bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recombinant Human Growth Hormone in the Treatment of Patients With Cystic Fibrosis
Authors: Phung Olivia J. , Coleman Craig I. , Baker Erica L. , Scholle Jennifer M. , Girotto Jennifer E. , Makanji Sagar S. , Chen Wendy T. , Talati Ripple , Kluger Jeffrey , White C. Michael 
Published: October 2010

CONTEXT:
Recombinant human growth hormone (rhGH) improves growth in patients with growth hormone deficiency or idiopathic short stature. Its role in patients with cystic fibrosis (CF) is unclear.

OBJECTIVE:
To review the effectiveness of rhGH in the treatment of patients with CF.

METHODS:
Medline and the Cochrane Central Register of Controlled Trials were searched from the earliest date through April 2010. Randomized controlled trials, observational studies, systematic reviews/meta-analyses, or case reports were included if rhGH therapy was administered to patients with CF and data on prespecified harms, intermediate outcomes, or final health outcomes were reported. When applicable, end points were pooled by using a random-effects model. The overall body of evidence was graded for each outcome as insufficient, low, moderate, or high.

RESULTS:
Ten unique controlled trials (n = 312) and 8 observational studies (n = 58) were included. On quantitative synthesis of controlled trials, several markers of pulmonary function, anthropometrics, and bone mineralization were significantly improved versus control. Results of single-arm observational studies for the aforementioned outcomes were generally supportive of findings in clinical trials. There is insufficient evidence to determine the effect of rhGH on intravenous antibiotic use during therapy, pulmonary exacerbations, health-related quality-of-life, bone consequences, or total mortality, but moderate evidence suggests that rhGH therapy reduces the rate of hospitalization versus control.

CONCLUSIONS:
rhGH improved almost all intermediate measures of pulmonary function, height, and weight in patients with CF. Improvements in bone mineral content are also promising. However, with the exception of hospitalizations, the benefits on final health outcomes cannot be directly determined at this time.
Lack of TRPM2 Impaired Insulin Secretion and Glucose Metabolisms in Mice
Authors: Uchida Kunitoshi , Dezaki Katsuya , Damdindorj Boldbaatar , Inada Hitoshi , Shiuchi Tetsuya , Mori Yasuo , Yada Toshihiko , Minokoshi Yasuhiko , Tominaga Makoto 
Published: October 2010

OBJECTIVE
TRPM2 is a Ca2+-permeable nonselective cation channel activated by adenosine dinucleotides. We previously demonstrated that TRPM2 is activated by coapplication of heat and intracellular cyclic adenosine 5′-diphosphoribose, which has been suggested to be involved in intracellular Ca2+ increase in immunocytes and pancreatic β-cells. To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knockout (TRPM2-KO) mice.

RESEARCH DESIGN AND METHODS
Oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT) were performed in TRPM2-KO and wild-type mice. We also measured cytosolic free Ca2+ in single pancreatic cells using fura-2 microfluorometry and insulin secretion from pancreatic islets.

RESULTS
Basal blood glucose levels were higher in TRPM2-KO mice than in wild-type mice without any difference in plasma insulin levels. The OGTT and IPGTT demonstrated that blood glucose levels in TRPM2-KO mice were higher than those in wild-type mice, which was associated with an impairment in insulin secretion. In isolated β-cells, smaller intracellular Ca2+ increase was observed in response to high concentrations of glucose and incretin hormone in TRPM2-KO cells than in wild-type cells. Moreover, insulin secretion from the islets of TRPM2-KO mice in response to glucose and incretin hormone treatment was impaired, whereas the response to tolbutamide, an ATP-sensitive potassium channel inhibitor, was not different between the two groups.

CONCLUSIONS
These results indicate that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins. Thus, TRPM2 may be a new target for diabetes therapy.
Stochastic tumor growth system with two different kinds of time delay
Authors: Dou Chun-Sheng , Li Di , Wang Can-Jun 
Published: October 2010

Abstract
The dynamical properties of a noise-driven tumor cell growth system are investigated when there exist two different kinds of time delays, in the deterministic and fluctuating forces, respectively. Using the approximation probability density approach, the delayed Fokker-Planck equation is obtained. The effects of two different time delays on the stationary probability distribution (SPD), the mean value and the mean passage time (MFPT) are discussed. It is found that the time delay τ1 in the deterministic force can enhance tumor cell number, while the time delay τ2 in the fluctuating force can induce a decrease in tumor cell numbers. On the other hand, while τ1 can hold back the extinction of tumor cells, τ2 can speed up their extinction.
Pattern selection processes and noise induced pattern-forming transitions in periodic systems with transient dynamics
Authors: Kharchenko Dmytro , Kharchenko Vasyl , Lysenko Iryna 
Published: October 2010

Abstract
We apply the phase field crystal method for nonequilibrium patterning to stochastic systems with an external source in which transient dynamics is essential. Considering a prototype model for a one-component periodic system subjected to external influence kind of irradiation we study properties of pattern selection processes and external noise induced pattern-forming transitions. These processes are examined by means of the structure function dynamics analysis. Nonequilibrium pattern-forming transitions are analyzed numerically.
Twist deformations of the supersymmetric quantum mechanics
Authors: Castro Paulo , Chakraborty Biswajit , Kuznetsova Zhanna , Toppan Francesco 
Published: October 2010

Abstract
The $$
\mathcal{N}
$$-extended Supersymmetric Quantum Mechanics is deformed via an abelian twist which preserves the super-Hopf algebra structure of its Universal Enveloping Superalgebra. Two constructions are possible. For even $$
\mathcal{N}
$$ one can identify the 1D
$$
\mathcal{N}
$$-extended superalgebra with the fermionic Heisenberg algebra. Alternatively, supersymmetry generators can be realized as operators belonging to the Universal Enveloping Superalgebra of one bosonic and several fermionic oscillators. The deformed system is described in terms of twisted operators satisfying twist-deformed (anti)commutators. The main differences between an abelian twist defined in terms of fermionic operators and an abelian twist defined in terms of bosonic operators are discussed.
Ein Modell zur Bilanzierung des holzerntebedingten Nährstoffentzugs auf Schweizer Waldböden
Authors: Lemm Renato , Thees Oliver , Hensler Urs , Hässig Jörg , Bürgi Anton , Zimmermann Stephan 
Published: October 2010

Abstract
A model named NBM was developed to judge quantitatively the risks of soil nutrient extraction due to timber harvesting in Switzerland. The model can be used for forest enterprises as well as for larger regions. It assesses nutrient extraction at the level of the single stand as part of a scenario analysis. The extraction of nine nutrients as a result of harvesting is quantified under conditions with different silvicultural and bucking methods. The results are then compared to the soil potentials and changes in these potentials. The simulation results are assessed with respect to sustainability. Two criteria are used to evaluate the long-term risk of nutrient deficiency. The validity of the model in a practical context is limited as more soil informations would be needed. The paper describes structure and functions of the model, its computational implementation, and the results obtained from its first application in the forest enterprise of Bremgarten, Wohlen, Waltenschwil. It ends with a critical analysis of this first implementation of the model.
Dual Effects of TRAIL in Suppression of Autoimmunity: The Inhibition of Th1 Cells and the Promotion of Regulatory T Cells
Authors: Ikeda Tokunori , Hirata Shinya , Fukushima Satoshi , Matsunaga Yusuke , Ito Takaaki , Uchino Makoto , Nishimura Yasuharu , Senju Satoru 
Published: October 2010

AbstractTRAIL is known to play a pivotal role in the inhibition of autoimmune disease. We previously demonstrated that administration of dendritic cells engineered to express TRAIL and myelin-oligodendrocyte glycoprotein reduced the severity of experimental autoimmune encephalomyelitis and suggested that CD4+CD25+ regulatory T cells (Tregs) were involved in mediating this preventive effect. In the current study, we investigated the effect of TRAIL on Tregs, as well as conventional T cells, using TRAIL-deficient mice. Upon induction of experimental autoimmune encephalomyelitis, TRAIL-deficient mice showed more severe clinical symptoms, a greater frequency of IFN-γ–producing CD4+ T (Th1) cells, and a lower frequency of CD4+Foxp3+ Tregs than did wild-type mice. In vitro, conventional T cells stimulated by bone marrow-derived dendritic cells (BM-DCs) from TRAIL-deficient mice showed a greater magnitude of proliferation than did those stimulated by BM-DCs from wild-type mice. In contrast, TRAIL expressed on the stimulator BM-DCs enhanced the proliferative response of CD4+CD25+ Tregs in the culture. The functional TRAILR, mouse death receptor 5 (mDR5), was expressed in conventional T cells and Tregs upon stimulation. In contrast, the decoy receptor, mDc-TRAILR1, was slightly expressed only on CD4+CD25+ Tregs. Therefore, the distinct effects of TRAIL may be due to differences in the mDc-TRAILR1 expression or the signaling pathways downstream of mouse death receptor 5 between the two T cell subsets. Our data suggest that TRAIL suppresses autoimmunity by two mechanisms: the inhibition of Th1 cells and the promotion of Tregs.
Differential Suppression of Tumor-Specific CD8+ T Cells by Regulatory T Cells
Authors: James Edward , Yeh Alex , King Cathy , Korangy Firouzeh , Bailey Ian , Boulanger Denise S. , Van den Eynde Benoît J. , Murray Nicholas , Elliott Tim J. 
Published: October 2010

Abstract
In the CT26 BALB/c murine model of colorectal carcinoma, depletion of regulatory T cells (Tregs) prior to tumor inoculation results in protective immunity to both CT26 and other BALB/c-derived tumors of diverse histological origin. In this paper, we show that cross-protection can be conferred by adoptively transferred CD8+ CTLs. Other schedules for inducing immunity to CT26 have been described, but they do not lead to cross-protection. We show that Treg ablation facilitates the development of new CTL specificities that are normally cryptic, and have mapped the root epitope of one of these responses. This work has allowed us to demonstrate how the specificity of CTL responses to tumor Ags can be controlled via differential suppression of CTL specificities by Tregs, and how this can result in very different physiological outcomes.
A Cyclooxygenase-2/Prostaglandin E2 Pathway Augments Activation-Induced Cytosine Deaminase Expression within Replicating Human B Cells
Authors: Lee Hyunjoo , Trott Joshua S. , Haque Shabirul , McCormick Steven , Chiorazzi Nicholas , Mongini Patricia K. A. 
Published: October 2010

Abstract
Within inflammatory environments, B cells encountering foreign or self-Ag can develop tertiary lymphoid tissue expressing activation-induced cytosine deaminase (AID). Recently, this DNA-modifying enzyme was detected in nonlymphoid cells within several inflamed tissues and strongly implicated in malignant transformation. This study examines whether a cyclooxygenase 2 (COX-2) pathway, often linked to inflammation, influences AID expression in activated B lymphocytes. In this paper, we report that dividing human B cells responding to surrogate C3d-coated Ag, IL-4, and BAFF express AID, as well as COX-2. A progressive increase in AID with each division was paralleled by a division-related increase in a COX-2–linked enzyme, microsomal PGE2 synthase-1, and the PGE2R, EP2. Cells with the greatest expression of AID expressed the highest levels of EP2. Although COX-2 inhibitors diminished both AID expression and IgG class switching, exogenous PGE2 and butaprost, a selective EP2 agonist, augmented AID mRNA/protein and increased the numbers of IgG+ progeny. Despite the latter, the proportion of IgG+ cells within viable progeny generally declined with PGE2 supplementation. This was not due to PGE2-promoted differentiation to plasma cells or to greater downstream switching. Rather, because phosphorylated ataxia telangiectasia mutated levels were increased in progeny of PGE2-supplemented cultures, it appears more likely that PGE2 facilitates AID-dependent DNA double-strand breaks that block B cell cycle progression or promote activation-induced cell death, or both. Taken together, the results suggest that a PGE2 feed-forward mechanism for augmenting COX-2 pathway proteins promotes progressively increased levels of AID mRNA, protein, and function.
Error-Prone DNA Repair Activity during Somatic Hypermutation in Shark B Lymphocytes
Authors: Zhu Catherine , Hsu Ellen 
Published: October 2010

Abstract
Sharks are representatives of the earliest vertebrates that possess an immune system utilizing V(D)J recombination to generate Ag receptors. Their Ab repertoire diversity is based in part on a somatic hypermutation process that introduces adjacent nucleotide substitutions of 2–5 bp. We have isolated mutant nonfunctional Ig rearrangements and intronic flank sequences to characterize the nonselected, intrinsic properties of this phenomenon; changes unique to shark were observed. Duplications and deletions were associated with N additions, suggesting participation of a DNA polymerase with some degree of template independence during the repair of DNA breaks initiated by activation-induced cytidine deaminase. Other mutations were consistent with some in vitro activities of mammalian translesion DNA polymerase η: tandem base substitutions, strand slippage, and small insertions/deletions. The nature of substitution patterns shows that DNA lesions at shark Ig genes recruit DNA repair factors with a species-specific repertoire of activities. We speculate that the tandem mutations are introduced by direct sequential misinsertions and that, in shark B cells, the mispairs tend to be extended rather than proofread. Despite extensive changes undergone by some mutants, the physical range of mutational activity remained restricted to VDJ and within the first 2-kb portion of the 6.8-kb J-C intron, perhaps a self-regulating aspect of activation-induced cytidine deaminase action that is conserved in evolution.
The Early Marginal Zone B Cell-Initiated T-Independent Type 2 Response Resists the Proteasome Inhibitor Bortezomib
Authors: Lang Veronika R. , Mielenz Dirk , Neubert Kirsten , Böhm Christina , Schett Georg , Jäck Hans-Martin , Voll Reinhard E. , Meister Silke 
Published: October 2010

Abstract
The proteasome inhibitor bortezomib is approved for the treatment of multiple myeloma and mantle cell lymphoma. We recently demonstrated that bortezomib eliminates autoreactive plasma cells in systemic lupus erythematosus mouse models, thereby representing a promising novel treatment for Ab-mediated diseases. In this study, we investigated the effects of bortezomib on the just developing and pre-existing T-dependent Ab response toward dinitrophenyl-keyhole limpet hemocyanin and the T-independent type 2 response toward (4-hydroxy-3-iodo-5-nitrophenyl)acetyl (NIP)-Ficoll in BALB/c mice. Bortezomib treatment strongly reduced T-dependent Ab titers mainly due to depletion of plasma cells. In contrast, the early T-independent type 2 response against i.v. administered NIP-Ficoll, which is predominantly dependent on marginal zone (MZ) B cells, resisted bortezomib. Upon bortezomib treatment, immunoproteasome subunits and the antiapoptotic unfolded protein response including NF-κB were induced in NIP-Ficoll–stimulated MZ B cells, but not in plasma cells and follicular B cells. In summary, bortezomib treatment decreases Ab titers arising from T-dependent immune responses predominantly by eliminating plasma cells. In contrast, the early T-independent type 2 response protecting the organism against blood-borne pathogens remains largely intact due to a remarkable resistance of MZ B cells against proteasome inhibition.
IL-23 and IL-17A, but Not IL-12 and IL-22, Are Required for Optimal Skin Host Defense against Candida albicans
Authors: Kagami Shinji , Rizzo Heather L. , Kurtz Stephen E. , Miller Lloyd S. , Blauvelt Andrew 
Published: October 2010

Abstract
IL-23 and Th17 cells play important roles in host defense against systemic infections with extracellular bacteria and fungi, although their roles in immunity against localized skin infections are less well defined. Here, the contributions of IL-23 and Th17 cytokines in host defense against cutaneous Candida albicans infection were evaluated. Mice deficient in IL-23 or IL-17A demonstrated delayed healing and decreased IL-17A production after skin infection with C. albicans compared with wild-type mice or mice deficient in IL-12 or IL-22. Histologic examination revealed epidermal hyperplasia overlying infected dermis four days postinoculation in wild-type mice. In IL-23–deficient mice, fungal burden was greater in skin, neither IL-17A nor IL-22 mRNAs were expressed postinfection, and these mice demonstrated only minimal epidermal hyperplasia. Exogenous recombinant IL-17A injected at the site of skin infection promoted more rapid healing of candidiasis in both wild-type mice and mice deficient in IL-23 and IL-12. Taken together, these results demonstrate that IL-23 and IL-17A, but not IL-12 and IL-22, are required for optimal host defense against cutaneous candidiasis. In addition, recombinant IL-17A may serve as a potential therapy to enhance healing in individuals with chronic cutaneous candidiasis.
Human Plasma Membrane-Derived Vesicles Halt Proliferation and Induce Differentiation of THP-1 Acute Monocytic Leukemia Cells
Authors: Ansa-Addo Ephraim A. , Lange Sigrun , Stratton Dan , Antwi-Baffour Samuel , Cestari Igor , Ramirez Marcel I. , McCrossan Maria V. , Inal Jameel M. 
Published: October 2010

Abstract
Plasma membrane-derived vesicles (PMVs) are small intact vesicles released from the cell surface that play a role in intercellular communication. We have examined the role of PMVs in the terminal differentiation of monocytes. The myeloid-differentiating agents all-trans retinoic acid/PMA and histamine, the inflammatory mediator that inhibits promonocyte proliferation, induced an intracellular Ca2+-mediated PMV (as opposed to exosome) release from THP-1 promonocytes. These PMVs cause THP-1 cells to enter G0–G1 cell cycle arrest and induce terminal monocyte-to-macrophage differentiation. Use of the TGF-β receptor antagonist SB-431542 and anti–TGF-β1 Ab showed that this was due to TGF-β1 carried on PMVs. Although TGF-β1 levels have been shown to increase in cell culture supernatants during macrophage differentiation and dendritic cell maturation, the presence of TGF-β1 in PMVs is yet to be reported. In this study, to our knowledge we show for the first time that TGF-β1 is carried on the surface of PMVs, and we confirm the presence within PMVs of certain leaderless proteins, with reported roles in myeloid cell differentiation. Our in vitro findings support a model in which TGF-β1–bearing PMVs, released from promonocytic leukemia cells (THP-1) or primary peripheral blood monocytes on exposure to sublytic complement or after treatment with a differentiation therapy agent, such as all-trans retinoic acid, significantly reduce proliferation of THP-1 cells. Such PMVs also induce the terminal differentiation of primary peripheral blood monocytes as well as THP-1 monocytes.
Distinct Roles of Vascular Endothelial Growth Factor Receptor-1– and Receptor-2–Mediated Signaling in T Cell Priming and Th17 Polarization to Lipopolysaccharide-Containing Allergens in the Lung
Authors: Kim You-Sun , Choi Seng-Jin , Tae You-Me , Lee Byung-Jae , Jeon Seong Gyu , Oh Sun-Young , Gho Yong Song , Zhu Zhou , Kim Yoon-Keun 
Published: October 2010

Abstract
Vascular endothelial growth factor (VEGF) is a key mediator in the development of airway immune dysfunction to inhaled allergens. However, the exact role of its receptors-mediated signaling is controversial. In this study, we evaluated the role of VEGF receptor (VEGFR)-1– and VEGFR-2–mediated signaling in T cell priming and polarization in the context of inhalation of LPS-containing allergens. A murine asthma model of mixed Th1 and Th17 cell responses was generated using intranasal sensitization with LPS-containing allergens. Pharmacologic intervention was performed during sensitization. In vivo production of VEGF and Th1- and Th17-polarizing cytokines (IL-12p70 and IL-6, respectively) were upregulated by airway exposure to LPS. Pharmacological intervention with a VEGFR-2–neutralizing Ab (anti-Flk1 mAb) abolished the production of IL-6 (but not IL-12p70) and the subsequent development of allergen-specific Th17 cell response. On the other hand, blocking VEGFR-1 signaling with a VEGFR-1 antagonist (anti-Flt1 hexapeptide) did not affect the production of IL-12p70 and IL-6. However, blocking VEGFR-1 signaling resulted in T cell tolerance rather than priming, mainly by inhibiting the maturation of lung dendritic cells, and their migration into lung-draining lymph nodes. These results suggest that T cell priming to LPS-containing allergens depends on VEGFR-1–mediated signaling, and the subsequent Th17 polarization depends on VEGFR-2 signaling.
Differential Localization of Effector and Memory CD8 T Cell Subsets in Lymphoid Organs during Acute Viral Infection
Authors: Jung Yong Woo , Rutishauser Rachel L. , Joshi Nikhil S. , Haberman Ann M. , Kaech Susan M. 
Published: October 2010

AbstractIt is unclear where within tissues subsets of effector and memory CD8 T cells persist during viral infection and whether their localization affects function and long-term survival. Following lymphocytic choriomeningitis virus infection, we found most killer cell lectin-like receptor G1 (KLRG1)loIL-7Rhi effector and memory cells, which are long-lived and high proliferative capacity, in the T cell zone of the spleen. In contrast, KLRG1hiIL-7Rlo cells, which appear terminally differentiated and have shorter life spans, were exclusively localized to the red pulp. KLRG1loIL-7Rhi T cells homed to the T cell zone using pertussis toxin-sensitive chemokine receptors and appeared to contact gp38+ stromal cells, which produce the chemokines CCL19 and CCL21 and the T cell survival cytokine IL-7. The transcription factors T-bet and B lymphocyte-induced maturation protein-1 controlled effector CD8 T cell splenic migration. Effector CD8 T cells overexpressing T-bet homed to the red pulp, whereas those lacking B lymphocyte-induced maturation protein-1 homed to the T cell zone. Upon memory formation, CD62L+ memory T cells were predominantly found in the T cell zone, whereas CD62L− cells were found in the red pulp. Thus, effector and memory CD8 T cell subset localization within tissues is linked to their differentiation states, and this may identify anatomical niches that regulate their longevity and homeostasis.