion seen in other viral infections, and so it was investigated as a possible mechanism of DHBV-mediated exclusion. However, a mutant large surface antigen which did not down-regulate CPD was still capable of inhibiting DHBV infection of PDHs. In addition, exclusion of DHBV-ClaI did not correlate with a decrease in CPD levels. Finally, virus binding assays and confocal microscopy analysis of infected PDHs indicated that the block in infection occurs after internalization of the second virus. We suggest that superinfection exclusion may result from the role of the L surface antigen as a regulator of intracellular trafficking.
Assembly of
Turnip Yellow Mosaic Virus
Replication Complexes: Interaction between the Proteinase and Polymerase Domains of the Replication Proteins
Authors: Jakubiec Anna , Notaise Julien , Tournier Vincent , Héricourt François , Block Maryse A. , Drugeon Gabrièle , van Aelst Linda , Jupin Isabelle 
Published: July 2004

ABSTRACT

Turnip yellow mosaic virus
(TYMV), a positive-strand RNA virus in the alphavirus-like supergroup, encodes two nonstructural replication proteins (140K and 66K), both of which are required for its RNA genome replication. The 140K protein contains domains indicative of methyltransferase, proteinase, and NTPase/helicase activities, while the 66K protein encompasses the RNA-dependent RNA polymerase domain. Recruitment of the 66K protein to the sites of viral replication, located at the periphery of chloroplasts, is dependent upon the expression of the 140K protein. Using antibodies raised against the 140K and 66K proteins and confocal microscopy, we report the colocalization of the TYMV replication proteins at the periphery of chloroplasts in transfected or infected cells. The replication proteins cofractionated in functional replication complexes or with purified chloroplast envelope membranes prepared from infected plants. Using a two-hybrid system and coimmunoprecipitation experiments, we also provide evidence for a physical interaction of the TYMV replication proteins. In contrast to what has been found for other members of the alphavirus-like supergroup, the interaction domains were mapped to the proteinase domain of the 140K protein and to a large region encompassing the core polymerase domain within the 66K protein. Coexpression and colocalization experiments confirmed that the helicase domain of the 140K protein is unnecessary for the proper recruitment of the 66K protein to the chloroplast envelope, while the proteinase domain appears to be essential for that process. These results support a novel model for the interaction of TYMV replication proteins and suggest that viruses in the alphavirus-like supergroup may have selected different pathways to assemble their replication complexes.