bluuebunny/crossref_metadata_2025 huggingface dataset:
The double‐bundle technique for anterior cruciate ligament reconstruction: a systematic overview
Authors: Steckel H. , Starman J. S. , Baums M. H. , Klinger H. M. , Schultz W. , Fu F. H.
Published: November 2006

In traditional anterior cruciate ligament reconstruction, there is a subset of patients complaining of knee instability, especially rotational instability, and athletes not able to return to their preinjury level of sports activity. Currently, controversy exists over the usefulness of the double bundle technique (DBT) in addressing these problems. In order to evaluate the DBT, we completed a literature review from 1969 to February 2006 focusing on anatomy, magnetic resonance imaging, graft incorporation, biomechanics, kinematics, surgical techniques, complications and outcome. The DBT is not a standardized technique, which makes it difficult to compare results. Cadaver studies have proven biomechanical advantages with respect to ap‐stability, but assessing the rotational stability remains difficult. There is a lack of available outcome studies with sufficient follow‐up to demonstrate the potential advantages of DBT. The theoretical advantages of DBT require careful evaluation with outcome, biomechanical and kinematic studies. In addition, studies are needed to address issues such as graft incorporation and complications. An advantage offered by DBT is the possibility to identify rupture patterns that can lead to surgical preservation of an intact and augmentation of an injured bundle. The approach of augmentating a single bundle technique reconstruction with adequate anterior–posterior but poor rotational stability is promising.
IMAGING DIAGNOSIS—BACTERIAL DISKOSPONDYLITIS IN A GOAT
Authors: LEVINE GWENDOLYN J. , BISSETT WESLEY T. , COLE ROBERT C. , JANKE JARED J. , NUNES JAIRO , PORTER BRIAN , LEVINE JONATHAN M.
Published: November 2006

A 3‐year‐old intact male Boer goat was evaluated for paraplegia. Computed tomography (CT) indicated the presence of diskospondylitis, which had previously not been reported in this species, and significant compressive myelopathy. Chronic bacterial pneumonia, epididymitis, nephritis, and soft‐tissue abscesses were believed to result in hematogenous spread of bacteria to the affected disk spaces.Staphylococcusspp. andArchanobacterium pyogeneswere both identified from postmortem cultures of the vertebral column.
Featuring the President as Free Trader: Television News Coverage of U.S. Trade Politics
Authors: RANKIN DAVID M.
Published: November 2006

This article analyzes national television news coverage of U.S. trade politics from 1988 to 2002, a period consisting of relatively visible debates over free trade agreements and trade relations. It examines how television news coverage of trade emphasizes foreign and domestic conflict and national threats and challenges, which coincide with the significant media focus on presidential trade leadership and the president's rhetorical support for free and freer trade. The article thus explores how media coverage of trade provides the president with a clear and consistent mediated advantage over political opposition, including congressional members and interest groups, when it comes to the nation's trade direction and policy.
Comparative and Functional Genomic Analyses of Iron Transport and Regulation in
Leptospira
spp
Authors: Louvel H. , Bommezzadri S. , Zidane N. , Boursaux-Eude C. , Creno S. , Magnier A. , Rouy Z. , Médigue C. , Girons I. Saint , Bouchier C. , Picardeau M.
Published: November 2006

The spirochetes of the
Leptospira
genus contain saprophytic and pathogenic members, the latter being responsible for leptospirosis. Despite the recent sequencing of the genome of the pathogen
L. interrogans
, the slow growth of these bacteria, their virulence in humans, and a lack of genetic tools make it difficult to work with these pathogens. In contrast, the development of numerous genetic tools for the saprophyte
L. biflexa
enables its use as a model bacterium.
Leptospira
spp. require iron for growth. In this work, we show that
Leptospira
spp. can acquire iron from different sources, including siderophores. A comparative genome analysis of iron uptake systems and their regulation in the saprophyte
L. biflexa
and the pathogen
L. interrogans
is presented in this study. Our data indicated that, for instance,
L. biflexa
and
L. interrogans
contain 8 and 12 genes, respectively, whose products share homology with proteins that have been shown to be TonB-dependent receptors. We show that some genes involved in iron uptake were differentially expressed in response to iron. In addition, we were able to disrupt several putative genes involved in iron acquisition systems or iron regulation in
L. biflexa
. Comparative genomics, in combination with gene inactivation, gives us significant functional information on iron homeostasis in
Leptospira
spp.
The Cytotoxic Fimbrial Structural Subunit of
Xenorhabdus nematophila
Is a Pore-Forming Toxin
Authors: Banerjee Jyotirmoy , Singh Jitendra , Joshi Mohan Chandra , Ghosh Shubhendu , Banerjee Nirupama
Published: November 2006

We have purified a fimbrial shaft protein (MrxA) of
Xenorhabdus nematophila
. The soluble monomeric protein lysed larval hemocytes of
Helicoverpa armigera
. Osmotic protection of the cells with polyethylene glycol suggested that the 17-kDa MrxA subunit makes pores in the target cell membrane. The internal diameter of the pores was estimated to be >2.9 nm. Electron microscopy confirmed the formation of pores by the fimbrial subunit. MrxA protein oligomerized in the presence of liposomes. Electrophysiological studies demonstrated that MrxA formed large, voltage-gated passive-diffusion channels in lipid bilayers.
Transcription Modulation of
Salmonella enterica
Serovar Typhimurium Promoters by Sub-MIC Levels of Rifampin
Authors: Yim Grace , de la Cruz Fernando , Spiegelman George B. , Davies Julian
Published: November 2006

Promoter-
lux
fusions that showed rifampin-modulated transcription were identified from a
Salmonella enterica
serovar Typhimurium 14028 reporter library. The transformation of a subset of fusions into mutants that lacked one of six global regulatory proteins or were rifampin resistant showed that transcription modulation was independent of the global regulators, promoter specific, and dependent on the interaction of rifampin with RNA polymerase.
Genome-Wide Analysis of Light Sensing inProchlorococcus
Authors: Steglich Claudia , Futschik Matthias , Rector Trent , Steen Robert , Chisholm Sallie W.
Published: November 2006

ProchlorococcusMED4 has, with a total of only 1,716 annotated protein-coding genes, the most compact genome of a free-living photoautotroph. Although light quality and quantity play an important role in regulating the growth rate of this organism in its natural habitat, the majority of known light-sensing proteins are absent from its genome. To explore the potential for light sensing in this phototroph, we measured its global gene expression pattern in response to different light qualities and quantities by using high-density Affymetrix microarrays. Though seven different conditions were tested, only blue light elicited a strong response. In addition, hierarchical clustering revealed that the responses to high white light and blue light were very similar and different from that of the lower-intensity white light, suggesting that the actual sensing of high light is mediated via a blue-light receptor. Bacterial cryptochromes seem to be good candidates for the blue-light sensors. The existence of a signaling pathway for the redox state of the photosynthetic electron transport chain was suggested by the presence of genes that responded similarly to red and blue light as well as genes that responded to the addition of DCMU [3-(3,4-dichlorophenyl)-1,1-N-N′-dimethylurea], a specific inhibitor of photosystem II-mediated electron transport.
Conservation and Variation between
Rhodobacter capsulatus
and
Escherichia coli
Tat Systems
Authors: Lindenstrauß Ute , Brüser Thomas
Published: November 2006

The Tat system allows the translocation of folded and often cofactor-containing proteins across biological membranes. Here, we show by an interspecies transfer of a complete Tat translocon that Tat systems are largely, but not fully, interchangeable even between different classes of proteobacteria. The Tat apparatus from the α-proteobacterium
Rhodobacter capsulatus
was transferred to a Tat-deficient
Escherichia coli
strain, which is a γ-proteobacterium. Similar to that of
E. coli
, the
R. capsulatus
Tat system consists of three components, rc-TatA, rc-TatB, and rc-TatC. A fourth gene (
rc-tatF
) is present in the
rc-tatABCF
operon which has no apparent relevance for translocation. The translational starts of
rc-tatC and rc-tatF
overlap in four nucleotides (ATGA) with the preceding
tat
genes, pointing to efficient translational coupling of
rc
-
tatB
,
rc
-
tatC
, and
rc-tatF
. We show by a variety of physiological and biochemical assays that the
R. capsulatus
Tat system functionally targets the
E. coli
Tat substrates TorA, AmiA, AmiC, and formate dehydrogenase. Even a Tat substrate from a third organism is accepted, demonstrating that usually Tat systems and Tat substrates from different proteobacteria are compatible with each other. Only one exceptional Tat substrate of
E. coli
, a membrane-anchored dimethyl sulfoxide (DMSO) reductase, was not targeted by the
R. capsulatus
Tat system, resulting in a DMSO respiration deficiency. Although the general features of Tat substrates and translocons are similar between species, the data indicate that details in the targeting pathways can vary considerably.
Crl Facilitates RNA Polymerase Holoenzyme Formation
Authors: Gaal Tamas , Mandel Mark J. , Silhavy Thomas J. , Gourse Richard L.
Published: November 2006

TheEscherichia coliCrl protein has been described as a transcriptional coactivator for the stationary-phase sigma factor σS. In a transcription system with highly purified components, we demonstrate that Crl affects transcription not only by the EσSRNA polymerase holoenzyme but also by Eσ70and Eσ32. Crl increased transcription dramatically but only when the σ concentration was low and when Crl was added to σ prior to assembly with the core enzyme. Our results suggest that Crl facilitates holoenzyme formation, the first positive regulator identified with this mechanism of action.
Depositing archived paraffin tissue core biopsy specimens in paraffin tissue microarrays using a paraffin tissue punch modified with a countersink: Figure 1
Authors: Vogel Ulrich Felix
Published: November 2006

Paraffin tissue microarrays (PTMAs) introduced by Kononenet alin 1998 have become a widely used technique in routine pathology and even more so in research. Kononen used a tissue puncher/arrayer (Beecher Instruments, Sun Prairie, WI, USA) to take paraffin tissue core biopsy specimens (PTCBs) of 0.6–2 mm in diameter from routine paraffin tissue blocks and transfer them to another paraffin block with up to 1000 holes. As pointed out by Mengelet al, however, it is not possible to use the Kononen/Beecher system to construct PTMAs out of archived PTCBs. To overcome this drawback in the extremely popular Beecher system, the paraffin tissue punch was modified by incorporating a conical 4 mm deep countersink. This countersink was milled with a conical precision cutter that can be bought in an ordinary hardware store (cost <US$5). The countersink facilitates the insertion of an archived PTCB into the paraffin tissue punch and enables the construction of PTMAs with previously archived PTCBs using the widely distributed Beecher system. Moreover, this paraffin tissue punch can be used for other systems to create PTMAs, such as the low-budget systems designed by Vogel.
Heteroduplex analysis for the three common HFE variants: methodology, reliablity and analysis of over 5000 requests for testing
Authors: Kingston Jeanne , Bowen Derrick , Sweeney Marion , Lawless Susan , Jackson Helen , Worwood Mark
Published: November 2006

Objective:

To describe the analysis of over 5300 patient samples for theHFEgenotype.

Methods:

Blood samples received from hospitals in England, Wales and Ireland were analysed with a single, multiplex PCR using heteroduplex generators for the C282Y, H63D and S65C variants of theHFEgene. PCR products labelled with fluorescent dyes were analysed by capillary electrophoresis. Genotype frequencies were analysed according to the reasons given for testing.

Results:

Analysis of 400 samples sent in duplicate revealed one error that was associated with reporting rather than the methodology. Of 5327 samples received, 1122 were for family testing, 2470 for diagnostic testing and in 1735 cases no reason was given. Overall, homozygosity for C282Y was found in 14% of samples received for family testing and in 16% of the remaining samples. Clinical indications such as “liver disease” were of little predictive value for homozygosity for C282Y, but this increased if a raised serum ferritin concentration or transferrin saturation was indicated. When the diagnosis was iron overload, 39% of subjects tested were homozygous for C282Y. Compound heterozygosity (C282Y/H63D) was more frequent than in the general population but the frequency was not further increased in subjects for whom there was a diagnosis of iron overload. The frequencies of heterozygosity for H63D or S65C and homozygosity for H63D were not significantly increased in any group compared with the general population frequency.

Conclusion:

These results demonstrate the reliability of the methodology and confirm the difficulty of identifying genetic haemochromatosis purely on the basis of clinical suspicion that haemochromatosis may be responsible for liver disease, diabetes or arthritis.
RECENT PROGRESS IN ERBIUM(III)-CORED COMPLEXES BASED ON DENDRITIC LIGANDS FOR ADVANCED PHOTONICS APPLICATIONS
Authors: BAEK NAM SEOB , KIM YONG HEE , KIM HWAN KYU
Published: November 2006

We present that the stable and inert Er(III) -encapsulated complexes based on naphthalene and anthracene ligands bearing a Fréchet aryl-ether dendron exhibit much stronger near-IR emission bands bands at 1530 nm, originated from the 4f–4f electronic transition of the first excited state (4 I 13/2) to the ground state (4 I 15/2) of the partially-filled 4f shell. A strong decrease in the fluorescence of G n-aryl ether dendron (n = 0 or 2) is accompanied by strongly increasing the fluorescence intensity of the luminescent anthracene or naphthalene ligand with the generation number of the dendrons. The strong decrease of fluorescence intensity of luminescent ligand such as naphthalene and anthracene units is accompanied by strongly increasing the near infrared (IR) emission of the Er 3+ ions in Er(III) -encapsulated complexes. It could be attributed to the efficient energy transfer process occurring between the aryl-ether dendron and anthracene moiety as well as between dendritic anthracene ligand and Er 3+ ion. Thus, the emission intensity of the lanthanide complexes, upon photoexcitation of aryl-ether dendrons at 290 nm, was dramatically enhanced with an increase in the generation number n of dendrons, due to the site-isolation and light-harvesting effects. In addition, Er 3+-[ G 2- An ]3(terpy) exhibits the stronger PL intensity than Er 3+-[ G 2- Na ]3(terpy)) by 2.5 times, upon photoexcitation of aryl-ether dendrons at 290 nm. It may be due to the fact that the anthracene ligand in Er 3+-[ G 2- An ]3(terpy)) has higher spectral overlap integral (J) value than the naphthalene ligand in Er 3+-[ G 2- Na ]3(terpy) by 1.5 times. Surprisingly, all Er(III) -cored dendrimer complexes have excellent thermal- and photo-stability as well as good solubility.
Single membrane tether extraction from adult and neonatal dermal microvascular endothelial cells
Authors: Chen Yong , Girdhar Gaurav , Shao Jin-Yu
Published: November 2006

Membrane tethers were found to be extracted from leukocytes and macrovascular endothelial cells (e.g., human umbilical vein endothelial cells or HUVECs) when a point pulling force was exerted. These tethers stabilize leukocyte rolling on the endothelium during the inflammatory response. However, little is known about tether extraction from other vascular cells like microvascular endothelial cells (MECs). In this study, we extracted tethers from both adult and neonatal dermal MECs with the micropipette aspiration technique. We found a linear relationship between the pulling force and tether growth velocity for both cell lines. This constitutive relationship is mainly determined by the membrane mechanical property and the underlying actin-based cytoskeleton for both attached and suspended endothelial cells. It is independent of cell surface receptor type, attachment state, cytokine stimulation, or cell lineage. For both types of MECs, the threshold forces are ∼50 pN and the effective viscosities are around 0.5 pN·s/μm. These results, which are close to what was obtained from HUVECs, indicate that homogeneity is preserved in terms of tether extraction among different types of endothelial cells, and simultaneous tethers are likely extracted when leukocytes roll on either microvascular or macrovascular surfaces.
Hprt-targeted transgenes provide new insights into smooth muscle-restricted promoter activity
Authors: Touw Ketrija , Hoggatt April M. , Simon Gina , Herring B. Paul
Published: November 2006

Mouse telokin and SM22α promoters have previously been shown to direct smooth muscle cell-specific expression of transgenes in vivo in adult mice. However, the activity of these promoters is highly dependent on the integration site of the transgene. In the current study, we found that the ectopic expression of telokin promoter transgenes could be abolished by flanking the transgene with insulator elements from the H19 gene. However, the insulator elements did not increase the proportion of mouse lines that exhibited consistent, detectable levels of transgene expression. In contrast, when transgenes were targeted to the hprt locus, both telokin and SM22α promoters resulted in reproducible patterns and levels of transgene expression in all lines of mice examined. Telokin promoter transgene expression was restricted to smooth muscle tissues in adult and embryonic mice. As reported previously, SM22α transgenes were expressed at high levels specifically in arterial smooth muscle cells; however, in contrast to randomly integrated transgenes, the hprt-targeted SM22α transgenes were also expressed at high levels in smooth muscle cells in veins, bladder, and gallbladder. Using hprt-targeted transgenes, we further analyzed elements within the telokin promoter required for tissue specific activity in vivo. Analysis of these transgenes revealed that the CArG element in the telokin promoter is required for promoter activity in all tissues and that the CArG element and adjacent AT-rich region are sufficient to drive transgene expression in bladder but not intestinal smooth muscle cells.
Muscle, liver, and pancreas: Three Musketeers fighting to control glycemia
Authors: Klip Amira , Vranic Mladen
Published: November 2006

This essay examines the historical significance of two APS classic papers that are freely available on line:

Wall JS, Steele R, de Bodo RC, and Altszuler N. Effect of insulin on utilization and production of circulating glucose. Am J Physiol 189: 43–50, 1957. ( http://ajplegacy.physiology.org/cgi/reprint/189/1/43 )

DeFronzo RA, Tobin JD, and Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol Endocrinol Metab Gastroinstest Physiol 6: E214–E223, 1979. ( http://ajpgi.physiology.org/cgi/reprint/237/3/G214 )
Heterogeneity in the Responses of Adjacent Neurons to Natural Stimuli in Cat Striate Cortex
Authors: Yen Shih-Cheng , Baker Jonathan , Gray Charles M.
Published: November 2006

When presented with simple stimuli like bars and gratings, adjacent neurons in striate cortex exhibit shared selectivity for multiple stimulus dimensions, such as orientation, direction, and spatial frequency. This has led to the idea that local averaging of neuronal responses provides a more reliable representation of stimulus properties. However, when stimulated with complex, time-varying natural scenes (i.e., movies), striate neurons exhibit highly sparse responses. This raises the question of how much response heterogeneity the local population exhibits when stimulated with movies, and how it varies with separation distance between cells. We investigated this question by simultaneously recording the responses of groups of neurons in cat striate cortex to the repeated presentation of movies using silicon probes in a multi-tetrode configuration. We found, first, that the responses of striate neurons to movies are brief (tens of milliseconds), decorrelated, and exhibit high population sparseness. Second, we found that adjacent neurons differed significantly in their peak firing rates even when they responded to the same frames of a movie. Third, pairs of adjacent neurons recorded on the same tetrodes exhibited as much heterogeneity in their responses as pairs recorded by different tetrodes. These findings demonstrate that complex natural scenes evoke highly heterogeneous responses within local populations, suggesting that response redundancy in a cortical column is substantially lower than previously thought.
A dynamical model of terrorism
Authors: Udwadia Firdaus , Leitmann George , Lambertini Luca
Published: November 2006

This paper develops a dynamical model of terrorism. We consider the population in a given region as being made up of three primary components: terrorists, those susceptible to both terrorist and pacifist propaganda, and nonsusceptibles, or pacifists. The dynamical behavior of these three populations is studied using a model that incorporates the effects of both direct military/police intervention to reduce the terrorist population, and nonviolent, persuasive intervention to influence the susceptibles to become pacifists. The paper proposes a new paradigm for studying terrorism, and looks at the long‐term dynamical evolution in time of these three population components when such interventions are carried out. Many important features—some intuitive, others not nearly so—of the nature of terrorism emerge from the dynamical model proposed, and they lead to several important policy implications for the management of terrorism. The different circumstances in which nonviolent intervention and/or military/police intervention may be beneficial, and the specific conditions under which each mode of intervention, or a combination of both, may be useful, are obtained. The novelty of the model presented herein is that it deals with the time evolution of terrorist activity. It appears to be one of the few models that can be tested, evaluated, and improved upon, through the use of actual field data.
On dynamics and stability of thin periodic cylindrical shells
Authors: Tomczyk Barbara
Published: November 2006

The object of considerations is a thin linear‐elastic cylindrical
shell having a periodic structure along one direction tangent to
the shell midsurface. The aim of this paper is to propose a new
averaged nonasymptotic model of such shells, which makes it
possible to investigate free and forced vibrations, parametric
vibrations, and dynamical stability of the shells under
consideration. As a tool of modeling we will apply the
tolerance averaging technique. The resulting equations have
constant coefficients in the periodicity direction. Moreover, in
contrast with models obtained by the known asymptotic
homogenization technique, the proposed one makes it possible to
describe the effect of the period length on the overall shell
behavior, called a length-scale effect.
Identification and Functional Characterization of a Novel Unspliced Transcript Variant of HIC-1 in Human Cancer Cells Exposed to Adverse Growth Conditions
Authors: Mondal Abdul Matin , Chinnadurai Sivasamy , Datta Kamal , Chauhan Shyam S. , Sinha Subrata , Chattopadhyay Parthaprasad
Published: November 2006

The wild-type p53 gene has been widely implicated in the regulation of hypermethylated in cancer-1 (HIC-1) transcription, a master growth regulatory gene with multiple promoters and, consequently, multiple alternatively spliced transcripts. We investigated the role of p53 (wild type and mutant, both endogenous and exogenous) in modulating the various HIC-1 transcripts. We discovered a novel unspliced HIC-1 transcript, identified as “f” in leukocytes and in the human cell lines U87MG (wild-type p53), U373MG (mutant p53), MCF-7 (wild-type p53), HeLa (p53 degraded by HPV18-E6 oncoprotein), and Saos-2 (p53 null). This transcript is initiated from a new transcription start site and has an intervening stop codon that would result in a possibly truncated 22-amino-acid polypeptide. When U87MG (wild-type p53) and MCF-7 cells (wild-type p53) were exposed to adverse growth conditions of serum starvation or treated with the chemotherapeutic agent cisplatin, cells underwent apoptosis and cell cycle arrest accompanied by increase in p53 and HIC-1 transcript levels. Although the increase of the HIC-1-spliced transcripts followed the increase of p53, increase in f transcript coincided with declining p53 and HIC-1 transcript and protein levels. Moreover, the levels of HIC-1 f transcript were not induced by exogenously transfected wild-type p53 in p53-mutated U373MG and p53-null Saos-2 cells, unlike the spliced transcripts that code for full-length HIC-1 protein. These findings suggest a working model wherein the status of f transcript, which is not under direct transcriptional control of wild-type p53, may influence the level of HIC-1 protein in cancer cells. (Cancer Res 2006; 66(21): 10466-77)
Androgens Modulate Expression of Transcription Intermediary Factor 2, an Androgen Receptor Coactivator whose Expression Level Correlates with Early Biochemical Recurrence in Prostate Cancer
Authors: Agoulnik Irina U. , Vaid Ajula , Nakka Manjula , Alvarado Misty , Bingman William E. , Erdem Halime , Frolov Anna , Smith Carolyn L. , Ayala Gustavo E. , Ittmann Michael M. , Weigel Nancy L.
Published: November 2006

Prostate cancer is an androgen-dependent disease; metastatic prostate cancer is typically treated by androgen receptor (AR) blockade. Recurrence after androgen ablation and evidence that AR continues to play a role in many prostate cancers has led to an examination of other factors that potentiate AR activity. AR is a ligand-activated transcription factor whose activity is regulated not only by hormone but also by the levels of coactivators recruited by AR to facilitate transcription. We sought to assess the consequences of reducing expression of the transcription intermediary factor 2 (TIF2) coactivator on prostate cancer cell growth and AR action in cell lines to examine TIF2 expression in prostate cancer and to correlate expression with clinical outcome. Depletion of TIF2 reduced expression of AR-induced target genes and slowed proliferation of AR-dependent and AR-independent prostate cancer cells. Remarkably, we found that TIF2 expression is directly repressed by high levels of androgens in multiple AR-expressing cell lines. Expression of a reporter containing 5′-flanking region of the TIF2 was repressed both by androgens and by the antagonist, Casodex. Expression of TIF2 correlates with biochemical (prostate-specific antigen) recurrence (P = 0.0136). In agreement with our in vitro findings, the highest expression of TIF2 was found in patients whose cancer relapsed after androgen ablation therapy, supporting the idea that AR blockade might activate pathways that lead to stimulation of AR-dependent and AR-independent proliferation of prostate epithelium. The elevated expression of TIF2 at low hormone levels likely aids in inducing AR activity under these conditions; treatment with Casodex has the potential to counteract this induction. (Cancer Res 2006; 66(21): 10594-602)
Loss of Nkx2.8 Deregulates Progenitor Cells in the Large Airways and Leads to Dysplasia
Authors: Tian Jianmin , Mahmood Radma , Hnasko Robert , Locker Joseph
Published: November 2006

Nkx2.8, a homeodomain transcription factor, has been characterized in liver cancer and in the developing central nervous system. We now show that this factor is also expressed in the lung, where it localizes in adults to a discrete population of tracheobronchial basal cells. To target the mouse gene, the first exon was replaced by a LacZ marker gene joined to the intact 5′-untranslated region. Marker expression was observed throughout the lower respiratory tract, beginning on E11 in a few cells of the distal lung buds. The region of expression then spread upward. By neonatal day 1, expression was greatest in the large airways and the Nkx2.8−/− mice exhibited generalized tracheobronchial hyperplasia. Bromodeoxyuridine (BrdUrd) labeling studies showed that a higher rate of bronchial cell proliferation persisted at 6 to 8 months. In adults, Nkx2.8 marker expression decreased with progressive differentiation into ciliated and secretory cells. The cell localizations and patterns of coexpression with BrdUrd and differentiation markers suggest a progenitor relationship: the cells that most strongly express Nkx2.8 seem to function as tracheobronchial stem cells. Moreover, Nkx2.8 acts to limit the number of these progenitor cells because the marker-expressing population was greatly expanded in Nkx2.8−/− mice. Increased proliferation and an altered progenitor relationship caused progressive bronchial pathology, which manifested as widespread dysplasia in the large airways of 1-year-old Nkx2.8−/− mice. (Cancer Res 2006; 66(21): 10399-407)
Activation of CDCA1-KNTC2, Members of Centromere Protein Complex, Involved in Pulmonary Carcinogenesis
Authors: Hayama Satoshi , Daigo Yataro , Kato Tatsuya , Ishikawa Nobuhisa , Yamabuki Takumi , Miyamoto Masaki , Ito Tomoo , Tsuchiya Eiju , Kondo Satoshi , Nakamura Yusuke
Published: November 2006

We found cotransactivation of cell division associated 1 (CDCA1) and kinetochore associated 2 (KNTC2), members of the evolutionarily conserved centromere protein complex, in non–small cell lung carcinomas (NSCLC). Immunohistochemical analysis using lung cancer tissue microarray confirmed high levels of CDCA1 and KNTC2 proteins in the great majority of lung cancers of various histologic types. Their elevated expressions were associated with poorer prognosis of NSCLC patients. Knockdown of either CDCA1 or KNTC2 expression with small interfering RNA significantly suppressed growth of NSCLC cells. Furthermore, inhibition of their binding by a cell-permeable peptide carrying the CDCA1-derived 19-amino-acid peptide (11R-CDCA1398-416) that correspond to the binding domain to KNTC2 effectively suppressed growth of NSCLC cells. As our data imply that human CDCA1 and KNTC2 seem to fall in the category of cancer-testis antigens, and that their simultaneous up-regulation is a frequent and important feature of cell growth/survival of lung cancer, selective suppression of CDCA1 or KNTC2 activity and/or inhibition of the CDCA1-KNTC2 complex formation could be a promising therapeutic target for treatment of lung cancers. (Cancer Res 2006; 66(21): 10339-48)
Lysyl Oxidase Mediates Hypoxic Control of Metastasis
Authors: Erler Janine T. , Giaccia Amato J.
Published: November 2006

Hypoxic cancer cells pose a great challenge to the oncologist because they are especially aggressive, metastatic, and resistant to therapy. Recently, we showed that elevation of the extracellular matrix protein lysyl oxidase (LOX) correlates with metastatic disease and is essential for hypoxia-induced metastasis. In an orthotopic rodent model of breast cancer, a small-molecule or antibody inhibitor of LOX abolished metastasis, offering preclinical validation of this enzyme as a therapeutic target. (Cancer Res 2006; 66(21): 10238-41)
Native-Directed Social Change in Canada and the United States
Authors: Champagne Duane
Published: November 2006

Before 1968, there was more diversity and more frequency of Native-directed social change in institutions, social movements, and religious movements in the United States than in Canada. When Canadian and U.S. nation-states exert direct administrative controls over Native communities and impose change, there are few options for self-directed change. Since 1968, Native nations in both countries enjoy greater possibilities for self-directed change, although the patterns are uneven and moving in somewhat different directions.
The ‘Immigrant Problem’
Authors: Sohoni Deenesh
Published: November 2006

This article examines present attempts to construct immigration as a social problem by studying the language and rhetoric of restrictionist groups on the World Wide Web in the aftermath of 9/11. The analysis of these websites reveals a variety of discourses that both describe and evaluate the consequences of recent immigration. The reasons against immigration currently being put forth include: defending the environment, enhancing national security and protecting jobs for native-born Americans. While the case can be made that these arguments are not based on hostility toward any specific group defined in terms of its racial, ethnic, cultural or religious characteristics, a case that typically is asserted by restrictionist groups themselves, my analysis reveals the existence of an alternative discourse defining those unworthy of participation in American society. My research also reveals that the most overtly nativist groups have the greatest number of web-links to other restrictionist groups, suggesting an attempt to appropriate multiple sources of restrictionist discourse to bolster and legitimize their own positions.
Adaptation and tradition in the pursuit of good health
Authors: Yu Wai-kam Sam
Published: November 2006

English

By examining the health strategies used by Chinese people in Britain and the responses of traditional Chinese societies to foreign medical practices, this article shows the significance of the studies of the ethnic minority groups' traditional values and/or practices to the development of ethnic-sensitive social work.

French

En examinant les stratégies sanitaires des Chinois en Grande-Bretagne et la position des sociétés chinoises à l'égard des pratiques médicales étrangères, cette recherche démontre l'importance d'étudier les valeurs traditionnelles des groupes ethniques minoritaires et de développer des pratiques de travail social qui tiennent compte de l'ethnicité.

Spanish

Mediante el examen de las estrategias de salud utilizadas por la población China en Gran Bretaña y las respuestas de las sociedades Chinas frente a las prácticas médicas extranjeras, este artículo muestra la importancia del estudio de los valores tradicionales y/o prácticas de los grupos étnicos minoritarios para el desarrollo de un trabajo social étnicamente sensible.
Cutting Parameters Optimization for Surface Roughness in Machining of GFRP Composites using Taguchi’s Method
Authors: Palanikumar K.
Published: November 2006

This article discusses the use of Taguchi’s method and Pareto ANOVA analysis for optimizing the cutting parameters in turning glass fiber reinforced plastic (GFRP) composites using a poly crystalline diamond (PCD) tool for minimizing surface roughness. The cutting parameters evaluated are cutting speed, feed rate, and depth of cut. An L27 orthogonal array, signal to noise ratio, and Pareto ANOVA analysis are used to analyze the effect of cutting parameters and its interactions. The experimental results suggest that the most significant process parameter is feed rate followed by cutting speed. The study shows that the Taguchi method and Pareto ANOVA are suitable for optimizing the cutting parameters with the minimum number of trials.
A Descriptive Analysis of Test Session Observation Checklist Ratings From the Woodcock Johnson III Standardization Sample
Authors: Frisby Craig L. , Osterlind Steven J.
Published: November 2006

Modern scale construction techniques have been used to develop scales measuring examiner ratings of examinees’ test session behavior (TSB) on Wechsler and Stanford-Binet intelligence tests. This study analyzes data from the Test Session Observation Checklist (TSOC), a measure developed by post hoc rational analysis, from a portion of the Woodcock Johnson Psychoeducational Battery-Third Edition standardization sample ( N = 5,769). Results indicate (a) most participants are rated as displaying minimal negative test session behaviors, (b) the seven TSOC items are organized into two components (General Impressions and Attention To Task) that explain roughly 54% of the variance in TSOC scores, and (c) race, sex, and age differences in component scores examined with and without covariates are consistent with results from prior TSB research.
Overview of Respiratory Failure in Older Adults
Authors: El Solh Ali A. , Ramadan Fadi H.
Published: November 2006

Older adults comprise 48% of the critically ill population in intensive care units and will continue to represent a substantial proportion of patients requiring intensive care for decades to come. Aging both decreases the reserve capacity of vital organs and increases the risk of concurrent illnesses that challenge the respiratory system, such as pneumonia, renal failure, or heart diseases. Because respiratory failure is one of the leading causes of death in intensive care units, implementation of strategies to prevent the need for reintubation should be considered early in the course of respiratory decompensation. For those who require mechanical ventilation, protocols to identify patients who are ready to wean should facilitate liberation from respiratory support and reduce complications of mechanical ventilation. Finally, allocation of potentially limited health care resources necessitates knowing about the risk-benefit of mechanical ventilation and other treatment for respiratory failure in this population.
Caring for the Frail Elderly in the Home: A Multidisciplinary Approach
Authors: Ehrlich Phyllis L.
Published: November 2006

As people live longer, maintaining independence in the home will become a significant health care issue. This article explains how one home care agency developed a comprehensive multidiscipli-nary program to identify, screen, assess, and treat the four common geriatric syndromes that affect quality of life for older people and are often the cause for nursing home admissions. The four syndromes are falls risk, incontinence, dementia, and depression. By screening for these four syndromes clinicians can develop care plans that address the needs of the frail elderly. Through an interdiscipli-nary approach, the team can work together to keep patients safe and independent in their own homes, allowing them to stay in their own environment with assistance if needed.
Functional Assessment: Process and Product
Authors: Siebert Carol
Published: November 2006

Functional assessment is both a process, eliciting information, and a product, a profile of patient performance. Because patient functional status affects payment and change in status (outcome) is a proxy for quality, there has been increasing emphasis on functional assessment accuracy and on assessment techniques. This emphasis on data collection and data accuracy has divorced functional assessment from its primary purpose: care planning. Effective functional assessment should yield a profile of the patient’s performance of daily activities, which guides care planning. Assessment of performance must identify the factors influencing performance, not solely the current performance status. Functional performance is a dynamic interaction of person, environment, and activity. When assessment is relinked to care planning and clinical reasoning is directed toward patient performance, functional assessment becomes not an end in itself but a starting point to achieve outcomes that make a difference in the daily lives of patients.
Freedom of choice and decision-making in health and social care
Authors: Tyrrell Jeanne , Genin Nathalie , Myslinski Michele
Published: November 2006

People with dementia represent a significant and growing proportion of patients, but little is known about their involvement in making choices about their health or social care. This study explored the experiences of French older patients with dementia and their caregivers about their participation in decision-making. Individual semi-directive interviews were conducted with patients ( n= 21) and their primary carer focusing on a recently made decision (to accept professional help at home, to attend a day centre, or to move into residential care). Five aspects of decision-making were explored: information received; being listened to; expression of opinion; time allowed to reflect on decision; and possibility of changing one's mind. Carers tended to be more satisfied than patients on most criteria. Many patients felt they had not been listened to sufficiently, and had limited freedom to participate in decision-making. Continuing education may help professionals to improve their ability to involve patients with dementia in decision-making concerning their care arrangements.
IL-21 receptor signaling is integral to the development of Th2 effector responses in vivo
Authors: Fröhlich Anja , Marsland Benjamin J. , Sonderegger Ivo , Kurrer Michael , Hodge Martin R. , Harris Nicola L. , Kopf Manfred
Published: November 2006

Interleukin 21 (IL-21) is a member of the common γ-chain family of cytokines, which influence a broad spectrum of immunologic responses. A number of studies have examined the function of IL-21, but its specific role in Th1/Th2-cell differentiation and related effector responses remains to be clarified. Thus, we generated IL-21R–deficient mice and have investigated the role of IL-21R signaling using a series of in vivo experimentally induced disease models. We first addressed the role of IL-21R signaling in Th2 immune responses by examining allergic airway inflammation, and Nippostrongylus brasiliensis and Heligmosomoides polygyrus antihelminth responses. In each of these systems, IL-21R signaling played a clear role in the development of Th2 responses. Comparatively, IL-21R signaling was not required for the containment of Leishmania major infection or the development of experimental autoimmune myocarditis, indicative of competent Th1 and Th17 responses, respectively. Adoptive transfer of T cells and analysis of IL-21R+/+/IL-21R−/− chimera mice revealed that IL-21R–signaling was central to Th2-cell survival or migration to peripheral tissues. Overall, our data show IL-21 plays a crucial role in supporting polarized Th2 responses in vivo, while appearing superfluous for Th1 and Th17 responses.
Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells
Authors: Forde Sinead , Tye Britt Jorgensen , Newey Sarah E. , Roubelakis Maria , Smythe Jon , McGuckin Colin P. , Pettengell Ruth , Watt Suzanne M.
Published: November 2006

Hematopoietic stem cell/hematopoietic progenitor cell (HSC/HPC) homing to specific microenvironmental niches involves interactions between multiple receptor ligand pairs. Although CXCL12/CXCR4 plays a central role in these events, CXCR4 regulators that provide the specificity for such cells to lodge and be retained in particular niches are poorly defined. Here, we provide evidence that the sialomucin endolyn (CD164), an adhesion receptor that regulates the adhesion of CD34+ cells to bone marrow stroma and the recruitment of CD34+CD38lo/− cells into cycle, associates with CXCR4. The class II 103B2 monoclonal antibody, which binds the CD164 N-linked glycan-dependent epitope or CD164 knockdown by RNA interference, significantly inhibits the migration of CD133+ HPCs toward CXCL12 in vitro. On presentation of CXCL12 on fibronectin, CD164 associates with CXCR4, an interaction that temporally follows the association of CXCR4 with the integrins VLA-4 and VLA-5. This coincides with PKC-ζ and Akt signaling through the CXCR4 receptor, which was disrupted on the loss of CD164 though MAPK signaling was unaffected. We therefore demonstrate a novel association among 3 distinct families of cell-surface receptors that regulate cell migratory responses and identify a new role for CD164. We propose that this lends specificity to the homing and lodgment of these cells within the bone marrow niche.
MEK blockade converts AML differentiating response to retinoids into extensive apoptosis
Authors: Milella Michele , Konopleva Marina , Precupanu Cristina M. , Tabe Yoko , Ricciardi Maria Rosaria , Gregorj Chiara , Collins Steven J. , Carter Bing Z. , D'Angelo Carmen , Petrucci Maria Teresa , Foà Robin , Cognetti Francesco , Tafuri Agostino , Andreeff Michael
Published: November 2006

The aberrant function of transcription factors and/or kinase-based signaling pathways that regulate the ability of hematopoietic cells to proliferate, differentiate, and escape apoptosis accounts for the leukemic transformation of myeloid progenitors. Here, we demonstrate that simultaneous retinoid receptor ligation and blockade of the MEK/ERK signaling module, using the small-molecule inhibitor CI-1040, result in a strikingly synergistic induction of apoptosis in both acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL) cells with constitutive ERK activation. This proapoptotic synergism requires functional RAR and RXR retinoid receptors, as demonstrated using RAR- and RXR-selective ligands and RAR-defective cells. In the presence of MEK inhibitors, however, retinoid-induced chromatin remodeling, target-gene transcription, and granulocytic differentiation are strikingly inhibited and apoptosis induction becomes independent of death-inducing ligand/receptor pairs; this suggests that apoptosis induction by combined retinoids and MEK inhibitors is entirely distinct from the classical “postmaturation” apoptosis induced by retinoids alone. Finally, we identify disruption of Bcl-2–dependent mitochondrial homeostasis as a possible point of convergence for the proapoptotic synergism observed with retinoids and MEK inhibitors. Taken together, these results indicate that combined retinoid treatment and MEK blockade exert powerful antileukemic effects and could be developed into a novel therapeutic strategy for both AML and APL.
Naphthoquinone enhances antigen-related airway inflammation in mice
Authors: Inoue K. , Takano H. , Hiyoshi K. , Ichinose T. , Sadakane K. , Yanagisawa R. , Tomura S. , Kumagai Y.
Published: November 2006

The current authors have previously demonstrated that diesel exhaust particles (DEP) enhance antigen-related airway inflammation in mice. Furthermore, a recent study has shown that organic chemicals in DEP, rather than their carbonaceous nuclei, are important contributors to the aggravating effects of airway inflammation. However, the components in DEP responsible for the enhancing effects on the model remain to be identified.

The current authors investigated the effects of naphthoquinone (NQ), one of the extractable chemical compounds of DEP, on antigen-related airway inflammation, local expression of cytokine proteins, and antigen-specific immunoglobulin (Ig) production in mice. Pulmonary exposure to NQ dose-dependently aggravated antigen-related airway inflammation, as characterised by infiltration of eosinophils and lymphocytes around the airways and an increase in goblet cells in the bronchial epithelium. Combined exposure to NQ and antigen enhanced the local expression of interleukin (IL)-4, IL-5, eotaxin, macrophage chemoattractant protein-1 and keratinocyte chemoattractant, compared with exposure to antigen or NQ alone. Also, NQ exhibited adjuvant activity for the antigen-specific production of IgG1and IgG2a.

These results provide the first experimental evidence that naphthoquinone can enhance antigen-related airway inflammationin vivo, and that naphthoquinone can, to some extent, partly play a role in the pathogenesis of diesel exhaust particle toxicity on the condition.