bluuebunny/crossref_metadata_2025 huggingface dataset:
The Stories We Tell: The Lives and Friendship of Two Older Black Lesbians
Authors: Hall Ruth L. , Fine Michelle
Published: May 2005

Research addressing the lives and friendships of older Black lesbians is virtually nonexistent. Using narrative analysis, we chronicle the lives of two older Black lesbians (73 and 85 years of age) through the lens of positive marginality. The concept of positive marginality asserts that living both inside and outside of the mainstream produces strengths rather than helplessness ( Mayo, 1982 ). We use four conceptual frames of reference to explore positive marginality: critical watching and reframing of life experiences on the margins, wise conversion of obstacles into opportunities, the subversion of social institutions, and the creation of safe spaces for people on the margin. From these two women's stories, we show how each, through lives of activism and seduction, created positive environments that defied traditional categories. We discuss how race, class, gender, sexual orientation, and aging affected their lives and how their friendship was an anchor for each. We offer their stories as a point of entry to future inquiry concerning older Black lesbians.
Healthcare assistants’ experiences and perceptions of participating in a training course
Authors: Keeney Sinead , Hasson Felicity , McKenna Hugh P.
Published: May 2005

Although the number of healthcare assistants (HCA) in employment has continued to increase, the provision of training and development for this role has, to date, been largely dependent upon the discretion of individual employers. In response to this, the Department of Health and Children in Ireland decided to establish a national training course for HCAs and commission its evaluation. As part of this evaluation, the views of the trainees on the national training course were explored. The behaviour, attitudes and experience of these trainees were explored, as was their perception of the relevance of the training course to their role in employment as a HCA. One‐to‐one semistructured interviews with 22 randomly selected trainees were conducted. All interview respondents felt that the training course had been beneficial. Findings indicated positive changes in practice following their training. The interview respondents indicated that they felt more confident in their ability to undertake delegated duties and believed that the skills learned on the course would be useful to them in their future work. Other issues, such as course duration, selection procedure and level of assessment, caused some dissatisfaction. The training course led to a significant improvement in the trainees’ knowledge and care skills. Suggestions for changes to the course from the trainee's perspective include amending the trainee selection procedure and improving the organization and content of the course and follow‐up support.
Collaborative solutions – clinical supervision and teacher support teams: reducing professional isolation through effective peer support
Authors: Bedward Julie , Daniels Harry R. J.
Published: May 2005

This article reports an evaluation of the implementation of clinical supervision for nurses in seven pilot sites within a National Health Service Trust in the United Kingdom. Focus groups and documentary analysis informed the development of a set of questionnaires that were used to collect qualitative and quantitative data from all participants within the pilot scheme. The questionnaires were administered twice at 12‐monthly intervals during the 2‐year study. Overall, the findings demonstrated a favourable response to clinical supervision, with practitioners identifying that it had been most useful for them in reducing professional isolation. However, detailed analysis of the development of clinical supervision within each pilot site revealed that some groups had been more successful than others in achieving a format that was effective and acceptable to all participants. This enabled factors to be identified which contribute to effective clinical support and factors which reduce its effectiveness. A comparison of these findings with those from an earlier study into teacher support teams – a school‐based system of peer support for teachers – suggest that both teaching and nursing professionals experience professional isolation. Involvement in peer support, in the form of clinical supervision or teacher support teams, could be effective at reducing this isolation and can thus enable practitioners to meet the requirements of clinical governance or performance management. However, effective peer support in the form of teacher support teams or clinical supervision does not occur spontaneously. A similar set of factors that contribute to the development of effective peer support was evident in both studies. These include formal training in the skills of supervision/support, the successful development of a sense of ownership among practitioners of the model of supervision/support, and ongoing support and facilitation from management and employers.
Clinical teachers in specialty practice settings: perceptions of their role within postgraduate nursing programs
Authors: Manias Elizabeth , Aitken Robyn
Published: May 2005

The purpose of this study was to determine the perceptions of clinical teachers of their role in the specialty practice setting, of their preparation for the clinical teaching role, and of how their role related to the aims of the university curriculum. The study was conducted with clinical teachers seconded from their clinical roles by a large metropolitan university School of Nursing. Using a survey instrument to address the aims, 37 clinical teachers completed the questionnaire, achieving a response rate of 62%. Contrary to previous research describing university teachers who attempt to fulfil both academic and clinical teaching roles, clinical teachers identified strongly with the clinical field, perceived themselves as experts, were confident to carry out nursing care, did not experience role conflict between student supervision and patient care, and believed that they could positively influence the quality of care. They nominated the provision of support to students in the clinical setting as the most important dimension of their role. Previous experience as a specialty nurse was reported as being the most effective preparation strategy for their role, with orientation sessions and regular academic–clinical teacher meetings being perceived as the least helpful. Clinical teachers perceived that their role in the university curriculum largely involved bridging the gap between theory and practice, and ensuring relevance of the curriculum. Thirty‐eight per cent of clinical teachers lectured at the university in addition to providing clinical support, suggesting that the model of seconding clinicians to the clinical teacher role may provide a better solution to narrowing the theory–practice gap than university teachers attempting to include clinical practice in their role. For the outcomes of this model to be optimized, clinical teachers should be helped to develop effective teaching skills and to have more realistic expectations of student outcomes.
Use of translucent indium tin oxide to measure stimulatory effects of a passive conductor during field stimulation of rabbit hearts
Authors: Knisley Stephen B. , Pollard Andrew E.
Published: May 2005

Biomathematical models and experiments have indicated that passive extracellular conductors influence field stimulation. Because metallic conductors prevent optical mapping under the conductor, we have evaluated a passive translucent indium tin oxide (ITO) thin-film conductor to allow mapping of transmembrane potential ( Vm) and stimulatory current under the conductor. A 1-cm ITO disk was patterned photolithographically and positioned between 0.3-cm2mesh shock electrodes on the ventricular epicardium of isolated perfused rabbit hearts stained with 4-{2-[6-(dibutylamino)-2-naphthylenal]ethenyl}-1-(3-sulfopropyl)-, hydroxide, inner salt (di-4-ANEPPS). For a 1-A, 10-ms shock during the action potential plateau, optical maps from fluorescence collected using emission ratiometry (excitation at 488 nm and emissions at 510–570 and >590 nm) indicated that the disk altered Vmby as much as the height of an action potential. Δ Vmbecame more positive near the edge of the disk, where the ITO conductance gradient was parallel to applied current, and more negative near the opposite edge, where the gradient was not parallel to current. For diastolic shocks, the disk expedited membrane excitation at the sites of positive Δ Vmin the heart and in a cardiac model with realistic ITO disk surface and interfacial conductances. Optical maps of ITO transmittance and the model indicated that the disk introduced anodal and cathodal stimulatory current at opposite edges of the disk. Thus ITO allows study of the stimulatory effects of a passive conductor in an electric field.
Functional alterations in cerebrovascular K+ and Ca2+ channels are comparable between simulated microgravity rat and SHR
Authors: Xie Man-Jiang , Zhang Li-Fan , Ma Jin , Cheng Hong-Wei
Published: May 2005

Exposure to microgravity leads to a sustained elevation in transmural pressure across the cerebral vasculature due to removal of hydrostatic pressure gradients. We hypothesized that ion channel remodeling in cerebral vascular smooth muscle cells (VSMCs) similar to that associated with hypertension may occur and play a role in upward autoregulation of cerebral vessels during microgravity. Sprague-Dawley rats were subjected to 4-wk tail suspension (Sus) to simulate the cardiovascular effect of microgravity. Large-conductance Ca2+-activated K+ (BKCa), voltage-gated K+ (KV), and L-type voltage-dependent Ca2+ (CaL) currents of Sus and control (Con) rat cerebral VSMCs were investigated with a whole cell voltage-clamp technique. Under the same experimental conditions, KV, BKCa, and CaL currents of cerebral VSMCs from adult spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were also investigated. KV current density decreased in Sus rats vs. Con rats [1.07 ± 0.14 ( n = 22) vs. 1.31 ± 0.28 ( n = 16) pA/pF at +20 mV ( P < 0.05)] and BKCa and CaL current densities increased [BKCa: 1.70 ± 0.37 ( n = 23) vs. 0.88 ± 0.22 ( n = 19) pA/pF at +20 mV ( P < 0.05); CaL: −2.17 ± 0.21 ( n = 35) vs. −1.31 ± 0.10 ( n = 26) pA/pF at +10 mV ( P < 0.05)]. Similar changes were also observed in SHR vs. WKY cerebral VSMCs: KV current density decreased [1.03 ± 0.33 ( n = 9) vs. 1.62 ± 0.64 ( n = 9) pA/pF at +20 mV ( P < 0.05)] and BKCa and CaL current densities increased [BKCa: 2.54 ± 0.47 ( n = 11) vs. 1.12 ± 0.33 ( n = 12) pA/pF at +20 mV ( P < 0.05); CaL: −3.99 ± 0.53 ( n = 12) vs. −2.28 ± 0.20 ( n = 10) pA/pF at +20 mV ( P < 0.05)]. These findings support our hypothesis, and their impact on space cardiovascular research is discussed.
Focal gap junction uncoupling and spontaneous ventricular ectopy
Authors: Gutstein David E. , Danik Stephan B. , Lewitton Steve , France David , Liu Fangyu , Chen Franklin L. , Zhang Jie , Ghodsi Newsha , Morley Gregory E. , Fishman Glenn I.
Published: May 2005

Genetic studies in the mouse have demonstrated that conditional cardiac-restricted loss of connexin43 (Cx43), the major ventricular gap junction protein, is highly arrhythmogenic. However, whether more focal gap junction remodeling, as is commonly seen in acquired cardiomyopathies, influences the propensity for arrhythmogenesis is not known. We examined electrophysiological properties and the frequency of spontaneous and inducible arrhythmias in genetically engineered chimeric mice derived from injection of Cx43-deficient embryonic stem cells into wild-type recipient blastocysts. Chimeric mice had numerous well-circumscribed microscopic Cx43-negative foci in their hearts, comprising ∼15% of the total surface area as determined by immunohistochemical analysis. Systolic function in the chimeric mice was significantly depressed as measured echocardiographically (19.0% decline in fractional shortening compared with controls, P < 0.05) and by invasive hemodynamics (17.6% reduction in change of pressure over time, P < 0.01). Chimeras had significantly more spontaneous arrhythmic events than controls ( P < 0.01), including frequent runs of nonsustained ventricular tachycardia in some of the chimeric mice. However, in contrast to mice with conditional cardiac-resticted loss of Cx43 in the heart, no sustained ventricular tachyarrhythmias were observed. We conclude that focal areas of uncoupling in the myocardium increase the likelihood of arrhythmic triggers, but more widespread uncoupling is required to support sustained arrhythmias.
Acute systemic hypoxia elevates venous but not interstitial potassium of dog skeletal muscle
Authors: Mo F. M. , Ballard H. J.
Published: May 2005

Potassium release through ATP-sensitive potassium (KATP) channels contributes to hypoxic vasodilation in the skeletal muscle vascular bed: It is uncertain whether KATP channels on muscle cells contribute to the process. Potassium from muscle cells must cross the interstitial space to reach the vascular tissues, whereas that from vascular endothelium would have a higher concentration in venous blood than in interstitial fluid. We determined the effect of systemic hypoxia on arterial, venous, and interstitial potassium in the constant-flow-perfused gracilis muscles of anesthetized dogs. Hypoxia reduced arterial Po2 from 138 to 25 and Pco2 from 28 to 26 mmHg. Arterial pH and potassium were well correlated ( r2 = 0.9): Both increased in early hypoxia and decreased during the postcontrol. In denervated muscles, perfusion pressure decreased from 95 to 76 mmHg by the end of the hypoxic period; neither venous nor interstitial potassium was elevated. In innervated muscles, perfusion pressure increased from 110 to 172 mmHg by the 11th min of hypoxia and then decreased to 146 mmHg by the end of the hypoxic period; venous potassium increased from 5.0 to 5.3 mM, but interstitial potassium remained unchanged. Glibenclamide abolished both the increase in venous potassium and the hypoxic vasodilation in the innervated muscle. Thus skeletal muscle cells were unlikely to have contributed to the release of potassium, which was suggested to originate from vascular endothelium. The sympathetic nerve supply may play a direct or indirect role in the opening of KATP channels under hypoxic conditions.
Cellular energy status modulates translational control mechanisms in ischemic-reperfused rat hearts
Authors: Crozier Stephen J. , Vary Thomas C. , Kimball Scot R. , Jefferson Leonard S.
Published: May 2005

Mechanisms regulating ischemia and reperfusion (I/R)-induced changes in mRNA translation in the heart are poorly defined, as are the factors that initiate these changes. Because cellular energy status affects mRNA translation under physiological conditions, it is plausible that I/R-induced changes in translation may in part be a result of altered cellular energy status. Therefore, the purpose of the studies described herein was to compare the effects of I/R with those of altered energy substrate availability on biomarkers of mRNA translation in the heart. Isolated adult rat hearts were perfused with glucose or a combination of glucose plus palmitate, and effects of I/R on various biomarkers of translation were subsequently analyzed. When compared with hearts perfused with glucose plus palmitate, hearts perfused with glucose alone exhibited increased phosphorylation of eukaryotic elongation factor (eEF)2, the α-subunit of eukaryotic initiation factor (eIF)2, and AMP-activated protein kinase (AMPK), and these hearts also exhibited enhanced association of eIF4E with eIF4E binding protein (4E-BP)1. Regardless of the energy substrate composition of the buffer, phosphorylation of eEF2 and AMPK was greater than control values after ischemia. Phosphorylation of eIF2α and eIF4E and the association of eIF4E with 4E-BP1 were also greater than control values after ischemia but only in hearts perfused with glucose plus palmitate. Reperfusion reversed the ischemia-induced increase in eEF2 phosphorylation in hearts perfused with glucose and reversed ischemia-induced changes in eIF4E, eEF2, and AMPK phosphorylation in hearts perfused with glucose plus palmitate. Because many ischemia-induced changes in mRNA translation are mimicked by the removal of a metabolic substrate under normal perfusion conditions, the results suggest that cellular energy status represents an important modulator of I/R-induced changes in mRNA translation.
Preserved left ventricular structure and function in mice with cardiac sympathetic hyperinnervation
Authors: Kiriazis Helen , Du Xiao-Jun , Feng Xinheng , Hotchkin Elodie , Marshall Tanneale , Finch Samara , Gao Xiao-Ming , Lambert Gavin , Choate Julia K. , Kaye David M.
Published: May 2005

Cardiac-specific overexpression of nerve growth factor (NGF), a neurotrophin, leads to sympathetic hyperinnervation of heart. As a consequence, adverse functional changes that occur after chronically enhanced sympathoadrenergic stimulation of heart might develop in this model. However, NGF also facilitates synaptic transmission and norepinephrine uptake, effects that would be expected to restrain such deleterious outcomes. To test this, we examined 5- to 6-mo-old transgenic (TG) mice that overexpress NGF in heart and their wild-type (WT) littermates using echocardiography, invasive catheterization, histology, and catecholamine assays. In TG mice, hypertrophy of the right ventricle was evident (+67%), but the left ventricle was only mildly affected (+17%). Left ventricular (LV) fractional shortening and fractional area change values as indicated by echocardiography were similar between the two groups. Catheterization experiments revealed that LV ±dP/d t values were comparable between TG and WT mice and responded similarly upon isoproterenol stimulation, which indicates lack of β-adrenergic receptor dysfunction. Although norepinephrine levels in TG LV tissue were approximately twofold those of WT tissue, TG plasma levels of the neuronal norepinephrine metabolite dihydroxyphenyglycol were fivefold those of WT plasma. A greater neuronal uptake activity was also observed in TG LV tissue. In conclusion, overexpression of NGF in heart leads to sympathetic hyperinnervation that is not associated with detrimental effects on LV performance and is likely due to concomitantly enhanced norepinephrine neuronal uptake.
Human eNOS gene delivery attenuates cold-induced elevation of blood pressure in rats
Authors: Wang Xiuqing , Cade Robert , Sun Zhongjie
Published: May 2005

We previously showed that chronic cold exposure inhibits endothelial nitric oxide synthase (eNOS) expression and decreases nitric oxide (NO) production. The aim of the present study was to evaluate the possible role of the NO system in the development of cold-induced hypertension (CIH) by testing the hypothesis that adenoviral delivery of human eNOS gene increases NO production and attenuates CIH in rats. The effect of in vivo delivery of adenovirus carrying human eNOS full-length cDNA (rAdv.heNOS) on CIH was tested using four groups of Sprague-Dawley rats (6 rats/group). Blood pressure (BP) did not differ among the four groups during the control period at room temperature (24°C). Two groups of rats received intravenous injection of rAdv.heNOS (1 × 109plaque-forming units/rat), and the other two groups received the same dose of rAdv.LacZ to serve as controls. After gene delivery, one rAdv.heNOS-treated group and one rAdv.LacZ-treated group were exposed to cold (6°C) while the remaining groups were kept at 24°C. We found that the BP of the rAdv.LacZ group increased significantly within 1 wk of exposure to cold and reached a peak level at week 5 (152.2 ± 6.4 mmHg). In contrast, BP (118.7 ± 8.4 mmHg) of the cold-exposed rAdv.heNOS group did not increase until 5 wk after exposure to cold. The rAdv.heNOS increased plasma and urine levels of NO significantly in cold-exposed rats, which indicates that eNOS gene transfer increased NO production. Notably, rAdv.heNOS decreased plasma levels of norepinephrine and plasma renin activity in cold-exposed rats, which suggests that eNOS gene transfer may decrease the activities of the sympathetic nervous system and the renin-angiotensin system. Immunohistochemical analysis showed that the transferred human eNOS was expressed in both endothelium and adventitia of mesenteric arteries. We conclude that 1) eNOS gene transfer attenuates CIH by increasing NO production and inhibiting the sympathetic nervous system and the renin-angiotensin system; and 2) the NO system appears to mediate this nongenetic, nonpharmacological, nonsurgical model of hypertension.
Role of IL-6 in neuroendocrine differentiation and chemosensitivity of non-small cell lung cancer
Authors: Chang Kuo-Ting , Huang Chi-Ying F. , Tsai Chun-Ming , Chiu Chao-Hua , Lok Ying-Yung
Published: May 2005

Interleukin-6 (IL-6) has been shown to regulate both growth and neuroendocrine (NE) differentiation in some types of human cancer cells, and erbB2 may be a critical component of IL-6 signaling. Non-small cell lung cancer (NSCLC) tumors that demonstrate NE properties have been suggested to have biological characteristics similar to small cell lung cancers with initial responsiveness to chemotherapy. We investigated whether IL-6 is implicated in the cell growth, NE differentiation, and chemosensitivity of NSCLC-NE cells. NSCLC-NE cells were treated with exogenous IL-6, and a subclone of an IL-6-transfected NSCLC cell line that constitutively expressed IL-6 receptor was also generated. These cells were assessed for cell proliferation by cell counting and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays, chemosensitivity to cisplatin and etoposide by MTT assays, and NE differentiation by observing morphological changes and immunoblotting for neuron-specific enolase (NSE). The IL-6-treated cells and the IL-6-transfected cells showed enhanced cell proliferation and downregulated NSE expression, but little change in chemosensitivity. In the culture medium, IL-6-transfected cells grew as looser aggregates than the parental cells. IL-6 could not activate the erbB genes. In conclusion, IL-6 can induce cell proliferation and NE dedifferentiation but has little effect on chemosensitivity in IL-6 receptor-expressing NSCLC-NE cells. The status of NSE expression is unlikely to be a crucial factor for chemosensitivity in NSCLC cells.
IL-6 induces neuroendocrine dedifferentiation and cell proliferation in non-small cell lung cancer cells
Authors: Chang Kuo-Ting , Tsai Chun-Ming , Chiou Yih-Chy , Chiu Chao-Hua , Jeng King-Song , Huang Chi-Ying F.
Published: May 2005

Interleukin-6 (IL-6) has been identified as an important growth regulator of lung cancer cells. Elevation of serum levels of IL-6 has been found in a subpopulation of lung cancer patients, but rarely in patients with benign lung diseases. Approximately 15% of non-small cell lung cancer (NSCLC) tumors exhibit neuroendocrine (NE) properties (NSCLC-NE) and have been suggested to have the biological characteristics similar to small cell lung cancer (SCLC) with early metastasis and initial responsiveness to chemotherapy. We recently showed that IL-6 promotes cell proliferation and downregulates the expression of neuron-specific enolase (NSE, one of the major NE markers) in NSCLC-NE cells. In this study, we show that IL-6 stimulates a transient increase of tyrosine phosphorylation of STAT3 in a dose-dependent fashion. Inhibition of STAT3 signaling pathway by either AG-490 (JAK2-specific inhibitor) or overexpression of STAT3Y705F (a dominant-negative STAT3) reverses NSE expression in IL-6- treated NSCLC-NE cells. In addition, IL-6 induces phosphorylation and activation of p38 MAPK. SB-203580, a p38 MAPK-specific inhibitor, inhibits IL-6-induced p38 MAPK phosphorylating activity and suppresses IL-6-stimulated cell proliferation. Together, our results indicate that STAT3 signaling pathway is involved in IL-6-induced NE differentiation and that p38 MAPK is associated with IL-6-stimulated growth regulation in NSCLC-NE cells. These data suggest that both kinase pathways play critical roles in the pathogenesis of NSCLC-NE malignancies, providing new molecular targets for future therapeutic approaches.
Differences in the translation efficiency and mRNA stability mediated by 5′-UTR splice variants of human SP-A1 and SP-A2 genes
Authors: Wang Guirong , Guo Xiaoxuan , Floros Joanna
Published: May 2005

Surfactant protein A (SP-A) plays an important role in host defense, modulation of inflammatory processes, and surfactant-related functions of the lung. The human SP-A (hSP-A) locus consists of two functional genes, SP-A1 and SP-A2. Several hSP-A 5′-untranslated region (UTR) splice variants for each gene have been characterized and shown to be translated in vitro and in vivo. In this report, we investigated the role of hSP-A 5′-UTR splice variants on SP-A production and molecular mechanisms involved. We used in vitro transient expression of hSP-A 5′-UTR constructs containing luciferase as the reporter gene and quantitative real-time PCR to study hSP-A 5′-UTR-mediated gene expression. We found that 1) the four (A′D′, ABD, AB′D′, and A′CD′) 5′-UTR splice variants under study enhanced gene expression, by increasing luciferase activity from 2.5- to 19.5-fold and luciferase mRNA from 4.3- to 8.8-fold compared with the control vector that lacked hSP-A 5′-UTR; 2) all four 5′-UTR splice variants studied regulated mRNA stability. The ABD variant exhibited the lowest rate of mRNA decay compared with the other three constructs (A′D′, AB′D′, and A′CD′). These three constructs also exhibited significantly lower rate of mRNA decay compared with the control vector; 3) based on the indexes of translational efficiency (luciferase activity/mRNA), ABD and AB′D′ exhibited higher translational efficiency compared with the control vector, whereas the translational efficiency of each A′D′ and A′CD′ was lower than that of the control vector. These findings indicate that the hSP-A 5′-UTR splice variants play an important role in both SP-A translation and mRNA stability.
Naturally occurring antisense RNA of histone H2a in mouse cultured cell lines
Authors: Nishida Hiromi , Tomaru Yasuhiro , Oho Yuko , Hayashizaki Yoshihide
Published: May 2005

Background

An antisense transcript of histone H2a that has no significant protein-coding region has been cloned from a mouse full-length cDNA library. In the present study, we evaluated this transcript by using RT-PCR and compared the expression patterns of the sense and antisense transcripts by using quantitative RT-PCR (qRT-PCR).

Results

This antisense RNA was expressed in three mouse cell lines. We call it ASH2a. ASH2a includes not only the complementary sequence of the transcript of Hist2h2aa2 (a replication-dependent histone H2a gene), but also that of the promoter of Hist2h2aa2. The upstream genomic sequence of the transcription start site of the ASH2a-coding gene (ASH2a) lacks both CCAAT and TATA boxes. This absence suggests that the regulation of ASH2a is different from that of the replication-dependent histone H2a genes. Findings from qRT-PCR indicated that the expression pattern of ASH2a was different from that of Hist2h2aa2. Expression of Hist2h2aa2 peaked at 2 to 4 h during S-phase, but that of ASH2a peaked at 1 h.

Conclusion

We showed the existence of ASH2a, a histone H2a antisense RNA, in mouse cultured cells. The expression pattern of ASH2a is different from that of the sense RNA.
T cell homeostasis in tolerance and immunity
Authors: Marleau Annette M , Sarvetnick Nora
Published: May 2005

The size of the peripheral T cell pool is remarkably stable throughout life, reflecting precise regulation of cellular survival, proliferation, and apoptosis. Homeostatic proliferation refers to the process by which T cells spontaneously proliferate in a lymphopenic host. The critical signals driving this expansion are “space,” contact with self-major histocompatibility complex (MHC)/peptide complexes, and cytokine stimulation. A number of studies have delineated an association between T cell lymphopenia, compensatory homeostatic expansion, and the development of diverse autoimmune syndromes. In the nonobese diabetic mouse model of type 1 diabetes, lymphopenia-induced homeostatic expansion fuels the generation of islet-specific T cells. Excess interleukin-21 facilitates T cell cycling but limited survival, resulting in recurrent stimulation of T cells specific for self-peptide/MHC complexes. Indeed, data from several experimental models of autoimmunity indicate that a full T cell compartment restrains homeostatic expansion of self-reactive cells that could otherwise dominate the repertoire. This review describes the mechanisms that govern T cell homeostatic expansion and outlines the evidence that lymphopenia presents a risk for development of autoimmune disease.
The mucosal immune system: from control of inflammation to protection against infections
Authors: Kaiserlian Dominique , Cerf-Bensussan Nadine , Hosmalin Anne
Published: May 2005

The IV meeting of the European Mucosal Immunology Group, held October 8–10, 2004, in Lyon, gathered fundamental and clinical research scientists to discuss the most recent updates on basic and clinical aspects of mucosal immunology. The meeting was focused on innate and acquired immune mechanisms underlying handling and immune recognition of commensals, allergens, and pathogens by the mucosal immune system and its outcome in health and disease as well as for vaccine development. The scientific program featured five topics of growing interest for fundamental research scientists and clinicians, including the role of commensal bacteria in mucosal immunity; function of dendritic cells in infection, inflammation, and tolerance; control of mucosal inflammation by regulatory T cells; novel routes and adjuvants for mucosal vaccines; and mucosal immunity against HIV infection and vaccination strategies.
Interferon-γ-activated STAT-1α suppresses MMP-9 gene transcription by sequestration of the coactivators CBP/p300
Authors: Ma Zhendong , Chang Mi Jung , Shah Reesha C , Benveniste Etty N
Published: May 2005

Interferon-γ (IFN-γ) is a pleiotropic cytokine involved in aspects of immune regulation, cell proliferation, and host defense mechanisms directed toward various cancers. Some of the biological functions of IFN-γ are achieved through inhibition of gene expression, although the mechanisms by which IFN-γ suppresses gene transcription are poorly understood. Herein, we demonstrate the molecular basis by which IFN-γ mediates suppression of the matrix metalloproteinase-9 (MMP-9) gene. IFN-γ-activated signal transducer and activator of transcription-1α (STAT-1α) suppresses MMP-9 gene transcription, which is dependent on phosphorylation of tyrosine 701 but not phosphorylation of serine 727. The coactivator cyclic AMP response element-binding protein-binding protein (CBP) is an important component of induction of MMP-9 gene transcription. IFN-γ induces the in vivo association of STAT-1α and CBP and decreases the association of CBP to the MMP-9 promoter. IFN-γ does not influence the stability of CBP nor does IFN-γ affect chromatin-remodeling events on the MMP-9 promoter. IFN-γ inhibits the assembly of the MMP-9 transcription complex by suppressing H3/H4 acetylation and inhibiting recruitment of Pol II to the MMP-9 promoter. These findings indicate that IFN-γ/STAT-1α exert their inhibitory effects by affecting multiple aspects of MMP-9 gene transcription.
Polysaccharide purified fromGanoderma luciduminduced activation and maturation of human monocyte-derived dendritic cells by the NF-κB and p38 mitogen-activated protein kinase pathways
Authors: Lin Yu-Li , Liang Yu-Chih , Lee Shiuh-Sheng , Chiang Bor-Luen
Published: May 2005

Ganoderma lucidum, a fungus native to China, has been widely used to promote health and longevity in the Chinese. The polysaccharide component with a branched (1→6)-β-D-glucan moiety of G. lucidum (PS-G) has been reported to exert anti-tumor activity and activation of natural killer cells. In this study, we investigated the effects of PS-G on human monocyte-derived dendritic cells (DC). Treatment of DC with PS-G resulted in the enhanced cell-surface expression of CD80, CD86, CD83, CD40, CD54, and human leukocyte antigen (HLA)-DR, as well as the enhanced production of interleukin (IL)-12p70, p40, and IL-10 and also IL-12p35, p40, and IL-10 mRNA expression, and the capacity for endocytosis was suppressed in DC. In addition, treatment of DC with PS-G resulted in enhanced T cell-stimulatory capacity and increased T cell secretion of interferon-γ and IL-10. Neutralization with antibodies against Toll-like receptor (TLR)-4 inhibited the PS-G-induced production of IL-12 p40 and IL-10, suggesting a vital role for TLR-4 in signaling DC upon incubation with PS-G. Further study showed that PS-G was able to augment inhibitor of κB (IκB) kinase and nuclear factor (NF)-κB activity and also IκBα and p38 mitogen-activated protein kinase (MAPK) phosphorylation. Further, inhibition of NF-κB by helenalin and p38 MAPK by SB98059 prevented the effects of PS-G in the expression of CD80, CD86, CD83, CD40, CD54, and HLA-DR and production of IL-12p70, p40, and IL-10 in various degrees. Taken together, our data demonstrate that PS-G can effectively promote the activation and maturation of immature DC, suggesting that PS-G may possess a potential in regulating immune responses.
Sphingosine 1-phosphate receptor agonist FTY720-phosphate causes marginal zone B cell displacement
Authors: Vora Kalpit A , Nichols Elizabeth , Porter Gene , Cui Yan , Keohane Carol Ann , Hajdu Richard , Hale Jeffery , Neway William , Zaller Dennis , Mandala Suzanne
Published: May 2005

FTY720 is an immunosuppressive agent that modulates lymphocyte trafficking. It is phosphorylated in vivo to FTY720-phosphate (FTY-P) and binds to a family of G protein-coupled receptors recognizing sphingosine 1-phosphate (S1P) as the natural ligand. It has previously been reported that FTY-P blocks egress of lymphocytes from the thymus and lymph nodes, resulting in peripheral blood lymphopenia. We now report that FTY-P also causes displacement of marginal zone (MZ) B cells to the splenic follicles, an effect that is similar to that observed after in vivo administration of lipopolysaccharide. This effect is specific to B cells in the MZ, as treatment with FTY-P does not cause redistribution of the resident macrophage population. A small but statistically significant decrease in the expression of β1 integrin on MZ B cells was observed with FTY-P treatment. The redistribution of MZ B cells from the MZ sinuses does not abolish the ability of these cells to respond to the T-independent antigen, trinitrophenol-Ficoll. It has been proposed that the displacement of MZ B cells to the follicles is an indication of cell activation. Consistent with this, FTY-P caused an increase in percentage of MZ B cells expressing activation markers CD9, CD1d, and CD24. These results suggest that S1P receptors on MZ B cells are responsible for their mobilization to follicles.
Identification of CCR2, flotillin, and gp49B genes as new G-CSF targets during neutrophilic differentiation
Authors: Iida Satoshi , Kohro Takahide , Kodama Tatsuhiko , Nagata Shigekazu , Fukunaga Rikiro
Published: May 2005

Granulocyte colony-stimulating factor (G-CSF) is a cytokine that stimulates myeloid progenitor cells to proliferate and differentiate into neutrophilic granulocytes. To identify genes induced by G-CSF during neutrophil differentiation, interleukin-3-dependent murine myeloid precursor FDC-P1 cells expressing the G-CSF receptor were stimulated with G-CSF, and the gene expression profile was characterized by DNA microarray analysis. In addition to known signal transducer and activator of transcription-3 target genes, such as suppressor of cytokine signaling-3 (SOCS3), JunB, and p19INK4D, we newly identified several G-CSF targets, including genes for the CC chemokine receptor-2 (CCR2), raft proteins flotillin-1 and flotillin-2, and immunoglobulin-like receptor gp49B. Real-time, quantitative polymerase chain reaction analyses revealed that the expression of these genes was induced in various myeloid cell lines by G-CSF. Furthermore, when HoxA9-immortalized bone marrow progenitors were induced by G-CSF to differentiate into mature neutrophils, all of these genes were strongly activated. These genes could be categorized into three groups based on their time-course of expression: immediate-early (∼20 min, SOCS3), mid-early (2–4 h, flotillin-1/2 and gp49B), and late (>12 h, CCR2). This suggests that different transcriptional mechanisms are involved in the regulation of these genes. We show that bone marrow neutrophils express functional CCR2, which suggest that CC chemokines may play previously unknown roles in neutrophil activation and chemotaxis.
Escherichia coliK1 inhibits proinflammatory cytokine induction in monocytes by preventing NF-κB activation
Authors: Selvaraj Suresh K , Prasadarao Nemani V
Published: May 2005

Phagocytes are well-known effectors of the innate immune system to produce proinflammatory cytokines and chemokines such as tumor necrosis factor α (TNF-α), interleukin (IL)-1β, and IL-8 during infections. Here, we show that infection of monocytes with wild-type Escherichia coli K1, which causes meningitis in neonates, suppresses the production of cytokines and chemokines (TNF-α, regulated on activation, normal T expressed and secreted, macrophage-inflammatory protein-1β, IL-1β, and IL-8). In contrast, infection of monocytes with a mutant E. coli, which lacks outer membrane protein A (OmpA– E. coli) resulted in robust production of cytokines and chemokines. Wild-type E. coli K1 (OmpA+ E. coli) prevented the phosphorylation and its degradation of inhibitor of κB, thereby blocking the translocation of nuclear factor (NF)-κB to the nucleus. OmpA+ E. coli-infected cells, subsequently subjected to lipopolysaccharide challenge, were crippled severely in their ability to activate NF-κB to induce cytokine/chemokine production. Selective inhibitors of the extracellular signal-regulated kinase (ERK) 1/2 pathway and p38 mitogen-activated protein kinase (MAPK), but not Jun N-terminal kinase, significantly reduced the activation of NF-κB and the production of cytokines and chemokines induced by OmpA– E. coli, indicating a role for these kinases in the NF-κB/cytokine pathway. It is interesting that the phosphorylation of ERK 1/2 and p38 MAPK was notably reduced in monocytes infected with OmpA+ E. coli when compared with monocytes infected with OmpA– E. coli, suggesting that the modulation of upstream events common for NF-κB and MAPKs by the bacterium is possible. The ability of OmpA+ E. coli K1 to inhibit the macrophage response temporarily may enable bacterial survival and growth within the host for the onset of meningitis by E. coli K1.
Impaired inflammatory angiogenesis, but not leukocyte influx, in mice lacking TNFR1
Authors: Barcelos L S , Talvani A , Teixeira A S , Vieira L Q , Cassali G D , Andrade S P , Teixeira M M
Published: May 2005

The majority of biological responses classically attributed to tumor necrosis factor α (TNF-α) is mediated by p55 receptor (TNFR1). Here, we aimed to clarify the biological role of TNFR1-mediated signals in an in vivo inflammatory angiogenesis model. Polyester-polyurethane sponges, used as a framework for tissue growth, were implanted in C57Bl/6 mice. These implants were collected at days 1, 7, and 14 post-implant for enzyme-linked immunosorbent assay or at days 7 and 14 for hemoglobin, myeloperoxidase, and N-acetylglucosaminidase measurements, used as indexes for angiogenesis, neutrophil, and macrophage accumulation, respectively. In TNFR1-deficient C57Bl/6 mice, there was a significant decrease in sponge vascularization but not in late inflammatory cell influx. It is interesting that levels of vascular endothelial growth factor were significantly lower in TNFR1-deficient than in wild-type mice at days 1 and 7. Levels of angiogenic chemokines, CC chemokine ligand 2/murine homologue of monocyte chemoattractant protein-1 and CXC chemokine ligand 1–3/keratinocyte-derived chemokine, were significantly lower in TNFR1-deficient mice at days 1 and 7 after implantation, respectively. These observations suggest that TNFR1-mediated signals have a critical role in sponge-induced angiogenesis, possibly by influencing the effector state of inflammatory cells and hence, modulating the angiogenic molecular network.
Proving Consent in Sexual Cases: Legislative Change and Cultural Evolution
Authors: McEwan Jenny
Published: May 2005

In England and Wales, the Sexual Offences Act 2003 has redefined crimes of serious sexual assault and introduced evidential presumptions in relation to consent. At the same time, the Criminal Justice Act 2003 has made changes to the law of evidence that may affect sexual offence trials. Its provisions must be understood in conjunction with judicial attempts to interpret the ‘rape shield’ provided by s. 41 of the Youth Justice and Criminal Evidence Act 1999.
Child Pornography: Balancing Substantive and Evidential Law to Safeguard Children Effectively from Abuse
Authors: Gillespie Alisdair A.
Published: May 2005

The law relating to child pornography in the United Kingdom has, over recent years, changed dramatically. These changes have been brought about by both legislation and case law. This article critically analyses the consequences of these changes and, in particular, considers the probity of apparent reverse burdens of proof created by the legislation. When the right to a fair trial is being examined, it is usual to balance the rights of the individual defendant and the rights of society to expect a smooth-running criminal justice system. The balancing act in this field is more complicated because those who are the subject of abusive images are the most vulnerable members of society, and thus the balance struck must not unduly constrain law enforcement agencies, preventing them from tackling the exploitation and abuse of children.
Einflussgrößen bei der Kalibrierung von Längenmessmitteln (Influence Quantities for Calibrations in Dimensional Metrology)
Authors: Thalmann Ruedi
Published: May 2005

Bei der Abschätzung der Messunsicherheit für die Kalibrierung von Längenmessmitteln ist eine Vielzahl von Einflussgrößen zu berücksichtigen. Durch eine Darstellung der Verfahrenselemente einerseits und der Einflussgrößen andererseits in einer Matrixstruktur können diese systematisch erfasst und Schwerpunkte identifiziert und diskutiert werden. Dank dem für die Ermittlung der Messunsicherheit notwendigen Validierungsverfahren und der Anwendung grundlegender Prinzipien der Längenmesstechnik kann der Messprozess entscheidend verbessert werden.
Messunsicherheiten bei der Drehmomentmessung (Uncertainties in the Measurement of the Torque)
Authors: Peschel Diedert , Röske Dirk
Published: May 2005

Die Darstellung und Weitergabe der Einheit des Drehmomentes spielt im Zusammenhang mit der stärker werdenden Forderung nach rückführbaren Messungen eine immer größere Rolle. Dabei müssen Betrachtungen über die möglichen Einflussgrößen und deren Beitrag zur Messunsicherheit angestellt werden. Im ersten Teil des Beitrags wird das Gebiet der Darstellung des Drehmomentes anhand der 1-kN·m-Drehmoment-Normalmesseinrichtung der PTB untersucht, während sich der zweite Teil dem Problem der Weitergabe der Einheit (Kalibrierung) widmet und dabei insbesondere verschiedene derzeit geltende Kalibriernormen vergleichend gegenüberstellt.
Significance of Well Locations and Flow Rates in Bioventing Systems Design
Authors: Abu‐El‐Sha'r Wa'il Y. , Al‐Zou'by Jehad Y.
Published: May 2005

The successful application of bioventing systems for in situ remediation of petroleum hydrocarbon‐contaminated sites depends on many factors including: moisture content, temperature, number and location of injection and extraction wells, as well as corresponding airflow rates. The importance of well locations and air flow rates has been explored in this study and their optimal values were obtained via the fixed well method. The design problem was formulated to maximize total contaminant mass removal within a given time frame subject to physical and budgetary constraints. The technique developed herein was applied to a field case study. Results indicate that optimal well locations are found along the mass centerline(s) of the contaminant plume. Furthermore, well location optimization was proven to be more important than pumping rate optimization.
Infrared Thermography and Fracture Analysis of Preferential Flow in Chalk
Authors: Rosenbom Annette E. , Jakobsen Peter R.
Published: May 2005

Preferential flow in fractured Cretaceous chalk has been investigated using infrared thermography (IRT) in a quarry in Denmark. Fracture mapping along the vertical quarry walls shows numerous horizontal fractures and four sets of vertical fractures respectively striking 25°, 60°, 145°, and 175°. Water flows out of the exposed walls mainly through fractures and to a minor extent by seepage through the matrix. To clarify which of the five fracture systems are hydraulically active, the exposure has been investigated using IRT. By making use of the contrast between the constant temperature of groundwater and the temperature of the exposed wall on a cold winter and a hot summer day, zones of groundwater discharge have been delineated. The results of the IRT suggest that the vertical shear fractures are the main hydraulically active conduits. Furthermore, the horizontal fractures are more hydraulically active in areas where they intersect a vertical stained fracture or in association with some flint layers. Stains of Fe3+and Mn were observed primarily in fractures with a strike of approximately 25° and 175°, suggesting that the water flows preferentially in these fracture sets. The possible influence of the regional setting on the flow pattern is considered. The results suggest that the combined use of detailed fracture analysis and IRT is a valuable method for providing the input data required for both modeling and monitoring of fractured media.
Simulation of Tracer Dispersion in Porous Media Using Lattice Boltzmann and Random Walk Models
Authors: Jiménez‐Hornero Francisco J. , Giráldez Juan V. , Laguna Ana
Published: May 2005

Pore‐scale flow and transport processes are generally difficult to simulate using conventional models. Two state‐of‐the‐art approaches are adopted in this study of solute transport in porous media. The first approach is a lattice Boltzmann model with the Bhatnagar, Gross, and Krook simplification (BGK) to determine both the advection and diffusion components of the transport process, while the second approach uses the BGK model to calculate the velocity field in conjunction with a random walk (RW) model to characterize diffusion (BGK/RW). Both approaches yield similar results. The BGK/RW model is an attractive alternative to the BGK model when it is necessary to simulate small values of the diffusion coefficient so as to avoid instabilities in the numerical solution. Nevertheless, the BGK/RW model is less accurate than the BGK model alone when compared with the analytic solution of the well‐known Taylor–Aris dispersion model.