bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functional analysis of human T lymphotropic virus type 2 Tax proteins
Authors: Sheehy Noreen , Lillis Lorraine , Watters Karen , Lewis Martha , Gautier Virginie , Hall William 
Published: April 2006

Abstract

Background
The Tax proteins encoded by human T lymphotropic virus type 1 (HTLV-1) and type 2 (HTLV-2) are transcriptional activators of both the viral long terminal repeat (LTR) and cellular promoters via the CREB and NFkB pathways. In contrast to HTLV-1, HTLV-2 has been classified into four distinct genetic subtypes A, B, C and D defined by phylogenetic analysis of their nucleotide sequences and the size and amino acid sequence of their Tax proteins. In the present study we have analysed and compared the transactivating activities of three Tax 2A and one Tax 2B proteins using LTR and NFkB reporter assays.

Results
We found that with the exception of the prototype Tax 2A Mo protein, the other two Tax 2A proteins failed to transactivate either the viral LTR or NFkB promoter in Jurkat and 293T cells. Loss of activity was not associated with either expression levels or an alteration in subcellular distribution as all Tax 2 proteins were predominantly located in the cytoplasm of transfected cells. Analysis of the sequence of the two inactive Tax 2A proteins relative to Mo indicated that one had six amino acid changes and the other had one change in the central region of the protein. Mutations present at the amino and the extreme carboxy termini of Mo resulted in the loss of LTR but not NFkB activation whereas those occurring in the central region of the protein appeared to abolish transactivation of both promoters. Analysis of the transactivation phenotypes of Tax 1, Tax 2A Mo and Tax 2B containing mutations identified in the present study or previously characterised Tax mutations showed that domains required for LTR and NFkB activation are very similar but not identical in all three Tax proteins.

Conclusion
Our results suggest that loss of activity of two Tax 2A proteins derived from different isolates is associated with multiple amino acid changes relative to Mo in domains required for the activation of the CREB or CREB and NFkB pathways and that these domains are very similar but not identical in Tax 2B and Tax 1. The loss of Tax function in 2A viruses may have implications for their biological and pathogenic properties.
Systemic inflammatory response in erderly patients following hernioplastical operation
Authors: Di Vita Gaetano , Balistreri Carmela Rita , Arcoleo Francesco , Buscemi Salvatore , Cillari Enrico , Donati Marcello , Garofalo Maria , Listì Florinda , Grimaldi Maria Paola , Patti Rosalia , Candore Giuseppina 
Published: April 2006

Abstract
The number of old and oldest old patients undergoing surgery of varying severity is increasing. Ageing is a process that changes the performances of most physiological systems and increases susceptibility to diseases and death; accordingly, host responses to surgical stress are altered with ageing and the occurrence of age-related increase in susceptibility to post-operative complications has been claimed. Twenty-four male patients undergoing Lichtenstein (LH) hernioplasty for unilateral inguinal hernia were included in this study and divided in two groups (Young and Old respectively), according to their age. As expression of the acute phase response, we measured changes in concentration of pro-inflammatory cytokines Tumor necrosis factor-α and Interleukin-1β, leukocytes, acute phase proteins C-reactive protein and α 1-antitrypsin. Elderly humans showed prolonged and strong inflammatory activity compared to younger subjects in response to surgical stress, indicating that the acute-phase response to surgical stress of elderly humans varies from that of the young, showing initial hyperactivity and a delayed termination of the response. Thus, the acute phase response to surgical stress is higher in old subjects, but the clinical significance of this remains unclear. It is not known whether a causal relationship exists between this stronger acute phase response and the increases in susceptibility to post-operative complications observed in aged patients.
A demonstration of modeling count data with an application to physical activity
Authors: Slymen Donald J , Ayala Guadalupe X , Arredondo Elva M , Elder John P 
Published: April 2006

AbstractCounting outcomes such as days of physical activity or servings of fruits and vegetables often have distributions that are highly skewed toward the right with a preponderance of zeros, posing analytical challenges. This paper demonstrates how such outcomes may be analyzed with several modifications to Poisson regression.Five regression models 1) Poisson, 2) overdispersed Poisson, 3) negative binomial, 4) zero-inflated Poisson (ZIP), and 5) zero-inflated negative binomial (ZINB) are fitted to data assessing predictors of vigorous physical activity (VPA) among Latina women. The models are described, and analytical and graphical approaches are discussed to aid in model selection.Poisson regression provided a poor fit where 82% of the subjects reported no days of VPA. The fit improved considerably with the negative binomial and ZIP models. There was little difference in fit between the ZIP and ZINB models. Overall, the ZIP model fit best. No days of VPA were associated with poorer self-reported health and less assimilation to Anglo culture, and marginally associated with increasing BMI. The intensity portion of the model suggested that increasing days of VPA were associated with more education, and marginally associated with increasing age. These underutilized models provide useful approaches for handling counting outcomes.
Assessing the effect of HAART on change in quality of life among HIV-infected women
Authors: Liu Chenglong , Weber Kathleen , Robison Esther , Hu Zheng , Jacobson Lisa P , Gange Stephen J 
Published: April 2006

Abstract

Background
The impact of highly active antiretroviral therapy (HAART) on health-related quality of life (QOL) of HIV-1 infected individuals in large prospective cohorts has not been well studied.

Objective
To assess the effect of HAART on QOL by comparing HIV-infected women using HAART with HIV-infected women remaining HAART naïve in the Women's Interagency HIV Study (WIHS), a multicenter prospective cohort study begun in 1994 in the US.

Methods
A 1:1 matching with equivalent (≤ 0.1%) propensity scores for predicting HAART initiation was implemented and 458 pairs were obtained. HAART effects were assessed using pattern mixture models. The changes of nine QOL domain scores and one summary score derived from a shortened version of the MOS-HIV from initial values were used as study outcomes.

Results
The background covariates of the treatment groups were well-balanced after propensity score matching. The 916 matched subjects had a mean age of 38.5 years and 42% had a history of AIDS diagnosis. The participants contributed a total of 4,292 person visits with a median follow-up time of 4 years. In the bivariate analyses with only HAART use and time as covariates, HAART was associated with short-term improvements of 4 QOL domains: role functioning, social functioning, pain and perceived health index. After adjusting for demographic, socioeconomic, biological and clinical variables, HAART had small but significant short-term improvements on changes in summary QOL (mean change: 3.25; P = 0.02), role functioning (6.99; P < 0.01), social functioning (5.74; P < 0.01), cognitive functioning (3.59; P = 0.03), pain (6.73; P < 0.01), health perception (3.67; P = 0.03) and perceived health index (4.87; P < 0.01). These QOL scores typically remained stable or declined over additional follow-up and there was no indication that HAART modified these trends.

Conclusion
Our study demonstrated significant short-term HAART effects on most QOL domains, but additional use of HAART did not modify long-term trends. These changes could be attributed to the direct effect of HAART and indirect HAART effect mediated through clinical changes.
The evolution of methods for the capture of human movement leading to markerless motion capture for biomechanical applications
Authors: Mündermann Lars , Corazza Stefano , Andriacchi Thomas P 
Published: April 2006

AbstractOver the centuries the evolution of methods for the capture of human movement has been motivated by the need for new information on the characteristics of normal and pathological human movement. This study was motivated in part by the need of new clinical approaches for the treatment and prevention of diseases that are influenced by subtle changes in the patterns movement. These clinical approaches require new methods to measure accurately patterns of locomotion without the risk of artificial stimulus producing unwanted artifacts that could mask the natural patterns of motion. Most common methods for accurate capture of three-dimensional human movement require a laboratory environment and the attachment of markers or fixtures to the body's segments. These laboratory conditions can cause unknown experimental artifacts. Thus, our understanding of normal and pathological human movement would be enhanced by a method that allows the capture of human movement without the constraint of markers or fixtures placed on the body. In this paper, the need for markerless human motion capture methods is discussed and the advancement of markerless approaches is considered in view of accurate capture of three-dimensional human movement for biomechanical applications. The role of choosing appropriate technical equipment and algorithms for accurate markerless motion capture is critical. The implementation of this new methodology offers the promise for simple, time-efficient, and potentially more meaningful assessments of human movement in research and clinical practice. The feasibility of accurately and precisely measuring 3D human body kinematics for the lower limbs using a markerless motion capture system on the basis of visual hulls is demonstrated.
Multicistronic lentiviral vectors containing the FMDV 2A cleavage factor demonstrate robust expression of encoded genes at limiting MOI
Authors: Chinnasamy Dhanalakshmi , Milsom Michael D , Shaffer James , Neuenfeldt James , Shaaban Aimen F , Margison Geoffrey P , Fairbairn Leslie J , Chinnasamy Nachimuthu 
Published: April 2006

Abstract

Background
A number of gene therapy applications would benefit from vectors capable of expressing multiple genes. In this study we explored the feasibility and efficiency of expressing two or three transgenes in HIV-1 based lentiviral vector. Bicistronic and tricistronic self-inactivating lentiviral vectors were constructed employing the internal ribosomal entry site (IRES) sequence of encephalomyocarditis virus (EMCV) and/or foot-and-mouth disease virus (FMDV) cleavage factor 2A. We employed enhanced green fluorescent protein (eGFP), O
6-methylguanine-DNA-methyltransferase (MGMT), and homeobox transcription factor HOXB4 as model genes and their expression was detected by appropriate methods including fluorescence microscopy, flow cytometry, immunocytochemistry, biochemical assay, and western blotting.

Results
All the multigene vectors produced high titer virus and were able to simultaneously express two or three transgenes in transduced cells. However, the level of expression of individual transgenes varied depending on: the transgene itself; its position within the construct; the total number of transgenes expressed; the strategy used for multigene expression and the average copy number of pro-viral insertions. Notably, at limiting MOI, the expression of eGFP in a bicistronic vector based on 2A was ~4 times greater than that of an IRES based vector.

Conclusion
The small and efficient 2A sequence can be used alone or in combination with an IRES for the construction of multicistronic lentiviral vectors which can express encoded transgenes at functionally relevant levels in cells containing an average of one pro-viral insert.
Inhibition of cytokine gene expression and induction of chemokine genes in non-lymphatic cells infected with SARS coronavirus
Authors: Spiegel Martin , Weber Friedemann 
Published: April 2006

Abstract

Background
SARS coronavirus (SARS-CoV) is the etiologic agent of the severe acute respiratory syndrome. SARS-CoV mainly infects tissues of non-lymphatic origin, and the cytokine profile of those cells can determine the course of disease. Here, we investigated the cytokine response of two human non-lymphatic cell lines, Caco-2 and HEK 293, which are fully permissive for SARS-CoV.

Results
A comparison with established cytokine-inducing viruses revealed that SARS-CoV only weakly triggered a cytokine response. In particular, SARS-CoV did not activate significant transcription of the interferons IFN-α, IFN-β, IFN-λ1, IFN-λ2/3, as well as of the interferon-induced antiviral genes ISG56 and MxA, the chemokine RANTES and the interleukine IL-6. Interestingly, however, SARS-CoV strongly induced the chemokines IP-10 and IL-8 in the colon carcinoma cell line Caco-2, but not in the embryonic kidney cell line 293.

Conclusion
Our data indicate that SARS-CoV suppresses the antiviral cytokine system of non-immune cells to a large extent, thus buying time for dissemination in the host. However, synthesis of IP-10 and IL-8, which are established markers for acute-stage SARS, escapes the virus-induced silencing at least in some cell types. Therefore, the progressive infiltration of immune cells into the infected lungs observed in SARS patients could be due to the production of these chemokines by the infected tissue cells.
Cerebrospinal fluid supports viability and proliferation of cortical cells in vitro, mirroring in vivo development
Authors: Miyan Jaleel A , Zendah Mahjiub , Mashayekhi Farhad , Owen-Lynch P Jane 
Published: April 2006

Abstract

Background
The central nervous system develops around a fluid filled compartment. Recently, attention has turned to the potential role of the fluid (cerebrospinal fluid, CSF) in the developmental process. In particular, the cerebral cortex develops from the germinal epithelium adjacent to the CSF with regulation of cell proliferation and differentiation provided by cells adjacent to the fluid-filled subarachnoid space.

Methods
Histological analysis of fetal rat cortical sections was used to follow the extent of in vivo cortical development. A quantitative analysis of proliferation and migration of cortical cells at E17 – E21 was obtained through immunocytochemical staining of bromodeoxyuridine (BrdU) -labelled cells. In vitro studies were performed on primary cortical cells at days E17-E20, maintained in either Neurobasal media or 100% fetal rat CSF for 72 h before analysis of proliferation.

Results
The proliferation potential of primary cortical cells varied depending on the age of extraction. E17 and E20 cells showed little proliferation while E18 and E19 cell showed the maximum. The CSF from fetuses of all ages tested, except E21, was able to maintain primary cortical cells from the developing fetus in vitro and to stimulate and support their proliferation in the absence of any additions. E17 cells showed little proliferation in any media while E19 cells showed maximum proliferation in E19 and E20 CSF.

Conclusion
CSF composition most probably changes with age, as does the proliferation potential of cells in the developing cerebral cortex. CSF alone supports viability as well as proliferation of cortical cells. CSF must therefore be regarded as an important environmental influence in brain development and can be used in vitro to maintain both the viability of cortical progenitor cells and their age-related proliferative potential.
In vitro cytotoxicity of Manville Code 100 glass fibers: Effect of fiber length on human alveolar macrophages
Authors: Zeidler-Erdely Patti C , Calhoun William J , Ameredes Bill T , Clark Melissa P , Deye Gregory J , Baron Paul , Jones William , Blake Terri , Castranova Vincent 
Published: April 2006

AbstractBackgroundSynthetic vitreous fibers (SVFs) are inorganic noncrystalline materials widely used in residential and industrial settings for insulation, filtration, and reinforcement purposes. SVFs conventionally include three major categories: fibrous glass, rock/slag/stone (mineral) wool, and ceramic fibers. Previousin vitrostudies from our laboratory demonstrated length-dependent cytotoxic effects of glass fibers on rat alveolar macrophages which were possibly associated with incomplete phagocytosis of fibers ≥ 17 μm in length. The purpose of this study was to examine the influence of fiber length on primary human alveolar macrophages, which are larger in diameter than rat macrophages, using length-classified Manville Code 100 glass fibers (8, 10, 16, and 20 μm). It was hypothesized that complete engulfment of fibers by human alveolar macrophages could decrease fiber cytotoxicity; i.e. shorter fibers that can be completely engulfed might not be as cytotoxic as longer fibers. Human alveolar macrophages, obtained by segmental bronchoalveolar lavage of healthy, non-smoking volunteers, were treated with three different concentrations (determined by fiber number) of the sized fibersin vitro. Cytotoxicity was assessed by monitoring cytosolic lactate dehydrogenase release and loss of function as indicated by a decrease in zymosan-stimulated chemiluminescence.ResultsMicroscopic analysis indicated that human alveolar macrophages completely engulfed glass fibers of the 20 μm length. All fiber length fractions tested exhibited equal cytotoxicity on a per fiber basis, i.e. increasing lactate dehydrogenase and decreasing chemiluminescence in the same concentration-dependent fashion.ConclusionThe data suggest that due to the larger diameter of human alveolar macrophages, compared to rat alveolar macrophages, complete phagocytosis of longer fibers can occur with the human cells. Neither incomplete phagocytosis nor length-dependent toxicity was observed in fiber-exposed human macrophage cultures. In contrast, rat macrophages exhibited both incomplete phagocytosis of long fibers and length-dependent toxicity. The results of the human and rat cell studies suggest that incomplete engulfment may enhance cytotoxicity of fiber glass. However, the possibility should not be ruled out that differences between human versus rat macrophages other than cell diameter could account for differences in fiber effects.
Antimigraine Drug, Zolmitriptan, Inhibits High-Voltage Activated Calcium Currents in a Population of Acutely Dissociated Rat Trigeminal Sensory Neurons
Authors: Morikawa Tomoko , Matsuzawa Yoshiyasu , Makita Koshi , Katayama Yoshifumi 
Published: April 2006

Background Triptans, 5-HT1B/ID agonists, act on peripheral and/or central terminals of trigeminal ganglion neurons (TGNs) and inhibit the release of neurotransmitters to second-order neurons, which is considered as one of key mechanisms for pain relief by triptans as antimigraine drugs. Although high-voltage activated (HVA) Ca2+ channels contribute to the release of neurotransmitters from TGNs, electrical actions of triptans on the HVA Ca2+ channels are not yet documented. Results In the present study, actions of zolmitriptan, one of triptans, were examined on the HVA Ca2+ channels in acutely dissociated rat TGNs, by using whole-cell patch recording of Ba2+ currents (IBa) passing through Ca2+ channels. Zolmitriptan (0.1–100 μM) reduced the size of IBa in a concentration-dependent manner. This zolmitriptan-induced inhibitory action was blocked by GR127935, a 5-HT1B/1D antagonist, and by overnight pretreatment with pertussis toxin (PTX). P/Q-type Ca2+ channel blockers inhibited the inhibitory action of zolmitriptan on IBa, compared to N-and L-type blockers, and R-type blocker did, compared to L-type blocker, respectively (p < 0.05). All of the present results indicated that zolmitriptan inhibited HVA P/Q- and possibly R-type channels by activating the 5-HT1B/1D receptor linked to Gi/o pathway. Conclusion It is concluded that this zolmitriptan inhibition of HVA Ca2+ channels may explain the reduction in the release of neurotransmitters including CGRP, possibly leading to antimigraine effects of zolmitriptan.
Comparison of P2X and TRPV1 Receptors in Ganglia or Primary Culture of Trigeminal Neurons and their Modulation by NGF or Serotonin
Authors: Simonetti Manuela , Fabbro Alessandra , D'Arco Marianna , Zweyer Marina , Nistri Andrea , Giniatullin Rashid , Fabbretti Elsa 
Published: April 2006

Background Cultured sensory neurons are a common experimental model to elucidate the molecular mechanisms of pain transduction typically involving activation of ATP-sensitive P2X or capsaicin-sensitive TRPV1 receptors. This applies also to trigeminal ganglion neurons that convey pain inputs from head tissues. Little is, however, known about the plasticity of these receptors on trigeminal neurons in culture, grown without adding the neurotrophin NGF which per se is a powerful algogen. The characteristics of such receptors after short-term culture were compared with those of ganglia. Furthermore, their modulation by chronically-applied serotonin or NGF was investigated. Results Rat or mouse neurons in culture mainly belonged to small and medium diameter neurons as observed in sections of trigeminal ganglia. Real time RT-PCR, Western blot analysis and immunocytochemistry showed upregulation of P2X3 and TRPV1 receptors after 1–4 days in culture (together with their more frequent co-localization), while P2X2 ones were unchanged. TRPV1 immunoreactivity was, however, lower in mouse ganglia and cultures. Intracellular Ca2+ imaging and whole-cell patch clamping showed functional P2X and TRPV1 receptors. Neurons exhibited a range of responses to the P2X agonist α, β-methylene-adenosine-5′-triphosphate indicating the presence of homomeric P2X3 receptors (selectively antagonized by A-317491) and heteromeric P2X2/3 receptors. The latter were observed in 16 % mouse neurons only. Despite upregulation of receptors in culture, neurons retained the potential for further enhancement of P2X3 receptors by 24 h NGF treatment. At this time point TRPV1 receptors had lost the facilitation observed after acute NGF application. Conversely, chronically-applied serotonin selectively upregulated TRPV1 receptors rather than P2X3 receptors. Conclusion Comparing ganglia and cultures offered the advantage of understanding early adaptive changes of nociception-transducing receptors of trigeminal neurons. Culturing did not prevent differential receptor upregulation by algogenic substances like NGF or serotonin, indicating that chronic application led to distinct plastic changes in the molecular mechanisms mediating pain on trigeminal nociceptors.