bluuebunny/crossref_metadata_2025 huggingface dataset:
Can Exercise Training With Weight Loss Lower Serum C-Reactive Protein Levels?
Authors: Okita Koichi , Nishijima Hirotaka , Murakami Takeshi , Nagai Tatsuya , Morita Noriteru , Yonezawa Kazuya , Iizuka Kenji , Kawaguchi Hideaki , Kitabatake Akira
Published: July 2004

Objective—

C-reactive protein (CRP), an obesity-related inflammatory marker, is a promising predictor for cardiovascular disease and may be a mediator for atherogenesis. It has been reported that diet-induced weight loss lowered CRP levels. However, the effect of exercise training, another therapy that can reduce weight, on CRP is still unclear. We examined effects of exercise training with weight loss on CRP levels and conventional cardiovascular risks.

Methods and Results—

A total of 227 apparently healthy women were recruited, and 199 subjects (average age 52 years) completed a 2-month weight reduction program consisting of supervised aerobic exercises. After the program, weight was reduced from 65.8 to 62.8 kg (
P
<0.0001), and all conventional variables were remarkably improved. Similarly, CRP levels were significantly decreased, from 0.63 (0.28 to 1.19) to 0.41 (0.18 to 0.80) mg/L (
P
<0.0001). However, in contrast to other variables, the changes in CRP levels were not proportionally associated with the extent of weight reduction. In the quartile analysis of % weight reduction, the largest weight reduction quartile did not show significant decreases in CRP levels, whereas moderate quartile showed remarkable CRP decreases.

Conclusions—

Exercise training with weight reduction disproportionately lowered CRP levels. Considering inflammatory status, there might be an optimal pace of exercise with weight loss.
Expression of Angiopoietin-2 in Endothelial Cells Is Controlled by Positive and Negative Regulatory Promoter Elements
Authors: Hegen Anja , Koidl Stefanie , Weindel Karin , Marmé Dieter , Augustin Hellmut G. , Fiedler Ulrike
Published: July 2004

Objective—

Angiopoietin-2 (Ang-2) is a non-signal transducing ligand of the endothelial receptor tyrosine kinase Tie-2. Ang-2 is produced by endothelial cells and acts as an autocrine regulator mediating vascular destabilization by inhibiting Angiopoietin-1-mediated Tie-2 activation. To examine the transcriptional regulation of Ang-2, we studied the Ang-2 promoter in endothelial cells and nonendothelial cells.

Methods and Results—

The human Ang-2 promoter contains a 585-bp region around the transcriptional start site (−109 to +476) that is sufficient to control endothelial cell-specific and cytokine-dependent Ang-2 expression. Strong repressor elements of Ang-2-promoter activity are located in the 5′-region of the promoter and in the first intron. The Ets family transcription factors Ets-1 and Elf-1 act as strong enhancers of endothelial cell Ang-2-promoter activity. Ets-binding sites −4 and −7 act as positive regulators, whereas Ets-binding site −3 acts as negative regulator. Demethylation experiments revealed that the Ang-2 gene (in contrast to the Tie-2 gene) is not controlled by imprinting.

Conclusions—

The data determine unique positive and negative regulatory mechanisms of endothelial cell Ang-2 expression and provide further evidence for the critical role of Ang-2 as a key autocrine regulator of vascular stability and responsiveness.
Antimonocyte Chemoattractant Protein-1 Gene Therapy Attenuates Graft Vasculopathy
Authors: Saiura Akio , Sata Masataka , Hiasa Ken-ichi , Kitamoto Shiro , Washida Miwa , Egashira Kensuke , Nagai Ryozo , Makuuchi Masatoshi
Published: July 2004

Objective—Accelerated coronary arteriosclerosis remains a major problem in the long-term survival of cardiac transplant recipients. However, the pathogenesis of graft vasculopathy is poorly understood, and there is no effective therapy. Transplant arteriosclerosis is characterized by early mononuclear cell attachment on the transplanted vessel followed by development of concentric neointimal hyperplasia. Early and persistent expression of monocyte chemoattractant protein-1 (MCP-1) in cardiac allografts has been implicated for the pathogenesis of transplant arteriosclerosis.

Methods and Results—We investigated whether anti-MCP-1 gene therapy can inhibit the development of intima hyperplasia in a mouse model of cardiac transplantation. Either the dominant-negative form of MCP-1 (7ND) or control vector was transfected into the skeletal muscles of B10.D2 mice. Cardiac allografts from DBA/2 mice were transplanted heterotopically into B10.D2 mice. 7ND gene transfer was associated with a significant reduction of the number of mononuclear cells accumulating in the lumen of the graft coronary arteries at 1 week and an attenuation of the development of the lesion at 8 weeks (intima/media ratio 0.79±0.05 versus 0.48±0.04).

Conclusions—The MCP-1/chemokine receptor 2 (CCR2) signaling pathway plays a critical role in the pathogenesis of graft vasculopathy. This new anti-MCP-1 gene therapy might be useful to treat graft vascular disease.
Renovascular Hypertension in Mice With Brain-Selective Overexpression of AT
1a
Receptors Is Buffered by Increased Nitric Oxide Production in the Periphery
Authors: Lazartigues Eric , Lawrence Andrew J. , Lamb Fred S. , Davisson Robin L.
Published: July 2004

We recently established a new transgenic mouse model with brain-restricted overexpression of angiotensin II (Ang II) type 1a receptors (NSE-AT
1a
) to unmask the role of the brain renin-angiotensin system in hypertension. To test the hypothesis that these mice would exhibit an early exacerbation of renovascular hypertension, NSE-AT
1a
and nontransgenic (NT) mice underwent 2-kidney-1-clip (2K1C) surgery and blood pressure (BP) and heart rate (HR) were recorded continuously by radiotelemetry for 28 days. Results show that NSE-AT
1a
mice developed hypertension much more rapidly than NT, and this was not attributable to genotype-related differences in plasma or brain Ang II levels. A marked bradycardia accompanied this early increase in BP in NSE-AT
1a
mice, as did a substantial cardiovascular region-specific downregulation of AT
1
receptor binding in brain but not in kidney. As BP reached its plateau in NT (≈1 week after clip), hypertension began to abate and eventually stabilized at significantly lower levels in NSE-AT
1a
mice despite marked elevations in Ang II levels in brain stem and hypothalamus at these later time points. This hypertension reversal and the bradycardia were prevented by chronic infusion of the nitric oxide synthase (NOS) blocker
l
-NAME. These data, along with evidence showing enhanced NOS expression and NO-mediated compensatory responses in 2K1C NSE-AT
1a
peripheral arteries during this later phase, suggest that activation of endogenous NO systems plays an important role in buffering the maintenance of hypertension caused by overexpression of AT
1a
receptors in the brain.
Does Transcatheter Closure of Patent Foramen Ovale Really “Shut the Door?”
Authors: Anzola G.P. , Morandi E. , Casilli F. , Onorato E.
Published: July 2004

Background and Purpose—

Transcatheter closure of patent foramen ovale (PFO) is increasingly being performed and monitored with transthoracic or transesophageal echocardiography, whereas contrast-enhanced transcranial Doppler (ce-TCD), which probably represents the most suitable tool to quantify right-to-left shunt (RLS) in the brain vessels, has been systematically overlooked. Our goal is to prospectively assess efficacy and safety of PFO transcatheter closure using ce-TCD.

Methods—

A total of 140 consecutive patients (mean age, 46±13 years; male/female ratio, 63/77) with PFO-related large RLS and no other recognized cause of focal cerebral ischemia underwent transcatheter closure. TCD was done preoperatively and 1 month after the procedure in all patients, after 3 months in 120, after 6 months in 112, and after 1 year in 104 patients.

Results—

Implantation was successful in all patients. During Valsalva strain, a large shunt was still detectable in 31 of 140 (22%), 15 of 120 (13%), 9 of 112 (8%), and 9 of 104 (9%) patients at the 1-, 3-, 6-, and 12-month visits, respectively. Periprocedural and postprocedural complications included atrial fibrillation in 8% and scintillating scotomata in 6% of patients. During the 1-year follow-up period, only 1 transient ischemic attack was recorded in a patient with paroxysmal atrial fibrillation and complete PFO closure.

Conclusions—

Transcatheter PFO closure in patients with cryptogenic stroke and large RLS may be less successful than reported previously. TCD appears the ideal tool to follow up the closure process and to identify early, during follow-up, those patients who will be left with a significant shunt. Atrial fibrillation is more common than believed previously and may underlie the occurrence of further cerebrovascular events despite complete PFO closure. Irritative visual phenomena may occur as a consequence of nickel toxicity.
Targets for Vascular Protection After Acute Ischemic Stroke
Authors: Fagan Susan C. , Hess David C. , Hohnadel Elizabeth J. , Pollock David M. , Ergul Adviye
Published: July 2004

Background—

Vascular damage caused by cerebral ischemia leads to edema, hemorrhage formation, and worsened outcomes in ischemic stroke patients. Therapeutic interventions need to be developed to provide vascular protection. The purpose of this review is to identify the pathophysiologic processes involved in vascular damage after ischemia, which may lead to strategies to provide vascular protection in ischemic stroke patients.

Summary of Comment—

The pathologic processes caused by vascular injury after an occlusion of a cerebral artery can be separated into acute (hours), subacute (hours to days), and chronic (days to months). Targets for intervention can be identified for all 3 stages. Acutely, superoxide is the predominant mediator, followed by inflammatory mediators and proteases subacutely. In the chronic phase, proapoptotic gene products have been implicated.

Conclusions—

Pharmacological agents designed to target specific pathologic and protective processes affecting the vasculature should be used in clinical trials of vascular protection after acute ischemic stroke.
Genetic Variation in
PPARG
Encoding Peroxisome Proliferator-Activated Receptor γ Associated With Carotid Atherosclerosis
Authors: Al-Shali Khalid Z. , House Andrew A. , Hanley Anthony J.G. , Khan Hafiz M.R. , Harris Stewart B. , Zinman Bernard , Mamakeesick Mary , Fenster Aaron , Spence J. David , Hegele Robert A.
Published: July 2004

Background and Purpose—

Peroxisome proliferator-activated receptor γ is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in
PPARG
has been associated with metabolic and cardiovascular end points.

Methods—

We investigated the relationship between 2 common
PPARG
polymorphisms, namely P12A and c.1431C>T, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound.

Results—

Using multivariate analysis, we found that subjects with ≥1
PPARG
A12 allele had less carotid IMT than others (0.72±0.03 versus 0.80±0.02 mm;
P
=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the
PPARG
c.1431T allele had greater TPV than others (124±18.4 versus 65.1±23.7 mm
3
;
P
=0.0079), with no between-genotype difference in IMT.

Conclusions—

The findings show an association between
PPARG
genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the
PPARG
A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis.
The Portable Bullhe Shah: Biography, Categorization, and Authorship in the Study Of Punjabi Sufi Poetry
Authors: Rinehart Robin
Published: July 2004

The Punjabi poet Bullhe Shah (1680-1758) is revered by Muslims, Hindus and Sikhs. In the extensive body of interpretive literature devoted to his life and work, scholars have contested his religious identity, characterizing Bullhe Shah in various ways, e. g. as a Sufi, a Vedantic Sufi, or a Vai ava Vedantic Sufi. This article examines the nature of the debates about Bullhe Shah's identity, and how these debates have shaped the varying portrayals of Bullhe Shah's life, the corpus of his poetry, and the characterization of his religious affiliation. I argue that a series of unexamined assumptions — about the nature of biography and its relation to the development of a worldview, about the categorization of religious identity, and about the nature of authorship — have created these conflicting portrayals of the poet and his work, making Bullhe Shah a kind of "portable" figure who is placed in widely divergent contexts. I conclude by arguing that Bullhe Shah's portability, or his placement within different contexts (for different purposes), is itself a useful topic for analysis, and provides the basis for a potentially more fruitful study not only of Bullhe Shah's life and work, but also of his audiences and their responses to him.
The Irony of Romans 13
Authors:   Carter
Published: July 2004

This article explores the possibility that Paul was using irony in his commendation of the state in Romans 13. It is proposed that the original audience of the letter shared with Paul a common experience of oppression at the hands of the authorities and were aware of the abuses that took place in the opening years of Nero's reign. The consequent implausibility of Paul's language would have alerted his readers to the presence of irony. They would have been able to set aside the surface meaning of the discourse and to recognise that Paul was using the established rhetorical technique of censuring with counterfeit praise. While the passage can be read as a straightforward injunction to submit to the authorities, an ironic reading of the text results in a subversion of the very authorities it appears to commend.
Die korinthische Gemeinde als Nebenadressat des Römerbriefs. Eigentextreferenzen des Paulus und Kommunikativer Kontext des längsten Paulusbriefes
Authors: Hartwig Charlotte , Theißen Gerd
Published: July 2004

The letter to the Romans is not only addressed to the Romans as the main addressees but indirectly to the Corinthians. When Paul was writing this letter he lived in the Corinthian congregation, continuing his dialogue with the Corinthians. This is why Paul reworked some topics from 1 and 2 Corinthians in order to correct them and to put them more exactly. The letter is thus embedded in his written and oral communication with the Corinthians. The Corinthians could understand some hints and allusions much better than the Romans.
Mt. 17:1-9 in 'Codex Schøjen'
Authors: Baarda Tjitze
Published: July 2004

The magnificent edition of a new Middle-Egyptian Coptic text of Matthew (Codex Schøjen), published by the late Hans-Martin Schenke, is an unexpected contribution to New Testament scholarship. Its text differs in many respects from all later Coptic versions including the famous Codex Scheide, published by the same author, which was written in the same dialect. This new and certainly most intriguing text requires a diligent investigation by textual critics in view of the far-reaching conclusions which Professor Schenke drew from its textual character. Only a thorough investigation of Matthew's text as far as it is preserved in this codex will enable textual critics to give a final and fair judgment of Schenke's hypotheses. This contribution can only be a first step to reach such a judgment.
Kaolin polytype evidence for a hot-fluid pulse along Caledonian thrusts during rifting of the European Margin
Authors: Parnell J. , Watt G. , Chen H. , Wycherley H. , Boyce A. , Elmore D. , Blumstein R. , Engel M. , Green P.
Published: July 2004

Sedimentary basins developed along the European margin during the earliest, Permian, stage of proto-Atlantic rifting, during a phase of high heat flow. The proximity of some basins to Caledonian thrusts has implied that rifts locally utilized the basement fabric. New mineralogical and palaeomagnetic data show that thrust planes in the Moine Thrust Zone channelled a pulse of hot fluid in Permian time. The fluids precipitated kaolin in fractures in the thrust zone, and with decreasing intensity away from the zone. The high-temperature polytype dickite is largely confined to major thrust planes. Stable H and O isotope analyses indicate that the parent fluid included meteoric water involved in a hydrothermal system. Coeval hydrothermal hematite has a chemical remanence that dates the fluid pulse as Permian. This is direct evidence for post-orogenic activity in the thrust zone, in which the thrusts vented excess heat during regional crustal extension. The example from the European margin exemplifies the importance of deep-seated structures in the release of heat, and the value of kaolinite polytype mapping as a tool to record anomalous palaeo-heat flow.
High-pressure Raman spectroscopic studies of FeS2 pyrite
Authors: Kleppe A. K. , Jephcoat A. P.
Published: July 2004

We report micro-Raman spectroscopic studies of FeS2 pyrite in the diamond-anvil cell under hydrostatic and non-hydrostatic conditions to 55 GPa at room temperature. Four out of five Ramanactive modes are resolved with helium as a pressure-transmitting medium to highest pressures. The fifth mode, Tg(2) [377 cm-1], is weak and unresolved lying ∼2 cm-1 from the intense Ag mode [379 cm-1] at 1 bar. We observe an increase in the separation of the Eg [344 cm-1] and Tg(1) [350 cm-1] modes under compression. All observed frequencies increase continuously with increasing pressure showing no evidence for a structural phase transition in accord with both X-ray diffraction and shock-wave studies. The Ag and Tg(1) modes gain significantly in intensity relative to the Eg mode with increasing pressure probably resulting from Raman resonance effects. The Tg(3) mode [430 cm-1] broadens unusually compared to the other pyrite modes with pressure. The Raman data are consistent with a contraction of the S-S and Fe-S bonds under pressure. The main effect of non-hydrostatic conditions on the Raman modes is a strong pressure-induced broadening; the pressure-dependence of the frequencies and relative intensities are not affected within the error of the measurements.
Assessment of the use of Raman spectroscopy for the determination of amphibole asbestos
Authors: Rinaudo C. , Belluso E. , Gastaldi D.
Published: July 2004

Raman spectroscopy was assessed for its ability to rapidly identify asbestos phases by submitting the amphiboles anthophyllite, amosite, crocidolite and tremolite to spectroscopic analysis. All the phases were characterized by using XRD, SEM, TEM (CTEM, SAED), AEM and EDS techniques. This study demonstrates that accurate identification of the mineralogical phase can be attained by analysing the position in the Raman spectrum of the bands corresponding to the symmetric stretching modes (vs) and to the antisymmetric stretching modes (vas) of the different Si—O linkages. Raman spectroscopy thus proves to be an effective technique for rapidly distinguishing the different fibrous minerals examined.
Garnet exsolution in garnet clinopyroxenite and clinopyroxenite xenoliths in early Cretaceous intrusions from the Xuzhou region, eastern China
Authors: Xu W. , Liu X. , Wang Q. , Lin J. , Wang D.
Published: July 2004

Exsolved garnet, sometimes associated with exsolved amphibole and zoisite, is abundant in aluminous clinopyroxene of garnet clinopyroxenite and clinopyroxenite xenoliths in the early Cretaceous dioriticmonzodioritic intrusions from the Xuzhou region, ∼100 km west of the Sulu ultrahigh-pressure (UHP) metamorphic terrane in eastern China. In addition to the mineral exsolutions, intergranular fine-grained garnet, zoisite, titanite, and sometimes amphibole are also present around the primary clinopyroxene grains. Clinopyroxene shows compositional gradients, with decreasing Al and increasing Si and Mg, adjacent to the garnet lamellae and intergranular garnet. In contrast, the exsolved and intergranular garnet is homogeneous in composition and typically more grossular-rich and pyrope- and almandinepoor than the coarse-grained primary garnet. The estimates ofPandTfor the precursor assemblage and garnet exsolution suggests a decrease of temperature from ∼950—1100ºC down to 620—780°C, and a nearly constant pressure from ∼15—20 kbar to 18 kbar, which are comparable with the metamorphic conditions of the associated eclogites. Therefore, garnet exsolution in garnet clinopyroxenite and clinopyroxenite xenoliths could be caused by high-pressure (HP) metamorphism. SHRIMP zircon U-Pb dating for the associated eclogite and gneiss xenoliths and Sm-Nd whole rock-garnet dating for the same eclogite demonstrate that parts of lower crust on the southeastern margin of the North China craton might be involved in the Triassic HP metamorphism due to the deep subduction of the Yangtze craton.
Systematic mineralogy and chemistry of gold-silver vein deposits in the Taebaeksan district, Korea: Distal relatives of a porphyry system
Authors: Pak S. J. , Choi S.-G. , Choi S.-H.
Published: July 2004

Gold-silver vein deposits in the Taebaeksan district, Korea, coexist in time and space with a variety of other deposit types such as skarns, hydrothermal carbonate replacement bodies and Carlin-like deposits and reflect proximity to a magmatic source. The seven gold-silver deposits within the district show common features such as multiple complex veins, an abundance (up to 30% in ore) of base-metal sulphides, a wide range of Ag/Au ratios and the common occurrence of carbonate. Quartz-vein textures indicate open-space-filling at shallow crustal levels. On the basis of Ag/Au ratios of ore, mode of occurrence, and associated mineral assemblages, the seven deposits studied can be classified as follows; Au-dominant type (Group I), Au-Ag type (Group II), Ag-dominant type (Group IIIA) and base-metal and Ag-dominant type (Group IIIB). Group I is characterized by paragenetically early Pb-Zn basemetal sulphides with electrum and late, rare Ag-sulphides and Ag-sulphosalts, whereas Group III contains more Ag-sulphides and/or Ag-sulphosalts. Group II is gold-rich, but transitional to Group III. The Au contents and FeS contents of electrum and sphalerite, respectively, from all of the deposits decreased as mineralization proceeded. Temperature and log fS2 conditions of gold-silver mineralization tend to decrease from Group I and II to Group III deposits (i.e. 340–270°C, –9.3 to –11.8 bar, 320–240°C, –9.5 to –10.3 bar, 250–160°C, –12.5 to –16.9 bar, respectively) as well as from the main to late stages of mineralization in each deposit. The systematic mineralogy and variation of physicochemical conditions in Groups I, II and III are thought to be due to their relative positions with respect to a magma source that is genetically related to a low-to-intermediate-sulphidation porphyry system. Au-rich deposits are proximal to a magmatic source, whereas Ag-rich deposits are more distal.
Thorium in crandallite-group minerals: an example from a Devonian bauxite deposit, Timan, Russia
Authors: Mordberg L. E.
Published: July 2004

A Th-rich mineral of the crandallite group has been investigated from the weathering profile of the Schugorsk bauxite deposit, Timan, Russia. It occurs within thin (up to 0.5 mm) organic-rich veinlets together with ‘leucoxene’ in the form of small shapeless grains which vary in size from 1—2 mm to 60—70 mm. Rare grains disseminated among boehmite crystals were also found. Microprobe analyses determined that the ThO2 content can be as high as 18 wt.%. The mineral composition is intermediate between crandallite CaAl3H(PO4)2(OH)6, goyazite SrAl3H(PO4)2(OH)6, Th-crandallite and svanbergite SrAl3PO4SO4(OH)6 in the beudantite group.

Comparatively high contents of Fe and Si and a very high positive Th and Fe content correlation (r = +0.98) suggest that the formula of the hypothetical Th-bearing end-member is ThFe3(PO4,SiO4)2(OH)6 with Th and Si substituting for REE and Prespectively (woodhouseite-type substitution). Another possible substitution is Th4+ + Ca2+ ⇋ 2REE3+ (florencite-type). A deficiency of cations in the X site can be explained by either the presence of carbon, undetectable by microprobe, in the crystal lattice or a lack of X-site cations due to radiation damage induced by Th. Some excess of cations in the B site (Al and Fe3+) can be explained by the presence of very small boehmite and hematite inclusions on the crandallite grain surfaces. Th-rich crandallite may be the result of alteration of an unidentified silicate mineral from the parent rock with a composition close to the simplified formula Fe2+ThSiO4(OH)2.
Elfstorpite synonymy with allactite; mineral and name discredited
Authors: Fontan F. , Holtstam D. , de Parseval P. , Permingeat F. , Mason B.
Published: July 2004

Holotype material and other specimens of ‘elfstorpite’ from the Sjögruvan deposit, Örebro, Sweden have been characterized by powder X-ray diffraction and chemical analysis. The mineral is indistinguishable from allactite, which has priority, and consequently ‘elfstorpite’ should be discredited. The IMA Commission on New Minerals and Mineral Names has approved the proposition.
Herbertsmithite, Cu3Zn(OH)6Cl2, a new species, and the definition of paratacamite
Authors: Braithwaite R. S. W. , Mereiter K. , Paar W. H. , Clark A. M.
Published: July 2004

One in four of the Cu-filled cation sites in clinoatacamite, the monoclinic polymorph of atacamite and botallackite, is angle- rather than Jahn-Teller-distorted. Experiments show that this site alone is susceptible to substitution by a non-Jahn-Teller distorting cation of suitable radius and charge, such as Zn2+, and also Ni2+, Co2+, Fe2+, Cd2+ and Mg2+. The crystal symmetry changes to rhombohedral when ∼⅓ of the Cu in this site is substituted by e.g. Zn, thus giving paratacamite; the Zn is essential for stability and forms, with larger proportions of Zn, a series to the end-member in which the site is fully occupied by Zn. This end-member, rhombohedral stoichiometric Cu3Zn(OH)6Cl2, has been characterized using natural specimens from Chile and Iran and is named herbertsmithite. The other cations mentioned behave similarly, producing stabilized rhombohedral paratacamites and end-members analogous to herbertsmithite, which if found in nature, as the Ni analogue has been, should be named species. Clinoatacamite, paratacamite and herbertsmithite have rather similar X-ray powder diffraction patterns, but are readily distinguished by infrared spectroscopy.

Zn-stabilized paratacamite forms blue-green crystals of rhombohedral habit, with vitreous lustre, e = 1.828-1.830, o = 1.835, uniaxial negative, weakly pleochroic O > E, density: 3.75 g cm-3, Mohs hardness: 3-3½; space group R, a = 13.654(5), c = 14.041(6) Å, Z = 24, with pronounced Rm substructure; six strongest XRD lines 5.452 (100), 2.895 (20), 2.760 (74), 2.262 (52), 1.817 (18), 1.708 (21).

Herbertsmithite forms dark green crystals of rhombohedral habit, with vitreous lustre, e = 1.817, o = 1.825, uniaxial negative, weakly pleochroic O > E, density: 3.95 g cm-3, Mohs hardness: 3-3½;; space group Rm with no superstructure observed, a = 6.834(1), c = 14.075(2) Å, Z = 3; six strongest XRD lines 5.466 (55), 4.702 (14), 2.764 (100), 2.266 (36), 1.820 (13), 1.709 (18).
Monocyte-like and mature macrophages produce CXCL13 (B cell–attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis
Authors: Carlsen Hege S. , Baekkevold Espen S. , Morton H. Craig , Haraldsen Guttorm , Brandtzaeg Per
Published: July 2004

The homeostatic chemokine CXCL13 (also called B cell-attracting chemokine 1 [BCA-1] or B-lymphocyte chemoattractant [BLC]) is constitutively expressed in secondary lymphoid tissue and initiates lymphoid neogenesis when expressed aberrantly in mice. CXCL13 has also been detected in chronic inflammation associated with human lymphoid neogenesis, suggesting a pathogenic role. Follicular dendritic cells (FDCs) are generally considered to be the major source of CXCL13 both in normal and aberrant lymphoid tissue. We show here, instead, that most CXCL13-expressing cells in rheumatoid arthritis and ulcerative colitis are of monocyte/macrophage lineage. They are located in irregular lymphoid aggregates within an FDC network, but also within and near smaller collections of B cells in diseased tissue where no FDCs are detected. Some of these CXCL13-expressing cells are CD14+, suggesting derivation from recently extravasated monocytes. Interestingly, monocytes from healthy donors stimulated in vitro with lipopolysaccharide secrete CXCL13. This induced production is enhanced after in vitro maturation of the monocytes toward macrophages but markedly decreased after maturation toward dendritic cells. Together, our findings strongly suggest that newly recruited monocytes/macrophages play a role for lymphoid neogenesis in human inflammatory diseases. Circulating monocytes are therefore potential candidates for future targeted therapy of chronic inflammation.
FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia
Authors: Pardanani Animesh , Brockman Stephanie R. , Paternoster Sarah F. , Flynn Heather C. , Ketterling Rhett P. , Lasho Terra L. , Ho Ching-Liang , Li Chin-Yang , Dewald Gordon W. , Tefferi Ayalew
Published: July 2004

A novel oncogenic mutation (FIP1L1-PDGFRA), which results in a constitutively activated platelet-derived growth factor receptor-α (PDGFRA), has been invariably associated with a primary eosinophilic disorder. The current study examines both the prevalence and the associated clinicopathologic features of this mutation in a cohort of 89 adult patients presenting with an absolute eosinophil count (AEC) of higher than 1.5 × 109/L. A fluorescence in situ hybridization (FISH)–based strategy was used to detect FIP1L1-PDGFRA in bone marrow cells. None of 8 patients with reactive eosinophilia displayed the abnormality, whereas the incidence of FIP1L1-PDGFRA in the remaining 81 patients with primary eosinophilia was 14% (11 patients). None (0%) of 57 patients with the hypereosinophilic syndrome (HES) but 10 (56%) of 19 patients with systemic mast cell disease associated with eosinophilia (SMCD-eos) carried the specific mutation. The bone marrow mast cell infiltration pattern in FIP1L1-PDGFRA+ SMCD-eos was distinctly diffuse with loose tumoral aggregates. Treatment with low-dose imatinib (100 mg/d) produced complete and durable responses in all 8 FIP1L1-PDGFRA+ cases treated. In contrast, only 40% partial response rate was seen in 10 HES cases. FIP1L1-PDGFRA is a relatively infrequent but treatment-relevant mutation in primary eosinophilia that is indicative of an underlying systemic mastocytosis.
Endocytosis, intracellular sorting, and processing of exosomes by dendritic cells
Authors: Morelli Adrian E. , Larregina Adriana T. , Shufesky William J. , Sullivan Mara L. G. , Stolz Donna Beer , Papworth Glenn D. , Zahorchak Alan F. , Logar Alison J. , Wang Zhiliang , Watkins Simon C. , Falo Louis D. , Thomson Angus W.
Published: July 2004

Exosomes are nanovesicles released by leukocytes and epithelial cells. Although their function remains enigmatic, exosomes are a source of antigen and transfer functional major histocompatibility complex (MHC)–I/peptide complexes to dendritic cells (DCs) for CD8+ T-cell activation. Here we demonstrate that exosomes also are internalized and processed by immature DCs for presentation to CD4+ T cells. Endocytosed exosomes are sorted into the endocytic compartment of DCs for processing, followed by loading of exosome-derived peptides in MHC-II molecules for presentation to CD4+ T cells. Targeting of exosomes to DCs is mediated via milk fat globule (MFG)–E8/lactadherin, CD11a, CD54, phosphatidylserine, and the tetraspanins CD9 and CD81 on the exosome and αv/β3 integrin, and CD11a and CD54 on the DCs. Circulating exosomes are internalized by DCs and specialized phagocytes of the spleen and by hepatic Kupffer cells. Internalization of blood-borne allogeneic exosomes by splenic DCs does not affect DC maturation and is followed by loading of the exosome-derived allopeptide IEα52-68 in IAb by host CD8α+ DCs for presentation to CD4+ T cells. These data imply that exosomes present in circulation or extracellular fluids constitute an alternative source of self- or allopeptides for DCs during maintenance of peripheral tolerance or initiation of the indirect pathway of allorecognition in transplantation.
Determination of relapse risk based on assessment of minimal residual disease during complete remission by multiparameter flow cytometry in unselected patients with acute myeloid leukemia
Authors: Kern Wolfgang , Voskova Daniela , Schoch Claudia , Hiddemann Wolfgang , Schnittger Susanne , Haferlach Torsten
Published: July 2004

Quantification of minimal residual disease (MRD) reveals significant prognostic information in patients treated for acute myeloid leukemia (AML). The application of multiparameter flow cytometry (MFC) for MRD assessment has resulted in significant prognostic information in selected cases in previous analyses. We analyzed MRD in unselected patients with AML in complete remission (CR) after induction (n = 58) and consolidation (n = 62) therapies. By using a comprehensive panel of monoclonal antibodies we identified at least one leukemia-associated aberrant immunophenotype (LAIP) in each patient. The degree of reduction between diagnosis and CR in LAIP-positive cells (log difference [LD]) as a continuous variable was significantly related to relapse-free survival (RFS) both after induction (P = .0001) and consolidation (P = .000 08) therapies, respectively. The LD determined after consolidation therapy was the only parameter related to overall survival (OS) (P = .005). Separation of patients based on the 75th percentile of LD after consolidation therapy resulted in groups with highly different RFS (83.3% versus 25.7%, P = .0034) and OS (87.5% versus 51.4%, P = .0507) at 2 years. Multivariate analysis identified LD as an independent prognostic factor for RFS at both checkpoints. MFC-based quantification of MRD reveals important prognostic information in unselected patients with AML in addition to cytogenetics and should be further evaluated and used in clinical trials.
Mutations of the SBDS gene are present in most patients with Shwachman-Diamond syndrome
Authors: Woloszynek Jill R. , Rothbaum Robert J. , Rawls Amy S. , Minx Patrick J. , Wilson Richard K. , Mason Philip J. , Bessler Monica , Link Daniel C.
Published: July 2004

Shwachman-Diamond Syndrome (SDS) is a rare multisystem disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction, and metaphyseal chondrodysplasia. Recent studies show that mutations of SBDS, a gene of unknown function, are present in the majority of patients with SDS. In the present study, we show that most, but not all, patients classified based on rigorous clinical criteria as having SDS had compound heterozygous mutations of SBDS. Full-length SBDS protein was not detected in leukocytes of SDS patients with the most common SBDS mutations, consistent with a loss-of-function mechanism. In contrast, SBDS protein was expressed at normal levels in SDS patients without SBDS mutations. These data confirm the absence of SBDS mutations in this subgroup of patients and suggest that SDS is a genetically heterogeneous disorder. The presence (or absence) of SBDS mutations may define subgroups of patients with SDS who share distinct clinical features or natural history.
Functional assessment and specific depletion of alloreactive human T cells using flow cytometry
Authors: Martins Sergio L. R. , St. John Lisa S. , Champlin Richard E. , Wieder Eric D. , McMannis John , Molldrem Jeffrey J. , Komanduri Krishna V.
Published: July 2004

Human T-cell alloreactivity plays an important role in many disease processes, including the rejection of solid organ grafts and graft-versus-host disease (GVHD) following allogeneic stem cell transplantation. To develop a better understanding of the T cells involved in alloreactivity in humans, we developed a cytokine flow cytometry (CFC) assay that enabled us to characterize the phenotypic and functional characteristic of T cells responding to allogeneic stimuli. Using this approach, we determined that most T-cell alloreactivity resided within the CD4+ T-cell subset, as assessed by activation marker expression and the production of effector cytokines (eg, tumor necrosis factor α [TNF]α) implicated in human GVHD. Following prolonged stimulation in vitro using either allogeneic stimulator cells or viral antigens, we found that coexpression of activation markers within the CD4+ T-cell subset occurred exclusively within a subpopulation of T cells that significantly increased their surface expression of CD4. We then developed a simple sorting strategy that exploited these phenotypic characteristics to specifically deplete alloreactive T cells while retaining broad specificity for other stimuli, including viral antigens and third-party alloantigens. This approach also was applied to specifically enrich or deplete human virus-specific T cells.
Biochemical enrichment and biophysical characterization of a taste receptor for L-arginine from the catfish, Ictalurus puntatus
Authors: Grosvenor William , Kaulin Yuri , Spielman Andrew I , Bayley Douglas L , Kalinoski D Lynn , Teeter John H , Brand Joseph G
Published: July 2004

Background

The channel catfish, Ictalurus punctatus, is invested with a high density of cutaneous taste receptors, particularly on the barbel appendages. Many of these receptors are sensitive to selected amino acids, one of these being a receptor for L-arginine (L-Arg). Previous neurophysiological and biophysical studies suggested that this taste receptor is coupled directly to a cation channel and behaves as a ligand-gated ion channel receptor (LGICR). Earlier studies demonstrated that two lectins, Ricinus communis agglutinin I (RCA-I) and Phaseolus vulgaris Erythroagglutinin (PHA-E), inhibited the binding of L-Arg to its presumed receptor sites, and that PHA-E inhibited the L-Arg-stimulated ion conductance of barbel membranes reconstituted into lipid bilayers.

Results

Both PHA-E and RCA-I almost exclusively labeled an 82–84 kDa protein band of an SDS-PAGE of solubilized barbel taste epithelial membranes. Further, both rhodamine-conjugated RCA-I and polyclonal antibodies raised to the 82–84 kDa electroeluted peptides labeled the apical region of catfish taste buds. Because of the specificity shown by RCA-I, lectin affinity was chosen as the first of a three-step procedure designed to enrich the presumed LGICR for L-Arg. Purified and CHAPS-solubilized taste epithelial membrane proteins were subjected successively to (1), lectin (RCA-I) affinity; (2), gel filtration (Sephacryl S-300HR); and (3), ion exchange chromatography. All fractions from each chromatography step were evaluated for L-Arg-induced ion channel activity by reconstituting each fraction into a lipid bilayer. Active fractions demonstrated L-Arg-induced channel activity that was inhibited by D-arginine (D-Arg) with kinetics nearly identical to those reported earlier for L-Arg-stimulated ion channels of native barbel membranes reconstituted into lipid bilayers. After the final enrichment step, SDS-PAGE of the active ion channel protein fraction revealed a single band at 82–84 kDa which may be interpreted as a component of a multimeric receptor/channel complex.

Conclusions

The data are consistent with the supposition that the L-Arg receptor is a LGICR. This taste receptor remains active during biochemical enrichment procedures. This is the first report of enrichment of an active LGICR from the taste system of vertebrata.
Characterisation of the Escherichia coli membrane structure and function during fedbatch cultivation
Authors: Shokri Atefeh , Larsson Gen
Published: July 2004

Background

Important parameters during recombinant protein production in Escherichia coli, such as productivity and protein activity, are affected by the growth rate. This includes the translocation of protein over the membrane to gain better folding capacity or reduced proteolysis. To vary the growth rate two techniques are available: fedbatch and continuous cultivation, both controlled by the ingoing feed rate.

Results

During fedbatch cultivation, E. coli contains phosphatidylethanolamine, phosphatidylglycerol, cardiolipin and saturated fatty acids in amounts which are stable with growth rate. However, the levels of cardiolipin are very high compared to continuous cultivation. The reason for fedbatch triggering of this metabolism is not known but hypothesised to result from an additional need for carbon and energy. The reason could be the dynamic and sometimes rapid changes in growth rate to which the fedbatch cell has at all times to adjust. The membrane flexibility, essential for translocation of various components, is however to some degree sustained by production of increased amounts of unsaturated fatty acids in phosphatidylglycerol. The result is a functionally stiff membrane which generally promotes low cell lysis and is constant with respect to protein leakage to the medium. At comparatively high growth rates, when the further stabilising effect of cyclic fatty acids is gone, the high level of unsaturated fatty acids results in a pronounced effect upon sonication. This is very much in contrast to the membrane function in continuous cultivation which shows very specific characteristics as a function of growth rate.

Conclusions

The stiff and unchanging fedbatch membrane should promote a stable behaviour during downstream processing and is less dependent on the time of harvest. However, optimisation of protein leakage can only be achieved in the continuously cultivated cell where leakage is twice as high compared to the constant leakage level in fedbatch. If leakage is undesired, continuous cultivation is also preferred since it can be designed to lead to the lowest values detected. Induction at low growth rate (<0.2 h-1) should be avoided with respect to productivity, in any system, since the specific and total protein production shows their lowest values at this point.
"Is there nothing more practical than a good theory?": Why innovations and advances in health behavior change will arise if interventions are used to test and refine theory
Authors: Rothman Alexander J
Published: July 2004

Theoretical and practical innovations are needed if we are to advance efforts to persuade and enable people to make healthy changes in their behavior. In this paper, I propose that progress in our understanding of and ability to promote health behavior change depends upon greater interdependence in the research activities undertaken by basic and applied behavioral scientists. In particular, both theorists and interventionists need to treat a theory as a dynamic entity whose form and value rests upon it being rigorously applied, tested and refined in both the laboratory and the field. To this end, greater advantage needs to be taken of the opportunities that interventions afford for theory-testing and, moreover, the data generated by these activities need to stimulate and inform efforts to revise, refine, or reject theoretical principles.
Cerebral injury during paediatric heart surgery: perfusion issues
Authors: Scallan Michael JH
Published: July 2004

Suboptimal neurodevelopmental outcome is common in children who have congenital heart disease. Its aetiology is often multifactorial. This review focuses on the role of cardiopulmonary bypass. Hypothermia is the mainstay of cerebral protection. Low flow and regional low flow are preferred to deep hypothermic circulatory arrest in many situations. Cooling and rewarming, aortopulmonary collaterals, pH, air emboli, the systemic inflammatory response, haematocrit, oxygenation, glucose and ultrafiltration can influence neurodevelopmental outcome. Although no pharmacological agents have been shown to have a beneficial effect on neurodevelopmental outcome in clinical practice in children, animal work on the use of steroids several hours before surgery is encouraging.
Perfusion technique for nonhaemic cardiopulmonary bypass prime in neonates and infants under 6 kg body weight
Authors: Merkle Frank , Boettcher Wolfgang , Schulz Fritz , Koster Andreas , Huebler Michael , Hetzer Roland
Published: July 2004

Background: Cardiopulmonary bypass (CPB) in neonates and infants is associated with significant haemodilution when priming of the CPB circuit is accomplished without transfusion of homologous blood components. The degree of haemodilution and, thus, the requirements for blood transfusion may be reduced when the CPB circuit is miniaturized without compromising patient safety.

Method: Between January 2002 and October 2003, selected neonates and small infants were operated on using a nonhaemic prime extracorporeal circuit. CPB priming volume could be reduced from 300 mL to 190 mL by using a dedicated neonatal CPB console with mast-mounted roller pump heads. Reduction of priming volume resulted from shortening of all CPB lines to the minimum, downsizing of all CPB lines, exclusion of unused CPB components, use of vacuum-assisted venous drainage and from close co-operation between the perfusionist, cardiac surgeon and anaesthesiologist. The reduction in priming volume was achieved without eliminating the arterial line filter as safety device.

Results: A total of nine patients weighing between 3.2 and 5.9 kg (mean 4.7 kg) and with a body surface area of 0.22 - 0.35m2 (mean 0.29m2) were operated on with the use of the modified neonatal CPB circuit and a nonhaemic prime. Bypass time varied from 38 to 167 min (mean 96 min). The mean haematocrit on CPB was 22.5% with a range of 17 - 29%. The postoperative course of all patients was uneventful.

Conclusion: A significant reduction in CPB priming volume makes nonhaemic prime CPB in neonates and small infants undergoing complex repair of congenital heart defects possible.