bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone-Resorbing Cells in Multiple Myeloma: Osteoclasts, Myeloma Cell Polykaryons, or Both?
Authors: Silvestris Franco , Ciavarella Sabino , De Matteo Monica , Tucci Marco , Dammacco Franco
Published: March 2009

Myeloma bone disease (MBD) leads to progressive destruction of the skeleton and is the most severe cause of morbidity in multiple myeloma. Its pathogenetic mechanisms are not fully understood, though the current evidence points to osteoclast (OC) hyperactivity coupled with defective osteoblast function unable to counteract bone resorption. OCs are generated in bone marrow by myeloid progenitors through increased levels of receptor activator of nuclear factor κB ligand and M-CSF, whose intracellular pathways propagate signals that activate sequential transcription factors, resulting in the production of major OC enzymes that drive specific functions such as acidification and degradation of the bone matrix. Osteolytic lesions, however, are not characterized by massive OC content, whereas malignant plasma cells, which are usually present in a high number, may occur as large multinucleated cells. The possibility that myeloma cells fuse and generate polykaryons in vivo is suggested by the in vitro formation of multinuclear cells that express tartrate-resistant acid phosphatase and produce pits and erosive lacunae on experimental osteologic substrates. Further, the detection in vivo of polykaryons with chromosome translocations typical of myeloma cells lends support to the view that myeloma polykaryons may act as functional OCs and participate in the skeletal destruction by resorbing bone.
Myeloma Bone Disease: Recent Advances in Biology, Diagnosis, and Treatment
Authors: Sezer Orhan
Published: March 2009

Bone disease is a hallmark of multiple myeloma (MM). Occurring in the majority of MM patients, it is associated with bone pain, fractures, and hypercalcemia and has major impacts on quality of life. Furthermore, bone resorption activity has been shown to be an independent risk factor for overall survival in patients with symptomatic MM. Myeloma is characterized by a unique form of bone disease with lytic bone destruction that is not followed by reactive bone formation (uncoupling). This review focuses on recent advances in our understanding of the biology of osteoclast activation and osteoblast inhibition in MM, diagnostic standards, and recent progress in treatment options for myeloma bone disease. Translational research has enabled a rapid transfer of mechanistic insights from the bench to the bedside and will hopefully result in better treatment options and outcome for patients in near future.
Performance of a solid-state frequency-shifted feedback laser in optical ranging
Authors: Ndiaye Cheikh , Hara Takefumi , Ito Hiromasa
Published: March 2009

The performance of a frequency-shifted feedback laser (FSFL) using a Nd:YVO4 crystal as gain medium was investigated as light source in high accuracy optical ranging based on optical-frequency domain reflectometry (OFDR). The FSFL generates a comb of chirped frequency components over a bandwidth of 45 GHz with chirp rates of 3.8×1017 Hz/s. In OFDR, distance accuracies better than 25 µm at a data measurement time of 2 ms were demonstrated at a standoff distance of 5 m. The results show that the FSFL is a promising light source for high accuracy, high speed 3D measurement applications.
Conceptualization, Measurement, and Improvement of Classroom Processes: Standardized Observation Can Leverage Capacity
Authors: Pianta Robert C. , Hamre Bridget K.
Published: March 2009

The authors advance an argument that placing observation of actual teaching as a central feature of accountability frameworks, teacher preparation, and basic science could result in substantial improvements in instruction and related social processes and a science of the production of teaching and teachers. Teachers’ behavioral interactions with students can be (a) assessed observationally using standardized protocols, (b) analyzed systematically with regard to sources of error, (c) validated for predicting student learning, and (d) changed (improved) as a function of specific and aligned supports provided to teachers; exposure to such supports is predictive of greater student learning gains. These methods have considerable promise; along with measurement challenges, some of which pertain to psychometrics, efficiency, and costs, they merit attention, rigorous study, and substantial research investments.
Personal Amplification for School-Age Children with Auditory Processing Disorders
Authors: Kuk Francis , Jackson Amy , Keenan Denise , Lau Chi-chuen
Published: March 2009

Background: Children with auditory processing disorders (APD) are described to have a signal-to-noise ratio (SNR) difficulty. Frequency-modulated (FM) systems have been reported to improve this situation. Yet the use of personal amplification that may be more portable has not
been attempted. Purpose: To determine whether personal amplification would result in improvement in speech-in-noise performances (attentiveness and speech recognition) and daily functioning in children with diagnosed APD. In addition, the desired hearing aid features (such as required
gain, directional microphone and noise reduction, and open-ear fitting) are examined. Research Design: A single-blind, longitudinal descriptive study in which subjects served as their own control in various hearing aid conditions. Study Sample: Fourteen normal hearing children
who had a diagnosis of APD and who were between the ages of 7 and 11 participated. Intervention: All subjects wore bilateral, mild-gain, behind-the-ear, wide dynamic range compression hearing aids fitted in an open-ear mode. Gain on the hearing aids was adjusted to provide approximately
10 dB of insertion gain for conversational input. Directional microphone and noise reduction were used on the hearing aids. Subjects wore the hearing aids home and were encouraged to use them as much as possible in their daily environments (school, home, and social activities). Subjects
were seen four times: an initial visit where hearing aids were fitted, then visits at 2 weeks, 3 months, and 6 months after the initial fitting. The majority of the testing was completed during these final three visits. Data Collection and Analysis: The children were evaluated on the
Northwestern University word-list (NU‐6) and the Auditory Continuous Performance Test (ACPT) in noise at most visits. The hearing aids were evaluated in the omnidirectional microphone mode only, omnidirectional microphone with noise reduction (NR) mode, and directional microphone with
NR mode. The children's parents and teachers were asked to complete the Children's Auditory Processing Performance Scale (CHAPS) questionnaire both before and at the end of the study. Results: The results showed that the use of hearing aids in the omnidirectional microphone mode alone
did not improve speech identification in noise over the unaided condition. However, the inclusion of the NR algorithm and directional microphones improved speech understanding in noise. Amplification reduced the number of errors on the ACPT and improved several areas on the CHAPS; however,
the results were not statistically significant. Conclusions: The use of mild-gain, open-ear fitting hearing aids with a directional microphone and noise reduction algorithm may be attempted on some children with APD on a trial basis.
An Electrophysiological Measure of Binaural Hearing in Noise
Authors: Weihing Jeffrey , Musiek Frank E.
Published: March 2009

Background: A common complaint of patients with (central) auditory processing disorder is difficulty understanding speech in noise. Because binaural hearing improves speech understanding in compromised listening situations, quantifying this ability in different levels of noise
may yield a measure with high clinical utility. Purpose: To examine binaural enhancement (BE) and binaural interaction (BI) in different levels of noise for the auditory brainstem response (ABR) and middle latency response (MLR) in a normal hearing population. Research Design:
An experimental study in which subjects were exposed to a repeated measures design. Study Sample: Fifteen normal hearing female adults served as subjects. Normal hearing was assessed by pure-tone audiometry and otoacoustic emissions. Intervention: All subjects were exposed to
0, 20, and 35 dB effective masking (EM) of white noise during monotic and diotic click stimulation. Data Collection and Analysis: ABR and MLR responses were simultaneously acquired. Peak amplitudes and latencies were recorded and compared across conditions using a repeated measures
analysis of variance (ANOVA). Results: For BE, ABR results showed enhancement at 0 and 20 dB EM, but not at 35 dB EM. The MLR showed BE at all noise levels, but the degree of BE decreased with increasing noise level. For BI, both the ABR and MLR showed BI at all noise
levels. However, the degree of BI again decreased with increasing noise level for the MLR. Conclusions: The results demonstrate the ability to measure BE simultaneously in the ABR and MLR in up to 20 dB of EM noise and BI in up to 35 dB EM of noise. Results also suggest
that ABR neural generators may respond to noise differently than MLR generators.
Investigation of Potential Cognitive Tests for Use with Older Adults in Audiology Clinics
Authors: Vaughan Nancy , Storzbach Daniel , Furukawa Izumi
Published: March 2009

Background: Cognitive declines in working memory and processing speed are hallmarks of aging. Deficits in speech understanding also are seen in aging individuals. A clinical test to determine whether the cognitive aging changes contribute to aging speech understanding difficulties
would be helpful for determining rehabilitation strategies in audiology clinics. Purpose: To identify a clinical neurocognitive test or battery of tests that could be used in audiology clinics to help explain deficits in speech recognition in some older listeners. Research Design:
A correlational study examining the association between certain cognitive test scores and speech recognition performance. Speeded (time-compressed) speech was used to increase the cognitive processing load. Study Sample: Two hundred twenty-five adults aged 50 through 75 years were participants
in this study. Both batteries of tests were administered to all participants in two separate sessions. Data Collection and Analysis: A selected battery of neurocognitive tests and a time-compressed speech recognition test battery using various rates of speech were administered. Principal
component analysis was used to extract the important component factors from each set of tests, and regression models were constructed to examine the association between tests and to identify the neurocognitive test most strongly associated with speech recognition performance. Results:
A sequencing working memory test (Letter-Number Sequencing [LNS]) was most strongly associated with rapid speech understanding. The association between the LNS test results and the compressed sentence recognition scores (CSRS) was strong even when age and hearing loss were controlled. Conclusions:
The LNS is a sequencing test that provides information about temporal processing at the cognitive level and may prove useful in diagnosis of speech understanding problems, and in the development of aural rehabilitation and training strategies.
The Recordability of Two Sonomotor Responses in Young Normal Subjects
Authors: McCaslin Devin L. , Jacobson Gary P. , Harry Todd
Published: March 2009

Background: It has been reported that up to 40% of patients over age 60 fail to generate a vestibular evoked myogenic potential (VEMP; Su et al, 2004). When this occurs it is difficult to determine whether the absent VEMP represents evidence of bilateral impairment of the vestibulocollic
reflex pathway or a normal age-related variant (i.e., idiopathic absence). Purpose: The purpose of the present investigation was to determine whether both VEMPs and PAMs could be recorded reliably in a sample of neurologically and otologically intact young adults. If both could be obtained
with high reliability in normal subjects, then the bilateral presence of PAM in the bilateral absence of VEMP, at least in younger patients, could be used to support the contention that the absent VEMP represented evidence of bilateral impairment. Research Design: A descriptive study.
Study Sample: Attempts were made to record both the VEMP and a second sonomotor response, the postauricular muscle potential (PAM) from 20 young adults. Results: Results showed both the VEMP and the PAM were present in 90% of the ears. Both the VEMP and PAM responses were bilaterally
absent for one subject. Also, the VEMP and PAM were unilaterally absent for two subjects. Subjects who generated VEMPs also generated a PAM in at least one ear. Conclusions: The present investigation represents an initial step in the determination of whether the presence of PAMs in
the absence of VEMPs can be used as a method of validating the presence of an impairment affecting the vestibulocollic reflex pathway.
Auditory Processing Disorder And Brain Pathology In A Preterm Child With Learning Disabilities
Authors: Iliadou Vassiliki , Bamiou Doris-Eva , Kaprinis Stergios , Kandylis Dimitrios , Vlaikidis Nikolaos , Apalla Kalliopi , Psifidis Anestis , Psillas George , Kaprinis George St
Published: March 2009

Background: Auditory processing disorders involve deficits in the processing of information in the auditory domain that are not due to higher order language, cognitive or other related factors. Purpose: To evaluate the possibility of structural brain abnormalities in preterm
children manifesting as auditory processing disorders. Research Design : A case report of a young girl, preterm at birth, with language difficulties, learning problems at school, and additional listening problems. Results: A diagnosis of a central auditory processing disorder
was made on the basis of severe deficits in three nonspeech temporal tests (the frequency and duration pattern and the random gap detection tests). Her brain MRI revealed large porencephalic cysts and thinning of the corpus callosum. Conclusions: The observed auditory deficits would
be compatible with a pressure effect of the cysts at a brainstem or higher level for the random gap detection test, and with the thinning of the corpus callosum for the pattern tests, the latter requiring interhemispheric transfer of information. The case highlights that preterm children with
learning difficulties may suffer from an auditory processing disorder, in the presence of structural brain abnormalities that are due to birth and neonatal complications.
The Importance of Audiologic Red Flags in Patient Management Decisions
Authors: Zapala David A. , Shaughnessy Kathryn , Buckingham Jill , Hawkins David B.
Published: March 2009

Background: It is essential that nonbenign forms of hearing impairment are recognized and addressed before audiological management is entertained. Purpose: To present an illustrative case and focused literature review of early red flag indicators for retrocochlear impairment,
as might be discerned from a patient's history or physical examination. Results: The presenting history and clinical course of a female patient with fatal adenocarcinoma presenting as a suspected retrocochlear mass is reviewed over the last four months of her life. Clinical signs, symptoms
and test results pointing to the diagnosis of “acoustic neuroma” and then “metastatic neoplasm” are reviewed along with selected supporting reference literature. The ambiguous clinical pictures at various points in her history are analyzed, with an effort to point out
how early audiological decisions may significantly impact patient's overall health. Conclusions: Clear communication with primary care physicians, vigilance when audiological results are ambiguous for active disease, and pre-established referral relationships with practitioners in the
neurologic and otologic disciplines are stressed as important requirements for audiologists who serve as entry points into hearing healthcare.
The Compact Semisubmersible Smit Semi 1 and 2: Design and Construction
Authors: Schepman G.J. , van Santen J.A. , Smallengange M.J.
Published: March 2009

Offshore exploitation of oil- and gas resources can only be maintained ifefficient support tools like vessels and its equipment are available. The SmitSemi's 1 and 2 are recognized as a new step forward in this approach. Designbackground reaching to the final design will be discussed ranging from theoverall layout, motional behaviour, stability up to the construction.

Introduction

As the exploitation of offshore oil-and gas reserves is steadily increasingduring the last decades, the requirements for efficient IRM and subseainstallation and construction work is growing. The North Sea market is nowadaysa multimillion dollar market. These platforms, subsea structures and pipelineshave to be maintained. The preferred approach of performing these tasks is thatof using modern equipment combined with a professional company. Currently thereis a need for new sophisticated equipment entering the market. The developmentand introduction of the two compact semi-submersibles Smit Semi 1 and 2 areregarded as a solution. In this paper, the development of vessel from thefeasibility stage up to the construction will be highlighted. Special attentionwill be given to new steps in the well-known concept of semi-submersibledesign.

Initial Design Specification

As the first step in the design process, the project team of SmitInternational and Marine Structure Consultants (MSC) established the designspecification for the new offshore support vessel. Based on the initial marketreview, the vessel should serve the Inspection, Repair and Maintenance (IRM)market and the light and medium installation and construction market (ref 4).Initially, extensive saturation diving operations were not specified as a majorelement of the vessel.
A New Rod Shear Device for the Measurement of the Degradation of Soil-Pile Interfaces
Authors: Felio G.Y. , Berthold C.S.
Published: March 2009

A laboratory model pile testing apparatus (Rod Shear) was developed toobtain a better understanding of the behavior of soil/pile interfaces under awide range of loading conditions. The instrumented model pile is capable ofmeasuring the frictional resistance mobilized during loading and the porepressures generated at the soil/pile interface. This article presents adescription of the Rod Shear, the method used to prepare the sample, and theprocedure to conduct the test. Preliminary results on Kaolin clay are included. Finally, a discussion regarding further research possibilities using this newRod Shear is given.

Introduction

Laboratory model pile tests are an inexpensive, versatile means of studyingthe behavior of cyclically loaded piles in clay. Safe and economical piles canbe designed without relying on expensive pile load tests or empiricalcorrelations, if the critical factors affecting pile capacity under static andcyclic loading can be determined. An optimum design is especially important foroffshore structures which require costly, large diameter, very long piles whichare subjected to cyclic wave storm loading and possibly earthquake loading. Laboratory model pile tests can be performed on a variety of soils undercontrolled conditions of lateral stress, vertical stress, degree ofconsolidation, and degree of saturation.

The purpose of this research was to develop an improved Rod Shear device, atriaxial-type test apparatus using an instrumented model pile, for determiningthe mechanism of degradation of skin friction in clays under cyclic axialloading.

The amount of load that the soil can support without failure is known as thesoil resistance or pile capacity. During cyclic loading, the ability of thesoil to carry a load may decrease. Less load is transferred from the pile tothe soil as the skin friction, i.e. the shear transfer, degrades. Past researchhas shown that the pile capacity under cyclic loads may be significantly lessthan the static capacity (Matlock and Holmquist [1]; Bogard and Matlock [2];Briaud and Felio [3]; Poulos [4,5,6]). The degradation of skin friction may bedue to changes in pore water pressure and the migration of pore water and/ordue to realignment of clay particles (Bogard and Matlock [2]).
4-1BB Functions As a Survival Factor in Dendritic Cells
Authors: Choi Beom K. , Kim Young H. , Kwon Patrick M. , Lee Sang C. , Kang Sang W. , Kim Moon S. , Lee Myoung J. , Kwon Byoung S.
Published: March 2009

4-1BB (CD137) is expressed on dendritic cells (DCs) and its biological function has remained largely unresolved. By comparing 4-1BB-intact (4-1BB+/+) and 4-1BB-deficient (4-1BB−/−) DCs, we found that 4-1BB was strongly induced on DCs during the maturation and that DC maturation was normal in the absence of 4-1BB. However, DC survival rate was low in the absence of 4-1BB, which was due to the decreased Bcl-2 and Bcl-xL in 4-1BB−/− DCs compared with 4-1BB+/+ DCs after DC maturation. Consistent with these results, 4-1BB−/− DCs showed an increased turnover rate in steady state and more severely decreased in spleen by injecting LPS compared with 4-1BB+/+ DCs. When OVA-pulsed DCs were adoptively transferred to recipient mice along with OVA-specific CD4+ T cells, 4-1BB−/− DCs did not properly migrate to the T cell zone in lymph nodes and poorly induced proliferation of CD4+ T cells, although both DCs comparably expressed functional CCR7. Eventually, 4-1BB−/− DCs generated a reduced number of OVA-specific memory CD4+ T cells compared with 4-1BB+/+ DCs. To further assess the role of 4-1BB on DC longevity in vivo, 4-1BB+/+ and 4-1BB−/− C57BL/6 were administrated with Propionibacterium acnes that develop liver granuloma by recruiting DCs. Number and size of granuloma were reduced in the absence of 4-1BB, but the inflammatory cytokine level was comparable between the mice, which implied that the granuloma might be reduced due to the decreased longevity of DCs. These results demonstrate that 4-1BB on DCs controls the duration, DC-T interaction, and, therefore, immunogenicity.
Immunologic and Therapeutic Synergy of IL-27 and IL-2: Enhancement of T Cell Sensitization, Tumor-Specific CTL Reactivity and Complete Regression of Disseminated Neuroblastoma Metastases in the Liver and Bone Marrow
Authors: Salcedo Rosalba , Hixon Julie A. , Stauffer Jimmy K. , Jalah Rashmi , Brooks Alan D. , Khan Tahira , Dai Ren-Ming , Scheetz Loretta , Lincoln Erin , Back Timothy C. , Powell Douglas , Hurwitz Arthur A. , Sayers Thomas J. , Kastelein Robert , Pavlakis George N. , Felber Barbara K. , Trinchieri Giorgio , Wigginton Jon M.
Published: March 2009

IL-27 exerts antitumor activity in murine orthotopic neuroblastoma, but only partial antitumor effect in disseminated disease. This study demonstrates that combined treatment with IL-2 and IL-27 induces potent antitumor activity in disseminated neuroblastoma metastasis. Complete durable tumor regression was achieved in 90% of mice bearing metastatic TBJ-IL-27 tumors treated with IL-2 compared with only 40% of mice bearing TBJ-IL-27 tumors alone and 0% of mice bearing TBJ-FLAG tumors with or without IL-2 treatment. Comparable antitumor effects were achieved by IL-27 protein produced upon hydrodynamic IL-27 plasmid DNA delivery when combined with IL-2. Although delivery of IL-27 alone, or in combination with IL-2, mediated pronounced regression of neuroblastoma metastases in the liver, combined delivery of IL-27 and IL-2 was far more effective than IL-27 alone against bone marrow metastases. Combined exposure to IL-27 produced by tumor and IL-2 synergistically enhances the generation of tumor-specific CTL reactivity. Potentiation of CTL reactivity by IL-27 occurs via mechanisms that appear to be engaged during both the initial sensitization and effector phase. Potent immunologic memory responses are generated in mice cured of their disseminated disease by combined delivery of IL-27 and IL-2, and depletion of CD8+ ablates the antitumor efficacy of this combination. Moreover, IL-27 delivery can inhibit the expansion of CD4+CD25+Foxp3+ regulatory and IL-17-expressing CD4+ cells that are otherwise observed among tumor-infiltrating lymphocytes from mice treated with IL-2. These studies demonstrate that IL-27 and IL-2 synergistically induce complete tumor regression and long-term survival in mice bearing widely metastatic neuroblastoma tumors.
IL-7 Dependence in Human B Lymphopoiesis Increases during Progression of Ontogeny from Cord Blood to Bone Marrow
Authors: Parrish Yasmin Khan , Baez Ineavely , Milford Terry-Ann , Benitez Abigail , Galloway Nicholas , Rogerio Jaqueline Willeman , Sahakian Eva , Kagoda Mercy , Huang Grace , Hao Qian-Lin , Sevilla Yazmar , Barsky Lora W. , Zielinska Ewa , Price Mary A. , Wall Nathan R. , Dovat Sinisa , Payne Kimberly J.
Published: March 2009

IL-7 is critical for B cell production in adult mice; however, its role in human B lymphopoiesis is controversial. One challenge was the inability to differentiate human cord blood (CB) or adult bone marrow (BM) hematopoietic stem cells (HSCs) without murine stroma. Here, we examine the role of IL-7 in human B cell development using a novel, human-only model based on coculturing human HSCs on primary human BM stroma. In this model, IL-7 increases human B cell production by >60-fold from both CB and adult BM HSCs. IL-7-induced increases are dose-dependent and specific to CD19+ cells. STAT5 phosphorylation and expression of the Ki-67 proliferation Ag indicate that IL-7 acts directly on CD19+ cells to increase proliferation at the CD34+ and CD34− pro-B cell stages. Without IL-7, HSCs in CB, but not BM, give rise to a small but consistent population of CD19lo B lineage cells that express EBF (early B cell factor) and PAX-5 and respond to subsequent IL-7 stimulation. Flt3 ligand, but not thymic stromal-derived lymhopoietin (TSLP), was required for the IL-7-independent production of human B lineage cells. As compared with CB, adult BM shows a reduction of in vitro generative capacity that is progressively more profound in developmentally sequential populations, resulting in an ∼50-fold reduction in IL-7-dependent B lineage generative capacity. These data provide evidence that IL-7 is essential for human B cell production from adult BM and that IL-7-induced expansion of the pro-B compartment is increasingly critical for human B cell production during the progression of ontogeny.
Clathrin- and Dynamin-Dependent Endocytic Pathway Regulates Muramyl Dipeptide Internalization and NOD2 Activation
Authors: Marina-García Noemí , Franchi Luigi , Kim Yun-Gi , Hu Yonjun , Smith David E. , Boons Geert-Jan , Núñez Gabriel
Published: March 2009

Muramyl dipeptide (MDP), the NOD2 agonist, induces NF-κB and MAPK activation leading to the production of antimicrobial and proinflammatory molecules. MDP is internalized into acidified vesicles in macrophages. However, the endocytic mechanism of MDP uptake that induces NOD2 signaling is unknown. We now report the identification of an endocytosis pathway dependent on clathrin and dynamin that mediates MDP internalization and NOD2 activation. Intracellular MDP uptake was inhibited by chlorpromazine, a drug that disrupts clathrin-dependent endocytosis, but not by compounds that block pinocytosis or cellular entry via scavenger or mannose receptors. In contrast, MDP uptake and NOD2-dependent signaling were unimpaired in macrophages deficient in PepT1, a peptide transporter previously implicated in MDP internalization. Both chlorpromazine and knockdown of clathrin expression by RNA interference attenuated MDP-induced NF-κB and MAPK activation. Furthermore, MDP uptake and NOD2-dependent signaling were impaired by inhibition of dynamin, a GTPase required for budding of clathrin-coated vesicles from the plasma membrane. Finally, bafilomycin A, a specific inhibitor of the vacuolar proton pump, blocked MDP accumulation in acidified vesicles and cytokine responses, suggesting that vacuolar maturation is important for MDP-induced NOD2 signaling. These studies provide evidence for a clathrin- and dynamin-dependent endocytosis pathway that mediates MDP uptake and NOD2 activation.
The Presence of a Matrix-Derived Neutrophil Chemoattractant in Bronchiolitis Obliterans Syndrome after Lung Transplantation
Authors: Hardison Matthew T. , Galin F. Shawn , Calderon Christopher E. , Djekic Uros V. , Parker Suzanne B. , Wille Keith M. , Jackson Patricia L. , Oster Robert A. , Young K. Randall , Blalock J. Edwin , Gaggar Amit
Published: March 2009

Lung transplantation is a therapeutic modality frequently used in end-stage lung disease. Unfortunately, lung transplant recipients have poor clinical outcomes, often due to the development of bronchiolitis obliterans syndrome (BOS). This process is often characterized by the pathologic findings of obliterative bronchiolitis: neutrophil influx and extracellular matrix remodeling leading to luminal obstruction and airway inflammation. The molecular mechanisms underlying BOS are poorly understood and disease-specific biomarkers are lacking. We report that in addition to increased levels of IL-8, the level of the neutrophil chemoattractant proline-glycine-proline (PGP) is elevated in BOS patient bronchoalveolar lavage (BAL) fluid. The enzymes responsible for generating PGP, matrix metalloproteases 8 and -9 and prolyl endopeptidase, are also elevated in these samples. Together, IL-8 and PGP account for most of the neutrophil chemoattractant capacity seen in BOS BAL fluid. Using specific neutralizing Abs to both IL-8 and PGP, we demonstrate that PGP is a prominent neutrophil chemoattractant found in BAL fluid from individuals at the time of diagnosis of BOS. These findings highlight the influence of a matrix-derived neutrophil chemoattractant in posttransplantation BOS and provide opportunities for the development of unique diagnostics and therapeutics to potentially improve disease outcomes.
CLEC-2 Is a Phagocytic Activation Receptor Expressed on Murine Peripheral Blood Neutrophils
Authors: Kerrigan Ann M. , Dennehy Kevin M. , Mourão-Sá Diego , Faro-Trindade Inês , Willment Janet A. , Taylor Philip R. , Eble Johannes A. , Reis e Sousa Caetano , Brown Gordon D.
Published: March 2009

CLEC-2 is a member of the “dectin-1 cluster” of C-type lectin-like receptors and was originally thought to be restricted to platelets. In this study, we demonstrate that murine CLEC-2 is also expressed by peripheral blood neutrophils, but only weakly by bone marrow or elicited inflammatory neutrophils. On circulating neutrophils, CLEC-2 can mediate phagocytosis of Ab-coated beads and the production of proinflammatory cytokines, including TNF-α, in response to the CLEC-2 ligand, rhodocytin. CLEC-2 possesses a tyrosine-based cytoplasmic motif similar to that of dectin-1, and we show using chimeric analyses that the activities of this receptor are dependent on this tyrosine. Like dectin-1, CLEC-2 can recruit the signaling kinase Syk in myeloid cells, however, stimulation of this pathway does not induce the respiratory burst. These data therefore demonstrate that CLEC-2 expression is not restricted to platelets and that it functions as an activation receptor on neutrophils.
Combined Effect of Antiretroviral Therapy and Blockade of IDO in SIV-Infected Rhesus Macaques
Authors: Boasso Adriano , Vaccari Monica , Fuchs Dietmar , Hardy Andrew W. , Tsai Wen-Po , Tryniszewska Elzbieta , Shearer Gene M. , Franchini Genoveffa
Published: March 2009

Increased activity of IDO, which catalyzes the degradation of Trp into kynurenine (Kyn), is observed during HIV/SIV infection, and it may contribute to the persistence of HIV/SIV by suppressing antiviral T cell responses. We administered the IDO inhibitor 1-methyl-d-tryptophan (d-1mT) for 13 days to SIV-infected rhesus macaques receiving antiretroviral therapy (ART). d-1mT treatment increased the plasma levels of Trp, without reducing the levels of Kyn, suggesting only a partial effect on IDO enzymatic activity. Surprisingly, d-1mT significantly reduced the virus levels in plasma and lymph nodes of ART-treated animals with incomplete responsiveness to ART. In SIV-infected animals that were not receiving ART, d-1mT was ineffective in reducing the plasma viral load and had only a marginal effect on the plasma Kyn/Trp ratio. Increased IDO and TGF-β mRNA expression in lymph nodes of ART-treated macaques after d-1mT treatment suggested that compensatory counterregulatory mechanisms were activated by d-1mT, which may account for the lack of effect on plasma Kyn. Finally, d-1mT did not interfere with the ART-induced T cell dynamics in lymph nodes (increased frequency of total CD4 T cells, increase of CD8 T cells expressing the antiapoptotic molecule Bcl2, and reduction of regulatory T cells). Thus, d-1mT appeared to synergize with ART in inhibiting viral replication and did not interfere with the beneficial immunologic effects of ART. Further studies are required to elucidate the immunologic or virologic mechanism by which d-1mT inhibited SIV replication in vivo.
Mechanism of the Salutary Effects of Estrogen on Kupffer Cell Phagocytic Capacity following Trauma-Hemorrhage: Pivotal Role of Akt Activation
Authors: Hsieh Chi-Hsun , Nickel Eike A. , Chen Jianguo , Schwacha Martin G. , Choudhry Mashkoor A. , Bland Kirby I. , Chaudry Irshad H.
Published: March 2009

Kupffer cells are macrophages in the liver whose major role is to clear circulating pathogens. Decreased phagocytic capacity of Kupffer cells may result in severe systemic infection. We tested the hypothesis that the depressed Kupffer cell phagocytic capacity following trauma-hemorrhage is enhanced by estrogen administration and this occurs due to maintenance of Fc receptor expression and cellular ATP content via the activation of Akt. Male C3H/HeN mice were subjected to sham operation or trauma-hemorrhage and sacrificed 2 h thereafter. Estrogen, with or without an estrogen receptor antagonist (ICI 182,780), a PI3K inhibitor (Wortmannin), or vehicle, was injected during resuscitation. Kupffer cell phagocytic capacity was tested in vivo. The expression of Fc receptors, of Akt phosphorylation, of p38 MAPK phosphorylation, of DNA binding activity of NF-κB and ATP content of Kupffer cells were also determined. Trauma-hemorrhage suppressed Kupffer cell phagocytosis by decreasing Fc receptor expression and Akt activation; however, it induced p38 MAPK activation and increased NF-κB activity. Cellular ATP levels were also decreased following trauma-hemorrhage. Administration of estrogen following trauma-hemorrhage increased phospho-Akt levels and normalized all the parameters described as well as plasma levels of TNF-α, IL-6, and IL-10. Coadministration of ICI 182,780 or Wortmannin abolished the beneficial effects of estrogen in improving the phagocytic capacity of Kupffer cells following trauma-hemorrhage. Thus, activation of Akt plays a crucial role in mediating the salutary effect of estrogen in restoring trauma-hemorrhage-induced suppression of Kupffer cell phagocytosis.
Activation of Microglia by Amyloid β Requires P2X7 Receptor Expression
Authors: Sanz Juana M. , Chiozzi Paola , Ferrari Davide , Colaianna Marilena , Idzko Marco , Falzoni Simonetta , Fellin Renato , Trabace Luigia , Di Virgilio Francesco
Published: March 2009

Extracellular ATP is a mediator of intercellular communication and a danger signal. Release of this and other nucleotides modulates microglia responses via P2Y and P2X receptors, among which the P2X7 subtype stands out for its proinflammatory activity and for up-regulation in a transgenic model of Alzheimer disease and in brains from Alzheimer disease patients. Here we show that amyloid β (Aβ) triggered increases in intracellular Ca2+ ([Ca2+]i), ATP release, IL-1β secretion, and plasma membrane permeabilization in microglia from wild-type but not from P2X7-deleted mice. Likewise, intra-hippocampal injection of Aβ caused a large accumulation of IL-1β in wild-type but not in P2X7−/− mice. These observations suggest that Aβ activates a purinergic autocrine/paracrine stimulatory loop of which the P2X7 receptor is an obligate component. Identification of the P2X7 receptor as a non-dispensable factor of Aβ-mediated microglia stimulation may open new avenues for the treatment of Alzheimer disease.
Microvascular lesions in the brain and retina: The age, gene/environment susceptibility–Reykjavik study
Authors: Qiu Chengxuan , Cotch Mary Frances , Sigurdsson Sigurdur , Klein Ronald , Jonasson Fridbert , Klein Barbara E. K. , Garcia Melissa , Jonsson Palmi V. , Harris Tamara B. , Eiriksdottir Gudny , Kjartansson Olafur , van Buchem Mark A. , Gudnason Vilmundur , Launer Lenore J.
Published: March 2009

Objective

To investigate whether the severity and location of cerebral white matter hyperintensities (WMHs) and brain infarcts are correlated with the signs of retinal microvascular abnormalities in the elderly.

Methods

The study included 4,176 men and women (mean age, 76 years) who participated in the Age, Gene/Environment Susceptibility (AGES)–Reykjavik Study. Digital retinal images of both dilated eyes were taken and evaluated for the presence of retinal focal arteriolar signs (focal arteriolar narrowing and arteriovenous nicking) and retinopathy lesions (retinal blot hemorrhages and microaneurysms). Brain magnetic resonance imaging scans were acquired and evaluated for the presence and distribution of cerebral infarcts and WMHs. Logistic and multinomial logistic models were constructed to estimate the association of retinal microvascular signs to brain lesions.

Results

Controlling for demographic and major cardiovascular risk factors, we found that retinal focal arteriolar signs, but not retinopathy lesions, were significantly associated with an increasing load of subcortical and periventricular WMHs. The strongest association was found between retinal arteriolar signs and a heavier WMH load, specifically in the subcortical frontal lobe, and periventricular frontal and parietal caps. There was a tendency toward bilateral retinal focal arteriolar narrowing being more strongly associated with the heavier load of subcortical WMHs. Arteriovenous nicking was significantly associated with subcortical infarcts.

Interpretation

In older adults, retinal focal arteriolar signs, but not retinopathy lesions, are correlated with the load of diffuse WMHs, particularly those located in the subcortical frontal lobe, and the periventricular frontal and parietal caps of the brain. Ann Neurol 2009;65:569–576
Heterogeneous dispersion of the compatibilizer in the injection molding of polyamide 6/polypropylene blends
Authors: Yang Wei , Tang Xue‐Gang , Xie Bang‐Hu , Zhu Yong‐Ping , Yang Ming‐Bo , Hou Meng
Published: March 2009

Four kinds of ethylene–proplene–diene/maleic anhydride compatibilized polyamide 6/polypropylene samples were prepared with different mixing sequences and showed significant differences in the Izod impact strength. The morphological features of these samples were characterized with scanning electron microscopy, and a heterogeneous dispersion of the compatibilizer in the injection‐molded samples was observed; this was related to the shear field in the skin and subskin layers during injection. A parameter, the transfer energy, is put forward to interpret the dispersion of the compatibilizer in the injection‐molded blends, and the results show that the transfer energy is a key factor in determining the transfer of the compatibilizer. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Dielectric analysis of chlorinated polyvinyl chloride stabilized with di‐n‐octyltin maleate
Authors: Mahrous Salah , Hanfy T. A.
Published: March 2009

Dielectric relaxation of chlorinated polyvinyl chloride stabilized with di‐n‐octyltin maleate has been studied in the frequency range 1 kHz–1 MHz at various temperatures between 300 and 450 K. A clear dielectric relaxation band (α‐type) associated with dipolar polarization has been observed in the studied range. The stabilizer molecules increase the segmental mobility of the polymer, and specific interaction occurs between both the CCl and CO polar groups. The temperature dependence of the relaxation process was analyzed by combining the critical free volume expression by Cohen and Turnbull with the Williams‐Landel‐Ferry (WLF) model of the thermal expansion of free and occupied volumes. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Synthesis, characterization and evaluation of novel methoxypolyethyleneglycol‐ grafted‐ poly(ester‐urethane)s for controlled release of repaglinide
Authors: Kumar S. Vijay , Shelke Namdev B. , Prasannakumar S. , Rokhade Ajit P. , Sherigara B. S. , Aminabhavi Tejraj M.
Published: March 2009

Novel biodegradable aliphatic poly(ester‐urethane)s (PEUs) based on polycaprolactone diol (PCL) and methoxypolyethyleneglycol grafted onto trimethylol propane (mPEG‐g‐TMP) were synthesized by solution polymerization technique and characterized using a variety of techniques. Microspheres ranging in size from 7 to 25 μm were prepared by the solvent evaporation technique and loaded with repaglinide up to 71 to 96%. Increasing molar ratios of mPEG‐g‐TMP propane with respect to polycaprolactone diol gave increase in particle size along with increase in % encapsulation efficiency. Surface morphology and spherical nature of the microspheres were confirmed by scanning electron microscopy (SEM). The release of repaglinide varied, depending upon the molar ratios of mPEG‐g‐TMP moieties with respect to PCL. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Study on microstructure of PET/nanopowder composites
Authors: Yin Hua , Yu Dingsheng
Published: March 2009

In this article, the microstructures of polyethylene terephthalate (PET)/nanopowder of butadiene‐styrene‐vinylpyridine (BSV) rubber, PET/nanocalcium carbonate, and PET/nanoorganoclay as well as the effects of mechanical properties and crystallization on PET were investigated. Scanning electron microscope (SEM) indicated that when the nanoparticles are added into PET, small spheroidicity‐shaped particles were seen in the SEM micrographs, and these particles were not nanopowders themselves. The crystallization of PET is improved with the incorporation of proper quantity of nanopowders of BSV and nanoorganoclay. Nanopowders of BSV and organoclay can enhance PET's mechanical properties but not the nanocalcium carbonate. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Electrical resistivity of polycarbonate/multiwalled carbon nanotube composites under varying injection molding conditions
Authors: Park Dong Hyun , Yoon Kwan Han , Park Young‐Bin , Lee Young Sil , Lee Young Jun , Kim Sang Wan
Published: March 2009

Multiwalled carbon nanotube (MWCNT)‐filled polycarbonate composites were prepared by a corotating intermeshing twin‐screw extruder. The surface resistivities of compression‐ and injection‐molded specimens were quite different, the difference ranging from 103 to 107 Ω/sq at varying MWCNT concentrations. The surface resistivity of the injection‐molded specimen at 2 wt % loading varied up to 105 Ω/sq in the specimen thickness direction and up 104 Ω/sq in the polymer flow direction with respect to the gate. The difference in surface resistivity with the positions of injection‐molded specimen was confirmed with the morphology, which showed the difference in MWCNT number density (numbers/surface area). There was no significant effect on surface resistivity with injection pressure, holding pressure, and molding temperature. The specimens prepared at the injection speed of 13 mm/s showed surface resistivities 103–104 Ω/sq depending on the positions, which was comparable with the compression‐molded specimens, which had a surface resistivity of 103 Ω/sq. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Synthesis and characterization of novel polyurethane crosslinked by linear oligo[bis‐(phenoxy)1.8(4‐hydroxybutaneoxy)0.2 phosphazene]
Authors: Zhou Yubo , Huang Xiaobin , Huang Yawen , Tang Xiaozhen
Published: March 2009

Linear oligo [bis‐(phenoxy)1.8 (4‐hydroxybutaneoxy)0.2 phosphazene] (OPHBP) was synthesized and characterized by Fourier transform infrared spectroscopy, nuclear magnetic resonance, and GPC. The obtained oligo [bis‐(phenoxy)1.8 (4‐hydroxybutaneoxy)0.2 phosphazene] was used as crosslinker to prepare a series of novel polyurethanes. Their structure and properties were measured through Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and water contact‐angle measurement. Compared with conventional polyurethane, novel polyurethanes exhibited better thermal stability, low temperature resistance, and hydrophobicity. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Effect of creep strain on the optomechanical properties and some structural properties of terylene fibers
Authors: Seisa E. A.
Published: March 2009

This article sheds light on the effect of creep strain [ϵ(t); %] on the optomechanical properties and some structure properties of terylene fibers at several constant applied loads. Automated multiple‐beam Fizeau fringes in transmission were used with a mechanical creep device attached to a wedge interferometer where the fiber was subjected to a constant load. This technique was used to determine the mean refractive indices and the mean birefringence values of terylene fibers under different conditions of ϵ(t). The obtained optical results were used to evaluate the optical orientation function, optical stress coefficient, density, crystallinity, and mean‐square density fluctuation with ϵ(t). The obtained results show that, under a constant load, the terylene fibers extended with time, the rate of which decreased with time. An empirical formula is suggested to represent the variation of ϵ(t) of terylene fibers with time, and the constants of this formula were determined. A mechanical model is proposed to represent ϵ(t) of terylene fibers, which consists of two Kelvin elements combined in series, which were used to provide an accurate fit to the experimental creep curve. The stress–strain curve via creep was studied to determine some mechanical parameters of the investigated fibers: Young's modulus, yield stress, and yield strain. Illustrations with microinterferograms, graphs, and tables are given. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009
Structural and material properties of a rapidly cured thermoplastic‐toughened epoxy system
Authors: Zhang Jin , Guo Qipeng , Fox Bronwyn
Published: March 2009

Thermoplastic‐toughened epoxy resins are widely used as matrices in modern composite prepreg systems. Rapid curing of thermoplastic‐toughened epoxy matrix composites results in different mechanical properties. To investigate the structure–property relationship, we investigated a poly(ether sulfone)‐modified triglycidylaminophenol/4,4′‐diamino diphenyl sulfone system that was cured at different heating rates. An intermediate dwell was also applied during the rapid heating of the thermoplastic‐modified epoxy system. We found that a higher heating rate led to a larger domain size of the phase‐separated macrostructure and also facilitated more complete phase separation. The intermediate dwell helped phase separation to proceed even further, leading to an even larger domain size of the macrostructure. A carbon‐fiber‐reinforced polymer matrix composite prepreg based on the poly(ether sulfone)‐modified multifunctional epoxy system was cured with the same schedule. The rapidly heated composite laminates exhibited higher mode I delamination fracture toughness than the slowly heated material. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009