bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using Microarray-based Molecular Cytogenetic Methods to Identify Chromosome Abnormalities
Authors: Shaffer Lisa G. , Bejjani Bassem A. 
Published: August 2009

CME Educational Objectives

1.
Differentiate between traditional banding methods and molecular cytogenetic techniques for chromosome analysis.

2.
Demonstrate the benefits and limitations to microarray-based methods for chromosome analysis.

3.
Interpret differences in detection rates between traditional chromosome analysis and microarray-based cytogenetics for the identification of chromosome abnormalities in children.
Partial Humeral Head Resurfacing and Latarjet Coracoid Transfer for Treatment of Recurrent Anterior Glenohumeral Instability
Authors: Moros Chris , Ahmad Christopher S. 
Published: August 2009

Bone deficiencies of either the humeral head or glenoid fossa may cause recurrent shoulder instability following soft tissue stabilization procedures. The engaging Hill-Sachs lesion, a major risk factor for instability, has been identified in a majority of patients with recurrent anterior instability. Guidance for surgical management of large humeral head deficiency presents few available options, with even fewer clinical data to support any one technique. Anteroinferior glenoid deficiency has also been a well-documented source of recurrent instability. The Latarjet coracoid transfer procedure corrects the glenoid defect by restoring the architecture of the inferior rim. Although coracoid transfer addresses containment on the glenoid, a concomitant large humeral head defect is at risk for engagement on the corrected glenoid. This article describes a case of a 50-year-old man presenting with recurrent right shoulder dislocations status post-open stabilization procedure 10 years prior. Radiologic evaluation demonstrated a large Hill-Sachs lesion with adjacent chondral derangement and a nonunion bony Bankart lesion.
The Arthrosurface HemiCap humeral head resurfacing prosthesis (Arthrosurface Inc, Franklin, Massachusetts) was used to address the Hill-Sachs lesion with a Latarjet coracoid transfer procedure. We were unable to identify examples in the literature of the HemiCap used in the correction of a Hill-Sachs lesion for recurrent anterior instability. The HemiCap prosthesis has the benefit of correcting the Hill-Sachs lesion and adjacent chondral defect while preserving uninvolved articular surface. The combination of surgical interventions produced a successful result.
Atraumatic Bilateral Femur Fracture in Long-Term Bisphosphonate Use
Authors: Goddard Maria S. , Reid Kristoff R. , Johnston James C. , Khanuja Harpal S. 
Published: August 2009

Postmenopausal women with osteoporosis are commonly treated with the bisphosphonate class of medications, one of the most frequently prescribed medications in the United States. In the past 4 years, reports have been published implying that long-term bisphosphonate therapy could be linked to atraumatic femoral diaphyseal fractures.
This article presents a case of a 67-year-old woman who presented with an atraumatic right femur fracture. She had a medical history notable for use of the bisphosphonate alendronate for 16 years before being switched to ibandronate for 1 year before presentation. She had sustained a similar fracture on the contralateral side 3 years previously.
This case report, in addition to a review of the literature, shows that use of the bisphosphonate class of medications for an extended period of time may result in an increased susceptibility to atraumatic femoral diaphyseal fractures. Some studies have suggested that the reason may be the mechanism of action of bisphosphonates, resulting in decreased bone turnover and remodeling. Studies have not shown if the entire class of medications produce a similar result, but patients who have been treated with any bisphosphonate for an extended period of time should be considered at risk. In patients who have already sustained a femoral diaphyseal fracture, imaging of the contralateral side should be performed to identify cortical thickening as an early sign of fracture risk. Patients should also be questioned about thigh pain.
Distal Femur Defects Reconstructed With Polymethylmethacrylate and Internal Fixation Devices: A Biomechanical Study
Authors: Uglialoro Anthony D. , Maceroli Michael , Beebe Kathleen S. , Benevenia Joseph , Patterson Francis R. 
Published: August 2009

Benign aggressive distal femur tumors are treated with curettage, adjuvant phenol or argon, and polymethylmethacrylate (PMMA) packing. For large defects, an internal fixation device is added to reduce the fracture risk. The purpose of this study is to compare the strength of locking plates to other fixation devices for stabilization of these defects.
Lateral condyle defects in young, fresh frozen femurs were packed with PMMA and augmented by internal fixation. Three groups of 4 matched pairs of femurs were organized for the following comparisons: (1) stacked Steinmann pins vs crossed screws; (2) stacked pins vs locking plates; and (3) crossed screws vs locking plates. Specimens were subjected to axial load-to-failure testing on an MTS machine.

There was no difference in load-to-failure strength (
P
=.177) using Steinmann pins or crossed screws. Locking plate constructs were stronger (
P
=.028) than Steinmann pin constructs. Locking plate constructs were also stronger (
P
<.001) than crossed-screw constructs. Steinmann pin constructs failed with severe intra-articular fractures; crossed screw constructs failed with bulging of the defects, articular impaction, and minimal fracture propagation. Locking plate constructs failed with extra-articular spiral shaft fractures.
Antibiotic Cement Screw for Postoperative Infection After Gamma Nailing
Authors: Noda Mitsuaki , Saegusa Yasuhiro , Takakura Yoshiyuki , Kuroda Ryosuke , Doita Minoru 
Published: August 2009

Few articles describe the management of postoperative infection occurring after the use of an intramedullary nail in the treatment of femoral intertrochanteric fractures. Implant removal is frequently selected for postoperative infection control, especially in chronic cases. However, removal of the intramedullary nail causes a high rate of femoral neck fractures, challenging surgeons to prevent such fractures with few guidelines for how this can be done.
This article presents 2 cases of postoperative infection following intramedullary nail implant in elderly women. After removal of the infected implant and meticulous debridement, an antibiotic cement screw (a cannulated screw enveloped with antibiotic-impregnated bone cement) was inserted from the lag screw hole into the femoral head. At the latest follow-up (mean, 18 months postoperatively), neither femoral neck fracture nor infection had occurred in either patient.
The antibiotic cement screw is expected to provide stability and prevent fracture at the femoral neck region, and its more intimate contact with the medullary canal allows a higher concentration of local antibiotics than intravenous application. The antibiotic cement screw is recommended especially for infection after gamma nailing.
We also introduce a simple, reproducible method for constructing an antibiotic cement screw large enough to fit the lag screw hole using bone cement, cannulated screw, antibiotics, and a chest tube.
Foxp3-Deficient Regulatory T Cells Do Not Revert into Conventional Effector CD4+ T Cells but Constitute a Unique Cell Subset
Authors: Kuczma Michal , Podolsky Robert , Garge Nikhil , Daniely Danielle , Pacholczyk Rafal , Ignatowicz Leszek , Kraj Piotr 
Published: August 2009

Abstract
Homeostasis in the immune system is maintained by specialized regulatory CD4+ T cells (Treg) expressing transcription factor Foxp3. According to the current paradigm, high-affinity interactions between TCRs and class II MHC-peptide complexes in thymus “instruct” developing thymocytes to up-regulate Foxp3 and become Treg cells. However, the loss or down-regulation of Foxp3 does not disrupt the development of Treg cells but abrogates their suppressor function. In this study, we show that Foxp3-deficient Treg cells in scurfy mice harboring a null mutation of the Foxp3 gene retained cellular features of Treg cells including in vitro anergy, impaired production of inflammatory cytokines, and dependence on exogenous IL-2 for proliferation and homeostatic expansion. Foxp3-deficient Treg cells expressed a low level of activation markers, did not expand relative to other CD4+ T cells, and produced IL-4 and immunomodulatory cytokines IL-10 and TGF-β when stimulated. Global gene expression profiling revealed significant similarities between Treg cells expressing and lacking Foxp3. These results argue that Foxp3 deficiency alone does not convert Treg cells into conventional effector CD4+ T cells but rather these cells constitute a distinct cell subset with unique features.
Alveolar Macrophages and Lung Dendritic Cells Sense RNA and Drive Mucosal IgA Responses
Authors: Bessa Juliana , Jegerlehner Andrea , Hinton Heather J. , Pumpens Paul , Saudan Philippe , Schneider Pascal , Bachmann Martin F. 
Published: August 2009

Abstract
The mechanisms regulating systemic and mucosal IgA responses in the respiratory tract are incompletely understood. Using virus-like particles loaded with single-stranded RNA as a ligand for TLR7, we found that systemic vs mucosal IgA responses in mice were differently regulated. Systemic IgA responses following s.c. immunization were T cell independent and did not require TACI or TGFβ, whereas mucosal IgA production was dependent on Th cells, TACI, and TGFβ. Strikingly, both responses required TLR7 signaling, but systemic IgA depended upon TLR7 signaling directly to B cells whereas mucosal IgA required TLR7 signaling to lung dendritic cells and alveolar macrophages. Our data show that IgA switching is controlled differently according to the cell type receiving TLR signals. This knowledge should facilitate the development of IgA-inducing vaccines.
ERK and Not p38 Pathway Is Required for IL-12 Restoration of T Cell IL-2 and IFN-γ in a Rodent Model of Alcohol Intoxication and Burn Injury
Authors: Li Xiaoling , Chaudry Irshad H. , Choudhry Mashkoor A. 
Published: August 2009

Abstract
Previous studies from our laboratory have shown that acute alcohol/ethanol (EtOH) intoxication combined with burn injury suppresses T cell IL-2 and IFN-γ production by inhibiting p38 and ERK activation. Because IL-12 plays a major role in Th1 differentiation and IFN-γ production, we examined whether diminished IL-2 and IFN-γ production after EtOH plus burn injury resulted from a decrease in IL-12. Furthermore, we investigated whether IL-12 utilizes the p38/ERK pathway to modulate T cell IL-2 and IFN-γ production after EtOH and burn injury. Male rats (∼250 g) were gavaged with 5 ml of 20% EtOH 4 h before ∼12.5% total body surface area burn or sham injury. Rats were sacrificed on day 1 after injury, and mesenteric lymph node T cells were isolated. T cells were stimulated with anti-CD3 in the absence or presence of rIL-12 (10 ng/ml) for 5 min and lysed. Lysates were analyzed for p38/ERK protein and phosphorylation levels using specific Abs and Western blot. In some experiments, T cells were cultured for 48 h with or without the inhibitors of p38 (10 μM SB203580/SB202190) or ERK (50 μM PD98059) to delineate the role of p38 and ERK in IL-12-mediated restoration of IL-2 and IFN-γ. Our findings indicate that IL-12 normalizes both p38 and ERK activation in T cells, but the results obtained using p38 and ERK inhibitors indicate that the restoration of ERK plays a predominant role in IL-12-mediated restoration of T cell IL-2 and IFN-γ production after EtOH and burn injury.
Immune Suppressive Activity and Lack of T Helper Differentiation Are Differentially Regulated in Natural Regulatory T Cells
Authors: Zeng Wei-ping , Chang Chawnshang , Lai Jiann-jyh 
Published: August 2009

Abstract
The mechanism for controlling Th cytokine expression in natural regulatory T (nTreg) cells is unclear. Here, it was found that under polarizing conditions Foxp3 did not affect Th1 cell, partially inhibited Th17 cell, but greatly inhibited Th2 cell differentiation of conventional CD4 T cells. Under the polarizing conditions, nTreg cells failed to differentiate into Th2 and Th17 cells, but differentiated into IFN-γ-producing cells. Such Foxp3-transduced CD4 T cells and nTreg cells expressed T-bet, GATA-3, or retinoic acid-related orphan receptor (ROR)γt, and retroviral GATA-3 and RORγt could not induce Th2 and Th17 differentiation from nTreg cells. However, regardless of their cytokine profiles, the Foxp3-transduced CD4 T cells and nTreg cells remained immune suppressive. These results suggested that it is possible to convert pathogenic Th cells to Treg-like cells for therapeutic application. In conclusion, our studies show that Foxp3 is sufficient for immune suppression, whereas the inhibition of cytokine expression requires additional mechanisms.
SHIP Represses the Generation of IL-3-Induced M2 Macrophages by Inhibiting IL-4 Production from Basophils
Authors: Kuroda Etsushi , Ho Victor , Ruschmann Jens , Antignano Frann , Hamilton Melisa , Rauh Michael J. , Antov Andrey , Flavell Richard A. , Sly Laura M. , Krystal Gerald 
Published: August 2009

Abstract
There is a great deal of interest in determining what regulates the generation of classically activated (M1) vs alternatively activated (M2) macrophages (Mφs) because of the opposing effects that these two Mφ subsets have on tumor progression. We show herein that IL-3 and, to a lesser extent, GM-CSF skew murine Mφ progenitors toward an M2 phenotype, especially in the absence of SHIP. Specifically, the addition of these cytokines, with or without M-CSF, to adherence- or lineage-depleted (Lin−) SHIP−/− bone marrow (BM) cells induces high levels of the M2 markers, arginase I, and Ym1 in the resulting mature Mφs. These in vitro-derived mature Mφs also display other M2 characteristics, including an inability to enhance anti-CD3-stimulated splenic T cell secretion of IFN-γ and low IL-12 and high IL-10 production in response to LPS. Not surprisingly, given that IL-3 and GM-CSF utilize STAT5 to trigger many downstream signaling pathways, this M2 phenotype is suppressed when STAT5−/− BM cells are used. Unexpectedly, however, this M2 phenotype is also suppressed when STAT6−/− BM cells are used, suggesting that IL-4- or IL-13-induced signaling might be involved. Consistent with this, we found that IL-3 and GM-CSF stimulate the production of IL-4, especially from SHIP−/− Lin− BM cells, and that neutralizing anti-IL-4 Abs block IL-3-induced M2 skewing. Moreover, we found that basophil progenitors within the Lin− BM are responsible for this IL-3- and GM-CSF-induced IL-4 production, and that SHIP represses M2 skewing not by preventing skewing within Mφs themselves but by inhibiting IL-4 production from basophils.
XBP-1-Deficient Plasmablasts Show Normal Protein Folding but Altered Glycosylation and Lipid Synthesis
Authors: McGehee Annette M. , Dougan Stephanie K. , Klemm Elizabeth J. , Shui Guanghou , Park Boyoun , Kim You-Me , Watson Nicki , Wenk Markus R. , Ploegh Hidde L. , Hu Chih-Chi Andrew 
Published: August 2009

Abstract
The accumulation of misfolded secreted IgM in the endoplasmic reticulum (ER) of X-box binding protein 1 (XBP-1)-deficient B cells has been held responsible for the inability of such cells to yield plasma cells, through the failure to mount a proper unfolded protein response. LPS-stimulated B cells incapable of secreting IgM still activate the XBP-1 axis normally, as follows: XBP-1 is turned on by cues that trigger differentiation and not in response to accumulation of unfolded IgM, but the impact of XBP-1 deficiency on glycoprotein folding and assembly has not been explored. The lack of XBP-1 compromised neither the formation of functional hen egg lysozyme-specific IgM nor the secretion of free κ-chains. Although XBP-1 deficiency affects the synthesis of some ER chaperones, including protein disulfide isomerase, their steady state levels do not drop below the threshold required for proper assembly and maturation of the Igα/Igβ heterodimer and MHC molecules. Intracellular transport and surface display of integral membrane proteins are unaffected by XBP-1 deficiency. Given the fact that we failed to observe any defects in folding of a variety of glycoproteins, we looked for other means to explain the requirement for XBP-1 in plasma cell development. We observed significantly reduced levels of phosphatidylcholine, sphingomyelin, and phosphatidylinositol in total membranes of XBP-1-deficient B cells, and reduced ER content. Terminal N-linked glycosylation of IgM and class I MHC was altered in these cells. XBP-1 hence has important roles beyond folding proteins in the ER.
TLR3-Stimulated Dendritic Cells Up-regulate B7-H1 Expression and Influence the Magnitude of CD8 T Cell Responses to Tumor Vaccination
Authors: Pulko Vesna , Liu Xin , Krco Christopher J. , Harris Kimberley J. , Frigola Xavier , Kwon Eugene D. , Dong Haidong 
Published: August 2009

Abstract
Agonists of TLR have been explored as vaccine adjuvants for tumor immunotherapy. However, their immunological consequences are not fully understood. Although TLR signaling increases the functional potential of dendritic cells (DCs) for priming T cells, coinduction of potentially negative immunoregulatory capacities may impair effector T cell generation. We examined the expression and function of B7 family costimulatory molecules on DCs after activation with the TLR3 agonist, polyinosinic:polycytidylic acid. We demonstrated that polyinosinic:polycytidylic acid consistently up-regulated both B7-2 and B7-H1 molecules on resident, migratory DCs from spleen and lymph nodes. Depletion or blockade of B7-H1 on activated DCs increased the magnitude of effector CD8 T cell expansion. DC-based or protein-based tumor vaccines, in combination with B7-H1 blockade, induced strong effector CD8 T cell responses, resulting in protective immunity against newly established tumors. Our studies suggest that TLR3 signaling has the potential to up-regulate both positive and negative coregulatory molecules on APCs. Selective blockade of negative regulatory molecules in combination with TLR3 agonist may be an effective strategy for increasing the efficacy of tumor vaccines.
Specific Requirements for Vγ9Vδ2 T Cell Stimulation by a Natural Adenylated Phosphoantigen
Authors: Vantourout Pierre , Mookerjee-Basu Jayati , Rolland Corinne , Pont Frédéric , Martin Hélène , Davrinche Christian , Martinez Laurent O. , Perret Bertrand , Collet Xavier , Périgaud Christian , Peyrottes Suzanne , Champagne Eric 
Published: August 2009

Abstract
Human Vγ9Vδ2 T lymphocytes recognize phosphorylated alkyl Ags. Isopentenyl pyrophosphate (IPP) was previously proposed as the main Ag responsible for Vγ9Vδ2 T cell activation by cancer cells. However, triphosphoric acid 1-adenosin-5′-yl ester 3-(3-methylbut-3-enyl) ester (ApppI), a metabolite in which the isopentenyl moiety is linked to ATP, was reported in cells activated with aminobisphosphonates. The contribution of this compound to tumor-stimulatory activity was thus examined. ApppI induces selective expansion of Vγ9Vδ2 T cells from PBMCs. In the absence of APCs, however, ApppI has little stimulatory activity on Vγ9Vδ2 T cells, and optimal activation with ApppI requires addition of a nucleotide pyrophosphatase releasing IPP plus AMP. Thus, ApppI has no intrinsic stimulatory activity. Nevertheless, stimulation by ApppI is strengthened by the presence of APCs. Moreover, in contrast to IPP, ApppI can be efficiently pulsed on dendritic cells as well as on nonprofessional APCs. Pulsed APCs display stable and phosphatase-resistant stimulatory activity, indicative of Ag modification. HPLC analysis of tumor cell extracts indicates that latent phosphoantigenic activity is stored intracellularly in the Vγ9Vδ2 cell-sensitive tumor Daudi and can be activated by a nucleotide pyrophosphatase activity. The presence of ApppI in Daudi cell extracts was demonstrated by mass spectrometry. Nucleotidic Ags such as ApppI are thus a storage form of phosphoantigen which may represent a major source of phosphoantigenic activity in tumor cells. The unique properties of ApppI may be important for the design of Ags used in anticancer immunotherapeutic protocols using Vγ9Vδ2 cells.
CD21/35 Promotes Protective Immunity to Streptococcus pneumoniae through a Complement-Independent but CD19-Dependent Pathway That Regulates PD-1 Expression
Authors: Haas Karen M. , Poe Jonathan C. , Tedder Thomas F. 
Published: August 2009

Abstract
Humoral immunity to T cell-independent type 2 Ags (TI-2 Ag) is critical for protection against encapsulated bacteria such as Streptococcus pneumoniae. The CD21/35 receptor is thought to promote protective humoral immunity to encapsulated bacteria by enabling complement-decorated capsular polysaccharides to coligate the CD21/35-CD19 signaling complex with the B cell Ag receptor (BCR), thereby enhancing Ag-specific B cell activation. However, Ab responses to S. pneumoniae type 3 capsular polysaccharide (PPS-3) and other strong TI-2 Ags were significantly impaired in CD21/35−/− but not C3−/− or C4−/− mice. B cells from CD21/35−/− mice expressed significantly higher levels of cell surface CD19. CD21/35−/− B cells exhibited enhanced BCR-induced calcium responses and significantly higher expression of the inhibitory programmed death-1 (PD-1) receptor following immunization with a TI-2 Ag or BCR crosslinking. Reducing CD19 expression in CD21/35−/− mice normalized BCR-induced calcium responses, PD-1 induction, and PPS-3-specific IgG3 responses and restored protection during S. pneumoniae infection. PD-1 blockade also selectively rescued PPS-3-specific IgG3 responses in CD21/35−/− mice. Thereby, CD21/35 promotes protective humoral immunity to S. pneumoniae and other strong TI-2 Ags through a complement-independent pathway by negatively regulating CD19 expression and PD-1 induction.
Temporal Induction Pattern of STAT4 Target Genes Defines Potential for Th1 Lineage-Specific Programming
Authors: Good Seth R. , Thieu Vivian T. , Mathur Anubhav N. , Yu Qing , Stritesky Gretta L. , Yeh Norman , O'Malley John T. , Perumal Narayanan B. , Kaplan Mark H. 
Published: August 2009

Abstract
STAT4 is a critical component in the development of inflammatory adaptive immune responses. It has been extensively characterized as a lineage-determining factor in Th1 development. However, the genetic program activated by STAT4 that results in an inflammatory cell type is not well defined. In this report, we use DNA isolated from STAT4-chromatin immunoprecipitation to perform chromatin immunoprecipitation-on-chip analysis of over 28,000 mouse gene promoters to identify STAT4 targets. We demonstrate that STAT4 binds multiple gene-sets that program distinct components of the Th1 lineage. Although many STAT4 target genes display STAT4-dependent IL-12-inducible expression, other genes displayed IL-12-induced histone modifications but lack induction, possibly due to high relative basal expression. In the subset of genes that STAT4 programs for expression in Th1 cells, IL-12-induced mRNA levels remain increased for a longer time than mRNA from genes that are not programmed. This suggests that STAT4 binding to target genes, while critical, is not the only determinant for STAT4-dependent gene programming during Th1 differentiation.