bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mast cell–derived TNF can promote Th17 cell–dependent neutrophil recruitment in ovalbumin-challenged OTII mice
Authors: Nakae Susumu , Suto Hajime , Berry Gerald J. , Galli Stephen J. 
Published: December 2006

AbstractBoth mast cells and IL-17 can contribute to host defense and pathology in part by orchestrating neutrophil recruitment, but the possible role of mast cells in IL-17–induced inflammation remains to be defined. We found that mast cells and IL-17, but neither IFN-γ nor FcRγ signaling, contributed significantly to the antigen (Ag)–dependent airway neutrophilia elicited in ovalbumin-specific T-cell receptor (TCR)–expressing C57BL/6-OTII mice, and that IFN-γ significantly suppressed IL-17–dependent airway neutrophilia in this setting. IL-18, IL-1β, and TNF each contributed significantly to the development of Ag- and T helper 17 (Th17 cell)–mediated airway neutrophilia. Moreover, IL-17 enhanced mast cell TNF production in vitro, and mast cell–associated TNF contributed significantly to Ag- and Th17 cell–mediated airway neutrophilia in vivo. By contrast, we detected no significant role for the candidate mediators histamine, PGD2, LTB4, CXCL10, or IL-16, each of which can be produced by mast cells and other cell types, in the neutrophil infiltration elicited in this model. These findings establish that mast cells and mast cell–derived TNF can significantly enhance, by FcRγ-independent mechanisms, the Ag- and Th17 cell–dependent development of a neutrophil-rich inflammatory response at a site of Ag challenge.
Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner
Authors: Hirbe Angela C. , Uluçkan Özge , Morgan Elizabeth A. , Eagleton Mark C. , Prior Julie L. , Piwnica-Worms David , Trinkaus Kathryn , Apicelli Anthony , Weilbaecher Katherine 
Published: December 2006

Abstract
Inhibition of osteoclast (OC) activity has been associated with decreased tumor growth in bone in animal models. Increased recognition of factors that promote osteoclastic bone resorption in cancer patients led us to investigate whether increased OC activation could enhance tumor growth in bone. Granulocyte colony-stimulating factor (G-CSF) is used to treat chemotherapy-induced neutropenia, but is also associated with increased markers of OC activity and decreased bone mineral density (BMD). We used G-CSF as a tool to investigate the impact of increased OC activity on tumor growth in 2 murine osteolytic tumor models. An 8-day course of G-CSF alone (without chemotherapy) significantly decreased BMD and increased OC perimeter along bone in mice. Mice administered G-CSF alone demonstrated significantly increased tumor growth in bone as quantitated by in vivo bioluminescence imaging and histologic bone marrow tumor analysis. Short-term administration of AMD3100, a CXCR4 inhibitor that mobilizes neutrophils with little effect on bone resorption, did not lead to increased tumor burden. However, OC-defective osteoprotegerin transgenic (OPGTg) mice and bisphosphonate-treated mice were resistant to the effects of G-CSF administration upon bone tumor growth. These data demonstrate a G-CSF–induced stimulation of tumor growth in bone that is OC dependent.
Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency–mediated growth suppression
Authors: Nurtjahja-Tjendraputra Effie , Fu Dong , Phang Juanita M. , Richardson Des R. 
Published: December 2006

AbstractIron (Fe) plays an important role in proliferation, and Fe deficiency results in G1/S arrest. Despite this, the precise role of Fe in cell-cycle control remains unclear. Cyclin D1 plays a critical function in G1 progression by interacting with cyclin-dependent kinases. Previously, we examined the effect of Fe depletion on the expression of cell-cycle control molecules and identified a marked decrease in cyclin D1 protein, although the mechanism involved was unknown. In this study, we showed that cyclin D1 was regulated posttranscriptionally by Fe depletion. Iron chelation of cells in culture using desferrioxamine (DFO) or 2-hydroxy-1-naphthylaldehyde isonicotinoyl hydrazone (311) decreased cyclin D1 protein levels after 14 hours and was rescued by the addition of Fe. Cyclin D1 half-life in control cells was 80 ± 15 minutes (n = 5), while in chelator-treated cells it was significantly (P < .008) decreased to 38 ± 3 minutes (n = 5). Proteasomal inhibitors rescued the Fe chelator–mediated decrease in cyclin D1 protein, suggesting the role of the proteasome. In Fe-replete cells, cyclin D1 was degraded in an ubiquitin-dependent manner, while Fe depletion induced a ubiquitin-independent pathway. This is the first report linking Fe depletion–mediated growth suppression at G1/S to a mechanism inducing cyclin D1 proteolysis.
New differentiation pathway for double-negative regulatory T cells that regulates the magnitude of immune responses
Authors: Zhang Dong , Yang Wei , Degauque Nicolas , Tian Yan , Mikita Allison , Zheng Xin Xiao 
Published: December 2006

AbstractRecent studies have demonstrated that in peripheral lymphoid tissues of normal mice and healthy humans, 1% to 5% of αβ T-cell receptor–positive (TCR+) T cells are CD4−CD8− (double-negative [DN]) T cells, capable of down-regulating immune responses. However, the origin and developmental pathway of DN T cells is still not clear. In this study, by monitoring CD4 expression during T-cell proliferation and differentiation, we identified a new differentiation pathway for the conversion of CD4+ T cells to DN regulatory T cells. We showed that the converted DN T cells retained a stable phenotype after restimulation and that furthermore, the disappearance of cell-surface CD4 molecules on converted DN T cells was a result of CD4 gene silencing. The converted DN T cells were resistant to activation-induced cell death (AICD) and expressed a unique set of cell-surface markers and gene profiles. These cells were highly potent in suppressing alloimmune responses both in vitro and in vivo in an antigen-specific manner. Perforin was highly expressed by the converted DN regulatory T cells and played a role in DN T-cell–mediated suppression. Our findings thus identify a new differentiation pathway for DN regulatory T cells and uncover a new intrinsic homeostatic mechanism that regulates the magnitude of immune responses. This pathway provides a novel, cell-based, therapeutic approach for preventing allograft rejection.
MMP-2, MT1-MMP, and TIMP-2 are essential for the invasive capacity of human mesenchymal stem cells: differential regulation by inflammatory cytokines
Authors: Ries Christian , Egea Virginia , Karow Marisa , Kolb Helmut , Jochum Marianne , Neth Peter 
Published: December 2006

AbstractHuman mesenchymal stem cells (hMSCs) represent promising tools in various clinical applications, including the regeneration of injured tissues by endogenous or transplanted hMSCs. The molecular mechanisms, however, that control hMSC mobilization and homing which require invasion through extracellular matrix (ECM) barriers are almost unknown. We have analyzed bone marrow–derivedhMSCs and detected strong expression and synthesis of matrix metalloproteinase 2 (MMP-2), membrane type 1 MMP (MT1-MMP), tissue inhibitor of metalloproteinase 1 (TIMP-1), and TIMP-2. The ability of hMSCs to traverse reconstituted human basement membranes was effectively blocked in the presence of synthetic MMP inhibitors. Detailed studies by RNA interference revealed that gene knock-down of MMP-2, MT1-MMP, or TIMP-2 substantially impaired hMSC invasion, whereas silencing of TIMP-1 enhanced cell migration, indicating opposing roles of both TIMPs in this process. Moreover, the inflammatory cytokines TGF-β1, IL-1β, and TNF-α up-regulated MMP-2, MT1-MMP, and/or MMP-9 production in these cells, resulting in a strong stimulation of chemotactic migration through ECM, whereas the chemokine SDF-1α exhibited minor effects on MMP/TIMP expression and cell invasion. Thus, induction of specific MMP activity in hMSCs by inflammatory cytokines promotes directed cell migration across reconstituted basement membranes in vitro providing a potential mechanism in hMSC recruitment and extravasation into injured tissues in vivo.
Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array
Authors: Gardina Paul J , Clark Tyson A , Shimada Brian , Staples Michelle K , Yang Qing , Veitch James , Schweitzer Anthony , Awad Tarif , Sugnet Charles , Dee Suzanne , Davies Christopher , Williams Alan , Turpaz Yaron 
Published: December 2006

Abstract

Background
Alternative splicing is a mechanism for increasing protein diversity by excluding or including exons during post-transcriptional processing. Alternatively spliced proteins are particularly relevant in oncology since they may contribute to the etiology of cancer, provide selective drug targets, or serve as a marker set for cancer diagnosis. While conventional identification of splice variants generally targets individual genes, we present here a new exon-centric array (GeneChip Human Exon 1.0 ST) that allows genome-wide identification of differential splice variation, and concurrently provides a flexible and inclusive analysis of gene expression.

Results
We analyzed 20 paired tumor-normal colon cancer samples using a microarray designed to detect over one million putative exons that can be virtually assembled into potential gene-level transcripts according to various levels of prior supporting evidence. Analysis of high confidence (empirically supported) transcripts identified 160 differentially expressed genes, with 42 genes occupying a network impacting cell proliferation and another twenty nine genes with unknown functions. A more speculative analysis, including transcripts based solely on computational prediction, produced another 160 differentially expressed genes, three-fourths of which have no previous annotation. We also present a comparison of gene signal estimations from the Exon 1.0 ST and the U133 Plus 2.0 arrays.
Novel splicing events were predicted by experimental algorithms that compare the relative contribution of each exon to the cognate transcript intensity in each tissue. The resulting candidate splice variants were validated with RT-PCR. We found nine genes that were differentially spliced between colon tumors and normal colon tissues, several of which have not been previously implicated in cancer. Top scoring candidates from our analysis were also found to substantially overlap with EST-based bioinformatic predictions of alternative splicing in cancer.

Conclusion
Differential expression of high confidence transcripts correlated extremely well with known cancer genes and pathways, suggesting that the more speculative transcripts, largely based solely on computational prediction and mostly with no previous annotation, might be novel targets in colon cancer. Five of the identified splicing events affect mediators of cytoskeletal organization (ACTN1, VCL, CALD1, CTTN, TPM1), two affect extracellular matrix proteins (FN1, COL6A3) and another participates in integrin signaling (SLC3A2). Altogether they form a pattern of colon-cancer specific alterations that may particularly impact cell motility.
Generation and characterization of a stable cell population releasing fluorescent HIV-1-based Virus Like Particles in an inducible way
Authors: Muratori Claudia , D'Aloja Paola , Superti Fabiana , Tinari Antonella , Sol-Foulon Nathalie , Sparacio Sandra , Bosch Valerie , Schwartz Olivier , Federico Maurizio 
Published: December 2006

Abstract

Background
The availability of cell lines releasing fluorescent viral particles can significantly support a variety of investigations, including the study of virus-cell interaction and the screening of antiviral compounds. Regarding HIV-1, the recovery of such biologic reagents represents a very hard challenge due to the intrinsic cytotoxicity of many HIV-1 products. We sought to overcome such a limitation by using a cell line releasing HIV-1 particles in an inducible way, and by exploiting the ability of a HIV-1 Nef mutant to be incorporated in virions at quite high levels.

Results
Here, we report the isolation and characterization of a HIV-1 packaging cell line, termed 18-4s, able to release valuable amounts of fluorescent HIV-1 based Virus-Like Particles (VLPs) in an inducible way. 18-4s cells were recovered by constitutively expressing the HIV-1 NefG3C mutant fused with the enhanced-green fluorescent protein (NefG3C-GFP) in a previously isolated inducible HIV-1 packaging cell line. The G3C mutation creates a palmitoylation site which results in NefG3C-GFP incorporation into virions greatly exceeding that of the wild type counterpart. Upon induction of 18-4s cells with ponasterone A and sodium butyrate, up to 4 μg/ml of VLPs, which had incorporated about 150 molecules of NefG3C-GFP per viral particle, were released into the culture supernatant. Due to their intrinsic strong fluorescence, the 18-4s VLPs were easily detectable by a novel cytofluorometric-based assay developed here. The treatment of target cells with fluorescent 18-4 VLPs pseudotyped with different glycoprotein receptors resulted in these becoming fluorescent as early as two hours post-challenge.

Conclusion
We created a stable cell line releasing fluorescent HIV-1 based VLPs upon induction useful for several applications including the study of virus-cell interactions and the screening of antiviral compounds.
Liver metastases of pancreatic acinar cell carcinoma with marked nuclear atypia and pleomorphism diagnosed by EUS FNA cytology : A case report with emphasis on FNA cytological findings
Authors: Peng Hong Q , Darwin Peter , Papadimitriou John C , Drachenberg Cinthia B 
Published: December 2006

Background:
Acinar cell carcinoma of the pancreas is a rare neoplasm. Although this tumor has been well characterized histologically, the morphological patterns in Fine Needle Aspiration Cytology have not been well defined. Unlike ductal adenocarcinomas, endocrine tumors, and solid pseudopapillary tumors of the pancreas with their characteristic FNA cytological features, acinar cell carcinomas pose a particular diagnostic challenge by sharing many cytomorphologic features with endocrine tumors of the pancreas.

Case presentation:
A 37-year-old man presented with lower chest and left upper quadrant abdominal pain. Computed tomography revealed a 7.8 x 7.3 cm irregular, partially cystic mass in the body and tail of the pancreas, and two lesions in the liver compatible with metastases. Subsequently, the patient underwent endoscopic ultrasound-guided fine needle aspiration on one of the two metastatic liver masses.

Conclusion:
We describe a case of pancreatic acinar cell carcinoma with unusual cytomorphologic features mimicking an endocrine tumor of pancreas, encountered in endoscopic ultrasound-guided fine needle aspiration of a metastatic liver mass and discuss the diagnostic approach for this unusual pancreatic tumor in fine needle aspiration cytology.
Role of histamine as a putative inhibitory transmitter in the honeybee antennal lobe
Authors: Sachse Silke , Peele Philipp , Silbering Ana F , Gühmann Martin , Galizia C Giovanni 
Published: December 2006

Abstract

Background
Odors are represented by specific spatio-temporal activity patterns in the olfactory bulb of vertebrates and its insect analogue, the antennal lobe. In honeybees inhibitory circuits in the AL are involved in the processing of odors to shape afferent odor responses. GABA is known as an inhibitory transmitter in the antennal lobe, but not all interneurons are GABAergic. Therefore we sought to analyze the functional role of the inhibitory transmitter histamine for the processing of odors in the honeybee AL.

Results
We optically recorded the representation of odors before, during and after histamine application at the input level (estimated from a compound signal), and at the output level (by selectively measuring the projection neurons). For both, histamine led to a strong and reversible reduction of odor-evoked responses.

Conclusion
We propose that histamine, in addition to GABA, acts as an inhibitory transmitter in the honeybee AL and is therefore likely to play a role in odor processing.
Quality of life and salivary output in patients with head-and-neck cancer five years after radiotherapy
Authors: Braam Pètra M , Roesink Judith M , Raaijmakers Cornelis PJ , Busschers Wim B , Terhaard Chris HJ 
Published: January 2007

Abstract
Background
To describe long-term changes in time of quality of life (QOL) and the relation with parotid salivary output in patients with head-and-neck cancer treated with radiotherapy.

Methods
Forty-four patients completed the EORTC-QLQ-C30(+3) and the EORTC-QLQ-H&N35 questionnaires before treatment, 6 weeks, 6 months, 12 months, and at least 3.5 years after treatment. At the same time points, stimulated bilateral parotid flow rates were measured.

Results
There was a deterioration of most QOL items after radiotherapy compared with baseline, with gradual improvement during 5 years follow-up. The specific xerostomia-related items showed improvement in time, but did not return to baseline. Global QOL did not alter significantly in time, although 41% of patients complained of moderate or severe xerostomia at 5 years follow-up. Five years after radiotherapy the mean cumulated parotid flow ratio returned to baseline but 20% of patients had a flow ratio <25%. The change in time of xerostomia was significantly related with the change in flow ratio (p = 0.01).

Conclusion
Most of the xerostomia-related QOL scores improved in time after radiotherapy without altering the global QOL, which remained high. The recovery of the dry mouth feeling was significantly correlated with the recovery in parotid flow ratio.
Routine versus Selective Abdominal Computed Tomography Scan in the Evaluation of Right Lower Quadrant Pain: A Randomized Controlled Trial
Authors: Lee Christopher C. , Golub Robert , Singer Adam J. , Cantu Roberto , Levinson Howard 
Published: December 2006

ObjectivesTo determine the role of abdominal computed tomography (CT) imaging in patients with right lower quadrant (RLQ) pain. The authors hypothesized that selective use of abdominal CT would reduce imaging without increasing the rates of negative appendectomy and perforated appendicitis.MethodsA prospective randomized clinical trial was conducted in a community teaching emergency department. Adult patients with acute RLQ abdominal pain with suspected acute appendicitis were included. Patients were randomized to mandatory (all patients) or selective (based on clinical evaluation) abdominal CT imaging. The primary outcome was the negative appendectomy rate.ResultsA total of 152 patients were randomized to selective (n= 80) and mandatory (n= 72) intervention groups. The mean (±SD) age was 34.1 (±3.5) years, and 48% were female. CT imaging was performed in 54 of 80 patients (68%; 95% confidence interval [CI] = 56% to 78%) in the selective group and in 70 of 72 patients (97%; 95% CI = 90% to 100%) in the mandatory group. There was a trend to a decreased rate of negative appendectomy in the mandatory group (1/39 [2.6%]; 95% CI = 0.5% to 13.2%) as compared with the selective group (6/43 [13.9%]; 95% CI = 6.6% to 27.3%), with a difference in prevalence rates of 11.3% (95% CI =−3.5% to 26.3%). There was also a trend to a decreased perforated appendix rate in the mandatory group (4/39 [10.3%]) as compared with the selective group (7/38 [18.4%]), with a difference in prevalence rates of 8.2% (95% CI =−8.0% to 24.4%).ConclusionsIn this small sample of adult patients with RLQ abdominal pain and suspected acute appendicitis, CT imaging was performed less frequently in the selective group and there was a trend with mandatory CT imaging to reduced rates of negative appendectomy and perforated appendices.
Atypical Clinical Features of Pediatric Appendicitis
Authors: Becker Theresa , Kharbanda Anupam , Bachur Richard 
Published: December 2006

BackgroundThe diagnosis of appendicitis remains challenging in children. Delays in diagnosis, or misdiagnosis, have important medical and legal implications. The typical, or classic, presentation of pediatric appendicitis has been modeled after adult disease; however, many children present atypically with subtle findings or unusual signs.ObjectivesTo determine the frequency of atypical clinical features among pediatric patients with appendicitis and to investigate which atypical features are the strongest negative predictors for appendicitis among patients being evaluated for appendicitis.MethodsChildren and adolescents with suspected appendicitis were enrolled over 20 consecutive months. Pediatric emergency physicians completed standardized data collection forms on eligible patients. Final diagnosis was determined by pathology or follow‐up telephone call. Typical and atypical findings were defined strictly a priori.ResultsSeven hundred fifty‐five patients were enrolled. The median age was 11.9 years (interquartile range [IQR]: 8.5, 14.9 yr); 36% of patients were diagnosed with appendicitis. Among patients with appendicitis, the most common atypical features included absence of pyrexia (83%), absence of Rovsing's sign (68%), normal or increased bowel sounds (64%), absence of rebound pain (52%), lack of migration of pain (50%), lack of guarding (47%), abrupt onset of pain (45%), lack of anorexia (40%), absence of maximal pain in the right lower quadrant (32%), and absence of percussive tenderness (31%). Forty‐four percent of patients with proven appendicitis had six or more atypical characteristics. The median number of atypical features for patients with proven appendicitis was five (IQR: 4.0, 7.0). The greatest negative predictors, on the basis of likelihood ratios, were as follows: white blood cell count (WBC) of <10,000 per cubic millimeter (likelihood ratios [LR], 0.18), absolute neutrophil count (ANC) of <7,500 per cubic millimeter (LR, 0.35), lack of percussive tenderness (LR, 0.50), lack of guarding (LR, 0.63), and no nausea or emesis (LR, 0.65).ConclusionsAppendicitis in pediatric patients is difficult to diagnose because children present with a wide variety of atypical clinical features. Forty‐four percent of patients with appendicitis presented with six or more atypical features. Two atypical features are the strongest negative predictors of appendicitis in children: WBC of <10,000 per cubic millimeter and an ANC of <7,500 per cubic millimeter.