bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Carotid and Transcranial Ultrasound Findings Compared with Clinical Classification and Stroke Severity in Acute Ischemic Stroke
Authors: Thomassen Lars , Waje-Andreassen Ulrike , Naess Halvor , Aarseth Jan , Russell David
Published: November 2005

Background: The aim of this study was to assess the association between cerebral hemodynamics and the clinical picture as defined by the Oxfordshire Community Stroke Project (OCSP) classification, as well as the clinical severity as defined by the National Institute of Health Stroke Scale (NIHSS) within the first 6 h of an acute middle cerebral artery (MCA) stroke onset. Methods: 70 unselected patients were grouped according to the OCSP classification and NIHSS. All patients immediately had extracranial and transcranial Doppler (TCD) ultrasound examinations. Results: In the study population as a whole, there was a significant association between intracranial vascular pathology and the OCSP classification (p < 0.001) as well as the NIHSS score (p < 0.001). In patients with severe stroke, however, TCD demonstrated the hypothesized proximal MCA1 occlusion in only 34% of patients with an OCSP-defined total anterior circulation syndrome and in 42% of patients with an NIHSS score of ≧15. In moderate stroke, the OCSP classification was misleading in almost half of the patients with a partial anterior circulation syndrome, i.e. a hypothesized distal MCA2 occlusion suitable for thrombolysis. Conclusions: Neither the OCSP classification nor the NIHSS grading provided reliable information about the site or presence of intracranial arterial occlusion in acute stroke within the first 6 h after stroke onset in the individual patient. The results of this study strongly suggest that selection of acute ischemic stroke patients for thrombolysis should also include an assessment of cerebral hemodynamics.
Expression of Tumor Necrosis Factor Alpha and Matrix Metalloproteinase-9 in Surgically Induced Necrotizing Scleritis
Authors: Seo Kyoung Yul , Lee Hyung Keun , Kim Eung Kweon , Lee Joon H.
Published: November 2005

Background: Surgically induced necrotizing scleritis is primarily managed with immunosuppressive regimens. Such treatments can alter inflammatory cytokines and products such as tumor necrosis factor-α (TNF-α) and matrix metalloproteinase-9 (MMP-9), which are an important proinflammatory cytokine and a tissue-degrading protease involved in necrosis of some ocular tissues. Object: To evaluate TNF-α and MMP-9 in the tear or sclera of surgically induced necrotizing scleritis. Methods: After tear collection from healthy and diseased eyes of 2 patients, immunoblot analysis using monoclonal antibody specific for human TNF-α and MMP-9 was performed. In another patient, scleral tissues were obtained during scleral allograft surgery, and the same immunoblot analysis was done. Results: The level of TNF-α and MMP-9 was increased in tear fluid from patients compared to that of control volunteers and returned to the control level after treatment. The diseased sclera showed an increased expression of MMP-9 compared to that of the normal donor sclera. Conclusions: TNF-α and MMP-9 may suggest disease activity of surgically induced necrotizing scleritis and can be altered by proper immunosuppressive treatment.
Comparative Analysis and Expression of Neuroserpin in Xenopus laevis
Authors: de Groot Dorien M. , Pol Christine , Martens Gerard J.M.
Published: November 2005

Serine protease inhibitors form a diverse family of proteins of which most members inhibit target serine proteases. Neuroserpin is a member of this family. Here, we have characterized neuroserpin in the nonmammalian species Xenopus laevis and found a high degree of aminoacid sequence conservation, especially of the reactive center loop, of the Xenopus protein compared to mammalian and chicken neuroserpin sequences, suggesting a conserved target specificity. Neuroserpin mRNA and protein were expressed throughout Xenopus development, while in the adult frog high mRNA expression was found in neuronal and neuroendocrine tissues, and the reproductive organs, and the neuroserpin protein was detected mainly in brain and pituitary. More specifically, in Xenopus pituitary neuroserpin mRNA was expressed higher in the neurointermediate lobe than in the pars distalis. At the protein level, we detected a 55-kDa neuroserpin protein in the pars nervosa, two neuroserpin proteins of 44- and 50-kDa in the melanotrope cells of the pars intermedia, and a 46-kDa product in the pars distalis. On the basis of its relatively high degree of sequence conservation and its expression pattern, we conclude that Xenopus neuroserpin may play an important physiological role, e.g. as a serine protease inhibitor during development, and for proper neuronal and neuroendocrine cell functioning.
Physiological Concentrations of Insulin Induce Endothelin-Dependent Vasoconstriction of Skeletal Muscle Resistance Arteries in the Presence of Tumor Necrosis Factor-α Dependence on c-Jun N-Terminal Kinase
Authors: Eringa Etto C. , Stehouwer Coen D. A. , Walburg Kimberley , Clark Andrew D. , van Nieuw Amerongen Geerten P. , Westerhof Nico , Sipkema Pieter
Published: December 2005

Objective—

Tumor necrosis factor-α (TNF-α) has been linked to obesity-related insulin resistance and impaired endothelium-dependent vasodilatation, but the mechanisms have not been elucidated. To investigate whether TNF-α directly impairs insulin-mediated vasoreactivity in skeletal muscle resistance arteries and the role of c-Jun N-terminal kinase (JNK) in this interference.

Methods and Results—

Insulin-mediated vasoreactivity of isolated resistance arteries of the rat cremaster muscle to insulin (4 to 3400 μU/mL) was studied in the absence and presence of TNF-α (10 ng/mL). Although insulin or TNF-α alone did not affect arterial diameter, insulin induced dose-dependent vasoconstriction of cremaster resistance arteries in the presence of TNF-α, (−12±1% at 272 μU/mL). Blocking endothelin receptors in the absence of TNF-α uncovered insulin-mediated vasodilatation (18±6% at 272 μU/mL) but not in the presence of TNF-α (2±2% at 272 μU/mL), showing that TNF-α inhibits vasodilator effects of insulin. Using digital imaging microscopy, we discovered that TNF-α activates JNK in arterial endothelium, visible as an increase in phosphorylated JNK. Moreover, inhibition of JNK with the cell-permeable peptide inhibitor L-JNKI abolished insulin-mediated vasoconstriction in the presence of TNF-α, showing that JNK is required for interaction between TNF-α and insulin.

Conclusions—

TNF-α inhibits vasodilator but not vasoconstrictor effects of insulin in skeletal muscle resistance arteries, resulting in insulin-mediated vasoconstriction in the presence of TNF-α. This effect of TNF-α is critically dependent on TNF-α–mediated activation of JNK.
Cellular Pathology of Atherosclerosis
Authors: Tull Samantha P. , Anderson Steve I. , Hughan Sascha C. , Watson Steve P. , Nash Gerard B. , Rainger G. Ed
Published: December 2005

Although platelets do not ordinarily bind to endothelial cells (EC), pathological interactions between platelets and arterial EC may contribute to the propagation of atheroma. Previously, in an in vitro model of atherogenesis, where leukocyte adhesion to EC cocultured with smooth muscle cells was greatly enhanced, we also observed attachment of platelets to the EC layer. Developing this system to specifically model platelet adhesion, we show that EC cocultured with smooth muscle cells can bind platelets in a process that is dependent on EC activation by tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β
1
. Recapitulating the model using EC alone, we found that a combination of TGF-β
1
and TNF-α promoted high levels of platelet adhesion compared with either agent used in isolation. Platelet adhesion was inhibited by antibodies against GPIb-IX-V or α
IIb
β
3
integrin, indicating that both receptors are required for stable adhesion. Platelet activation during interaction with the EC was also essential, as treatment with prostacyclin or theophylline abolished stable adhesion. Confocal microscopy of the surface of EC activated with TNF-α and TGF-β
1
revealed an extensive matrix of von Willebrand factor that was able to support the adhesion of flowing platelets at wall shear rates below 400 s
−1
. Thus, we have demonstrated a novel route of EC activation which is relevant to the atherosclerotic microenvironment. EC activated in this manner would therefore be capable of recruiting platelets in the low-shear environments that commonly exist at points of atheroma formation.
Effects of Somatosensory Stimulation on Use-Dependent Plasticity in Chronic Stroke
Authors: Sawaki Lumy , Wu Carolyn W.-H. , Kaelin-Lang Alain , Cohen Leonardo G.
Published: December 2005

Background and Purpose—

There is a need to develop strategies to enhance the beneficial effects of motor training, including use-dependent plasticity (UDP), in neurorehabilitation. Peripheral nerve stimulation (PNS) modulates motor cortical excitability in healthy humans and could influence training effects in stroke patients.

Methods—

We compared the ability of PNS applied to the (1) arm, (2) leg, and (3) idle time to influence training effects in the paretic hand in 7 chronic stroke patients. The end point measure was the magnitude of UDP.

Results—

UDP was more prominent with arm stimulation (increased by 22.8%) than with idle time (by 2.9%) or leg stimulation (by 6.4%).

Conclusions—

PNS applied to the paretic limb paired with motor training enhances training effects on cortical plasticity in stroke patients.
Tumor Necrosis Factor-α–238G>A Promoter Polymorphism Is Associated With Increased Risk of New Hemorrhage in the Natural Course of Patients With Brain Arteriovenous Malformations
Authors: Achrol Achal S. , Pawlikowska Ludmila , McCulloch Charles E. , Poon K. Y. Trudy , Ha Connie , Zaroff Jonathan G. , Johnston S. Claiborne , Lee Chanhung , Lawton Michael T. , Sidney Stephen , Marchuk Douglas A. , Kwok Pui-Yan , Young William L.
Published: December 2005

Background and Purpose—

Identification of single-nucleotide polymorphisms (SNPs) associated with increased risk of new intracranial hemorrhage (ICH) after brain arteriovenous malformation (BAVM) diagnosis would facilitate risk stratification and identify potential targets for therapeutic intervention.

Methods—

Patients with BAVM were longitudinally followed. Primary outcome was new ICH after diagnosis; censoring events were last follow-up or any BAVM treatment. We genotyped 4 promoter SNPs in 2 inflammatory cytokine genes: interleukin-6 (IL-6–174G>C; IL-6–572G>C) and tumor necrosis factor-α (TNF-α–238G>A; TNF-α–308G>A). Association of genotype with risk of new ICH was screened using χ
2
; SNPs associated with new ICH were further characterized using Cox proportional hazards.

Results—

We genotyped 280 patients (50% female; 59% white, mean±SD age at diagnosis 37±17 years; 40% presenting with ICH). TNF-α–238G>A was associated with increased risk of new ICH after diagnosis (χ
2
;
P
=0.003). After adjusting for age, race/ethnicity, and clinical presentation, the risk of new ICH was increased for patients with TNF-α–238 AG genotype (hazard ratio, 4.01;
P
=0.015). No other SNP was found to be associated with new ICH.

Conclusion—

A TNF-α SNP was associated with increased risk of new ICH in the natural course of BAVMs. The role of inflammatory cytokines in the pathogenesis of BAVM hemorrhage merits further study.
Intracerebral Hemorrhage-Induced Brain Injury Is Aggravated in Senescence-Accelerated Prone Mice
Authors: Lee Jae-Chul , Cho Geum-Sil , Choi Byung-Ok , Chun Kim Hyoung , Kim Yong-Sun , Kim Won-Ki
Published: December 2005

Background and Purpose—

In cerebral stroke, the overall mortality rate of older individuals is higher than that of younger individuals. We therefore investigated aging-related changes in brain tissue damage and immune response in response to intracerebral hemorrhage (ICH) in mice.

Methods—

ICH was induced by microinjecting autologous whole blood (5 μL) into the striatum of 4- or 14-month-old senescence-accelerated prone (SAMP8) mice or senescence-accelerated resistant (SAMR1) mice.

Results—

In all groups, neurological deficits occurred within 6 hours and gradually improved after the first day, but improvement was most delayed in 14-month-old SAMP8 mice. Isolectin B4-positive and amoeboid microglia/macrophages were abundantly distributed around and inside the hemorrhagic lesions in 14-month-old SAMP8 mice. In contrast, myeloperoxidase-immunoreactive neutrophils and reactive astrocytes with intensified glial fibrillary acidic protein–stained processes and swollen cytoplasm did not differ in number or distribution between SAMP8 and SAMR1 mice. Regardless of their age, the immunoreactivity of Mn-SOD, a major antioxidant enzyme in mitochondria, was much weaker in SAMP8 than in SAMR1 mice. The expression of inducible nitric oxide, however, was higher in old SAMP8 mice than in the other experimental groups.

Conclusions—

These results suggest that activated microglia/monocytes may aggravate intracerebral hemorrhagic damage in old SAMP8 mice. Further studies on the exact role of activated microglia/monocytes and the altered activities of antioxidant enzymes in old SAMP8 mice may provide useful information for ICH-induced brain injury in relation with aging.
Physiotherapy Coupled With Dextroamphetamine for Rehabilitation After Hemiparetic Stroke
Authors: Gladstone David J. , Danells Cynthia J. , Armesto Armi , McIlroy William E. , Staines W. Richard , Graham Simon J. , Herrmann Nathan , Szalai John P. , Black Sandra E.
Published: December 2005

Background and Purpose—

Hemiparesis is the commonest disabling deficit caused by stroke. In animals, dextroamphetamine (AMPH) paired with training enhances motor recovery, but its clinical efficacy is uncertain.

Methods—

In a randomized, double-blind, placebo-controlled trial, 71 stroke patients were stratified by hemiparesis severity and randomly assigned to 10 sessions of physiotherapy coupled with either 10 mg AMPH or placebo. Study treatments were administered by 1 physiotherapist, beginning 5 to 10 days after stroke and continuing twice per week for 5 weeks. Outcomes were assessed by 1 physiotherapist at baseline, after each treatment session, at 6 weeks, and at 3 months. The primary outcome was motor recovery (impairment level) on the Fugl-Meyer (FM) scale. Secondary outcomes assessed mobility, ambulation, arm/hand function, and independence in activities of daily living.

Results—

Baseline hemiparesis was severe overall (mean FM score 27.7±20.0). Motor scores improved during treatment in both groups (mean change, baseline to 3 months 29.5±16.6). Repeated-measures ANOVA revealed no significant differences in recovery between the treatment groups for the entire cohort (n=67) or for subgroups with a severe hemiparesis (n=43), moderate hemiparesis (n=24), or cortically based stroke (n=26). In the moderate subgroup, there was a significant drug×time interaction for upper extremity motor recovery (F=5.14;
P
<0.001), although there was a significant baseline imbalance in motor scores in this subgroup.

Conclusion—

In stroke patients with a severe motor deficit, 10 mg AMPH coupled with physiotherapy twice per week for 5 weeks in the early poststroke period provided no additional benefit in motor or functional recovery compared with physiotherapy alone. Patients with moderate severity hemiparesis deserve further investigation. Increased intensity and longer duration drug/therapy dosing regimens should be explored, targeting the upper and lower limbs separately.
Transient Ischemic Attacks in Rural and Urban Northern Portugal
Authors: Correia Manuel , Silva Mário R. , Magalhães Rui , Guimarães Laura , Carolina Silva M.
Published: December 2005

Background and Purpose—

There are no community-based studies on the incidence of transient ischemic attacks (TIAs) in Portugal. This study was designed to determine TIA incidence and the risk of stroke occurrence in rural and urban populations in northern Portugal.

Methods—

All suspected first-ever TIAs occurring between October 1998 and September 2000 in 18 677 residents in a rural municipality and 86 023 living in the city of Porto were entered into a population-based registry. Standard definitions and comprehensive sources of information were used for identification of patients who were followed up at 3 and 12 months after the TIA.

Results—

During a 24-month period, 141 patients with a first-ever TIA were registered, 36 in rural and 104 in urban areas. The vascular territory was carotid in 66.7% of the patients, vertebrobasilar in 29.1%, and undetermined in 4.3%. The overall crude annual incidence rate per 1000 was 0.67 (95% CI, 0.45 to 1.04), 0.61 (95% CI, 0.38 to 1.01) for rural, and 0.96 (95% CI, 0.43 to 2.33) for urban populations. The risk of stroke within the first 7 days of the index event was 12.8% (95% CI, 7.3 to 18.3), reaching 21.4% (95% CI, 14.6 to 28.1) at 1 year. Three factors were associated with stroke occurrence within 120 days after TIA: patients’ age ≥65 years and an episode in the carotid distribution lasting ≥3 hours.

Conclusions—

The incidence of TIA in northern Portugal, particularly in rural populations, ranks among the highest reported in community-based studies, following closely the stroke incidence trend (ACINrpc). Early recognition of TIA by patients and physicians is crucial for effective stroke prevention.
Detection of Mesoscale Seasonal and Interannual Variation in the Vegetation of the Amazon Basin
Authors: Logsdon Miles G. , Weeks Robin , Smith Milton , Richey Jeffery E. , Ballester Victoria , Shimabukoro Yosio
Published: November 2005

In the Amazon basin, seasonal and interannual spectral changes measured by satellites result from anthropogenic disturbance and from the interaction between climate variation and the surface cover. Measurements of spectral change, and the characterization of that change, provide information concerning the physical processes evident at this mesoscale. A 17-yr sequence of daily Advanced Very High Resolution Radiometer (AVHRR) global area coverage (GAC) images were analyzed to produce a monthly record of surface spectral change encompassing El Niño–Southern Oscillation (ENSO) cycles. Monthly cloud-free composite images from daily AVHRR data were produced by linear filters that minimized the finescale spatial variance and allowed for a wide range analysis within a consistent mathematical framework. Here the use of a minimized local variance (MLV) filter that produced spatially smooth images in which major land-cover boundaries and spatial gradients are clearly represented is discussed. Changes in the configuration of these boundaries and the composition of the landscape elements they defined are described in terms of quantitative changes in landscape pattern. The time series produced with the MLV filter revealed a marked seasonal difference in the pattern of the landscape and structural differences over the length of the time series. Strikingly, the response of the region to drier El Niño years appears to be delayed in the MLV series, the maximum response being in the year following El Niño with little or no change seen during El Niño.
Residential Development Patterns and Neighborhood Satisfaction
Authors: Kearney Anne R.
Published: December 2005

Alternative patterns of residential development, going by names such as cluster housing and conservation subdivisions, opt to preserve large areas of shared outdoor space by increasing housing density on portions of the parcel. These alternative approaches arguably help preserve environmental quality, but how do they affect the people who live there? This study explored the impacts of residential density and nature areas on residents' satisfaction with their neighborhood. Survey results from 361 participants in nine different residential subdivisions showed that density and proximity to shared nature areas did not have a large impact on neighborhood satisfaction. More important were opportunities to visit nearby shared space and having views of nature from the home.
Free-Market Ideology and Environmental Degradation
Authors: Heath Yuko , Gifford Robert
Published: December 2005

The effects of support for free-market ideology and environmental apathy were investigated to identify some bases for not believing in global climate change. A survey of community residents' ( N= 185) beliefs about global climate change also assessed ecocentrism, anthropocentrism, perceived knowledge about climate change, and self-efficacy. The beliefs that global climate change is not occurring, is mainly not human caused, will also have positive consequences and that weaker intentions to undertake ameliorative actions were significantly associated with greater support for free-market ideology, greater environmental apathy, less ecocentrism, and less self-efficacy. About 40% of the variance in each belief and 56% of the variance in the behavioral intention was explained by these factors. The results suggest that the relation between support for free-market ideology and the beliefs about global climate change is mediated by environmental apathy.
A Comparison of Environmental Values and Attitudes Between Chinese in Canada and Anglo-Canadians
Authors: Deng Jinyang , Walker Gordon J. , Swinnerton Guy
Published: December 2005

This study examines similarities and differences in environmental values and attitudes between two cultural groups—Chinese in Canada and Anglo-Canadians. The results indicate that Chinese are more supportive of social-altruistic values than are Anglo-Canadians. However, the two groups are not significantly different in biospheric values. Moreover, both groups are significantly different in two of four new environmental paradigm (NEP) subscales— limits to growth and antianthropocentrism—whereas their attitudes toward the other two NEP subscales— eco-crisis and balance-of-nature—are similar. Study results also suggest that biospheric values are closely related to the NEP, whereas social-altruistic values are not. In addition, acculturation does not consistently affect all six subscales, suggesting that Chinese in Canada may have adopted a selective acculturation pattern. Finally, this study's findings also endorse some previous research that proposes that value orientations may be more helpful in understanding environmental concern than sociodemographic variables such as age, education, and income.
Why are Energy Policies Acceptable and Effective?
Authors: Steg Linda , Dreijerink Lieke , Abrahamse Wokje
Published: December 2005

This article examines which policy features affect the perceived effectiveness and acceptability of pricing policies aimed to reduce CO2 emissions. A survey study was conducted among 112 Dutch respondents in 2003. As hypothesized, incentives and policies targeting efficiency behavior were perceived to be more effective and acceptable than were disincentives and policies targeting curtailment behavior. Policies targeting direct energy use were evaluated as more effective than those targeting indirect energy use. No significant differences were found between the acceptability of policies targeting direct and indirect energy savings. As expected, push measures were perceived to be more effective and acceptable when revenues are allocated within the energy domain rather than to general funds. Pull measures were evaluated as more effective when they are funded from within the energy domain rather than from general public funds. The way pull measures are funded did not significantly affect their acceptability.
Large-Scale Environmental Knowledge
Authors: Kweon Byoung-Suk , Ellis Christopher D. , Lee Sang-Woo , Rogers George O.
Published: December 2005

This article compares self-reported and objectively measured physical features in a large-scale environment. Environmental perception has been studied through object perception research but little is known about perception in full-scale environments. Also, few studies examine differences between self-reported and objective environments including the potential effects of distance and content. In this study, a questionnaire, satellite imagery, and geographic information system data were used. Results indicate that self-reported environments are different from objective environments. In addition, self-reported responses separate natural and built environments into two different dimensions. Water combines self-reported and objective measurements into a single dimension. Further analysis revealed that content (natural vs. built) and distance (300 ft vs. 1,500 ft) are important factors influencing the relationships between self-reported and objective environmental measurements. By better understanding relationships between self-reported and objective environments, landscape planners and designers can choose the most appropriate data type for analyzing specific planning and design decisions.
Plans, habitation and slum redevelopment
Authors: Chatterji Roma
Published: December 2005

This article describes the process by which governmental technologies such as mapping and enumeration constitute new types of community by looking at housing practices in a slum, Dharavi, in Mumbai. The article is divided into three sections. In the first section present a review of the slum development policies, focusing specifically on the shifting relations between the government and the slum population. It is through this interface that the first attempts at forming collective identities take place in Dharavi. I discuss this in the second section, with special reference to a people's organisation (PROUD) and its constitution of a public voice. The third section returns to the theme of governmental policy from the perspective of politics and I show the relation between different kinds of community through which citizenship may be understood in the volatile aftermath of the riots in Dharavi in 1992–93.
Becoming a man
Authors: Staples James
Published: December 2005

This article, which draws on fieldwork with a community of leprosy-affected people in south India, explores the contrasting ways in which ideas about social completeness might be invoked in different contexts. Following an overview of how notions of ‘personhood’ and ‘adulthood’ in India have thus far been theorised, I go on to examine how my informants managed to construct their identities as ‘children’ in relation to foreign donors, without simultaneously surrendering claims to adult status. Since relationships with various categories of outsiders were only one set of routes through which my informants constituted themselves, the second half of the article focuses on the generational demarcations between the leprosy-affected people who founded the community, and their healthy sons. Ethnographic examples illustrate how there are different ways of becoming a man and an adult, but also that these different ways draw on shared Indian idioms of what it is to be a complete person.
Migration inhibitory factor up-regulates vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 via Src, PI3 kinase, and NFκB
Authors: Amin M. Asif , Haas Christian S. , Zhu Kui , Mansfield Pamela J. , Kim Michael J. , Lackowski Nicholas P. , Koch Alisa E.
Published: November 2005

Cell adhesion molecules are critical in monocyte (MN) recruitment in immune-mediated and hematologic diseases. We investigated the novel role of recombinant human migration inhibitory factor (rhMIF) in up-regulating vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) and their signaling pathways in human MNs. rhMIF-induced expression of VCAM-1 and ICAM-1 was significantly higher compared with nonstimulated MNs. rhMIF induced MN VCAM-1 and ICAM-1 expression in a concentration-dependent manner (P < .05). Antisense oligodeoxynucleotides (ODNs) and inhibitors of Src, PI3K, p38, and NFκB significantly reduced rhMIF-induced MN VCAM-1 and ICAM-1 expression (P < .05). However, Erk1/2 and Jak2 were not involved. Silencing RNA directed against MIF, and inhibitors of Src, PI3K, NFκB, anti–VCAM-1, and anti–ICAM-1 significantly inhibited rhMIF-induced adhesion of HL-60 cells to human dermal microvascular endothelial cells (HMVECs) or an endothelial cell line, HMEC-1, in cell adhesion assays, suggesting the functional significance of MIF-induced adhesion molecules (P < .05). rhMIF also activated MN phospho-Src, -Akt, and -NFκB in a time-dependent manner. rhMIF induced VCAM-1 and ICAM-1 up-regulation in 12 hours via Src, PI3K, and NFκB as shown by Western blotting and immunofluorescence. MIF and MIF-dependent signaling pathways may be a potential target for treating diseases characterized by up-regulation of cell adhesion molecules.
SLAM/SLAM interactions inhibit CD40-induced production of inflammatory cytokines in monocyte-derived dendritic cells
Authors: Réthi Bence , Gogolák Péter , Szatmari Istvan , Veres Ágota , Erdôs Erika , Nagy Laszlo , Rajnavölgyi Éva , Terhorst Cox , Lányi Árpád
Published: November 2005

Signaling lymphocyte activation molecule (SLAM, CD150, or SLAMF1) is a self-ligand receptor on the surface of activated T- and B-lymphocytes, macrophages, and dendritic cells (DCs). Here we examine the effect of SLAM/SLAM interactions on CD40L-induced CD40 signaling pathways in human DCs. CD40L-expressing L929 cells induced DCs to produce interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-12, which was strongly inhibited by coexpression of SLAM on the surface of the L929 cells. Similarly, transfection of DCs with SLAM strongly reduced CD40L-induced IL-12 production. Furthermore, the negative effect of SLAM/SLAM interactions on CD40L-induced DC activation was also detected in the presence of lipopolysaccharide (LPS). LPS-induced IL-12 secretion, however, was not inhibited by SLAM engagement. CD40L-activated DCs affected by exposure to SLAM/SLAM engagement were impaired in their ability to induce differentiation of naive T lymphocytes into interferon-γ (IFN-γ)–producing T-helper 1 (Th1) effector cells. These inhibitory effects were not the result of a general unresponsiveness of DCs to CD40L, as SLAM/SLAM interactions did not prevent CD40L-induced up-regulation of CD83, CD86, or human leukocyte antigen (HLA)–DQ on the surface of DCs. Taken together, the results indicate that SLAM/SLAM interactions inhibit CD40-induced signal transduction in monocyte-derived dendritic cells, an effect that was not detectable in earlier studies using anti-SLAM monoclonal antibodies.
Expression of rearranged TCRγ genes in natural killer cells suggests a minor thymus-dependent pathway of lineage commitment
Authors: Veinotte Linnea Lora , Greenwood Chelsea Pamela , Mohammadi Nastaran , Parachoniak Christine Anna , Takei Fumio
Published: November 2005

Natural killer (NK) cells are thought to develop from common lymphoid progenitors in the bone marrow. However, immature thymocytes also retain NK potential. Currently, the contribution of the thymus-dependent pathway in normal steady-state NK-cell development is unknown. Here, we show that TCRγ genes are rearranged in approximately 5% of neonatal and 1% of adult mouse splenic NK cells, and similar levels are detected in NK cells from TCRβ,δ double-knockout mice, excluding the possibility of T-cell contamination. NK-cell TCRγ gene rearrangement is thymus dependent because this rearrangement is undetectable in nude mouse NK cells. These results change the current view of NK-cell development and show that a subset of NK cells develops from immature thymocytes that have rearranged TCRγ genes.
Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors
Authors: Piqueras Bernard , Connolly John , Freitas Heidi , Palucka Anna Karolina , Banchereau Jacques
Published: November 2005

Host response to viral infection involves distinct effectors of innate and adaptive immunity, whose mobilization needs to be coordinated to ensure protection. Here we show that influenza virus triggers, in human blood dendritic-cell (DC) subsets (ie, plasmacytoid and myeloid DCs), a coordinated chemokine (CK) secretion program with 3 successive waves. The first one, occurring at early time points (2 to 4 hours), includes CKs potentially attracting effector cells such as neutrophils, cytotoxic T cells, and natural killer (NK) cells (CXCL16, CXCL1, CXCL2, and CXCL3). The second one occurs within 8 to 12 hours and includes CKs attracting effector memory T cells (CXCL8, CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11). The third wave, which occurs after 24 to 48 hours, when DCs have reached the lymphoid organs, includes CCL19, CCL22, and CXCL13, which attract naive T and B lymphocytes. Thus, human blood DC subsets carry a common program of CK production, which allows for a coordinated attraction of the different immune effectors in response to viral infection.
TGF-β1 and serum both stimulate contraction but differentially affect apoptosis in 3D collagen gels
Authors: Kobayashi Tetsu , Liu Xiangde , Kim Hui Jung , Kohyama Tadashi , Wen Fu-Qiang , Abe Shinji , Fang Qiuhong , Zhu Yun Kui , Spurzem John R , Bitterman Peter , Rennard Stephen I
Published: December 2005

Apoptosis of fibroblasts may be key for the removal of cells following repair processes. Contraction of three-dimensional collagen gels is a model of wound healing and remodeling. Here two potent inducers of contraction, TGF-β1 and fetal calf serum (FCS) were evaluated for their effect on fibroblast apoptosis in contracting collagen gels. Human fetal lung fibroblasts were cultured in floating type I collagen gels, exposed to TGF-β1 or FCS, and allowed to contract for 5 days. Apoptosis was evaluated using TUNEL and confirmed by DNA content profiling. Both TGF-β1 and serum significantly augmented collagen gel contraction. TGF-β1 also increased apoptosis assessed by TUNEL positivity and DNA content analysis. In contrast, serum did not affect apoptosis. TGF-β1 induction of apoptosis was associated with augmented expression of Bax, a pro-apoptotic member of the Bax/Bcl-2 family, inhibition of Bcl-2, an anti-apoptotic member of the same family, and inhibition of both cIAP-1 and XIAP, two inhibitors of the caspase cascade. Serum was associated with an increase in cIAP-1 and Bcl-2, anti-apoptotic proteins. Interestingly, serum was also associated with an apparent increase in Bax, a pro-apoptotic protein. Blockade of Smad3 with either siRNA or by using murine fibroblasts deficient in Smad3 resulted in a lack of TGF-β induction of augmented contraction and apoptosis. Contraction induced by different factors, therefore, may be differentially associated with apoptosis, which may be related to the persistence or resolution of the fibroblasts that accumulate following injury.
The distance-profile representation and its application to detection of distantly related protein families
Authors: Ku Chin-Jen , Yona Golan
Published: November 2005

Background

Detecting homology between remotely related protein families is an important problem in computational biology since the biological properties of uncharacterized proteins can often be inferred from those of homologous proteins. Many existing approaches address this problem by measuring the similarity between proteins through sequence or structural alignment. However, these methods do not exploit collective aspects of the protein space and the computed scores are often noisy and frequently fail to recognize distantly related protein families.

Results

We describe an algorithm that improves over the state of the art in homology detection by utilizing global information on the proximity of entities in the protein space. Our method relies on a vectorial representation of proteins and protein families and uses structure-specific association measures between proteins and template structures to form a high-dimensional feature vector for each query protein. These vectors are then processed and transformed to sparse feature vectors that are treated as statistical fingerprints of the query proteins. The new representation induces a new metric between proteins measured by the statistical difference between their corresponding probability distributions.

Conclusion

Using several performance measures we show that the new tool considerably improves the performance in recognizing distant homologies compared to existing approaches such as PSIBLAST and FUGUE.
Immunochemical, biomolecular and biochemical characterization of bovine epithelial intestinal primocultures
Authors: Rusu Dorina , Loret Suzanne , Peulen Olivier , Mainil Jacques , Dandrifosse Guy
Published: December 2005

Background

Cultures of enterocytes and colonocytes represent valuable tools to study growth and differentiation of epithelial cells. In vitro models may be used to evaluate passage or toxicity of drugs, interactions of enteropathogenes bacteria strains with intestinal epithelium and other physiologic or pathologic phenomenon involving the digestive tract.

Results

Cultures of bovine colonocytes and jejunocytes were obtained from organoid-enriched preparations, using a combination of enzymatic and mechanical disruption of the intestine epithelium, followed by an isopicnic centrifugation discarding most single cells.

Confluent cell monolayers arising from plated organoids exhibited epithelium typical features, such as the pavement-like structure, the presence of apical microvilli and tight junctions. Accordingly, cells expressed several markers of enterocyte brush border (i.e. maltase, alkaline phosphatase and fatty acid binding protein) as well as an epithelial cytoskeleton component (cytokeratin 18). However, enterocyte primocultures were also positive for the vimentin immunostaining (mesenchyme marker). Vimentin expression studies showed that this gene is constitutively expressed in bovine enterocytes. Comparison of the vimentin expression profile with the pattern of brush border enzymes activities, suggested that the decrease of cell differentiation level observed during the enterocyte isolation procedure and early passages of the primoculture could result from a post-transcriptional de-repression of vimentin synthesis. The low differentiation level of bovine enterocytesin vitrocould partly be counteracted adding butyrate (1–2 mM) or using a glucose-deprived culture medium.

Conclusion

The present study describes several complementary approaches to characterize bovine primary cultures of intestinal cells. Cultured cells kept their morphologic and functional characteristics during several generations.
Kinetic analysis of dynamic 18F-fluoromisonidazole PET correlates with radiation treatment outcome in head-and-neck cancer
Authors: Thorwarth Daniela , Eschmann Susanne-Martina , Scheiderbauer Jutta , Paulsen Frank , Alber Markus
Published: December 2005

Background

Hypoxia compromises local control in patients with head-and-neck cancer (HNC). In order to determine the value of [18F]-fluoromisonidazole (Fmiso) with regard to tumor hypoxia, a patient study with dynamic Fmiso PET was performed. For a better understanding of tracer uptake and distribution, a kinetic model was developed to analyze dynamic Fmiso PET data.

Methods

For 15 HNC patients, dynamic Fmiso PET examinations were performed prior to radiotherapy (RT) treatment. The data was analyzed using a two compartment model, which allows the determination of characteristic hypoxia and perfusion values. For different parameters, such as patient age, tumor size and standardized uptake value, the correlation to treatment outcome was tested using the Wilcoxon-Mann-Whitney U-test. Statistical tests were also performed for hypoxia and perfusion parameters determined by the kinetic model and for two different metrics based on these parameters.

Results

The kinetic Fmiso analysis extracts local hypoxia and perfusion characteristics of a tumor tissue. These parameters are independent quantities. In this study, different types of characteristic hypoxia-perfusion patterns in tumors could be identified.

The clinical verification of the results, obtained on the basis of the kinetic analysis, showed a high correlation of hypoxia-perfusion patterns and RT treatment outcome (p = 0.001) for this initial patient group.

Conclusion

The presented study established, that Fmiso PET scans may benefit from dynamic acquisition and analysis by a kinetic model. The pattern of distribution of perfusion and hypoxia in the tissue is correlated to local control in HNC.
How do caregivers know when to take their child for immunizations?
Authors: Shaw Kate M , Barker Lawrence E
Published: November 2005

Background

Childhood vaccinations help reduce and eliminate many causes of morbidity and mortality among children. The objective of this study was to compare 4:3:1:3:3 (4+ doses of diphtheria and tetanus toxoids and pertussis vaccine, 3+ doses of poliovirus vaccine, 1+ doses of measles-containing vaccine, 3+ doses ofHaemophilus influenzaetype b vaccine, and 3+ doses of hepatitis B vaccine) coverage among children whose caregivers learned by different methods when their child's most recent immunization was needed.

Methods

Between July 2001 and December 2002, a portion of households receiving the National Immunization Survey were asked how they knew when to take the child in for his/her most recent immunization. Responses were post-coded into several categories: 'Doctor/nurse reminder at previous immunization visit', 'Shot card/record', 'Reminder/recall', and 'Other'. Respondents could give more than one answer. Children who did not receive any vaccines, had ≤ 1 visits for vaccinations, or whose caregiver did not provide an answer to the question were excluded from analyses. Chi-square analyses were used to compare 4:3:1:3:3 coverage among 19–35 month old children.

Results

Children whose caregivers indicated that a doctor/nurse told them at a previous immunization visit when to return for the next immunization had significantly greater 4:3:1:3:3 coverage than those who did not choose the response (77.2% vs. 70.1%, p < 0.01). However, no significant difference in coverage was found between households that did/did not indicate that reminder/recalls (71.0% vs. 75.5%, p = 0.24) helped them remember when to take their child for their most recent immunization visit; only borderline significance was found between those that did/did not choose shot cards (70.6% vs. 76.2%, p = 0.07).

Conclusion

A doctor or nurse's reminder during an immunization visit of the next scheduled immunization visit effectively encourages caregivers to bring children in for immunizations, providing an inexpensive and easy way to effectively increase immunization coverage.
Quality of life in post-menopausal osteoporosis
Authors: Bianchi Maria Luisa , Orsini Maria Rosa , Saraifoger Silvia , Ortolani Sergio , Radaelli Giovanni , Betti Simonetta
Published: December 2005

Background

To evaluate the impact of osteoporosis on the patients' quality of life, particularly in the absence of fractures.

Methods

100 post-menopausal women (age 50-85) - 62 with uncomplicated primary osteoporosis and 38 with primary osteoporosis complicated by vertebral fractures; all already treated - were studied using two validated questionnaires: Qualeffo-41 for quality of life in osteoporosis, and Zung for depression. Data were compared to those of 35 controls of comparable age, affected by a different chronic disease (hypothyroidism).

Results

Family history of osteoporosis and T-score of spine were similar in the two subgroups of osteoporotic women. Body mass index, age at menopause and education level were similar in the two subgroups of osteoporotic women and in the control group.

The patients affected by osteoporosis perceived it as a disease affecting their personal life with undesirable consequences: chronic pain (66% of women with fractures and 40% of women without fractures), impaired physical ability, reduced social activity, poor well-being (21% of women without fractures) and depressed mood (42% of women irrespective of fractures). Overall, 41% of the women showed a reduced quality of life. On the contrary, in the control group only 11% reported a reduced quality of life.

Conclusion

The quality of life of osteoporotic patients should be investigated even before fractures, in order to develop appropriate counselling, support and care interventions to help patients develop efficient strategies for accepting the disease and coping with it.
Large mobile thrombus in non-atherosclerotic thoracic aorta as the source of peripheral arterial embolism
Authors: Malyar Nasser M , Janosi Rolf A , Brkovic Zoran , Erbel Raimund
Published: November 2005

The presence of thrombi in the atherosclerotic and/or aneurysmatic aorta with peripheral arterial embolism is a common scenario. Thrombus formation in a morphologically normal aorta, however, is a rare event. A 50 years old woman was admitted to the mergency department for pain, coldness, and anesthesia in the the left foot. She had a 25 years history of cigarette smoking, a history of postmenopausal hormone replacement therapy (HRT), hypercholesterolemia and hyperfibrinogenemia. An extensive serologic survey for hypercoagulability, including antiphospholipid antibodies, and vasculitis disorders was negative. Transesophageal echocardiography revealed a large, pedunculated and hypermobile thrombus attached to the aortic wall 5 cm distal of the left subclavian artery. The patient was admitted to the surgery department, where a 15 cm long fresh, parietal thrombus could be removed from the aorta showing no macroscopic wall lesions or any other morphologic abnormalities.

This case report demonstrates the possibility of evolving a large, pedunculated thrombus in a morphologically intact aorta in a postmenopausal woman with thrombogenic conditions such as hyperfibrinogenemia, hypercholesterolemia, smoking and HRT. For these patients, profiling the individual risk and weighing the benefits against the potential risks is warranted before prescribing HRT.
Primary care use of antipsychotic drugs: an audit and intervention study
Authors: Mortimer Ann M , Shepherd Charles J , Rymer Michael , Burrows Alison
Published: November 2005

Background

Concerns regarding the use of antipsychotic medication in secondary care suggested an examination of primary care prescribing.

Aim

To audit and intervene in the suboptimal prescribing of antipsychotic drugs to primary care patients.

Design of study

Cross-sectional prevalence: subsequent open treatment intervention.

Setting

Seven of the 29 practices in the Eastern Hull Primary Care Trust.

Methods

Criteria for best practice were developed, against which prescribing standards were tested via audit. Patients identified as suboptimally prescribed for were invited to attend an expert review for intervention.

Results

1 in 100 of 53,000 patients was prescribed antipsychotic treatment. Diagnoses indicating this were impossible to ascertain reliably. Half the regimes failed one or more audit criteria, leaving diagnosis aside. Few practices agreed to patients being approached: of 179 invitations sent, only 40 patients attended. Of 32 still taking an antipsychotic drug, 26 required changes. Mean audit criteria failed were 3.4, lack of psychotic disorder diagnosis and problematic side effects being most frequent. Changes were fully implemented in only 16 patients: reasons for complete or partial failure to implement recommendations included the wishes or inaction of patients and professionals, and worsening of symptoms including two cases of antipsychotic withdrawal syndrome.

Conclusion

Primary care prescribing of antipsychotic drugs is infrequent, but most is unsatisfactory. Intervention is hampered by pluralistic reluctance: even with expert guidance, rationalisation is not without risk. Use of antipsychotic drugs in primary care patients whose diagnosis does not warrant this should be avoided.

How this fits in

This study adds to concerns regarding high levels of off-licence use of potentially harmful medication. It adds evidence of major difficulties in rationalizing suboptimal regimes despite expert input. Relevance to the clinician is that it is better to avoid such regimes in the first place especially if there is no clear 'exit strategy': if in doubt, seek a specialist opinion.