bluuebunny/crossref_metadata_2025 huggingface dataset:
Interleukin 25 in Allergic Airway Inflammation
Authors: Tamachi Tomohiro , Maezawa Yuko , Ikeda Kei , Iwamoto Itsuo , Nakajima Hiroshi
Published: June 2006

T helper 2 (Th2) cells induce allergic inflammation through the production of cytokines such as interleukin (IL)-4, IL-5 and IL-13. Recently, it has been demonstrated that a novel IL-17 family cytokine IL-25 (IL-17E) is a product of activated Th2 cells and mast cells. Interestingly, when systemically administered to mice, IL-25 induces IL-4, IL-5 and IL-13 production from undefined non-T/non-B cells and then induces Th2-type immune responses such as blood eosinophilia and increased serum immunoglobulin E levels. In addition, we have recently shown that IL-25 mRNA is expressed in the lung after an inhaled antigen challenge in sensitized mice and that neutralization of the produced IL-25 by soluble IL-25 receptor decreases antigen-induced eosinophil and CD4+ T cell recruitment into the airways. Moreover, we have shown that the enforced expression of IL-25 in the lung significantly enhances antigen-induced Th2 cytokine production and eosinophil recruitment into the airways, and that the IL-25-mediated enhancement of antigen-induced eosinophil recruitment is inhibited by the depletion of CD4+ T cells. Thus, it is suggested that IL-25 plays an important role in enhancing allergic airway inflammation by a CD4+ T-cell-dependent mechanism.
Intraductal Papillary Mucinous Neoplasms of the Pancreas
Authors: Al-Refaie W.B. , Choi E.A. , Tseng J.F. , Tamm E.P. , Lee J.H. , Lee J.E. , Evans D.B. , Pisters P.W.T.
Published: June 2006

The introduction of the exocrine pancreatic classification by the World Health Organization and improvements in pancreatic imaging have led to an improved understanding of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. As a result, IPMNs of the pancreas are increasingly being recognized as a separate disease entity. IPMNs are characterized by the cystic dilatation of the pancreatic duct and its branches, with papillary projections. There are three histological subtypes of IPMNs: main duct, branch duct, and mixed. The degree of atypia ranges from adenoma to frank invasive carcinoma. The lymph nodes are involved considerably less frequently than they are in pancreatic adenocarcinoma. Most patients are symptomatic at diagnosis and require a diagnostic workup similar to that for patients with pancreatic adenocarcinoma. Although some investigators continue to advocate total pancreatectomy, the evidence in support of this is decreasing. Partial pancreatectomy remains the treatment option. Intraoperative assessment of the resection surgical margins is an important component of surgical resection. Additionally, controversy also exists regarding the nature of the follow-up and the need for adjuvant chemoradiation therapy in the patient. Unlike ductal adenocarcinomas, IPMNs follow a relatively indolent course; the 5-year survival rate in patients with invasive IPMNs is 57%. A mural nodule and a main pancreatic duct diameter greater than 5 mm have been found to be predictors of malignancy.
Estimation of Radiation Dose during Diagnostic X-Ray Examinations of Newborn Babies and 1-Year-Old Infants
Authors: Brindhaban A. , Eze C.U.
Published: June 2006

Objective: It was the aim of this study to investigate radiation doses for commonly performed paediatric X-ray examinations (skull, chest, abdomen and pelvis) in public hospitals in Kuwait in order to establish national reference or guidance dose levels. Materials and Method: Exposure factors used for six commonly performed X-ray examinations – antero-posterior (AP) chest, lateral chest, AP abdomen, AP skull, lateral skull and AP pel vis – were obtained from various hospitals, and entrance surface doses (ESD) were measured using a Victoreen model 660 survey meter. Effective doses (E) and the corresponding risk of developing fatal malignancies were calculated using published conversion factors and methods recommended by the International Commission of Radiological Protection for newborn babies to 1-year-old infants. Results: The range of ESD values was 26– 668 µGy for newborn babies and 40–700 µGy for 1-year- old infants. The range of E values was about 4–150 µSv for the two age groups. The risk of developing long-term stochastic effects due to radiation exposure ranges between 0.6 and 23.4 per million. Conclusion: The range of ESD values, E values and risk of development of fatal malignancies obtained in this study can be used as a guide for the risk-benefit analysis of an X-ray examination for newborn babies and 1-year-old infants. Tube voltages used for these examinations should be kept above 60 kV, whenever possible, to minimise the radiation dose.
Effort-Induced Venous Thrombosis of the Upper Limbs
Authors: Youssef M.Y.Z. , Al Taweel T. , Asfar S. , Abdella N.
Published: June 2006

Objective: To report 3 patients who presented with effort-induced thrombosis of the upper limbs. Case Presentations and Intervention: The 1st patient presented with a 2-week history of fever, shortness of breath, and increasing swelling of the neck after strenuous manual work. The 2nd patient presented with a 2-day history of pain, swelling, and discolouration of the right upper limb following a session of intense weight lifting. The 3rd patient presented with a 2-day history of swelling, pain, and discolouration of the left upper limb due to repeated rotatory movements of the arm at work. In all 3 cases, the diagnosis of effort-induced thrombosis of subclavian and axillary veins was made. In the 1st case, the lesion was bilateral and complicated by superior vena cava obstruction. In the 2nd and in the 3rd case, right and left subclavian veins were thrombosed, respectively. After consulting the vascular team, anticoagulation therapy was initiated in all 3 cases. The patients described showed gradual recovery with eventual recanalization of the thrombosed veins on follow-up. Conclusions: These cases indicate the need to consider thrombosis of the subclavian vein as a part of the differential diagnosis in a patient with a history of strenuous manual work. Therapeutic options include immediate anticoagulation or thrombolysis, while vascular surgery should remain an option for cases with underlying anatomical anomalies.
Penile Zipper Injury
Authors: Nakagawa Tatsuo , Toguri Allan G.
Published: June 2006

Objective: To report 2 cases with pediatric penile trauma due to penile zipper injury. Clinical Presentation and Intervention: Two boys presented to the emergency service because of penile zipper injury. The zipper was cut away and removed from the foreskin by cutting the median bar of the sliding piece of the zipper and the zipper teeth with a bone cutter. After opening the zipper teeth, the zipper fell apart, which allowed its removal from their foreskin. There was minimal trauma to the foreskin and the boys were sent home on the same day. Conclusion: Penile entrapment in a zipper is a presentation that may be seen in any emergency department. The 2 boys were treated successfully by cutting the median bar of the sliding piece of the zipper.
Thermal Reactions of Blood Vessels in Vascular Stroke and Heatstroke
Authors: Thulesius Olav
Published: June 2006

Research on the pathophysiology and treatment of brain damage with special focus on thermal vascular responses is the subject of this minireview. Interruption of cerebral blood supply by vascular obstruction, temporary cardiac arrest or hyperthermia causes a sudden attack of vascular stroke or heatstroke with serious consequences. It may not induce immediate cell death, but can precipitate a complex biochemical cascade leading to a delayed neuronal loss. When testing thermal vasomotor responses by stepwise cooling of isolated carotid arteries, a temperature-proportional dilatation was observed while heating induced the opposite response: a marked vasoconstriction. General hyperthermia with an increased oxygen demand combined with a reduction of blood supply therefore is a serious consequence. At the cellular level an important mechanism involving hyperthermia is the temperature-dependent regulation of K+ channel tone of vascular smooth muscle. Further, their inhibition through temperature elevation causes vasoconstriction. In heatstroke, which can induce platelet aggregation and the release of the vasoconstrictor serotonin, arterial cooling attenuates this response. General hypothermia is induced to prevent or attenuate neurological damage in stroke. The procedure is not without serious side effects. Therefore, rapid institution of selective brain cooling has been considered in adults and in infants with postpartum encephalopathy.
Estrogen, Cognitive Function and Negative Symptoms in Female Schizophrenia
Authors: Ko Young-Hoon , Joe Sook-Haeng , Cho Woong , Park Jeong-Hyun , Lee Jung-Jae , Jung In-Kwa , Kim Leen , Kim Seung-Hyun
Published: June 2006

The aim of this study was to evaluate the relationship of serum reproductive hormone levels with cognitive function and negative symptoms in schizophrenic women during the follicular phase of the menstrual cycle. Thirty-five women with chronic schizophrenia who had minimal positive symptoms participated in this study. We evaluated the correlation of serum reproductive hormone levels with the Scale for the Assessment of Negative Symptoms (SANS) and cognitive function tests such as the Immediate Visual Recognition Scale, Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Tests A and B, and Digit Symbol Test. The patients were divided into two subgroups (low estradiol group and normal estradiol group) using the normal serum reference range for estradiol. Significant correlation between SANS subcategories, such as Alogia and Attention Impairment, and estradiol were found. Moreover, significant relationships between the estradiol level and the Oral Fluency Test, List Recall Scale with List Acquisition Scale, Trail Making Test B and Digit Symbol Test were observed. In the low estradiol group, the SANS scores, except for Anhedonia-Asociality and Avolition-Apathy, were significantly higher than those in the normal estradiol group. Patients in the low estradiol group had a significantly lower performance in the cognitive function tests, except Visual Recognition Scale, when compared to patients in the normal estradiol group. These results suggest that for schizophrenic women of reproductive age, lower levels of estrogen are associated with more severe negative symptomatology as well as reduced performance in cognitive function, especially verbal performance and executive functioning.
Anti-Inflammatory Activity of Thymol: Inhibitory Effect on the Release of Human Neutrophil Elastase
Authors: Braga Pier Carlo , Dal Sasso Monica , Culici Maria , Bianchi Tiziana , Bordoni Luca , Marabini Laura
Published: June 2006

Elastase, a serine proteinase released by activated human neutrophils, can degrade a wide variety of biomacromolecules including elastin, and is considered a marker of inflammatory diseases. As the logical strategy to protect tissue is to inhibit excessive elastase activity, experimental and clinical researches have concentrated on trying to find efficient elastase inhibitors. As thymol, one of the major components of thyme oil with a phenolic structure, has been credited with a series of pharmacological properties, that include antimicrobial and antioxidant effects, the aim of this study was to explore whether it can also interfere with the release of elastase by human neutrophils stimulated with the synthetic chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (fMLP). After the neutrophils were incubated with increasing amounts of thymol (2.5, 5, 10, 20 µg/ml), elastase release was initiated by fMLP and measured using MeO-Suc-Ala-Ala-Pro-Val-MCA. The results showed that thymol inhibited fMLP-induced elastase release in a concentration-dependent manner, with the effects of 10 and 20 µg/ml being statistically significant. The behavior of cytosolic calcium mobilization revealed by fura-2 closely resembled that of elastase, thus suggesting that they may be related. The hydrophobic nature of thymol means that it can approach ion channel proteins through the lipid phase of the membrane, alter the local environment of calcium channels and thus inhibit capacitative calcium entry. In brief, thymol inactivates calcium channels machinery, thus triggering a corresponding reduction in elastase. The antibacterial and antimycotic activity of thymol is already well known, but our findings that it inhibits elastase extend our knowledge of the anti-inflammatory activity of this interesting molecule that is already credited with antioxidant activity. These two latter characteristics make thymol a molecule that can have helpful effects in controlling the inflammatory processes present in many infections.
Addition of a Short Course of Chemotherapy Did Not Improve Outcome in Patients with Localized Marginal B-Cell Lymphoma of the Orbit
Authors: Avilés Agustin , Neri Natividad , Calva Angel , Huerta-Guzmán Judith , Cleto Sergio , Nambo M. Jesús
Published: June 2006

Objectives: Primary orbital malignant lymphoma (POML) is a rare malignancy, thus treatment remains to be defined. The present study was designed to define if the use of radiotherapy is sufficient in these patients or if the use of adjuvant chemotherapy would improve the outcome. Methods: Between 1983 and 1995, 98 previously untreated patients diagnosed with POML, stage IE, were randomly allocated to receive either radiotherapy (34–40 Gy) or the same radiotherapy combined with chemotherapy including anthracycline. The median follow-up was 11.4 years (range 9.8–10.8 years). Results: Complete response was similar in both arms: 98% (95% confidence interval, CI: 89–100%) in the radiotherapy arm, and 100% (95% CI: 89–100%) in the combined therapy group. At a median follow-up of 16.4 years, event-free survival was 94% (95% CI: 87–100%) and 85% (95% CI: 88–100%), respectively. Overall survivals were: 96% (95% CI: 89–99%) and 91% (95% CI: 83–98%). No statistical differences were found. Acute and late toxicities were mild. Conclusions: The addition of chemotherapy is of no further benefit, since the results did not differ, thus, radiotherapy will be considered as the treatment of choice in POML patients.
An In-Depth Review of the Evidence Linking Dietary Salt Intake and Progression of Chronic Kidney Disease
Authors: Jones-Burton Charlotte , Mishra Shiraz I. , Fink Jeffrey C. , Brown Jeanine , Gossa Weyinshet , Bakris George L. , Weir Matthew R.
Published: June 2006

Background: Dietary salt has been debated for decades as having a potentially deleterious influence on human health. Objectives: To determine the quality of research and the relationship between dietary salt and markers for progression of kidney disease. Methods: Data sources included 7 electronic databases comprehensively searched for literature published between January 1, 1966, and August 31, 2004, and a manual search of bibliographies of relevant papers, and consultation with experts in the field. Differences between the paired reviewers were reconciled through consensus or by a content expert. Results: Sixteen studies met the inclusion-exclusion criteria and were identified for review; however, the study methodologies were extremely heterogeneous. Conclusions commonly cited in the studies include: variations in salt consumption are directly correlated with albuminuria, and an increase in salt consumption is associated with an acute increase in glomerular filtration rate, while a reduction in salt consumption may slow the rate of renal function loss. Conclusions: The available published information, while highly variable in methods and quality, suggests that variations in dietary salt consumption directly influence albuminuria, with increasing salt intake associated with worsening albuminuria; however, results are inadequate and conflicting on the effects of dietary salt consumption on renal function, especially over a prolonged time. There was no evidence of a detrimental effect of reduced salt intake. On the other hand, there is consistent experimental evidence to link increased salt exposure with kidney tissue injury. On the basis of these data, we believe that dietary salt restriction should be considered in patients with chronic kidney disease.
VEGF Activates Receptor-Operated Cation Channels in Human Microvascular Endothelial Cells
Authors: Cheng H.-W. , James A.F. , Foster R.R. , Hancox J.C. , Bates D.O.
Published: June 2006

Objective—

Vascular endothelial growth factor (VEGF) exerts many of its effects by stimulating endothelial calcium influx, but little is known about channels mediating VEGF-induced cation entry. The aim of this study was to measure and characterize for the first time the VEGF-activated cation current in human microvascular endothelial cells (HMVECs).

Methods and Results—

Whole-cell patch-clamp recordings were made from HMVECs. During applied voltage ramps, VEGF activated a current that reversed at 0 mV, was sensitive to gadolinium, and required extracellular cations. Noise analysis yielded a single-channel conductance of 27 pS. The current was not dependent on intracellular calcium stores, and was not blocked by inositol triphosphate (IP
3
) receptor or serine/threonine kinase inhibition but was partially inhibited by flufenamic acid. A similar current was activated by 1-oleoyl-2-acetyl-
sn
-glycerol (OAG), a membrane-permeant analog of diacylglycerol (DAG). To determine whether VEGF could activate recombinant ion channels with similar properties, we investigated the effect of VEGF on Chinese hamster ovary cells cotransfected with VEGFR2 and the canonical transient receptor potential (TRPC) channels, TRPC3 or TRPC6. VEGF induced a similar current to that described above in VEGFR2-TRPC3 and VEGFR2-TRPC6 cells but not in cells transfected with either cDNA alone.

Conclusions—

VEGF activates a receptor-operated cation current in HMVECs and OAG can activate directly a similar current in these cells. VEGF is also able to activate heterologously expressed TRPC3/6 channels through VEGFR2.
Diabetic Vascular Disease
Authors: Goldberg Ira J. , Dansky Hayes M.
Published: June 2006

It is well known that humans with diabetes have more atherosclerosis and its complications. The causes of this relationship are, however, unclear. Although recent data show that improved glycemic control reduces arterial disease in type 1 diabetes, other studies have shown that subjects with “prediabetes” have more cardiovascular disease before the development of hyperglycemia. Thus, either hyperglycemia and/or lack of insulin actions are toxic to arteries, or metabolic derangements exclusive of hyperglycemia are atherogenic. For >50 years animal models of diabetes and atherosclerosis have been used to uncover potential mechanisms underlying diabetes associated cardiovascular disease. Surprisingly, diabetes alone increases vascular disease in only a few select animal models. Increased atherosclerosis has been found in several animals and lines of genetically modified mice; however, diabetes often also leads to greater hyperlipidemia. This makes it difficult to separate the toxic effects of insulin lack and/or hyperglycemia from those caused by the lipids. These studies are reviewed, as well as more recent investigations using new methods to create diabetic-atherosclerotic models.
Role of Bone Marrow–Derived CC-Chemokine Receptor 5 in the Development of Atherosclerosis of Low-Density Lipoprotein Receptor Knockout Mice
Authors: Potteaux Stéphane , Combadière Christophe , Esposito Bruno , Lecureuil Cedric , Ait-Oufella Hafid , Merval Régine , Ardouin Patrice , Tedgui Alain , Mallat Ziad
Published: June 2006

Objective—

CC chemokine receptor CCR5 is expressed by atheroma-associated cells and could mediate leukocyte attraction into developing lesions. We examined the role of bone marrow-derived CCR5 in the development of atherosclerotic lesions after 8, 12, or 35 weeks of high-fat diet.

Methods and Results—

Low-density lipoprotein-receptor (LDLr)-deficient mice were lethally irradiated and transplanted with CCR5
+/+
or CCR5
−/−
bone marrow. After 8 weeks of fat diet, CCR5 deficiency in leukocytes led to 30% decrease of macrophage accumulation within the fatty streak (
P
<0.05), with no change in lesion size. After 12 weeks of fat diet, CCR5 deficiency also resulted in 30% decrease of plaque-macrophage accumulation (
P
<0.005), associated with 16% reduction in lesion size in the aortic sinus (
P
=0.13), despite a significant increase in total cholesterol levels (
P
=0.03). Lesions with CCR5 deficiency showed 52% reduction in matrix metalloproteinase (MMP)-9 expression (
P
=0.02) and 2-fold increase in collagen accumulation (
P
<0.0001). These changes were associated with a significant increase of interleukin (IL)-10 mRNA expression in spleens of CCR5
−/−
mice compared with CCR5
+/+
controls. In addition, we found enhanced IL-10 production by CCR5-deficient peritoneal macrophages and decreased tumor necrosis factor (TNF)-α production by CCR5
−/−
T cells in comparison with CCR5
+/+
controls. CCR5
−/−
and CCR5
+/+
reconstituted animals showed no differences in plaque size or composition after 35 weeks of high-fat diet despite the persistent absence of CCR5 in plaques of mice reconstituted with CCR5
−/−
bone marrow.

Conclusion—

Bone marrow-derived CCR5 favors the development of an inflammatory and collagen-poor plaque phenotype in association with decreased macrophage-derived IL-10 and enhanced T cell-derived TNF-α. These effects are not sustained in the very advanced stages of atherosclerosis.
Joint Linkage and Association of Six Single-Nucleotide Polymorphisms in the Factor XIII-A Subunit Gene Point to V34L As the Main Functional Locus
Authors: de Lange Marlies , Andrew Toby , Snieder Harold , Ge Dongliang , Futers T. Simon , Standeven Kristina , Spector Tim D. , Grant Peter J. , Ariëns Robert A.S.
Published: June 2006

Objective—

Activated factor XIII (FXIII) crosslinks fibrin to enhance the mechanical strength of a blood clot and increase its resistance to fibrinolysis. The prevalence of a common variant in the FXIII-A gene (V34L) has been reported to be lower in patients with myocardial infarction and ischemic stroke than in controls, suggesting a protective role for this polymorphism in vascular diseases. The current study investigated 6 single-nucleotide polymorphisms (SNPs) within the FXIII A-subunit gene to locate functional polymorphism(s) responsible for variation in FXIII activation.

Methods and Results—

A total of 201 dizygotic twin pairs were genotyped for 1 promoter and all common nonsynonymous coding polymorphisms in the FXIII A-subunit gene: −246G>A, V34L, Y204F, P564L, V650I, and E651Q. Tests of linkage, association, and combined linkage and association were performed using QTDT software. Significant linkage to the V34L polymorphism (
P
=5×10
−12
) as well as association (
P
=3×10
−49
) was observed. Adjusting for association while performing linkage made the linkage signal disappear for the V34L polymorphism (from χ
2
=47.55,
P
=5×10
−12
to χ
2
=1.30,
P
=0.25). Only haplotypes containing the 34L allele showed association with FXIII activation.

Conclusion—

Testing multiple SNPs in the FXIII A-subunit gene indicates that V34L is the main functional polymorphism influencing FXIII activation.
Diabetes Promotes Cardiac Stem Cell Aging and Heart Failure, Which Are Prevented by Deletion of the p66
shc
Gene
Authors: Rota Marcello , LeCapitaine Nicole , Hosoda Toru , Boni Alessandro , De Angelis Antonella , Padin-Iruegas Maria Elena , Esposito Grazia , Vitale Serena , Urbanek Konrad , Casarsa Claudia , Giorgio Marco , Lüscher Thomas F. , Pelicci Pier Giuseppe , Anversa Piero , Leri Annarosa , Kajstura Jan
Published: June 2006

Diabetes leads to a decompensated myopathy, but the etiology of the cardiac disease is poorly understood. Oxidative stress is enhanced with diabetes and oxygen toxicity may alter cardiac progenitor cell (CPC) function resulting in defects in CPC growth and myocyte formation, which may favor premature myocardial aging and heart failure. We report that in a model of insulin-dependent diabetes mellitus, the generation of reactive oxygen species (ROS) leads to telomeric shortening, expression of the senescent associated proteins p53 and p16
INK4a
, and apoptosis of CPCs, impairing the growth reserve of the heart. However, ablation of the p66
shc
gene prevents these negative adaptations of the CPC compartment, interfering with the acquisition of the heart senescent phenotype and the development of heart failure with diabetes. ROS elicit 3 cellular reactions: low levels activate cell growth, intermediate quantities trigger cell apoptosis, and high amounts initiate cell necrosis. CPC replication predominates in diabetic p66
shc−/−
, whereas CPC apoptosis and myocyte apoptosis and necrosis prevail in diabetic wild type. Expansion of CPCs and developing myocytes preserves cardiac function in diabetic p66
shc−/−
, suggesting that intact CPCs can effectively counteract the impact of uncontrolled diabetes on the heart. The recognition that p66
shc
conditions the destiny of CPCs raises the possibility that diabetic cardiomyopathy is a stem cell disease in which abnormalities in CPCs define the life and death of the heart. Together, these data point to a genetic link between diabetes and ROS, on the one hand, and CPC survival and growth, on the other.
Intrinsic Activated Microglia Map to the Peri-infarct Zone in the Subacute Phase of Ischemic Stroke
Authors: Price Christopher J.S. , Wang Dechao , Menon David K. , Guadagno Joe V. , Cleij Marcel , Fryer Tim , Aigbirhio Franklin , Baron Jean-Claude , Warburton Elizabeth A.
Published: June 2006

Background and Purpose—

Microglial activation is an important component of the neuroinflammatory response to ischemic stroke. Experimental studies have outlined such patterns temporally and spatially. In vivo studies in stroke patients have relied on positron emission tomography and (R)-PK11195, a ligand that binds peripheral benzodiazepine binding sites. In this study we sought to establish temporal and spatial patterns of microglial activation in ischemic stroke with particular emphasis on a defined peri-infarct zone.

Methods—

Using this technique, we studied carotid territory ischemic stroke patients in 3 time windows up to 30 days after ictus. Controls were studied in a single session. [
11
C](R)-PK11195 injection was followed by 3-dimensional acquisition over 60 minutes. Cerebral blood volume (CBV) was measured afterward with the use of standard C
15
O paradigms. Analysis employed the reference tissue model in which ipsilateral cerebellum was used to generate parametric binding potential maps corrected for CBV. Data were coregistered to T1-based MRI. Using control data to identify 99% confidence limits, a region of interest analysis was applied to identify significant binding in core infarction, contralateral hemisphere, and within a defined peri-infarct zone.

Results—

Four patients (mean age, 66 years) were imaged across 9 sessions. Four age-matched controls were studied. Within this model, ipsilateral cerebellum was validated as a reference tissue. With the use of control-derived confidence limits and correction for CBV, significant binding potential rises were identified beyond 72 hours and extending to 30 days in core infarction, contralateral hemisphere, and peri-infarct zone.

Conclusions—

In ischemic stroke patients, minimal activation of microglia is seen before 72 hours. Beyond this, binding potential rises in core infarction, peri-infarct zone, and contralateral hemisphere to 30 days. This may represent a therapeutic opportunity that extends beyond time windows traditionally reserved for neuroprotection.
Alteplase at 0.6 mg/kg for Acute Ischemic Stroke Within 3 Hours of Onset
Authors: Yamaguchi Takenori , Mori Etsuro , Minematsu Kazuo , Nakagawara Jyoji , Hashi Kazuo , Saito Isamu , Shinohara Yukito
Published: June 2006

Background and Purpose—

Based on previous studies comparing different recombinant tissue plasminogen activator (rt-PA) doses, we performed a clinical trial with 0.6 mg/kg, which is lower than the internationally approved dosage of 0.9 mg/kg, aiming to assess the efficacy and safety of alteplase in acute ischemic stroke for the Japanese.

Methods—

Our prospective, multicenter, single-arm, open-label trial was designed with a target sample size of 100 patients. The primary end points were the proportion of patients with a modified Rankin Scale (mRS) score of 0 to 1 at 3 months and the incidence of symptomatic intracranial hemorrhage (sICH) within 36 hours. Thresholds for these end points were determined by calculating 90% CIs of weighted averages derived from published reports. The protocol was defined according to the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA stroke study with slight modifications.

Results—

Among the 103 patients enrolled, 38 had an mRS of 0 to 1 at 3 months; this proportion (36.9%) exceeded the predetermined threshold of 33.9%. sICH within 36 hours occurred in 6 patients; this incidence (5.8%) was lower than the threshold of 9.6%.

Conclusions—

In patients receiving 0.6 mg/kg alteplase, the outcome and the incidence of sICH were comparable to published data for 0.9 mg/kg. These findings indicate that alteplase, when administered at 0.6 mg/kg to Japanese patients, might offer a clinical efficacy and safety that are compatible with data reported in North America and the European Union for a 0.9 mg/kg dose.
Hospital
Authors: Turner Bryan S.
Published: June 2006

Hospitals are traditional sites, not only of care, but of knowledge production. The word ‘hospital’ is derived from ‘hospitality’, and is also associated with ‘spital’, ‘hotel’ and ‘hospice’. In medieval society, the hospice was a place of rest, security and entertainment. The Knights Hospitallers were an order of military monks that took its historical origin from a hospital founded in Jerusalem in 1048. Before the rise of the modern research hospital, these spitals had a more general function as charitable institutions for the care and maintenance of the aged, infirm and impoverished. Hospitals were important in the historical emergence of the university, but with the dominance of bio-medical sciences medical faculties have become increasingly separated geographically and administratively from other faculties. Medical research is dominated by private corporations and increasingly medical knowledge exists outside the conventional procedures and norms of scientific research.
The Political
Authors: Valentine Jeremy
Published: June 2006

This article looks at the problems of the co-determination of the political within western metaphysics and political reflection, and considers solutions that are figured in terms of failure and incompletion. The focus is on the relation of the political to political modernity, its defenders and attackers, and those who seek to overcome the opposition.
Religion
Authors: Turner Bryan S.
Published: June 2006

The emergence of a science of religion and religions in which the sacred became a topic of disinterested, objective inquiry was itself an important statement about the general character of social change and can be taken as an index of secularization. It implies a level of critical self-reflexive scrutiny in society. In the West, the study of ‘religion’ as a topic of independent inquiry was initially undertaken by theologians who wanted to understand how Christianity could be differentiated from other religions. The problem of religious diversity had arisen as an inevitable consequence of colonial contact with other religious traditions and with phenomena that shared a family resemblance with religion, such as fetishism, animism and magic. The science of religion implies a capacity for self-reflection and criticism, and it is often claimed that other religions do not possess such a science of religion. While different cultures give religion a different content, Christianity was defined as a world religion. In Hegel's dialectical scheme, the increasing self-awareness of the Spirit was a consequence of the historical development of Christianity. The contemporary scientific study of religion and religions is confronted by significant epistemological problems that are associated with globalization, and the traditional question about the nature of religion has acquired a new intensity.
Information
Authors: Yoshimi Shunya
Published: June 2006

Although the concept of information is an inherently qualitative entity implying the capacity for meaning creation, in the historical development of this concept there has been a consistent emphasis on quantitative aspects. The generalization of the information concept from a specialized military term to a concept of broad social application occurred during the period when society as a whole became militarized in the 1930s and 1940s. After the Second World War, with the development of systematic information theory and the spread of computers in society, the military associations of the information concept gradually became obscured. But the popularity of information society theory in Japan and the USA indicates a need to review the military associations of its key concept. Today, with the development and spread of numerous global and local media, the information phenomena are experienced in a manner that far outstrips the narrow confines of the concept's history. So the concept of information needs to be understood as a field of struggle in which different definitions confront each other leading to the creation of new practices and alternative concepts.
Life (Vitalism)
Authors: Lash Scott
Published: June 2006

This entry is about the concept of vitalism. The currency of vitalism has reemerged in the context of the changes in the sciences, with the rise of ideas of uncertainty and complexity, and the rise of the global information society. This is because the notion of life has always favoured an idea of becoming over one of being, of movement over stasis, of action over structure, of flow and flux. The global information order seems to be characterized by ‘flow’. There are three important generations of modern vitalists. There is a generation of 1840–45 including Nietzsche and the sociologist Tarde; the generation of 1860 including the philosopher Bergson and the sociologist Simmel; and the generation of 1925–33 including Deleuze, Foucault and Negri. Vitalist or neo-vitalist themes are particularly useful in the analysis of life itself, but thinkers such as Donna Haraway and Katharine Hayles put things in reverse. They understand not the media in terms of life, but life in terms of media. Thus a mediatic principle or algorithmic principle also structures life. If classical vitalism conceives of life as flow and in opposition to the structures that would contain and stop it, then neo-vitalism would seem to have its roots in something like a media or information heuristic. Thus there is talk today that ‘information is alive’.
Complexity
Authors: Urry John
Published: June 2006

The term ‘complexity’ has recently sprung into the physical and social sciences, humanities and semi-popular writings. ‘Complexity’ practices are constituted as something of a self-organizing global network that is spreading ‘complexity’ notions around the globe. There is a new ‘structure of feeling’ that complexity approaches both signify and enhance. Such an emergent structure of feeling involves a greater sense of contingent openness to people, corporations and societies, of the unpredictability of outcomes in time–space, of a charity towards objects and nature, of the diverse and non-linear changes in relationships, households and persons, and of the sheer increase in the hyper-complexity of products, technologies and socialities.
Translation
Authors: Sakai Naoki
Published: June 2006

Translation is an act of articulation that takes place in the social topos of difference or incommensurability. The topos of difference, to which translation is a response, is anterior to the conceptual difference of species or particularities. Yet, translation is often represented as a process of establishing equivalence according to the model of communication. This misapprehension of translation derives from the confusion of the act of translation with its representation. By representing translation that is unrepresentable in itself through the schema of co-figuration, the representation of translation inscribes and re-inscribes the twin figures of languages between which a transfer of information is supposed to have taken place. This whole regime organized around the schema of co-figuration is a historical construct of modernity that has worked powerfully to project national/ethnic languages and the international world, only within which national languages are possible. Our task is to historicize this regime of translation.
Space
Authors: Thrift Nigel
Published: June 2006

The turn to space is best understood as part of a more general struggle to produce a material thinking that has preoccupied social theory over the last 20 years or so. Its effect has been to multiply both the number of inhabitations that are understood to exist and the sensory registers through which they can be characterized. Most particularly, this proliferation of inhabitations has meant that nearness has been replaced by distribution as a guiding metaphor and ambition. The paper is in three parts. Using the work of Julie Mehretu as a guide, the first part considers the different ways in which space makes a difference. The second part then uses three vignettes to understand the range of spaces that can be produced and how they become attuned. Finally, there is a brief conclusion.
Science
Authors: Roberts Celia , Mackenzie Adrian
Published: June 2006

How could social scientists and cultural theorists take responsibility in engaging with science? How might they develop an experimental sensibility to the links between the production of knowledge and the production of existence or forms of life? Critically outlining key fields in the social and cultural studies of science, we interrogate a number of approaches to these questions. The first approach tries to make sense of how science operates in relation to economic, political and cultural forces. The second analyses science as a form of embodied work or practice. The third engages with science as collaborative-collective elaboration of events, ranging across cultural theory, contemporary art and participant ethnographies. This outline sketches a vector of responsibility across this diverse range of engagements, suggesting that contemporary movements between science and other knowledges constitute ethical and political imperatives.
Library
Authors: Cubitt Sean
Published: June 2006

The modern library derives from a vision of public service developed in the 19th century. At various times in the past a commercial service, an educational resource, a religious domain and a political institution, the library today exists in various forms, including all these but in addition the professional libraries held by law firms and scientific or technological associations, multimedia lending libraries and certain areas of the world-wide web.
Legislating the Good
Authors: Glanzer Perry L. , Milson Andrew J.
Published: June 2006

In this article, the authors trace the historical context of character education legislation in the United States, analyze and evaluate current legislative trends, and discuss the inherent dangers in legislating the good. The survey concludes that at no other time in history have Americans attempted to legislate such a specific vision of character education. The authors evaluate this legislation using the criteria of local choice, programmatic integration, comprehensiveness, community involvement, K-12 implementation, and allocation of staff development resources. Their evaluation reveals that few state laws meet these criteria and that some laws even contradict the spirit of comprehensive character education. They conclude that these inadequacies are fatal flaws in current attempts to legislate character.
Accuracy of Noninvasive Core Temperature Measurement in Acutely Ill Adults: The State of the Science
Authors: Hooper Vallire D. , Andrews Jeannette O.
Published: June 2006

Accurate temperature measurement is critical to the assessment and management of temperature fluctuation in the acutely ill adult. Unfortunately, an accurate, noninvasive method to measure core temperature has yet to be established, and current instruments produce a wide range of temperatures for any given patient. This article provides an integrative review of studies comparing selected invasive and noninvasive temperature measurement methods in acutely ill, hospitalized adult patients. Medline and CINAHL databases were searched to locate published studies on temperature measurement in the adult hospitalized patient. A partial list of primary search terms included core temperature measurement, oral temperature measurement, temporal artery thermometry, and tympanic thermometers. Studies that were data based and included comparison of a tympanic, temporal artery, and/or oral noninvasive temperature measurement to a pulmonary artery or esophageal invasive core measurement in an adult population were included in the analysis. The search method produced 223 publications and abstracts for initial review; 23 (10%) met the inclusion criteria. The only study evaluating the use of temporal artery thermometry in the adult population found the instrument to be unreliable. Results also indicate that high-quality evidence supporting the accuracy of tympanic thermometry, the preferred instrument for noninvasive core temperature measurement in many acute care settings, is lacking, and in fact, the most recent high-quality studies evaluating the accuracy of this instrument fail to show support for its use. Evidence does, however, support the use of oral thermometry as an accurate means of temperature assessment in the adult, acutely ill population.
Integrating Molecular Genetics Analyses Into Clinical Research
Authors: Schutte Debra L. , McCarthy Ann Marie , Floria-Santos Milena , Hanrahan Kirsten , Murray Jeffrey C. , Kleiber Charmaine
Published: June 2006

The integration of molecular genetics approaches into the study of complex health phenomena is an increasingly important and available strategy for researchers across the health science disciplines. Pain sensation and response to painful stimuli are examples of complex health phenomena that are particularly amenable to molecular genetics approaches. Both human and animal model research suggests that differences in these responses may be related, in part, to variation in the genes that modulate sensation and behavior. The authors are currently managing a large cross-disciplinary research effort to identify child characteristics, including genotypes, that predict the degree of distress displayed by children following a painful medical procedure (i.e., IV insertion). The purpose of this article is to describe the strategies used to integrate molecular genetics methods into this project. The authors discuss the steps needed to complete this process, including (a) establishing a collaboration with genetics researchers and laboratory facilities, (b) developing and implementing a plan to manage biologic samples, and (c) incorporating genetics into the informed consent process.
Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions
Authors: Balajthy Zoltán , Csomós Krisztián , Vámosi György , Szántó Attila , Lanotte Michel , Fésüs László
Published: June 2006

Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2–/– mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2–/– mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract–induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.
A critical role for the transcription factor Scl in platelet production during stress thrombopoiesis
Authors: McCormack Matthew P. , Hall Mark A. , Schoenwaelder Simone M. , Zhao Quan , Ellis Sarah , Prentice Julia A. , Clarke Ashleigh J. , Slater Nicholas J. , Salmon Jessica M. , Jackson Shaun P. , Jane Stephen M. , Curtis David J.
Published: June 2006

The generation of platelets from megakaryocytes in the steady state is regulated by a variety of cytokines and transcription factors, including thrombopoietin (TPO), GATA-1, and NF-E2. Less is known about platelet production in the setting of stress thrombopoiesis, a pivotal event in the context of cytotoxic chemotherapy. Here we show in mice that the transcription factor Scl is critical for platelet production after chemotherapy and in thrombopoiesis induced by administration of TPO. Megakaryocytes from these mice showed appropriate increases in number and ploidy but failed to shed platelets. Ultrastructural examination of Scl-null megakaryocytes revealed a disorganized demarcation membrane and reduction in platelet granules. Quantitative real-time polymerase chain reaction showed that Scl-null platelets lacked NF-E2, and chromatin immunoprecipitation analysis demonstrated Scl binding to the NF-E2 promoter in the human megakaryoblastic-cell line Meg-01, along with its binding partners E47, Lmo2, and the cofactors Ldb1 and GATA-2. These findings suggest that Scl acts up-stream of NF-E2 expression to control megakaryocyte development and platelet release in settings of thrombopoietic stress.
Expansion of FOXP3high regulatory T cells by human dendritic cells (DCs) in vitro and after injection of cytokine-matured DCs in myeloma patients
Authors: Banerjee Devi K. , Dhodapkar Madhav V. , Matayeva Elyana , Steinman Ralph M. , Dhodapkar Kavita M.
Published: June 2006

CD4+CD25+FOXP3+ regulatory T cells (Treg's) play an important role in the maintenance of immune tolerance. The mechanisms controlling the induction and maintenance of Treg's in humans need to be defined. We find that human myeloid dendritic cells (DCs) are superior to other antigen presenting cells for the maintenance of FOXP3+ Treg's in culture. Coculture of DCs with autologous T cells leads to an increase in both the number of Treg's, as well as the expression of FOXP3 protein per cell both in healthy donors and myeloma patients. DC-mediated expansion of FOXP3high Treg's is enhanced by endogenous but not exogenous interleukin-2 (IL-2), and DC-T-cell contact, including the CD80/CD86 membrane costimulatory molecules. DCs also stimulate the formation of Treg's from CD25- T cells. The efficacy of induction of Treg's by DCs depends on the nature of the DC maturation stimulus, with inflammatory cytokine-treated DCs (Cyt-DCs) being the most effective Treg inducers. DC-induced Treg's from both healthy donors and patients with myeloma are functional and effectively suppress T-cell responses. A single injection of cytokine-matured DCs led to rapid enhancement of FOXP3+ Treg's in vivo in 3 of 3 myeloma patients. These data reveal a role for DCs in increasing the number of functional FOXP3high Treg's in humans.