bluuebunny/crossref_metadata_2025 huggingface dataset:
School-based Cognitive-Behavioural Therapy Group Intervention for Refugee Children who have Experienced War-related Trauma
Authors: Ehntholt Kimberly A. , Smith Patrick A. , Yule William
Published: April 2005

This study evaluated the effectiveness of a school-based group intervention designed for children who have experienced trauma. Twenty-six children (aged 11-15 years) who were refugees or asylum-seekers from war-affected countries participated. The manual-based intervention consisted of cognitive-behavioural therapy (CBT) techniques and was implemented within secondary schools. The treatment group ( n = 15) received six sessions of group CBT over a 6-week period, while the control group ( n = 11) were placed on a waiting list for 6 weeks and then invited to enter treatment. Children in the CBT group showed statistically significant, but clinically modest improvements following the intervention, with decreases in overall severity of post-traumatic stress symptoms. Significant improvements were also found in overall behavioural difficulties and emotional symptoms. Children in the waiting list control group did not show any improvements over the same period. However, follow-up data, which were only available for a small subset of eight children, suggest that gains in the CBT group were not maintained at 2-month follow-up.
‘The danger zone of Europe’
Authors: Hammond Andrew
Published: April 2005

This article argues that the Balkans formed one of the major sources of alterity for the West in the decade following the end of the Cold War. Taking the place of the erstwhile communist Other, the region was constructed in journalism, political statement and travel writing as a zone of backwardness, barbarism and violence which threatened to engulf the civilized and democratic West. Using travel writing as a source material, this article argues more specifically that the ideological scepticism and aesthetic conventions of postmodernism have been an important influence on contemporary balkanism, as they have been on the representation of other non-western locations. Although the role of the Balkans has now been superseded by Al-Qaida and the ‘international terror network’, the post-1989 representational styles continue to have devastating political and economic effects in the region.
Turn the beat around
Authors: Kooijman Jaap
Published: April 2005

Published in 1979, Richard Dyer’s ‘In Defence of Disco’ is one of the best-read but relatively little-used essays in pop music studies, queer studies and cultural studies. With his essay, not only does Dyer demystify the ‘authenticity’ of music genres such as folk and rock, but also validates and celebrates the in authenticity of disco by recognizing its political potential. This review article revisits Dyer’s ‘In Defence of Disco’ and subsequently discusses those few academic works that do build upon and expand his original arguments, proving the significance of this radical essay.
Reducing Intergroup Bias: The Moderating Role of Ingroup Identification
Authors: Crisp Richard J. , Beck Sarah R.
Published: April 2005

Recent work developing interventions designed to reduce intergroup bias has sometimes yielded disparate findings. We tested whether the varying effectiveness of such interventions may have a motivational basis. In two experiments we examined whether differential ingroup identification moderated the effectiveness of a differentiation-reducing intervention strategy. In Experiment 1, thinking of characteristics shared between the ingroup and outgroup reduced ingroup favoritism to a greater extent for lower identifiers than for higher identifiers. In Experiment 2 we replicated this finding with different target groups and evaluative measures while controlling for information load. We discuss the implications of this work for developing social psychological models of bias-reduction.
Awareness context theory and the dynamics of dementia
Authors: Hellström Ingrid , Nolan Mike , Lundh Ulla
Published: April 2005

This article presents the initial results of an ongoing constructivist grounded theory study (Charmaz, 2000) exploring the impact of dementia on the everyday life and relationships of older spousal couples. Using a process of ‘emergent fit’ (Glaser, 1978) and drawing upon data from 74 interviews with 20 spouse couples living with dementia, it considers the relevance of ‘awareness context theory’ (Glaser & Strauss, 1965) and the ‘dynamics of dementia’ (Keady, 1999) to an understanding of interpersonal relationships among spouses. The combination of existing literature and new data provide further insights into how couples actively work to ‘construct’ awareness in a way that, for the majority, maintains both a sense of ‘self’ for the person with dementia (PWD) and the integrity of the relationship between couples. It is suggested that a ‘mutual acknowledgement’ of the diagnosis and a subsequent focus on maintaining a meaningful life in the present combine to create a ‘nurturative relational context’ in which living with dementia unfolds.
Cleveland’s Lakefront: Its Development and Planning
Authors: Keating Dennis , Krumholz Norman , Wieland Ann Marie
Published: April 2005

This article explores the history of planning and development of Cleveland’s lakefront from the mid-nineteenth century through the most recent plans of late 2004. It shows that commercial uses, tied to different forms of transportation, dominated planning objectives, as distinct from recreational uses and attempts to expand public access. The most recent plans seek a better balance between private and public interests in future uses of Cleveland’s waterfront, but there is a lack of consensus among the competing interest groups.
Defective Vav expression and impaired F-actin reorganization in a subset of patients with common variable immunodeficiency characterized by T-cell defects
Authors: Paccani Silvia Rossi , Boncristiano Marianna , Patrussi Laura , Ulivieri Cristina , Wack Andreas , Valensin Silvia , Hirst Tim R. , Amedei Amedeo , del Prete Gianfranco , Telford John L. , D'Elios Mario M. , Baldari Cosima T.
Published: April 2005

Common variable immunodeficiency (CVID) is a primary immune disorder characterized by impaired antibody production, which is in many instances secondary to defective T-cell function (T-CVID). We have previously identified a subset of patients with T-CVID characterized by defective T-cell receptor (TCR)-dependent protein tyrosine phosphorylation. In these patients, ZAP-70 fails to be recruited to the TCR as the result of impaired CD3ζ phosphorylation, which is, however, not dependent on defective Lck expression or activity. Here we show that neither Fyn nor CD45 is affected in these patients. On the other hand, T-CVID T cells show dramatic defects in the Vav/Rac pathway controlling F-actin dynamics. A significant deficiency in Vav protein was indeed observed; in 3 of 4 patients with T-CVID, it was associated with reduced VAV1 mRNA levels. The impairment in Vav expression correlated with defective F-actin reorganization in response to TCR/CD28 coengagement. Furthermore, TCR/CD28-dependent up-regulation of lipid rafts at the cell surface, which requires F-actin dynamics, was impaired in these patients. The actin cytoskeleton defect could be reversed by reconstitution of Vav1 expression in the patients' T cells. Results demonstrate an essential role of Vav in human T cells and strongly suggest Vav insufficiency in T-CVID. (Blood. 2005;106:626-634)
Arf6: a new player in FcγRIIIA lymphocyte-mediated cytotoxicity
Authors: Galandrini Ricciarda , Micucci Federica , Tassi Ilaria , Cifone Maria Grazia , Cinque Benedetta , Piccoli Mario , Frati Luigi , Santoni Angela
Published: April 2005

The activation of phosphoinositide metabolism represents a critical step in the signaling pathways leading to the activation of cytolytic machinery, but its regulation is partially understood. We report here that the stimulation of the low-affinity receptor for immunoglobulin G (IgG) (FcγRIIIA, CD16) on primary human natural killer (NK) cells induces a phosphatidylinositol 3-kinase (PI3K)–dependent activation of the small G protein Arf6. We first demonstrate a functional role for Arf6-dependent signals in the activation of the antibody-dependent cellular cytotoxicity (ADCC) attributable to the control of secretion of lytic granule content. We also show that Arf6 couples CD16 to the lipid-modifying enzymes phosphatidylinositol4phosphate 5-kinase type I alpha (PI5KIα) and phospholipase D (PLD) that are involved in the control of granule secretion; Arf6, but not Rho family small G proteins RhoA and Rac1, is required for receptor-induced PI5KIα membrane targeting as well as for PI5KIα and PLD activation. Our findings suggest that Arf6 plays a crucial role in the generation of a phosphatidylinositol4,5-bisphosphate (PIP2) plasma membrane pool required for cytolytic granule-mediated target cell killing.
Impaired interferon-γ production as a consequence of STAT4 deficiency after autologous hematopoietic stem cell transplantation for lymphoma
Authors: Robertson Michael J. , Chang Hua-Chen , Pelloso David , Kaplan Mark H.
Published: April 2005

Production of interferon γ (IFN-γ) is critical for optimal antitumor immunotherapy in several preclinical animal models. Interleukin-12 (IL-12)–induced IFN-γ production is markedly defective after autologous stem cell transplantation. Quantitative deficiency in CD4 T cells, relative increase in CD25+CD4+ T cells, and bias toward T helper 2 (Th2) differentiation are not the primary mechanisms of defective IFN-γ production. IL-12 receptor β1 (IL-12Rβ1) and IL-12Rβ2 are expressed at equivalent or higher levels on posttransplantation patient peripheral blood mononuclear cells (PBMCs) as compared with control PBMCs. IL-12–induced tyrosine phosphorylation of signal transducer and activator of transcription 4 (STAT4) was undetectable or barely detectable in posttransplantation patient PBMCs, whereas IL-4–induced tyrosine phosphorylation of STAT6 did not differ in posttransplantation patient and control PBMCs. Levels of STAT4 protein were decreased by 97% in posttransplantation patient PBMCs. Levels of STAT4 mRNA were also significantly decreased in posttransplantation patient PBMCs. Incubation with IL-12 and IL-18 in combination partially reversed the defective IFN-γ production by posttransplantation patient PBMCs. IFN-γ production in response to IL-12 plus IL-18 did not require increased expression of STAT4 but was dependent on the activity of p38 mitogen-activated protein kinase (MAPK). These results indicate that defective IFN-γ production is due to an intrinsic deficiency in STAT4 expression by posttransplantation patient lymphocytes and suggest strategies for circumventing this deficiency in cancer immunotherapy.
Human mesenchymal stem cells xenografted directly to rat liver are differentiated into human hepatocytes without fusion
Authors: Sato Yasushi , Araki Hironobu , Kato Junji , Nakamura Kiminori , Kawano Yutaka , Kobune Masayoshi , Sato Tsutomu , Miyanishi Koji , Takayama Tetsuji , Takahashi Minoru , Takimoto Rishu , Iyama Satoshi , Matsunaga Takuya , Ohtani Seiji , Matsuura Akihiro , Hamada Hirofumi , Niitsu Yoshiro
Published: April 2005

Hepatic transdifferentiation of bone marrow cells has been previously demonstrated by intravenous administration of donor cells, which may recirculate to the liver after undergoing proliferation and differentiation in the recipient's bone marrow. In the present study, to elucidate which cellular components of human bone marrow more potently differentiate into hepatocytes, we fractionated human bone marrow cells into mesenchymal stem cells (MSCs), CD34+ cells, and non-MSCs/CD34- cells and examined them by directly xenografting to allylalcohol (AA)-treated rat liver. Hepatocyte-like cells, as revealed by positive immunostaining for human-specific alpha-fetoprotein (AFP), albumin (Alb), cytokeratin 19 (CK19), cytokeratin 18 (CK18), and asialoglycoprotein receptor (AGPR), and by reverse transcription-polymerase chain reaction (RT-PCR) for expression of AFP and Alb mRNA, were observed only in recipient livers with MSC fractions. Cell fusion was not likely involved since both human and rat chromosomes were independently identified by fluorescence in situ hybridization (FISH). The differentiation appeared to follow the process of hepatic ontogeny, reprogramming of gene expression in the genome of MSCs, as evidenced by expression of the AFP gene at an early stage and the albumin gene at a later stage. In conclusion, we have demonstrated that MSCs are the most potent component in hepatic differentiation, as revealed by directly xenografting into rat livers. (Blood. 2005;106:756-763)
High versus standard doses interferon-alpha in the treatment of naïve chronic hepatitis C patients in Taiwan: a 10-year cohort study
Authors: Yu Ming-Lung , Dai Chia-Yen , Chen Shinn-Cherng , Lee Li-Po , Hsieh Ming-Yen , Lin Zu-Yau , Hsieh Ming-Yuh , Wang Liang-Yen , Tsai Jung-Fa , Chang Wen-Yu , Chuang Wan-Long
Published: April 2005

Background

Interferon-alpha monotherapy is effective in less than one-third patients with chronic hepatitis C. The dose-effect, tolerability and durability of interferon-alpha treatment and its long-term effect on the prevention of cirrhosis and hepatocellular carcinoma in naïve Taiwanese patients with chronic hepatitis C have not been well investigated. We conducted the present cohort study treated with high and standard interferon-alpha to illustrate the issues.

Methods

We performed a long-term virologic and histological follow-up of 214 chronic hepatitis C patients treated with interferon-alpha, 3 million units (3-MU, n = 80) or 6-MU (n = 134) thrice weekly for 24 weeks, in Taiwan between 1992 and 2001.

Results

There was no difference in the incidence of discontinuation between 3-MU and 6-MU groups (4/80, 5.0% versus 10/134. 7.5%). The 6-MU group had similar incidence of adverse events with the 3-MU group, except that 6-MU group had significantly higher incidence of psychological manifestations, mainly presented as irritability. The rates of sustained virological response (SVR) were significantly higher in 6-MU regimen (37.1%) than in 3-MU regimen (23.7%, p < 0.05) in per protocol analysis. Based on multivariate analysis, baseline viral load was strongly associated with SVR, followed by hepatitis C virus genotype, interferon-alpha regimen, and liver fibrosis. A histological improvement in necroinflammatory activity, but not in fibrosis was observed in the follow-up biopsy performed 0.5–5.5 years (mean: 1.9 years, n = 51) after end-of-treatment. Among patients without SVR, there was more activity improvement in 6-MU group. The durability of SVR was 100% (18/18) and 97.8% (45/46) for 3-MU and 6-MU group, respectively, in a mean follow-up period of 6.81 years (5.25–9.18 years). For 163 baseline non-cirrhotic patients, 9 of 84 (10.7%) non-responders and 3 of 79 (3.8%) sustained responders progressed to cirrhosis during a mean follow-up period of 5.52 and 5.74 years, respectively (p = 0.067, Kaplan-Meier survival analysis, log-rank test). For all 200 patients, hepatocellular carcinoma was detected in 12 of 113 (10.6%) non-responders and one of 87 (1.1%) sustained responders during a mean follow-up period of 5.67 and 5.73 years, respectively (p < 0.01, Kaplan-Meier survival analysis, log-rank test).

Conclusion

We confirm the dose effect of interferon-alpha in chronic hepatitis C. Six-MU regimen had better efficacy than 3-MU regimen in virologic and histological responses. Both regimens had good tolerability and durability in Taiwan. Sustained response could reduce the incidence of cirrhotic change and hepatocarcinogenesis.
A freely accessible, evidence based, objective system of analysis of posterior capsular opacification ; Evidence for its validity and reliability
Authors: Aslam Tariq M , Patton Niall , Graham Jim
Published: April 2005

Background

The aim of this study was to develop a system of computerised analysis of digital images of posterior capsule opacification (PCO) that is evidence based, objective and freely available. The paper will present evidence for the reliability and validity of the developed system.

Methods

The system of PCO analysis was developed considering current published evidence on visual significance of PCO and additional investigative analysis of PCO images. Details of the image processing and analysis steps are discussed and a final system that measures an entropy score weighted toward proximity to central areas is described. In order to assess validity, the systems ability to measure PCO progression is assessed along with the visual significance of its final computerised scores. Reliability of the system is also assessed.

Results

The final system runs successfully and is simple to use. Analyses of PCO by the system show an ability to detect early progression of PCO as well as detection of visually significant PCO. Images with no clinical PCO produce very low scores in the analysis. Reliability of the system of analysis is shown to be satisfactory.

Conclusion

This paper presents a system of PCO analysis that is evidence based, objective and clinically useful. Substantial evidence is provided for its validity and reliability.
Localization and gene expression of steroid sulfatase by RT-PCR in cumulus cells and relationship to serum FSH levels observed during in vitro fertilization
Authors: Otsuka Yukiko , Yanaihara Atsushi , Iwasaki Shinji , Hasegawa Junichi , Yanaihara Takumi , Okai Takashi
Published: April 2005

Background

The purpose of this study was to localize the expression of steroid sulfatase (STS) in cumulus cells and to determine the relationship between STS mRNA expression and the serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and progesterone.

Methods

The subject group included 49 women (29 to 44 years old) for whom in vitro fertilization treatment was indicated. All subjects gave informed consent. One hundred fourteen samples of cumulus-oocyte complex (COC) were obtained under microscopic observation. Part of the COC was stained by STS antibody. RNA was extracted by phenol-chloroform method and real-time PCR was performed. Serum of each patient was collected and was measured by ELISA.

Results

Some of the cumulus samples were stained by STS antibody. The expression of STS mRNA in all samples was confirmed by quantitative RT-PCR. Although there was no significant correlation between the level of STS mRNA and the serum levels of estradiol, progesterone and LH, there was a statistically significant negative correlation between the level of STS mRNA expression and the serum level of FSH (n = 105, p = 0.018, r = -0.22).

Conclusion

These results have demonstrated for the first time the expression of STS in cumulus cells by immunohistological stainings and real-time RT-PCR. STS expression in cumulus cells may be related to the control of the local steroidal environment in the oocyte. Serum FSH may control STS mRNA expression from the results of RT-PCR, although the correlation was low.
Exogenous recombinant human growth hormone effects during suboptimal energy and zinc intake
Authors: Rising Russell , Scaglia Julio F , Cole Conrad , Tverskaya Rozalia , Duro Debora , Lifshitz Fima
Published: April 2005

Background

Energy and Zinc (Zn) deficiencies have been associated with nutritional related growth retardation as well as growth hormone (GH) resistance. In this study, the relationship between suboptimal energy and/or Zn intake and growth in rats and their response to immunoreactive exogenous recombinant human GH (GHi), was determined.

Results

Rats treated with GHi and fed ad-libitum energy and Zn (100/100) had increased IGFBP-3 (p < 0.05) as compared with NSS (215 ± 23 vs. 185 ± 17 ng/ml) along with similar body weight gain. Rats treated with GHi and fed suboptimal energy and full Zn (70/100) had significantly increased weight gain (109.0 ± 18.2 vs. 73.8 ± 11.0 g) and serum IGF-I levels (568 ± 90 vs. 420 ± 85 ng/ml), along with decreased total body water (TBW; 61.0 ± 1.6 vs. 65.7 ± 2.1%) as compared to NSS controls. However, body weight gain was reduced (p < 0.05) as compared with rats fed ad-libitum energy. Growth hormone treated rats fed only suboptimal Zn (100/70), had increased weight gain (217.5 ± 13.2 vs. 191.6 ± 17.9 g; p < 0.05) compared to those given NSS. These rats gained weight in similar amounts to those fed full Zn. Rats treated with GHi and fed both suboptimal energy and Zn (70/70) showed similar results to those fed suboptimal energy with appropriate Zn (70/100), along with significant increases in IGFBP-3 levels (322 ± 28 vs. 93 ± 28 ng/ml). All restricted rats had reduced 24-h EE (kcal/100 g BW) and physical activity index (oscillations/min/kg BW) and GHi did not overcome these effects.

Conclusion

These results suggest that GHi enhances weight gain in rats with suboptimal energy and Zn intake but does not modify energy expenditure or physical activity index. Suboptimal Zn intake did not exacerbate the reduced growth or decrease in energy expenditure observed with energy restriction.
Early rheumatoid arthritis is characterized by a distinct and transient synovial fluid cytokine profile of T cell and stromal cell origin
Authors: Raza Karim , Falciani Francesco , Curnow S John , Ross Emma J , Lee Chi-Yeung , Akbar Arne N , Lord Janet M , Gordon Caroline , Buckley Christopher D , Salmon Mike
Published: April 2005

Pathological processes involved in the initiation of rheumatoid synovitis remain unclear. We undertook the present study to identify immune and stromal processes that are present soon after the clinical onset of rheumatoid arthritis (RA) by assessing a panel of T cell, macrophage, and stromal cell related cytokines and chemokines in the synovial fluid of patients with early synovitis. Synovial fluid was aspirated from inflamed joints of patients with inflammatory arthritis of duration 3 months or less, whose outcomes were subsequently determined by follow up. For comparison, synovial fluid was aspirated from patients with acute crystal arthritis, established RA and osteoarthritis. Rheumatoid factor activity was blocked in the synovial fluid samples, and a panel of 23 cytokines and chemokines measured using a multiplex based system. Patients with early inflammatory arthritis who subsequently developed RA had a distinct but transient synovial fluid cytokine profile. The levels of a range of T cell, macrophage and stromal cell related cytokines (e.g. IL-2, IL-4, IL-13, IL-17, IL-15, basic fibroblast growth factor and epidermal growth factor) were significantly elevated in these patients within 3 months after symptom onset, as compared with early arthritis patients who did not develop RA. In addition, this profile was no longer present in established RA. In contrast, patients with non-rheumatoid persistent synovitis exhibited elevated levels of interferon-γ at initiation. Early synovitis destined to develop into RA is thus characterized by a distinct and transient synovial fluid cytokine profile. The cytokines present in the early rheumatoid lesion suggest that this response is likely to influence the microenvironment required for persistent RA.
In vivo validation of the adequacy calculator for continuous renal replacement therapies
Authors: Ricci Zaccaria , Salvatori Gabriella , Bonello Monica , Pisitkun Tirak , Bolgan Irene , D'Amico Giuseppe , Dan Maurizio , Piccinni Pasquale , Ronco Claudio
Published: April 2005

Introduction

The study was conducted to validate in vivo the Adequacy Calculator, a Microsoft Excel-based program, designed to assess the prescription and delivery of renal replacement therapy in the critical care setting.

Methods

The design was a prospective cohort study, set in two intensive care units of teaching hospitals. The participants were 30 consecutive critically ill patients with acute renal failure treated with 106 continuous renal replacement therapies (CRRT). Urea clearance computation was performed with the Adequacy Calculator (KCALC). Simultaneous blood and effluent urea samples were collected to measure the effectively delivered urea clearance (KDEL) at the beginning of each treatment and, during 73 treatments, between the 18th and 24th treatment hour. The correlation between 179 computed and 179 measured clearances was assessed. Fractional clearances for urea were calculated as spKt/V (where sp represents single pool, K is clearance, t is time, and V is urea volume of distribution) obtained from software prescription and compared with the delivered spKt/V obtained from empirical data.

Results

We found that the value of clearance predicted by the calculator was strongly correlated with the value obtained from computation on blood and dialysate determination (r = 0.97) during the first 24 treatment hours, regardless of the renal replacement modality used. The delivered spKt/V (1.25) was less than prescribed (1.4) from the Adequacy Calculator by 10.7%, owing to therapy downtime.

Conclusion

The Adequacy Calculator is a simple tool for prescribing CRRT and for predicting the delivered dose. The calculator might be a helpful tool for standardizing therapy and for comparing disparate treatments, making it possible to perform large multi-centre studies on CRRT.
HLA-DO transduced in human monocyte-derived dendritic cells modulates MHC class II antigen processing
Authors: Bellemare-Pelletier Angélique , Tremblay Jessy , Beaulieu Sylvie , Boulassel Mohamed-Rachid , Routy Jean-Pierre , Massie Bernard , Lapointe Réjean , Thibodeau Jacques
Published: April 2005

Through the regulation of human leukocyte antigen (HLA)-DM (DM) in B cells, HLA-DO (DO) modulates positively or negatively the presentation of specific peptides. Transduction of DO into human blood monocyte-derived dendritic cells (MoDC) has been proposed as a mean of modifying the peptide repertoire of major histocompatibility complex class II molecules. However, maturation of DC induced by inflammatory stimuli or possibly the adenoviral vector itself triggers acidification of vesicles and shuts down transcription of the class II transactivator gene as well as de novo biosynthesis of class II-related molecules and DM activity. In these conditions, it is unclear that transduced DO could alter the peptide repertoire. Our Western blot and reverse transcriptase-polymerase chain reaction analyses revealed that human DC derived from blood monocytes express small amounts of DOα. Transduction of DOβ alone resulted in the accumulation of a small pool of DO in DM+ CD63+ vesicles and at the plasma membrane of mature DC. The cell-surface increase in class II-associated invariant chain peptide (CLIP)/class II complexes is in line with an inhibitory role of DO on DM. Cotransduction of DOα and DOβ only slightly increased CLIP and DO levels at the cell surface. Together with the fact that a large fraction of transduced DO remains in the endoplasmic reticulum, this suggests that DM is limiting in these conditions. DO expression did not affect a mixed lymphocyte reaction but reduced presentation of the exogenous gp100 antigen to a specific T cell clone. These results show that transduced DO modulates antigen presentation in human mature MoDC, evoking the possible use of this chaperone for immunotherapy.
TNFR1-induced sphingomyelinase activation modulates TCR signaling by impairing store-operated Ca2+ influx
Authors: Church Leigh D , Hessler Gabriele , Goodall John E , Rider David A , Workman Creg J , Vignali Dario A A , Bacon Paul A , Gulbins Erich , Young Stephen P
Published: April 2005

Tumor necrosis factor α (TNF-α) is a potent, pleiotrophic cytokine, which is proinflammatory but can also suppress T lymphocyte function. In chronic inflammatory disease such as rheumatoid arthritis, exposure of T cells to TNF-α alters their ability to mount a response by modulating the T cell receptor (TCR) signaling pathway, but the mechanisms involved remain obscure. Here, we investigated the specific role of TNF receptor 1 (TNFR1) signaling in the modulation of the TCR signaling pathway. We observed a down-regulation of the intracellular calcium ([Ca2+]i) signal in Jurkat T cells after just 30 min exposure to TNF-α, and maximum suppression was reached after 3 h. This effect was transient, and signals returned to normal after 12 h. This depression of [Ca2+]i was also observed in human CD4+ T lymphocytes. The change in Ca2+ signal was related to a decrease in the plasma membrane Ca2+ influx, which was apparent even when the TCR signal was bypassed using thapsigargin to induce a Ca2+ influx. The role of TNF-α-induced activation of the sphingolipid cascade in this pathway was examined. The engagement of TNFR1 by TNF-α led to a time-dependent increase in acid sphingomyelinase (SMase; ASM) activity, corresponding with a decrease in cellular sphingomyelin. In parallel, there was an increase in cellular ceramide, which correlated directly with the decrease in the magnitude of the Ca2+ response to phytohemagglutinin. Exogenous addition of SMase or ceramide mimicked the effects of TNFR1 signals on Ca2+ responses in Jurkat T cells. Direct evidence for the activation of ASM in this pathway was provided by complete abrogation of the TNF-α-induced inhibition of the Ca2+ influx in an ASM-deficient murine T cell line (OT-II+/+ASM−/−). This potent ability of TNF-α to rapidly modulate the TCR Ca2+ signal via TNFR1-induced ASM activation can explain its suppressive effect on T cell function. This TNFR1 signaling pathway may play a role as an important regulator of T cell responses.
Mucosal application of plasmid-encoded IL-15 sustains a highly protective anti-Herpes simplex virus immunity
Authors: Toka Felix N , Rouse Barry T
Published: April 2005

In a DNA immunization against Herpes simplex virus (HSV), we examined the ability of plasmid-encoded interleukin-15 (pIL-15) to induce and maintain the mucosal B and T cell immune response. pIL-15 generated memory CD8+ T cell responses that were threefold higher and mainly maintained in the spleen, but high levels of immunoglobulin A antibodies were induced and maintained long-term in the vaginal mucosa. Both of these enhanced components of the immune responses were recalled rapidly upon challenge with a lethal dose of HSV McKrae, affording protection in mice immunized with codelivery of pIL-15. Our results show for the first time that intranasal administration of pIL-15 along with plasmid-encoded glycoprotein B of HSV leads to enhancement of primary and memory CD8+ T cell responses as well as humoral immune response. Therefore, a mucosal immunization strategy that incorporates a potent cytokine such as IL-15 as an adjuvant might induce protective mucosal immune responses that constitute the initial barrier at mucosal portals of pathogen entry.
Adaptation of VOR to Coriolis Stimulation
Authors: ADENOT SOPHIE , JARCHOW THOMAS , YOUNG LAURENCE R.
Published: April 2005

Abstract: The vestibulo‐ocular reflex (VOR) is normally characterized by the gain and phase of slow‐phase velocity (SPV) relative to the stimulus velocity. Although this is perfectly satisfactory for steady‐state sinusoidal oscillations about a single axis, it is less useful when applied to transient responses. The well‐known decay of nystagmus following a step change of head velocity approximately follows a double exponential, with an initial amplitude (A), a long time constant (τ), and an adaptation time constant (τa). We have developed a means of representing the transient response for a complex head velocity stimulus as experienced during high‐speed artificial gravity (AG) experiments. When a subject, lying supine on a rotating horizontal platform, makes a yaw head movement of amplitude θ, the vertical semicircular canals experience a step in angular velocity. The pitch stimulus is equal to the change in the component of the centrifuge angular velocity (ωc) aligned with the interaural axis, and gives rise to a vertical VOR. The magnitude of the step change is ωc sin θ. The SPV is approximated by an exponential decay of amplitude A and single time constant τ, and then normalized relative to this stimulus step. MATLAB scripts filter the raw eye position data to remove noise, blinks, and saccades, differentiate the signal, and remove fast phases to obtain SPV. The amplitude of the fitted SPV exponential is divided by ωc sin θ to obtain the normalized SPV. A and τ are shown to behave differently as subjects adapt to repeated head movements of different amplitudes.
Yellow Filters Can Improve Magnocellular Function: Motion Sensitivity, Convergence, Accommodation, and Reading
Authors: RAY N J. , FOWLER S , STEIN J F.
Published: April 2005

Abstract: The magnocellular system plays an important role in visual motion processing, controlling vergence eye movements, and in reading. Yellow filters may boost magnocellular activity by eliminating inhibitory blue input to this pathway. It was found that wearing yellow filters increased motion sensitivity, convergence, and accommodation in many children with reading difficulties, both immediately and after three months using the filters. Motion sensitivity was not increased using control neutral density filters. Moreover, reading‐impaired children showed significant gains in reading ability after three months wearing the filters compared with those who had used a placebo. It was concluded that yellow filters can improve magnocellular function permanently. Hence, they should be considered as an alternative to corrective lenses, prisms, or exercises for treating poor convergence and accommodation, and also as an aid for children with reading problems.
Is an Internal Model of Head Orientation Necessary for Oculomotor Control?
Authors: BARNETT‐COWAN MICHAEL , DYDE RICHARD T. , HARRIS LAURENCE R.
Published: April 2005

Abstract: In order to test whether the control of eye movement in response to head movement requires an internal model of head orientation or instead can rely on directly sensing information about head orientation and movement, perceived gravity was separated from physical gravity to see which dominated the eye‐movement response. Internal model theory suggests that the oculomotor response should be driven by perceived, internalized gravity, whereas the direct sensing theory predicts it should always be driven by vestibularly sensed gravity. Subjects lay on an airbed either supine or on their side and were sinusoidally translated along their dorsoventral body axis. The direction of perceived gravity was separated from physical gravity by performing the experiments in a room built on its side with the direction of its “floor” orthogonal to both physical gravity and the subject's translation. The swinging sum of the imposed sinusoidal acceleration with physical gravity was thus in a plane orthogonal to its sum with perceived gravity. Oculomotor responses to these swinging vectors were looked for and responses were found only to the sum of the acceleration with physical gravity, not perceived gravity. It was concluded that an internal model is not used to drive these compensatory eye movements.
Gaze Position Corrective Eye Movements in Normal Subjects and in Patients with Vestibular Deficits
Authors: PENG GRACE C.Y. , MINOR LLOYD B. , ZEE DAVID S.
Published: April 2005

Abstract: Eye movements in response to high‐acceleration head rotations (thrusts) in the horizontal plane from patients with unilateral (UVD) or bilateral vestibular loss (BVD) were recorded. The rapid, gaze‐position corrections (GPCs) that appeared when vestibulo‐ocular reflex (VOR) slow phases were undercompensatory were characterized. For comparison, eye movements from normal subjects who were asked to generate saccades in the direction opposite head rotation (in the same direction as slow phases) were recorded. This normal‐subject model produced responses with spatial and temporal characteristics similar to those from GPCs in patients as follows: When head rotations were generated actively, compared with passively, gaze‐position errors and corresponding GPCs were smaller and occurred earlier. During passively generated head thrusts, GPCs still occurred when head rotations were made in total darkness, though their accuracy decreased as the requirement for maintaining gaze on a specific location in space was relaxed. Time of onset of GPCs was not rigidly tied to head kinematics (peak velocity or peak acceleration). Speeds of GPCs, however, were lower than speeds of similar‐sized, head‐fixed saccades. Finally, during passive and active head thrusts in patients, sustained, high‐frequency (20 to 30 Hz) oscillations that appeared as tiny saccades were occasionally observed, one immediately following the other, resembling a compensatory slow‐phase response. Taken together, the results suggest that one strategy for overcoming a VOR deficit is to enlist the saccadic system to produce an oculomotor response that is required to compensate for head rotation. This response may come in the form of high‐velocity GPCs or smaller‐amplitude oscillations.
Relative Atrophy of the Flocculus and Ocular Motor Dysfunction in SCA2 and SCA6
Authors: YING S H , CHOI S I , LEE M , PERLMAN S L , BALOH R W , TOGA A W , ZEE D S
Published: April 2005

Abstract: Two hereditary ataxia syndromes show distinct profiles of region‐specific atrophy and ocular motor deficits. Selective pontine atrophy is associated with slowed saccades in ataxin‐2 mutations, and selective floccular atrophy is associated with impaired pursuit and gaze‐holding abnormalities in Ca(V)2.1 mutations. Although the flocculus seems to be spared relative to the pons in ataxin‐2 mutations, and pursuit and gaze‐holding appear to be relatively normal, these can be difficult to assess at the bedside, as corrective saccades are also slow and hard to discern. Here, we show the presence of significant floccular atrophy compared with controls in both ataxin‐2 and Ca(V)2.1 mutations, which raises the possibility that abnormalities of smooth pursuit or gaze‐holding are present in both conditions.
About the Effects of Velocity Saturation on Smooth Pursuit
Authors: BUIZZA ANGELO , RAMAT STEFANO
Published: April 2005

Abstract: By means of simple simulations and based on experimental results from the literature, it is argued that correct consideration of the well known velocity saturation of the smooth pursuit eye movement system may suggest new insight into some intriguing aspects of this system's behavior.
Human Surge Linear Vestibulo‐Ocular Reflex during Tertiary Gaze Viewing
Authors: TIAN JUN‐RU , CRANE BENJAMIN T. , DEMER JOSEPH L.
Published: April 2005

Abstract: The otolith‐mediated linear vestibulo‐ocular reflex (IVOR) was studied in 9 normal humans undergoing transient whole‐body surges at 0.5 g peak acceleration while viewing targets eccentrically placed in tertiary positions that combined horizontal and vertical eccentricities at distance of 15, 25, or 50 cm both in darkness and light. Mean velocity gain (±SEM) for the horizontal component was 0.61 ± 0.04 in darkness and increased to 0.72 ± 0.03 for visible targets (P < 0.05), and for the vertical component was 0.54 ± 0.02 in darkness, not significantly different from horizontal component gain. For visible targets, vertical component gain significantly increased to 0.63 ± 0.04 (P < 0.05) with visible targets, but remained significantly less than horizontal component gain.
The Origin of Downbeat Nystagmus: An Asymmetry in the Distribution of On‐Directions of Vertical Gaze‐Velocity Purkinje Cells
Authors: MARTI S.RAH , STRAUMANN DOMINIK , GLASAUER S.EFAN
Published: April 2005

Abstract: Various hypotheses on the origin of cerebellar downbeat nystagmus (DBN) have been presented; the exact pathomechanism, however, is still not known. Based on previous anatomical and electrophysiological studies, we propose that an asymmetry in the distribution of on‐directions of vertical gaze‐velocity Purkinje cells leads to spontaneous upward ocular drift in cerebellar disease, and therefore, to DBN. Our hypothesis is supported by a computational model for vertical eye movements.
Retention of Saccadic Adaptation in Humans
Authors: ALAHYANE NADIA , PÉLISSON DENIS
Published: April 2005

Abstract: In the present study, we tested in human subjects the persistence of the oculomotor changes resulting from saccadic adaptation up to 19 days after exposure to the double step target protocol. The main results indicate that the reduction of saccade gain related to the adaptation session (mean gain change of 5 subjects = 22 +/− 4.7%) was partially but significantly retained after 1 day and 5 days (mean amount of retention = 36 +/− 17% and 19.7 +/− 13.3%, respectively) but was no longer significant at day 11 and 19. Unexpectedly, gain changes were larger for leftward than for rightward saccades. No change in saccade dynamics was observed. These data suggest that in humans, adaptive mechanisms induce long lasting changes in visually‐guided saccade amplitude, probably reflecting plastic changes in the brain.
Single or Combined Oblique Muscle Surgery in Acquired and Congenital Superior Oblique Palsy
Authors: STEFFEN H , KOLLING G H
Published: April 2005

Abstract: Oblique muscle surgery with weakening of the inferior oblique muscle alone or in combination with a tuck of the superior oblique tendon reduces in a dose‐dependent relationship the vertical deviation in patients with an acquired or congenital superior oblique palsy. Reduction of cyclotropia and the V‐sign is less dose dependent.
Binocular Control of Saccades in Idiopathic Parkinson's Disease
Authors: VERSINO MAURIZIO , ZAVANONE CHIARA , COLNAGHI SILVIA , BELTRAMI GIORGIO , PACCHETTI CLAUDIO , ZANGAGLIA ROBERTA , COSI VITTORIO
Published: April 2005

Abstract: We focused on the saccade disconjugate control in idiopathic Parkinson's disease patients. Our data showed that in IPD patients the saccade precision was differently impaired in the two eyes—namely, the disconjugate component was larger than in controls—more for the remembered than for the reflexive task.
Increased Pituitary Vascular Endothelial Growth Factor-A in Dopaminergic D2 Receptor Knockout Female Mice
Authors: Cristina C. , Díaz-Torga G. , Baldi A. , Góngora A. , Rubinstein M. , Low M. J. , Becú-Villalobos D.
Published: April 2005

Vascular endothelial growth factor (VEGF)-A is an important angiogenic cytokine in cancer and pathological angiogenesis and has been related to the antiangiogenic activity of dopamine in endothelial cells. We investigated VEGF expression, localization, and function in pituitary hyperplasia of dopamine D2 receptor (D2R)-knockout female mice. Pituitaries from knockout mice showed increased protein and mRNA VEGF-A expression when compared with wild-type mice. In wild-type mice, prolonged treatment with the D2R antagonist, haloperidol, enhanced pituitary VEGF expression and prolactin release, suggesting that dopamine inhibits pituitary VEGF expression. VEGF expression was also increased in pituitary cells from knockout mice, even though these cells proliferated less in vitro when compared with wild-type cells, as determined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium proliferation assay, proliferating cell nuclear antigen expression, and [3H]thymidine incorporation. In contrast to other animal models, estrogen did not increase pituitary VEGF protein and mRNA expression and lowered serum prolactin secretion in vivo and in vitro in both genotypes. VEGF (10 and 30 ng/ml) did not modify pituitary cell proliferation in either genotype and increased prolactin secretion in vitro in estrogen-pretreated cells of both genotypes. But conditioned media from D2R−/− cells enhanced human umbilical vein cell proliferation, and this effect could be partially inhibited by an anti-VEGF antiserum. Finally, using dual-labeling immunofluorescence and confocal laser microscopy, we found that in the hyperplastic pituitaries, VEGF-A was mostly present in follicle-stellate cells. In conclusion, pituitary VEGF expression is under dopaminergic control, and even though VEGF does not promote pituitary cellular proliferation in vitro, it may be critical for pituitary angiogenesis through paracrine actions in the D2R knockout female mice.
Follicular Cells Acquire Sertoli Cell Characteristics after Oocyte Loss
Authors: Guigon Céline J. , Coudouel Noëlline , Mazaud-Guittot Séverine , Forest Maguelone G. , Magre Solange
Published: April 2005

Although it has been suggested that in mammals the loss of female germ cells may induce the masculinization of the ovarian compartment, there has been as yet no conclusive demonstration. To directly address that question, the present study has been designed to determine the fate of follicular cells after oocyte loss. Using γ-irradiation to selectively deplete oocytes in nongrowing follicles in female rats, we show that follicular cells in oocyte-depleted follicles survive, proliferate, and subsequently acquire morphological characteristics of Sertoli cells: elongated cytoplasm, basal location of the nucleus, and specific Sertoli cell junctions, the ectoplasmic specializations. These Sertoli-like cells express, however, the female-specific marker FOXL2 (Forkhead L2) but not the male sex-specific marker SOX-9 (Sry-type high-mobility-group box transcription factor-9) underlying the maintenance of molecular characteristics of granulosa cells. Before transdifferentiating into Sertoli-like cells, follicular cells of oocyte-depleted follicles initiate the expression of anti-Mullerian hormone and inhibin α-subunit that are typically synthesized by granulosa cells from the onset of follicular growth. Experimental modifications of the endocrine balance of the irradiated females show that there is a close relationship between plasma FSH levels and the occurrence of Sertoli-like cells. In addition to providing experimental evidence for the crucial role of the oocyte in granulosa cell phenotype maintenance, these results emphasize that the transdifferentiation of granulosa cells into Sertoli cells occurs in a multistep fashion, requiring the maturation of granulosa cells and depending on the endocrine milieu.
Luteinizing Hormone-Induced Extracellular-Signal Regulated Kinase Activation Differently Modulates Progesterone and Androstenedione Production in Bovine Theca Cells
Authors: Tajima Kimihisa , Yoshii Kumiko , Fukuda Shin , Orisaka Makoto , Miyamoto Kaoru , Amsterdam Abraham , Kotsuji Fumikazu
Published: April 2005

It has been reported that gonadotropins promoted phosphorylation of ERK/MAPK in granulosa cells. However, little is known about the effects of gonadotropin on ERK activity in theca cells. This study explores how LH/forskolin controls ERK phosphorylation in cultured bovine theca cells. Effects of ERK on steroidogenesis were also investigated. Phosphorylation of ERK in bovine theca cells was augmented by LH and forskolin in 5 min; it decreased thereafter below basal levels in 20 min. Nevertheless, phosphorylation of the ERK kinase, MEK, was unaffected. Addition of H89 (a protein kinase A inhibitor) significantly reduced the effect of LH/forskolin on ERK phosphorylation. A potent MEK inhibitor PD98059 eliminated ERK phosphorylation and augmented progesterone production concomitantly with the elevation of intracellular steroidogenic acute regulatory protein mRNA in LH/forskolin-stimulated theca cells. In contrast to progesterone production, androgen production was diminished significantly by inhibition of ERK with decreased intracellular P450c17 mRNA levels. Taking these results together, we conclude that LH/cAMP leads to phosphorylation of ERK in a biphasic manner through MEK-independent pathway in bovine theca cells. Protein kinase A-induced phosphatase could possibly contribute to the phosphorylation process. Furthermore, modulation of ERK phosphorylation involves control of thecal steroidogenesis via modulation of the expression of steroidogenic acute regulatory protein and P450c17.