bluuebunny/crossref_metadata_2025 huggingface dataset:
In vivoimaging detects a transient increase in brain arachidonic acid metabolism: a potential marker of neuroinflammation
Authors: Lee Helen , Villacreses Nelly E. , Rapoport Stanley I. , Rosenberger Thad A.
Published: November 2004

In a rat model of neuroinflammation produced by an intracerebral ventricular infusion of bacterial lipopolysaccaride (LPS), we measured the coefficients of incorporation (k*) of arachidonic acid (AA, 20 : 4n−6) from plasma into each of 80 brain regions, using quantitative autoradiography and intravenously injected [1–14C]AA. Compared with control rats infused with artificial cerebrospinal fluid (aCSF),k* was increased significantly in 25 brain areas, many of them close to the CSF compartments, following 6‐days of LPS infusion. The increases, ranging from 31 to 76%, occurred in frontal, motor, somatosensory, and olfactory cortex, thalamus, hypothalamus, and septal nuclei, and basal ganglia. Following 28 days of LPS infusion,k* was increased significantly in only two brain regions. Direct analyses of microwaved brain showed that 93 ± 3 (SD) and 94 ± 4% of brain radioactivity was in the organic extract as radiolabeled AA in the 6‐day control and LPS‐infused animals, respectively, compared with 91 ± 3 and 87 ± 6% in the 28‐day control and LPS‐infused animals. These results confirm that brain AA metabolism is disturbed after 6 days of LPS exposure, show this increase is transient, and that these changes can be detected and localized usingin vivoimaging with radiolabeled AA.
Recombinant DNA vaccine encoding multiple domains related to inhibition of neurite outgrowth: a potential strategy for axonal regeneration
Authors: Xu Gang , Nie Du‐Yu , Chen Ju‐Tao , Wang Chao‐Yang , Yu Feng‐Gang , Sun Li , Luo Xue‐Gang , Ahmed Sohail , David Samuel , Xiao Zhi‐Cheng
Published: November 2004

Myelin‐derived proteins, such as tenascin‐R (TN‐R), myelin associate glycoprotein (MAG), and Nogo‐A, inhibit the CNS regeneration. By targeting specifically the inhibitory epitopes, we have investigated whether vaccination with a recombinant DNA molecule encoding multiple domains of myelin inhibitors may be useful in CNS repair. We show here that the recombinant DNA vaccine is able to activate the immune system but does not induce experimental autoimmune encephalomyelitis (EAE) in Lewis rats. Importantly, it promotes axonal regeneration in a spinal cord injury model. Thus, the application of DNA vaccine, encoding multiple specific domains of major inhibitory proteins and/or their receptors, provides another promising approach to overcome the inhibitory barriers during CNS regeneration.
STARTING DOWN THE ROAD TO POWER: THE DENVER AREA LABOR FEDERATION
Authors: Luce Stephanie , Nelson Mark
Published: November 2004

The growing influence of an antilabor Republican party is placing organized labor in Denver under siege. In the last several years, led by the revitalized Denver Area Labor Federation, unions are challenging aggressive efforts by the state political establishment. The article examines the historical trajectory of labor's fall and how the labor council today is combating the efforts to crush unions in the city. Since the mid‐1990s, the Denver Area Labor Federation (DALF) has undergone striking changes. This article examines the historical background of the DALF and the broader Denver area labor movement, and analyzes the labor movement's efforts to revive local labor power. In this essay, we review the work of DALF, and analyze the efforts to build power at the local level. In particular, we assess DALF according to six criteria: (1) coalition building; (2) preparing for governance; (3) shifting the public debate; (4) leadership development; (5) tangible victories; and (6) new organizing. Finally, we conclude with a discussion of some of the challenges DALF has faced in meeting their goals and the lessons we can draw from DALF's experience.1
Renal effects of Tamm-Horsfall protein (uromodulin) deficiency in mice
Authors: Bachmann Sebastian , Mutig Kerim , Bates James , Welker Pia , Geist Beate , Gross Volkmar , Luft Friedrich C. , Alenina Natalia , Bader Michael , Thiele Bernd J. , Prasadan Krishna , Raffi Hajamohideen S. , Kumar Satish
Published: November 2004

The Tamm-Horsfall protein (THP; uromodulin), the dominant protein in normal urine, is produced exclusively in the thick ascending limb of Henle's loop. THP mutations are associated with disease; however, the physiological role of THP remains obscure. We generated THP gene-deficient mice (THP −/−) and compared them with wild-type (WT) mice. THP −/− mice displayed anatomically normal kidneys. Steady-state electrolyte handling was not different between strains. Creatinine clearance was 63% lower in THP −/− than in WT mice ( P < 0.05). Sucrose loading induced no changes between strains. However, water deprivation for 24 h decreased urine volume from 58 ± 9 to 28 ± 4 μl·g body wt−1·24 h−1 in WT mice ( P < 0.05), whereas in THP −/− mice this decrease was less pronounced (57 ± 4 to 41 ± 5 μl·g body wt−1·24 h−1; P < 0.05), revealing significant interstrain difference ( P < 0.05). We further used RT-PCR, Northern and Western blotting, and histochemistry to study renal transporters, channels, and regulatory systems under steady-state conditions. We found that major distal transporters were upregulated in THP −/− mice, whereas juxtaglomerular immunoreactive cyclooxygenase-2 (COX-2) and renin mRNA expression were both decreased in THP −/− compared with WT mice. These observations suggest that THP influences transporters in Henle's loop. The decreased COX-2 and renin levels may be related to an altered tubular salt load at the macula densa, whereas the increased expression of distal transporters may reflect compensatory mechanisms. Our data raise the hypothesis that THP plays an important regulatory role in the kidney.
Simultaneous Contribution of Two Rod Pathways to AII Amacrine and Cone Bipolar Cell Light Responses
Authors: Trexler E. Brady , Li Wei , Massey Stephen C.
Published: November 2004

Rod signals traverse several synapses en route to cone bipolar cells. In one pathway, rods communicate directly with cones via gap junctions. In a second pathway, signals flow rods-rod bipolars-AII amacrines-cone bipolars. The relative contribution of each pathway to retinal function is not well understood. Here we have examined this question from the perspective of the AII amacrine. AIIs form bidirectional electrical synapses with on cone bipolars. Consequently, as on cone bipolars are activated by outer plexiform inputs, they too should contribute to the AII response. Rod bipolar inputs to AIIs were blocked by AMPA receptor antagonists, revealing a smaller, non-AMPA component of the light response. This small residual response did not reverse between −70 and +70 mV and was blocked by carbenoxolone, suggesting that the current arose in on cone bipolars and was transmitted to AIIs via gap junctions. The residual component was evident for stimuli 2 log units below cone threshold and was prolonged for bright stimuli, demonstrating that it was rod driven. Because the rod bipolar-AII pathway was blocked, the rod-driven residual current likely was generated via the rod-cone pathway activation of on cone bipolars. Thus for a large range of intensities, rod signals reach the inner retina by both rod bipolar-AII and rod-cone coupling pathways.
Peaked Encoding of Relative Luminance in Macaque Areas V1 and V2
Authors: Peng Xinmiao , Van Essen David C.
Published: November 2004

It is widely presumed that throughout the primate visual pathway neurons encode the relative luminance of objects (at a given light adaptation level) using two classes of monotonic function, one positively and the other negatively sloped. Based on computational considerations, we hypothesized that early visual cortex also contains neurons preferring intermediate relative luminance values. We tested this hypothesis by recording from single neurons in areas V1 and V2 of alert, fixating macaque monkeys during presentation of a large, spatially uniform patch oscillating slowly in luminance and surrounded by a static texture background. A substantial subset of neurons responsive to such low spatial frequency luminance stimuli in both areas exhibited prominent and statistically reliable response peaks to intermediate rather than minimal or maximal luminance values. When presented with static patches of different luminance but of the same spatial configuration, most neurons tested retained a preference for intermediate relative luminance. Control experiments using luminance modulation at multiple low temporal frequencies or reduced amplitude indicate that in the slow luminance-oscillating paradigm, responses were more strongly modulated by the luminance level than the rate of luminance change. These results strongly support our hypothesis and reveal a striking cortical transformation of luminance-related information that may contribute to the perception of surface brightness and lightness. In addition, we tested many luminance-sensitive neurons with large chromatic patches oscillating slowly in luminance. Many cells, including the gray-preferring neurons, exhibited strong color preferences, suggesting a role of luminance-sensitive cells in encoding information in three-dimensional color space.
Pharmacological Properties and Functional Role of a TRP-Related Ion Channel in Lobster Olfactory Receptor Neurons
Authors: Bobkov Yuriy V. , Ache Barry W.
Published: November 2004

Odors activate lobster olfactory receptor neurons (ORNs) through phosphoinositide signaling that appears to target a Na+-gated nonselective cation channel. The Na+-gated channel is a potential member of the growing family of transient receptor potential (TRP) channels. Here, we test the effect of potential antagonists on the channel in cell-free patches from cultured lobster ORNs. We show that the channel is antagonized by H+ and the TRP channel blockers 2-aminoethoxydiphenyl borate, SKF96365 , ruthenium red, Al3+, Gd3+, and La3+. We then use this enhanced antagonist profile together with the agonists Na+ and Ca2+ to implicate the channel in signal amplification in the cells.
Identification of new targets ofDrosophilapre-mRNA adenosine deaminase
Authors: Xia Shuli , Yang Jinghua , Su Yingjun , Qian Jiang , Ma Enbo , Haddad Gabriel G.
Published: November 2004

Adenosine deaminase acting on RNA (ADAR) in Drosophila and mammals has recently become the target of numerous investigations. It is now clear that this protein has a number of functions in the nervous system. Indeed, the mutation of ADAR in Drosophila (dADAR) results in many pathological and physiological changes, such as sensitivity to hypoxia and neuronal degeneration. To understand the full scope of dADAR function, it is crucial to identify new dADAR targets. A polyclonal antibody against inosine was developed and used to enrich inosine-containing mRNAs. The efficiency of immunoaffinity purification was confirmed for the Q/R editing site of GluR-B pre-mRNA that has been edited by ADAR2 to generate inosines at the editing site. This approach was applied to enrich inosine-containing mRNAs from total mRNAs of wild-type and dADAR mutant flies, respectively. The enriched mRNA portion was then amplified and hybridized with Drosophila cDNA arrays. With this method, over 500 mRNAs were identified as potential dADAR targets by showing a higher amount in the enriched mRNA portion from wild-type flies than from dADAR mutant flies. The occurrence of A-to-G conversion in these mRNAs was further analyzed by comparing over 7,000 Drosophila cDNAs sequences with their genomic sequences. A final list of 62 candidates was generated from the overlap of the two approaches. Twelve genes from the final list were further examined by sequencing the RT-PCR products of these genes from wild-type and dADAR mutant flies. Seven of the 12 genes were proven to have A-to-G changes in the wild-type but not in mutant flies. We conclude that the combination of immunoaffinity enrichment of inosine-containing mRNA, DNA microarrays, and sequence comparison could facilitate the discovery of new dADAR substrates, which in turn allows us to better understand the targets of dADAR and the biological function of A-to-I RNA editing in flies.
Early Intertwin Differences in Myocardial Performance During the Twin-to-Twin Transfusion Syndrome
Authors: Raboisson M.J. , Fouron J.C. , Lamoureux J. , Leduc L. , Grignon A. , Proulx F. , Gamache S.
Published: November 2004

Background—

In the twin-to-twin transfusion syndrome (TTTS), pressure rather than volume overload is increasingly considered as a key factor in the pathogenesis of the cardiomyopathy of the recipient twin. If this is the case, cardiac dysfunction should be among the first signs observed with TTTS. The objective of this study was to determine whether intertwin differences in myocardial function are modified early in the course of TTTS and whether they can help to differentiate this condition from intrauterine growth restriction (IUGR).

Methods and Results—

Eight variables were analyzed on the first fetal echocardiography on 21 pairs of twins with TTTS and 11 with IUGR. No difference was found between the 2 groups for the cardiothoracic ratio, pulsatility indices in the umbilical and middle cerebral arteries, and peak velocity of the middle cerebral artery. Significant difference was found for ventricular septal thickness, but with no association with the conditions under study. With TTTS, left ventricular shortening fraction was consistently greater in the donor twins, and myocardial performance indices (MPIs) were elevated in the recipient twins. This increase in MPI was caused by a lengthening of the isovolumic periods compared with those of the donor twin: left ventricular and right ventricular isovolumic periods 0.105±0.047 and 0.097±0.026 seconds, respectively, for the recipient twins versus 0.0561±0.46 and 0.065±0.03 seconds, respectively, for the donor twins (
P
<0.001). These changes in the isovolumic periods were mainly due to significant prolongation of isovolumic relaxation times. A change in left ventricular MPI ≥0.09 combined with a change in right ventricular MPI ≥0.05 would identify a TTTS with a sensitivity of 75% and a false-positive rate of 9%.

Conclusions—

The observed diastolic function impairment goes along with the pressure-overload pathogenic concept proposed in TTTS. Assessment of intertwin difference in MPI is a valuable tool for early differential diagnosis between TTTS and isolated IUGR.
Technique and Results of Linear Ablation at the Mitral Isthmus
Authors: Jaïs Pierre , Hocini Mélèze , Hsu Li-Fern , Sanders Prashanthan , Scavee Christophe , Weerasooriya Rukshen , Macle Laurent , Raybaud Florence , Garrigue Stéphane , Shah Dipen C. , Le Metayer Philippe , Clémenty Jacques , Haïssaguerre Michel
Published: November 2004

Background—

This prospective clinical study evaluates the feasibility and efficacy of combined linear mitral isthmus ablation and pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF).

Methods and Results—

One hundred consecutive patients (13 women; age 55±10 years) with drug-refractory, symptomatic paroxysmal AF underwent PV isolation and linear ablation of the cavotricuspid isthmus and the mitral isthmus (lateral mitral annulus to the left inferior PV). They were compared with 100 consecutive patients (14 women; age, 52±10 years) undergoing PV isolation and cavotricuspid ablation without mitral isthmus ablation. Bidirectional mitral isthmus block was confirmed by demonstrating (1) a parallel corridor of double potentials during coronary sinus (CS) pacing, (2) an activation detour by pacing either side of the line, and (3) differential pacing techniques. Isolation of all PVs and cavotricuspid isthmus ablation were performed successfully in all. Mitral isthmus block was achieved in 92 patients after 20±10 minutes of endocardial radiofrequency application and an additional 5±4 minutes of epicardial radiofrequency application from within the CS in 68, resulting in a conduction delay of 151±26 ms during CS pacing. Thirty-two patients with mitral isthmus ablation compared with 49 without had recurrent atrial arrhythmia (
P
=0.02) requiring further ablation. At 1 year after the last procedure, 87 patients with mitral isthmus ablation and 69 without (
P
=0.002) were arrhythmia free without antiarrhythmic drugs, mitral isthmus ablation being the only factor associated with long-term success (RR for AF recurrence, 0.2; CI, 0.1 to 0.4;
P
<0.001).

Conclusions—

Catheter ablation of the mitral isthmus results consistently in demonstrable conduction block and is associated with a high cure rate for paroxysmal AF.
Inhibition of Vascular Smooth Muscle Cell Proliferation and Neointimal Formation in Injured Arteries by a Novel, Oral Mitogen-Activated Protein Kinase/Extracellular Signal–Regulated Kinase Inhibitor
Authors: Gennaro Giuseppa , Ménard Catherine , Michaud Sophie-Élise , Deblois Denis , Rivard Alain
Published: November 2004

Background—

Mitogen-activated protein kinases (MAPKs) are rapidly induced after arterial injury in different animal models. However, their precise role in vascular smooth muscle cell (VSMC) proliferation and neointimal formation in vivo remains to be determined.

Methods and Results—

We investigated the properties of a novel, selective inhibitor of the upstream kinase, MAPK/extracellular signal–regulated kinase, that is orally active (PD0185625). In vitro, PD0185625 was shown to abrogate p44/p42 MAPK activation in VSMCs after serum stimulation. This was associated with a dose-dependent inhibition of VSMC proliferation. In vivo, PD0185625 was administered orally to rats (200 mg · kg
−1
· d
−1
) beginning 2 days before balloon injury of the left carotid artery and for 2 weeks thereafter. Treatment with PD0185625 led to nearly complete inhibition of p44/p42 MAPK activation after balloon injury. This resulted in a significant decrease in VSMC proliferation (BrdU incorporation) at day 7 after injury. Moreover, neointimal formation was significantly reduced in PD0185625-treated animals at 14 and 28 days after arterial injury. We found that PD0185625 did not increase the rate of apoptotic cell death but prevented cell cycle progression and induced a G1 block.

Conclusions—

PD0185625 reduced neointimal formation after arterial injury. The mechanism involved inhibition of VSMC proliferation via a G1 block of the cell cycle. Orally active selective MAPK inhibitors could represent a novel therapeutic approach for vascular diseases.
Gelatin Hydrogel Microspheres Enable Pinpoint Delivery of Basic Fibroblast Growth Factor for the Development of Functional Collateral Vessels
Authors: Hosaka Akihiro , Koyama Hiroyuki , Kushibiki Toshihiro , Tabata Yasuhiko , Nishiyama Nobuhiro , Miyata Tetsuro , Shigematsu Hiroshi , Takato Tsuyoshi , Nagawa Hirokazu
Published: November 2004

Background—

Various growth factors promote collateral vessel development and are regarded as promising for the treatment of vascular occlusive diseases. However, an efficacious delivery system for them has yet to be established. We devised a strategy to augment functional collateral vessels by using acidic gelatin hydrogel microspheres (AGHMs) incorporating basic fibroblast growth factor (bFGF). The aim of the present study was to investigate the hypothesis that by intra-arterial (IA) administration of bFGF-impregnated AGHMs, bFGF could be delivered from AGHMs trapped in distal small-diameter vessels and thereby induce functional collateral vessels with an assured blood supply through the process of arteriogenesis.

Methods and Results—

Various sizes of AGHMs (3 mg) incorporating
125
I-labeled bFGF were injected into the left internal iliac artery of a rabbit model of hindlimb ischemia. Less than 50% of radioactivity accumulated in the ischemic hindlimb after injection of AGHMs that were 10 μm in diameter, whereas ≈80% of radioactivity was counted in the ischemic limb after administration of 29- or 59-μm-diameter AGHMs. Calf blood pressure ratio and the ratio of regional blood flow of the bilateral hindlimbs immediately before and after IA administration of 29-μm–diameter AGHMs showed no significant change. Then we evaluated the function of the developed collateral vessels 28 days after IA administration of bFGF-impregnated, 29-μm-diameter AGHMs. IA administration of bFGF-impregnated AGHMs induced marked collateral vessel improvement compared with IA administration of phosphate buffered saline–treated AGHMs and intramuscular administration of bFGF-impregnated AGHMs.

Conclusions—

IA administration of bFGF-impregnated, 29-μm-diameter AGHMs strongly induced functional collateral vessels without worsening ischemia, indicating the possible therapeutic usefulness of this approach.
Sex Differences in the Mate Selection Process Of the Monogamous, Biparental Convict Cichlid, Archocentrus Nigrofasciatum
Authors: Itzkowitz  , Santangelo Nick
Published: November 2004

Compared to polygynous species, monogamous males and females are considered more similar in their mate choosiness, yet few studies have explored the mate selection process between the sexes. Here, we examined this mate selection process in the monogamous convict cichlid, Archocentrus nigrofasciatus. We presented an individual (i.e. the selector) of each sex with a choice of two alternative, visually and tactilely isolated, mates. Tanks were video taped each day until the selector fish spawned with one of the potential mates (i.e. the accepted mate). The number of visits, length of visits, and courtship interactions were recorded. Selecting females spent significantly more time with accepted versus rejected males (i.e. females expressed a time-based preference for their chosen males), but there was no significant difference in the number of visits made to either male. Selecting females did not court accepted and rejected males differently, but rejected males courted at a significantly higher rate than did accepted males. Although selecting females expressed a time-based preference for accepted males, they continued to visit and court rejected males throughout the mate choice process; thus females did not terminate their selection process until they spawned. In contrast to selecting females, selecting males did not spend a significantly different amount of time with accepted and rejected females while visiting both females equally. Furthermore, selecting males courted accepted females significantly more than they courted rejected females. Thus, males expressed their mate preferences through courtship whereas females expressed them through time spent. Males also courted more than females. Many of these sex differences curiously resemble those of a polygynous social system, which we suggest perhaps indicates polygynous ancestral origins.
Non-breeding Nazca Boobies (Sula Granti) Show Social and Sexual Interest in Chicks: Behavioural and Ecological Aspects
Authors: Porter Elaine , Anderson David , Ferree Elise
Published: November 2004

Adult Nazca boobies (Sula granti) show an unusual interest in both conspecific and congeneric nestlings, visiting them at their nest sites and performing mixtures of affiliative, aggressive, and sexual behaviours. Using a 20 year database from a large Nazca booby colony on Isla Española, Galápagos Islands, Ecuador, we describe the behaviour and the individuals performing the behaviour. Non-parental Adult Visitors ('NAVs') are typically 'unemployed' (non-breeding birds or recently failed breeders), and make visits of 1-60 min to unguarded chicks. Males and females are equally likely to exhibit the behaviour, if they are unemployed; since most unemployed birds are male, due to a sex ratio bias, most NAVs are male. Very young chicks and chicks nearing fledging are not visited, because young chicks are always attended by protective parents, and old chicks can defend themselves. When acting affiliatively, NAVs may simply stand by the chick, or may preen it and present gifts of pebbles and feathers. Aggression by the NAV often leaves scratches on the chick's body, but seldom causes the chick's death directly. However, landbirds take blood-meals from the scratches during food shortages, deepening the wound and eventually killing the chick. The least common NAV behaviour is sexual, in which adults perform male copulatory behaviour with the chick. Sexual behaviour occurs in 14.3% of visits by males, and 6.8% of visits by females. NAV behaviour is the direct or indirect cause of mortality of up to 24.6% of chicks, representing up to 41.6% of all deaths, in a given year. Approximately 80% of non-breeding birds in a given year show NAV behaviour, and since most adults are non-breeders at some point in life, most adults show NAV behaviour at some point. We propose a number of hypotheses to explain the causation of this puzzling and ecologically important behaviour.
Resistance to the root-knot nematode Meloidogyne fallax in Solanum sparsipilum: analysis of the mechanisms
Authors: Kouassi Abou Bakari , Kerlan Marie-Claire , Sobczak Miroslaw , Dantec Jean-Paul , Rouaux Claudia , Ellissèche Daniel , Mugniéry Didier
Published: November 2004

The genotype 88S.329.15 of Solanum sparsipilum was studied in order to analyse the genetic basis and the mechanisms of its resistance to Meloidogyne fallax. In infected plants grown at 20°C, juveniles invaded the root system with a clear delay and a lower infection rate in comparison to the susceptible S. tuberosum genotype BF15 H1. No defence reaction occurred during root invasion and migration toward the vascular cylinder. The juveniles induced development of feeding sites usually composed of several giant cells, which contained condensed cytoplasm, only small vacuoles, enlarged nuclei with pronounced nucleoli and almost no endoplasmic reticulum. Abundant necrosis of surrounding parenchymatous vascular cylinder cells lead to the degeneration of the giant cells. More than 90% of the invading juveniles failed to develop. The others developed as males. The resistance inheritance was analysed on 128 F1 hybrids obtained using the susceptible line BF15 H1 as the female parent and 88S.329.15 as the male parent. Among the progenies, 68 genotypes produced a necrotic reaction to nematode infection and 60 produced no necrosis. This 1 : 1 segregation pattern suggests a monogenic control of this defence reaction. Unlike the resistant parent 88S.329.15, some M. fallax females developed in the roots of necrotically responding hybrids. There was a normal distribution of mean numbers of adult females found in the roots of these genotypes. This result suggests that the ability of the resistant genotype 88S.329.15 to suppress development of females is quantitatively inherited and likely to be controlled by more than one locus. These data indicate that the mechanism of resistance is different from the resistance to Meloidogyne incognita conferred by the Mi gene of tomato.
"Religion" and the Problem of the Governable Self; or How to Live in a Less than Perfect Nation
Authors: McCutcheon Russell
Published: November 2004

The category "religion"—along with the binary pairs that attend it (e.g., sacred/secular, Church/State, etc.)—deserves as much attention as has been devoted by scholars throughout the human sciences to the social and political roles played by other pairs, such as pure/impure, raw/cooked, male/female, and citizen/foreigner. Just as with these pairings, the church/state binary refers not to stable and separable zones of human practice, but is part of a classification system that manages a competitive social and political economy by segmenting certain forms of behavior and organization—whether as a means to authorize or deauthorize them. When understood to refer to an inner zone of experience and feeling, the rhetorics of "religion" and "faith" should therefore be studied as techniques of governance, not as neutrally descriptive names given to pre-existent things existing in the world or in the human heart.
C1 inhibitor prevents Gram-negative bacterial lipopolysaccharide-induced vascular permeability
Authors: Liu Dongxu , Zhang Dong , Scafidi Jennifer , Wu Xiao , Cramer Cort C. , Davis Alvin E.
Published: November 2004

Gram-negative bacterial endotoxemia may lead to the pathological increase of vascular permeability with systemic vascular collapse, a vascular leak syndrome, multiple organ failure (MOF), and/or shock. Previous studies demonstrated that C1 inhibitor (C1INH) protects mice from lipopolysaccharide (LPS)–induced lethal septic shock via a direct interaction with LPS. Here, we report that C1INH blocked the LPS-induced increase in transendothelial flux through an endothelial monolayer. In addition, LPS-mediated detachment of cultured endothelial cells was prevented with C1INH. C1INH also inhibited LPS-induced endothelial cell apoptosis as demonstrated by suppression of DNA fragmentation and annexin V expression. As illustrated by laser scanning confocal microscopy, C1INH completely blocked the binding of fluorescein isothiocyanate (FITC)–LPS to human umbilical vein endothelial cells (HUVECs). C1INH protected from localized LPS-induced increased plasma leakage in C57BL/6J mice and in C1INH-deficient mice. Local vascular permeability in response to LPS was increased to a greater extent in C1INH-deficient mice compared with wild-type littermate controls and was reversed by treatment with C1INH. Systemic administration of LPS to mice resulted in increased vascular permeability, which was reduced by C1INH. Therefore, these studies demonstrate that C1INH, in addition to its role in suppression of LPS-mediated macrophage activation, may play an important role in the prevention of LPS-mediated increased vascular permeability, endothelial cell injury, and multiple organ failure.
Stimulation with 4-1BB (CD137) inhibits chronic graft-versus-host disease by inducing activation-induced cell death of donor CD4+ T cells
Authors: Kim Juyang , Choi Woon S. , La Soojin , Suh Jae-Hee , Kim Byoung-Sam , Cho Hong R. , Kwon Byoung S. , Kwon Byungsuk
Published: November 2004

4-1BB, a member of the tumor necrosis factor (TNF) receptor superfamily, is a costimulator for activated T cells. Previous studies have established that treatment with agonistic anti–4-BB monoclonal antibody (3H3) is effective in reversing the progression of spontaneous systemic lupus erythematosus. Its therapeutic effect is mediated by suppression of autoantibody production. In this report, we show that a single injection of 3H3 blocks chronic graft-versus-host disease (cGVHD) in the parent-into-F1 model. In particular, donor CD4+ T cells are rapidly eliminated from host spleens by activation-induced cell death after 4-1BB triggering. Since donor CD4+ T cells are required for the development of cGVHD, and 3H3-mediated inhibition of autoantibody production occurs without donor CD8+ T cells, 3H3 blocks cGVHD by preventing alloreactive donor CD4+ T cells from activating host B cells. Importantly, 3H3 treatment can reverse the progression of advanced cGVHD. Our findings indicate that agonistic anti–4-1BB monoclonal antibody has potential as an immunotherapeutic agent for preventing and treating cGVHD.
The earliest subpopulation of mouse thymocytes contains potent T, significant macrophage, and natural killer cell but no B-lymphocyte potential
Authors: Balciunaite Gina , Ceredig Rhodri , Rolink Antonius G.
Published: November 2004

The B-lymphocyte potential of progenitor thymocytes and whether the thymus is colonized by common lymphocyte progenitor cells have been subjects of considerable debate. Herein, we have used limiting dilution analysis to determine the lineage potential of phenotypically defined subpopulations of CD4–CD8– double-negative thymocytes. Culture systems used showed single-hit kinetics and had a high plating efficiency for B-, myeloid, and natural killer cell development. The T-cell potential of sorted cells was confirmed by transferring cells to fetal thymus organ cultures. Our results indicate that the earliest population of CD117+ double-negative cells, although containing potent T-cell developmental potential and significant myeloid and natural killer potential, does not have any residual B-cell potential. Gene transcription analysis also indicated that these double-negative cells contained abundant T and myeloid, but not B cell–specific transcripts. The implications of these results within the context of current models of thymocyte development are discussed.
Prospective isolation and global gene expression analysis of the erythrocyte colony-forming unit (CFU-E)
Authors: Terszowski Grzegorz , Waskow Claudia , Conradt Peter , Lenze Dido , Koenigsmann Jessica , Carstanjen Dirk , Horak Ivan , Rodewald Hans-Reimer
Published: November 2004

The erythrocyte colony-forming unit (CFU-E) is a rare bone marrow (BM) progenitor that generates erythrocyte colonies in 48 hours. The existence of CFU-Es is based on these colonies, but CFU-Es have not been purified prospectively by phenotype. We have separated the “nonstem,” “nonlymphoid” compartment (lineage marker [lin]–c-Kit+Sca-1–IL-7Rα–) into interleukin 3 receptor α negative (IL-3Rα–) and IL-3Rα+ subsets. Within IL-3Rα– but not IL-3Rα+ cells we have identified TER119–CD41–CD71+ erythrocyte-committed progenitors (EPs). EPs generate CFU-E colonies at about 70% efficiency and generate reticulocytes in vivo. Depletion of EPs from BM strongly reduces CFU-E frequencies. EPs lack potential for erythrocyte burst-forming unit, megakaryocyte, granulocyte (G), and monocyte (M) colonies, and for spleen colony-forming units. Chronically suppressed erythropoiesis in interferon consensus sequence-binding protein (ICSBP)–deficient BM is associated with reduced frequencies of both the EP population and CFU-E colonies. During phenylhydrazine-induced acute anemia, numbers of both the EP population and CFU-E colonies increase. Collectively, EPs (lin–c-Kit+Sca-1–IL-7Rα–IL-3Rα–CD41–CD71+) account for most, if not all, CFU-E activity in BM. As a first molecular characterization, we have compared global gene expression in EPs and nonerythroid GM progenitors. These analyses define an erythroid progenitor-specific gene expression pattern. The prospective isolation of EPs is an important step to analyze physiologic and pathologic erythropoiesis.
A probabilistic model for the evolution of RNA structure
Authors: Holmes Ian
Published: November 2004

Background

For the purposes of finding and aligning noncoding RNA gene- and cis-regulatory elements in multiple-genome datasets, it is useful to be able to derive multi-sequence stochastic grammars (and hence multiple alignment algorithms) systematically, starting from hypotheses about the various kinds of random mutation event and their rates.

Results

Here, we consider a highly simplified evolutionary model for RNA, called "The TKF91 Structure Tree" (following Thorne, Kishino and Felsenstein's 1991 model of sequence evolution with indels), which we have implemented for pairwise alignment as proof of principle for such an approach. The model, its strengths and its weaknesses are discussed with reference to four examples of functional ncRNA sequences: a riboswitch (guanine), a zipcode (nanos), a splicing factor (U4) and a ribozyme (RNase P). As shown by our visualisations of posterior probability matrices, the selected examples illustrate three different signatures of natural selection that are highly characteristic of ncRNA: (i) co-ordinated basepair substitutions, (ii) co-ordinated basepair indels and (iii) whole-stem indels.

Conclusions

Although all three types of mutation "event" are built into our model, events of type (i) and (ii) are found to be better modeled than events of type (iii). Nevertheless, we hypothesise from the model's performance on pairwise alignments that it would form an adequate basis for a prototype multiple alignment and genefinding tool.
Hospitalization for heart disease, stroke, and diabetes mellitus among Indian-born persons: a small area analysis
Authors: Muennig Peter , Jia Haomiao , Khan Kamran
Published: November 2004

Background

We set out to describe the risk of hospitalization from heart disease, stroke, and diabetes among persons born in India, all foreign-born persons, and U.S.-born persons residing in New York City.

Methods

We examined billing records of 1,083,817 persons hospitalized in New York City during the year 2000. The zip code of each patient's residence was linked to corresponding data from the 2000 U.S. Census to obtain covariates not present in the billing records. Using logistic models, we evaluated the risk of hospitalization for heart disease, stroke and diabetes by country of origin.

Results

After controlling for covariates, Indian-born persons are at similar risk of hospitalization for heart disease (RR = 1.02, 95% confidence interval 1.02, 1.03), stroke (RR = 1.00, 95% confidence interval, 0.99, 1.01), and diabetes mellitus (RR = 0.96 95% confidence interval 0.94, 0.97) as native-born persons. However, Indian-born persons are more likely to be hospitalized for these diseases than other foreign-born persons. For instance, the risk of hospitalization for heart disease among foreign-born persons is 0.70 (95% confidence interval 0.67, 0.72) and the risk of hospitalization for diabetes is 0.39 (95% confidence interval 0.37, 0.42) relative to native-born persons.

Conclusions

South Asians have considerably lower rates of hospitalization in New York than reported in countries with national health systems. Access may play a role. Clinicians working in immigrant settings should nonetheless maintain a higher vigilance for these conditions among Indian-born persons than among other foreign-born populations.
Physical function and associations with diet and exercise: Results of a cross-sectional survey among elders with breast or prostate cancer
Authors: Demark-Wahnefried Wendy , Clipp Elizabeth C , Morey Miriam C , Pieper Carl F , Sloane Richard , Snyder Denise Clutter , Cohen Harvey J
Published: November 2004

Background

Functional decline threatens independent living and is common among individuals diagnosed with cancer, especially those who are elderly. The purpose of this study was to explore whether dietary and exercise practices are associated with physical function status among older cancer survivors.

Methods

Mailed surveys were used to ascertain data on physical function, dietary fat, fruit and vegetable (F&V) consumption, and exercise among elderly diagnosed with early stage (I-II) breast (N = 286) or prostate cancer (N = 402) within the past 18 months.

Results

Sixty-one percent of respondents reported diets with <30% of energy from fat, 20.4% reported F&V intakes of 5+ daily servings, and 44.6% reported regular vigorous exercise. Significant, independent associations were found between physical functioning and reported dietary fat intake, F&V consumption, and exercise. A simultaneous multiple regression model controlled for age, race, gender, time since diagnosis and concurrent health behaviors yielded the following estimates: (1) 0.2 increase in the SF-36 physical function subscale (PFS) score with each reported 1% decrease in percent energy from fat (p < .0001); (2) 0.9 increase in the SF-36 PFS score for each reported serving of F&V/day (p = .0049); and (3) 15.4 increase in the SF-36 PFS score with a positive response for regular vigorous exercise (p < .0001).

Conclusions

Results of this cross-sectional survey suggest that regular vigorous exercise and consumption of diets low in fat and rich in F&Vs are associated with higher levels of physical functioning among older cancer survivors. Interventions that promote healthful lifestyle change may deliver considerable benefit within this ever increasing and vulnerable population.
A swimming robot actuated by living muscle tissue
Authors: Herr Hugh , Dennis Robert G
Published: November 2004

Biomechatronics is the integration of biological components with artificial devices, in which the biological component confers a significant functional capability to the system, and the artificial component provides specific cellular and tissue interfaces that promote the maintenance and functional adaptation of the biological component. Based upon functional performance, muscle is potentially an excellent mechanical actuator, but the larger challenge of developing muscle-actuated, biomechatronic devices poses many scientific and engineering challenges. As a demonstratory proof of concept, we designed, built, and characterized a swimming robot actuated by two explanted frog semitendinosus muscles and controlled by an embedded microcontroller. Using open loop stimulation protocols, the robot performed basic swimming maneuvers such as starting, stopping, turning (turning radius ~400 mm) and straight-line swimming (max speed >1/3 body lengths/second). A broad spectrum antibiotic/antimycotic ringer solution surrounded the muscle actuators for long term maintenance, ex vivo. The robot swam for a total of 4 hours over a 42 hour lifespan (10% duty cycle) before its velocity degraded below 75% of its maximum. The development of functional biomechatronic prototypes with integrated musculoskeletal tissues is the first critical step toward the long term objective of controllable, adaptive and robust biomechatronic robots and prostheses.
Perioperative factors determine outcome after surgery for severe acute pancreatitis
Authors: De Waele Jan J , Hoste Eric , Blot Stijn I , Hesse Uwe , Pattyn Piet , de Hemptinne Bernard , Decruyenaere Johan , Vogelaers Dirk , Colardyn Francis
Published: November 2004

Introduction

There is evidence that postponing surgery in critically ill patients with severe acute pancreatitis (SAP) leads to improved survival, but previous reports included patients with both sterile and infected pancreatic necrosis who were operated on for various indications and with different degrees of organ dysfunction at the moment of surgery, which might be an important bias. The objective of this study is to analyze the impact of timing of surgery and perioperative factors (severity of organ dysfunction and microbiological status of the necrosis) on mortality in intensive care unit (ICU) patients undergoing surgery for SAP.

Methods

We retrospectively (January 1994 to March 2003) analyzed patients admitted to the ICU with SAP. Of 124 patients, 56 were treated surgically; these are the subject of this analysis. We recorded demographic characteristics and predictors of mortality at admission, timing of and indications for surgery, and outcome. We also studied the microbiological status of the necrosis and organ dysfunction at the moment of surgery.

Results

Patients' characteristics were comparable in patients undergoing early and late surgery, and there was a trend toward a higher mortality in patients who underwent early surgery (55% versus 29%, P = 0.06). In univariate analysis, patients who died were older, had higher organ dysfunction scores at the day of surgery, and had sterile necrosis more often; there was a trend toward earlier surgery in these patients. Logistic regression analysis showed that only age, organ dysfunction at the moment of surgery, and the presence of sterile necrosis were independent predictors of mortality.

Conclusions

In this cohort of critically ill patients operated on for SAP, there was a trend toward higher mortality in patients operated on early in the course of the disease, but in multivariate analysis, only greater age, severity of organ dysfunction at the moment of surgery, and the presence of sterile necrosis, but not the timing of the surgical intervention, were independently associated with an increased risk for mortality.
New insights into the molecular mechanism of interleukin-10-mediated immunosuppression
Authors: Grütz Gerald
Published: November 2004

Interleukin-10 (IL-10) is an important immunomodulatory cytokine, which has attracted much attention because of its anti-inflammatory properties. It reduces antigen presentation and inhibits T cell activation. IL-10-treated myeloid cells lose their ability to respond toward the endotoxin lipopolysaccharide (LPS) with the production of several proinflammatory mediators. Thereby, IL-10 limits excessive inflammatory reactions in response to endotoxin as it occurs in colitis or endotoxin shock. Mice can be tolerized toward endotoxin shock when pretreated with a sublethal dose of LPS. This can be mimicked in vitro as LPS desensitization, resulting in a similar LPS hyporesponsiveness as observed with IL-10 pretreatment. However, an early block in LPS signaling characterizes LPS desensitization, whereas IL-10 seems to target late events. Controversial reports have been published where IL-10 would interfere with the induction of proinflammatory mediators, and little is known about the molecular mechanisms behind the anti-inflammatory activities of IL-10. Some recent publications have tried to gain more insight into the molecular mechanism of IL-10 by gene-expression profiling and functional studies in myeloid-derived cells. These results are reviewed here and compared with the progress that has been made to understand the induction of endotoxin tolerance by LPS itself.
Design and statistical issues in the homocysteinemia in kidney and end stage renal disease (HOST) study
Authors: Jamison Rex L , Hartigan Pamela , Gaziano J Michael , Fortmann Stephen P , Goldfarb David S , Haroldson Jeffrey A , Kaufman James , Lavori Philip , McCully Kilmer S , Robinson Killian
Published: November 2004

The Homocysteine Study (HOST) Veterans Affairs Cooperative Studies Program No. 453, is a prospective, randomized, two arm, double blind study of patients with end stage renal disease (ESRD) or advanced chronic kidney disease (ACKD, defined as an estimated creatinine clearance of 30 ml/min or less). Its primary objective is to determine whether administration of high doses of three vitamins, folic acid, vitamin B6 and vitamin B12, to lower the high plasma homocysteine levels, will reduce all cause mortality. The secondary objectives are to examine whether the treatment lowers the incidence of myocardial infarction, stroke, amputation of a lower extremity, a composite of death and the foregoing three events, the plasma homocysteine level, and, in ESRD patients undergoing hemodialysis, thrombosis of the vascular access. A unique feature of this trial is that after initial evaluation at enrollment and one return visit the follow up is exclusively by phone (or, if necessary, by mail). The subject is contacted every three months throughout the duration of the study from a central location. The study drug is shipped to the patient from a central location rather supplied locally. In a two year enrollment period, 2006 patients are to be enrolled. The duration of the observation period is four to six years. Data will be stored and analyzed at a coordinating center. The study design has the power to detect a reduction in all cause mortality rate of 17%. Issues related to the unique features of the design of this study are discussed.