bluuebunny/crossref_metadata_2025 huggingface dataset:
Congenital limb abnormality in a Thoroughbred foal in Trinidad
Authors: Muñoz K. A. , Coombs D. K.
Published: October 2009

A congenital defect of the right hindlimb of a 36‐h‐old Thoroughbred foal as reported for the first time in Trinidad, West Indies. The foal was subjected to euthanasia and radiographs of both hindlimbs revealed that the bones distal to P1 of the right hindlimb only, were missing. Insertion of both the superficial and deep digital flexor tendons were found to be on the most proximal aspect of P1. Necropsy revealed no other congential defects.
CT and MR Imaging of the Paranasal Sinuses in Cystic Fibrosis
Authors: Eggesbø Heidi B. , Ringertz S. , Haanæs O. C. , Dølvik S. , Erichsen A. , Stiris M. , Kolmannskog F.
Published: October 2009

Purpose: To compare CT and MR findings of the paranasal sinuses in patients with cystic fibrosis (CF) with microbiology and histopathology. Further, to compare microbiology from the maxillary sinuses, nasopharynx and sputum.

Material and Methods: CT and MR imaging of the paranasal sinuses were performed in 10 CF patients. Endoscopy and maxillary sinus aspirates were obtained (guided by the MR findings) and analyzed microbiologically and histologically. Samples from the nasopharynx and sputum were analyzed microbiologically.

Results: CT and MR were equal in displaying the extent of soft tissue masses, which at CT were homogeneous, while MR showed heterogeneous signals. MR images also demonstrated circumscribed areas with signal void at the STIR sequence with corresponding high to intermediate signal at the T1-weighted sequence. P. aeruginosa was frequently cultured from these areas which we named the “black hole sign”. Maxillary sinus cultures revealed the same bacteria as nasopharynx and sputum cultures combined.

Conclusion: MR images were superior to CT in differentiating soft tissue masses in the paranasal sinuses in CF patients. Bacteria with potential for specialized iron uptake mechanisms were present in areas with signal void at the STIR sequence. Our hypothesis is that the MR “black hole sign” can be explained by paramagnetic properties related to bacterial agents.
Comparison of Planar and Spect Scintimammography with 99mTc-Sestamibi in the Diagnosis of Breast Carcinoma
Authors: Danielsson R. , Boná B. , Ågren B. , Svensson L. , Aspelin P.
Published: October 2009

Purpose: To compare results of planar and SPECT breast imaging with 99mTc-MIBI in detecting primary breast cancer.

Material and Methods: Twenty-six consecutive patients with 34 suspected breast lesions underwent both planar and SPECT scintimammography. Ten minutes after injection of 700 MBq 99mTc-MIBI, 2 prone lateral projections were obtained, followed by a supine anterior projection. Forty minutes after injection, a SPECT study was done. All lesions were operated upon and verified with histopathology.

Results: A sensitivity of 85% and specificity of 88% of planar scintimammography in diagnosis of primary breast lesions were achieved. The corresponding values for SPECT were 61% and 64%.

Conclusion: The diagnostic accuracy of planar scintimammography was not improved by using SPECT imaging.
Internal Mammary Artery Embolization for Hemoptysis
Authors: Hashimoto M. , Heianna J. , Okane K. , Izumi J. , Watarai J.
Published: October 2009

Purpose: The purpose of this study was to determine the factors influencing development of blood supply from the internal mammary artery and to discuss the value of embolization of the abnormal branches from this vessel using small particles following occlusion of the normal distal branches using microcoils in treating hemoptysis.

Material and Methods: Five patients with hemoptysis underwent internal mammary artery embolization with coaxial microcatheter systems. Bronchoscopy, chest radiographs, and CT were performed to determine the site and extent of the basic disease before embolotherapy in all patients.

Results: In all patients, pulmonary lesions had extended from the lung to the adjacent pleural surface at the anterior lung field. Four patients underwent embolization from the proximal portion of the internal mammary artery following distal coil embolization. One patient who underwent only proximal embolization had recurrent bleeding.

Conclusion: The internal mammary artery contributes to the perfusion of lesions responsible for hemoptysis when the basic lesion involves the pulmonary parenchyma adjacent to the anterior pleural surface. Initial distal occlusion of the internal mammary artery may improve the efficacy of embolization of this artery for hemoptysis.
Ultrasonography of Malignant Breast Neoplasms
Authors: Skaane P. , Sauer T.
Published: October 2009

Purpose: To analyze the malignant breast neoplasms missed as tumor on ultrasonography (US).

Material and Methods: A total of 355 malignant tumors were confirmed at histology among 2,985 consecutive patients who underwent breast US. There were no prospectively recorded mammographic findings in 28 of the 355 tumors. The remaining 327 tumors included 16 ductal carcinomas in situ (DCIS) and 66 invasive carcinomas with suspicious microcalcifications on mammography. Excluding these 82 tumors because US would not have been indicated using strict criteria, a subpopulation of 245 noncalcified invasive malignant tumors remained for analysis. The neoplasms missed as tumor on US were analyzed for the whole tumor group (n=355) and the subpopulation (n=245).

Results: 42 (11.8%) of the 355 malignant neoplasms were missed as tumor on US, including 6 (2.5%) of the 243 palpable and 36 (32.1%) of the 112 nonpalpable malignancies. Most of the missed tumors were DCIS and microinvasive ductal carcinomas dominated by DCIS. In the subpopulation, 14 (5.7%) of the 245 malignancies were missed as tumor on US, including 4 (2.2%) of the 180 palpable and 10 (15.4%) of the 65 nonpalpable lesions. Of the 245 malignancies, 6 (2.4%) had a normal US finding, including 2 palpable retropapillary tumors and 4 incidental findings at histology.

Conclusion: Using strict criteria for performing US as an adjunct to mammography, by far the most malignant breast neoplasms are diagnosed as a tumor on US.
MR Imaging in Biofix-Osteosynthesis
Authors: Lohman M. , Partio E. K. , Vehmas T. , Kivisaari A. , Kivisaari L.
Published: October 2009

Purpose: Osteosynthesis by means of bioresorbable implants, mostly of self-reinforced poly-L-lactide (SR-PLLA), has been used in humans for about 10 years. The aim of this study was to examine the controversy between histological studies confirming fragmentation of the biomaterial and radiological studies showing no breaking of the material.

Material and Methods: Six patients with displaced malleolar fractures operatively treated with biodegradable SR-PLLA screws underwent MR examinations at 1.5 T, immediately postoperatively and after one to two years.

Results: The biodegradable osteosynthetic screws were clearly seen on all MR images. Of 12 screws, 6 were broken at the final examination (5 syndesmotic transfixation screws and 1 screw through the growth cartilage).

Conclusion: The breaking of a biodegradable osteosynthesis is possible to document on MR images.
Applications of Signal Detection Theory to Geographic Information Science
Authors: Griffin Amy L. , Bell Scott
Published: October 2009

Signal detection theory (SDT) is a framework used by psychologists to study decision making under uncertain conditions. While we often know a great deal about how different methodological choices can affect the outcome of an analysis, we know less about how information end users interpret and understand competing outcomes in the context of the decisions they are trying to make. We contend that such information would be useful and assert that SDT analysis is one method of building this understanding. We provide an introduction to SDT methods and an example of the methods applied to a navigation experiment, discuss why SDT may be useful for GIScientists, and provide several examples of other potential application areas.
fMRI and Human Subjects Research in Cartography
Authors: Lobben Amy , Lawrence Megan , Olson Judy M.
Published: October 2009

In the past decade, the use of functional magnetic resonance imaging (fMRI) has grown, both in the number of studies published and in the number of disciplines finding application for functional brain research facilitated by this data-gathering method. A review of fMRI research in perceptual grouping and figure/ground and in visual search and attention is of interest in the effort to understand the human use of maps. These studies provide physiological evidence that can at least tentatively be interpreted as supporting principles in map design. Although they are not specifically cartographic, these studies dovetail with some of the human-user research in cartography. The question of how these studies of very specific phenomena, using very limited graphics, fit the overall picture of map use is an open one. At the very least, they provide an additional window into the processes of map use.
Navigation Tasks with Small-Display Maps: The Sum of the Parts Does Not Equal the Whole
Authors: Dillemuth Julie A.
Published: October 2009

A key strength of a map for navigation is that it can show the features of an environment and their spatial relationships over an area too large to be perceived through direct experience. This characteristic is important for navigation, including planning travel, making decisions while en route, and developing a user's cognitive map. But what happens on a small display, such as that of a cell phone, when, instead of seeing the entire area of interest, the user can view only a discrete section of the map at any time? This article presents research investigating the implications of a small display for map use and spatial knowledge acquisition. A research study was conducted with 80 participants using a map to answer distance and direction questions in one of four viewable-extent conditions, ranging from 10% to 100% of the map viewable at a time. Map-use results showed that small viewable extents hindered performance with respect to accuracy and response time but had no effect on participants’ confidence in their performance on the navigation tasks. Tests of spatial knowledge acquisition showed differences across conditions for recall tasks, but a sketch-map analysis revealed no differences based on viewable extent.
Issues of Change Detection in Animated Choropleth Maps
Authors: Goldsberry Kirk , Battersby Sarah
Published: October 2009

One primary utility of animated maps is their ability to depict change over time and space; unfortunately, recent research suggests that humans frequently fail to perceive changes within dynamic graphics. However, different types of dynamic graphics include different manifestations of change. For example, an animated proportional-symbol map possesses different change properties than an animated choropleth map. This article examines issues of change on animated choropleth maps. We identify relevant limitations of the human visual system that pertain to animated map reading, including change blindness and foveal versus peripheral attention, and introduce methods to quantify the magnitude of change that separates individual scenes within choropleth animations. These methods are useful for measuring and describing changes that confront users of animated choropleth maps. We also characterize the transitional behaviours of enumeration units and discuss the influences of data classification and other cartographic controls on change within animated choropleth maps.
Comparison of bioactive coils and bare platinum coils for treatment of intracranial aneurysms: a matched-pair analysis
Authors: Geyik Serdar , Ertugrul Ozgur , Yavuz Kivilcim , Geyik Pinar , Saatci Isil , Cekirge H. Saruhan
Published: October 2009

Object

The primary goal of this matched-pair analysis was to evaluate the durability of the treatment results with Cerecyte coils in comparison with that of bare platinum coils in terms of angiographic occlusion rates at follow-up.

Methods

Eighty aneurysms treated with Cerecyte coils were included in this study to carry out a matched-pair analysis. Every aneurysm treated with Cerecyte coils was matched with an aneurysm treated with bare platinum coils. Matching of the aneurysms was done according to the aneurysm size, location, neck size, initial occlusion grade, and clinical presentation.

Results

The initial treatment results were similar in both groups as part of a matching protocol. Subgroup analysis revealed a significant difference in the durability of occlusion in aneurysms that showed Raymond Class I obliteration on follow-up angiograms (69 [86.2%] in the Cerecyte group vs 51 [63.8%] in the control group, p = 0.002). Further thrombosis to Raymond Class I occlusions was higher in the Cerecyte group (17 [77.3%] of 22 vs 8 [36.4%] of 22 aneurysms).

Conclusions

Cerecyte coils provide further thrombosis and more durable results than bare platinum coils following coil embolization of cerebral aneurysms.
A comparison of World Health Organization tumor grades at recurrence in patients with non–skull base and skull base meningiomas
Authors: McGovern Susan L. , Aldape Kenneth D. , Munsell Mark F. , Mahajan Anita , DeMonte Franco , Woo Shiao Y.
Published: October 2009

Object

Despite a favorable outcome for most patients with WHO Grade I meningiomas, a subset of these patients will have recurrent or progressive disease that advances to a higher grade and requires increasingly aggressive therapy. The goal of this study was to identify clinical characteristics associated with the recurrence of benign meningiomas and their acceleration to atypical and malignant histological types.

Methods

Records of 216 patients with WHO Grade I, II, or III meningioma that were initially treated between 1965 and 2001 were retrospectively reviewed. Median follow-up was 7.2 years.

Results

Patients with non–skull base cranial meningiomas (82 of 105 [78%]) were more likely to have undergone a gross-total resection than patients with skull base meningiomas (32 of 78 [41%]; p < 0.001). Consequently, patients with Grade I non–skull base cranial meningiomas had better 5-year recurrence-free survival (69%) than patients with Grade I skull base meningiomas (56%) or Grade II or III tumors at any site (50%; p = 0.005). Unexpectedly, patients with non–skull base tumors who experienced a recurrence (8 of 22 [36%]) were more likely than patients with skull base tumors (1 of 19 [5%]) to have a higher grade tumor at recurrence (p = 0.024). Furthermore, the median MIB-1 labeling index of Grade I non–skull base cranial meningiomas (2.60%) was significantly higher than that of Grade I skull base tumors (1.35%; p = 0.016).

Conclusions

Cranial meningiomas that occur outside of the skull base are more likely to have a higher MIB-1 labeling index and recur with a higher grade than those within the skull base, suggesting that non–skull base cranial tumors may have a more aggressive biology than skull base tumors.
Infection control knowledge and practices related to HIV among Nigerian dentists
Authors: Uti Omolara Gbonjubola , Agbelusi Gbemisola A. , Jeboda Sonny Olukayode , Ogunbodede Eyitope
Published: October 2009

BACKGROUND: Many diseases including HIV/AIDS can be transmitted in the dental setting when effective infection control procedures are ignored. The aim of this study, therefore, was to evaluate the infection control knowledge and practices of Nigerian dentists in the era of HIV/AIDS.
METHODOLOGY: Information on knowledge of transmission of HIV, occupational vulnerability, infection control practices, and opinion on adequacy of infection control facilities were gathered from dentists through a self-administered questionnaire. Knowledge was assessed on a total score of 20 questions.
RESULTS: Only 3.6% of the dentists had poor knowledge. Younger males and dentists working in teaching hospitals had significantly better knowledge than their counterparts. While 40.8% believed HIV could be transmitted through saliva, only 43.2% knew it could be transmitted through the conjunctiva.
Most (93.2%) wore gloves routinely and the most common barrier to glove use was non-availability. Most (79.2%) used autoclaves for sterilization; however, chemical disinfectants and boiling were also used. The majority (72.4%) believed the facilities for infection control in their centres were inadequate. Close to half of the respondents (47.6%; n = 118) rated the occupational risk of becoming infected with HIV as high.
CONCLUSION: The results of this study have shown that while the level of knowledge of the dentists was generally acceptable, there were still some misconceptions on the transmission and occupational vulnerability of HIV. It also indicates only partial compliance with recommended infection control procedures among Nigerian dentists as a result of inadequate supplies.
Association of low birth weight and placental malarial infection in Nigeria
Authors: Aribodor Dennis N. , Nwaorgu Obioma C. , Eneanya Christine I. , Okoli Ikechukwu , Pukkila-Worley Reed , Etaga Harrison O.
Published: October 2009

BACKGROUND: Malaria causes significant morbidity and mortality among pregnant women in Nigeria. However, the contribution of malaria infection to neonatal development is incompletely understood. Here we determined the prevalence of placental malarial infection in six communities in Anambra State, Nigeria, between 2005 and 2006, and compare these data to neonatal birth weight.
METHODOLOGY: Blood samples were obtained from the placenta of 500 parturient mothers and examined for the presence of malaria parasites. Newborn birth weight was then compared with the malaria status of their mothers.
RESULTS: Placental malarial infection was found in 322 of 500 mothers (64.4%). The prevalence of infection did not differ among the six different Nigerian communities (P = 0.978). Furthermore, there was no difference in infection rates between rural and urban areas (64.9% vs. 64.0%, respectively, P = 0.827). Interestingly, neonates born from mothers with placental malaria had lower birth weights than neonates born from uninfected mothers [2500 g (range 1900 g - 3200 g) vs. 3800 g (range 3200 g - 4700 g), P < 0.001]. Forty-five percent (145/322) of the newborns born from infected mothers were of low birth weight (defined as birth weight less than 2,500 g).
CONCLUSION: Malaria infection during pregnancy is common in Nigeria and is likely associated with low newborn birth weight.
Treatment of autoimmune thrombocytopenia in a case of chronic hepatitis C with ursodeoxycholic acid
Authors: Naz Hasan , Aslan Vahap
Published: October 2009

Pegylated interferon (PEG-IFN) alpha and ribavirin therapy has become the standard treatment in chronic hepatitis C virus (HCH)-infected patients. While thrombocytopenia associated with IFN use is frequently observed among these patients, autoimmune thrombocytopenia is one of the rarely observed adverse effects. In the present report, we present a case with chronic HCV infection in which autoimmune thrombocytopenia developed at week 7 of PEG-IFN alpha 2b plus ribavirin therapy. The patient subsequently received ursodeoxycholic acid (UDCA) treatment. Although there is not an adequate number of studies on this subject, it was concluded that the use of UDCA in cases of autoimmune thrombocytopenia that have developed due to PEG-IFN treatment in chronic HCV infection is a favorable option.
Increased Expression of IL-33 in Severe Asthma: Evidence of Expression by Airway Smooth Muscle Cells
Authors: Préfontaine David , Lajoie-Kadoch Stéphane , Foley Susan , Audusseau Séverine , Olivenstein Ron , Halayko Andrew J. , Lemière Catherine , Martin James G. , Hamid Qutayba
Published: October 2009

IL-33, a new member of the IL-1 cytokine family, promotes Th2 inflammation, but evidence on the implications of this cytokine in asthma is lacking. IL-33 would be mainly expressed by structural cells, but whether proinflammatory cytokines modulate its expression in airway smooth muscle cells (ASMC) is unknown. Endobronchial biopsies were obtained from adults with mild (n = 8), moderate (n = 8), severe (n = 9), asthma and from control subjects (n = 5). Immunocytochemistry, laser-capture microdissection, reverse transcriptase, and real-time quantitative PCR were used for determining IL-33 expression in the lung tissues. ASMC isolated from resected lung specimens were cultured with proinflammatory cytokines and with dexamethasone. IL-33 expression by ASMC was determined by PCR, ELISA, and Western blotting. Higher levels of IL-33 transcripts are detected in biopsies from asthmatic compared with control subjects, and especially in subjects with severe asthma. ASMC show IL-33 expression at both protein and mRNA levels. IL-33 and TNF-α transcript levels correlate in the lung tissues, and TNF-α up-regulates IL-33 expression by cultured ASMC in a time- and dose-dependent manner. IFN-γ also increases IL-33 expression and shows synergistic effect with TNF-α. Dexamethasone fails to abolish TNF-α-induced IL-33 up-regulation. IL-33 expression increases in bronchial biopsies from subjects with asthma compared with controls, as well as subjects with asthma severity. ASMC are a source of the IL-33 cytokine. Our data propose IL-33 as a novel inflammatory marker of severe and refractory asthma.
In Vivo Expansion of Activated Naive CD8+ T Cells and NK Cells Driven by Complexes of IL-2 and Anti-IL-2 Monoclonal Antibody As Novel Approach of Cancer Immunotherapy
Authors: Tomala Jakub , Chmelova Helena , Mrkvan Tomas , Rihova Blanka , Kovar Marek
Published: October 2009

IL-2 is potent imunostimulatory molecule that plays a key role in T and NK cell activation and expansion. IL-2 is approved by the FDA to treat metastatic renal cancer and melanoma, but its extremely short half-life and serious toxicities are significant limitations of its use. It was reported that in vivo biological activity of IL-2 can be increased by association of IL-2 with anti-IL-2 mAb (S4B6). IL-2/S4B6 mAb immunocomplexes were described to be highly stimulatory for NK and memory CD8+ T cells and intermediately also for regulatory T cells. IL-2/JES6-1 mAb immunocomplexes are stimulatory solely for regulatory T cells. In this study we show that although both mentioned IL-2 immunocomplexes are less potent than free IL-2 in vitro, they possess extremely high stimulatory activity to expand activated naive CD8+ T cells in vivo. IL-2 immunocomplexes expand activated naive CD8+ T cells several hundred-fold times after four doses and more than 1000-fold times after six doses (1.5 μg/dose of IL-2), whereas free IL-2 given at the same dosage shows negligible activity. IL-2/S4B6 mAb immunocomplexes also induce massive expansion of NK cells (40% of DX5+NK1.1+ cells in spleen). Importantly, activated naive CD8+ T cells expanded by IL-2 immunocomplexes form robust population of functional memory cells. We also demonstrate in two distinct tumor models that IL-2/S4B6 mAb immunocomplexes possess considerable antitumor activity. Finally, by using radioactively labeled IL-2, we provide for first time direct evidence that IL-2 immunocomplexes have much longer half-life in circulation than free IL-2, being ∼3 h vs <15 min, respectively.
Cutting Edge: Responder T Cells Regulate Human DR+ Effector Regulatory T Cell Activity via Granzyme B
Authors: Ashley Charles W. , Baecher-Allan Clare
Published: October 2009

MHC class II expression identifies an effector subset of human CD4+CD25highFoxP3high natural regulatory T cells (DR+ Tregs) that induces more rapid suppression and exhibits higher FoxP3 expression than the remaining Treg population. Although Tregs are known to be highly sensitive to apoptosis, in this study we demonstrate that this sensitivity is primarily a feature of DR+ Tregs. Granzyme B (GzmB) is strongly expressed by nonregulatory responder CD4 T cells, whereas effector DR+ Tregs express little GzmB. Strong TCR stimulation markedly increases the expression of GzmB in all dividing responder CD4 T cells and mitigates the suppression by DR+ Tregs. DR+ Treg suppressive activity reemerges if GzmB is neutralized. We show that responder cells actively kill effector Tregs by producing GzmB in response to strong TCR stimulation. Thus, the production of GzmB by strongly activated CD4 T cells represents a mechanism by which CD4 T cells resist Treg suppression.
CD94 Defines Phenotypically and Functionally Distinct Mouse NK Cell Subsets
Authors: Yu Jianhua , Wei Min , Mao Hsiaoyin , Zhang Jianying , Hughes Tiffany , Mitsui Takeki , Park Il-kyoo , Hwang Christine , Liu Shujun , Marcucci Guido , Trotta Rossana , Benson Don M. , Caligiuri Michael A.
Published: October 2009

Understanding of heterogeneous NK subsets is important for the study of NK cell biology and development, and for the application of NK cell-based therapies in the treatment of disease. Here we demonstrate that the surface expression of CD94 can distinctively divide mouse NK cells into two approximately even CD94low and CD94high subsets in all tested organs and tissues. The CD94high NK subset has significantly greater capacity to proliferate, produce IFN-γ, and lyse target cells than does the CD94low subset. The CD94high subset has exclusive expression of NKG2A/C/E, higher expression of CD117 and CD69, and lower expression of Ly49D (activating) and Ly49G2 (inhibitory). In vivo, purified mouse CD94low NK cells become CD94high NK cells, but not vice versa. Collectively, our data suggest that CD94 is an Ag that can be used to identify functionally distinct NK cell subsets in mice and could also be relevant to late-stage mouse NK cell development.
Cutting Edge: Importance of IL-6 and Cooperation between Innate and Adaptive Immune Receptors in Cellular Vaccination with B Lymphocytes
Authors: Vanden Bush Tony J. , Buchta Claire M. , Claudio Jennifer , Bishop Gail A.
Published: October 2009

B lymphocytes are a potential alternative to dendritic cell immunotherapy, with the advantages of relative abundance in peripheral blood and the ability to function as APCs. Although B cells express multiple receptors that induce costimulatory molecules, B cell vaccine studies have focused primarily on CD40 stimulation. To optimize the potential efficacy of B cell vaccines (Bvac), we compared the capacity of differentially stimulated B cells to induce Ag-specific CD8+ T cell responses in vivo. CD40- or TLR7-stimulated B cell APCs induced similar CD8+ T cell responses, but costimulation through the BCR and TLR7 produced a more effective Bvac as measured by T cell stimulation and the protection of mice from an infectious pathogen. This increased effectiveness depended upon enhanced production of IL-6 by BCR plus TLR7-stimulated B cells. These findings reveal alternative stimulation strategies for the production of effective Bvac and identify a key role for IL-6 in B cell Ag presentation and cellular vaccines.
Primary Human Tumor Cells Expressing CD155 Impair Tumor Targeting by Down-Regulating DNAM-1 on NK Cells
Authors: Carlsten Mattias , Norell Håkan , Bryceson Yenan T. , Poschke Isabel , Schedvins Kjell , Ljunggren Hans-Gustaf , Kiessling Rolf , Malmberg Karl-Johan
Published: October 2009

The activating NK cell receptor DNAX accessory molecule-1 (DNAM-1) contributes to tumor immune surveillance and plays a crucial role in NK cell-mediated recognition of several types of human tumors, including ovarian carcinoma. Here, we have analyzed the receptor repertoire and functional integrity of NK cells in peritoneal effusions from patients with ovarian carcinoma. Relative to autologous peripheral blood NK cells, tumor-associated NK cells expressed reduced levels of the DNAM-1, 2B4, and CD16 receptors and were hyporesponsive to HLA class I-deficient K562 cells and to coactivation via DNAM-1 and 2B4. Moreover, tumor-associated NK cells were also refractory to CD16 receptor stimulation, resulting in diminished Ab-dependent cellular cytotoxicity against autologous tumor cells. Coincubation of NK cells with ovarian carcinoma cells expressing the DNAM-1 ligand CD155 led to reduction of DNAM-1 expression. Therefore, NK cell-mediated rejection of ovarian carcinoma may be limited by perturbed DNAM-1 expression on tumor-associated NK cells induced by chronic ligand exposure. Thus, these data support the notion that tumor-induced alterations of activating NK cell receptor expression may hamper immune surveillance and promote tumor progression.
The E3 Ubiquitin Ligase Cbl-b Regulates Expansion but Not Functional Activity of Self-Reactive CD4 T Cells
Authors: St. Rose Marie-Clare , Qui Harry Z. , Bandyopadhyay Suman , Mihalyo Marianne A. , Hagymasi Adam T. , Clark Robert B. , Adler Adam J.
Published: October 2009

Cbl-b is an E3 ubiquitin ligase that limits Ag responsiveness in T cells by targeting TCR-inducible signaling molecules. Cbl-b deficiency thus renders T cells hyperresponsive to antigenic stimulation and predisposes individuals toward developing autoimmunity. In part because Cbl-b−/− T cells do not require CD28 costimulation to become activated, and insufficient costimulation is a critical parameter that confers anergy induction over effector differentiation, it has been hypothesized that Cbl-b−/− T cells are resistant to anergy. This possibility has been supported in models in which anergy is normally induced in vitro, or in vivo following exposure to soluble Ag boluses. In the current study, we characterized the response of Cbl-b−/− CD4 T cells in an in vivo system in which anergy is normally induced by a constitutively expressed peripheral self-Ag. Cbl-b expression increased in self-Ag-induced anergic wild-type CD4 T cells, and Cbl-b−/− CD4 T cells underwent more robust proliferation and expansion upon initially encountering cognate self-Ag compared with wild-type counterparts. Nevertheless, both wild-type and Cbl-b−/− CD4 T cells ultimately developed the same impaired ability to respond to antigenic restimulation. The more extensive expansion that occurred during the initial induction of anergy did, however, allow the anergic CD4 T cells to expand to greater numbers when they were functionally resuscitated following replacement of the initial source of tolerizing self-Ag with a viral form of the same Ag.
Dominant Role of Antigen Dose in CD4+Foxp3+ Regulatory T Cell Induction and Expansion
Authors: Turner Michael S. , Kane Lawrence P. , Morel Penelope A.
Published: October 2009

The definitions of tolerogenic vs immunogenic dendritic cells (DC) remain controversial. Immature DC have been shown to induce T regulatory cells (Treg) specific for foreign and allogeneic Ags. However, we have previously reported that mature DC (mDC) prevented the onset of autoimmune diabetes, whereas immature DC (iDC) were therapeutically ineffective. In this study, islet-specific CD4+ T cells from BDC2.5 TCR-transgenic mice were stimulated in the absence of exogenous cytokine with iDC or mDC pulsed with high- or low-affinity antigenic peptides and examined for Treg induction. Both iDC and mDC presenting low peptide doses induced weak TCR signaling via the Akt/mammalian target of rapamycin (mTOR) pathway, resulting in significant expansion of Foxp3+ Treg. Furthermore, unpulsed mDC, but not iDC, also induced Treg. High peptide doses induced strong Akt/mTOR signaling and favored the expansion of Foxp3neg Th cells. The inverse correlation of Foxp3 and Akt/mTOR signaling was also observed in DO11.10 and OT-II TCR-transgenic T cells and was recapitulated with anti-CD3/CD28 stimulation in the absence of DC. IL-6 production in these cultures correlated positively with Ag dose and inversely with Treg expansion. Studies with T cells or DC from IL-6−/− mice revealed that IL-6 production by T cells was more important in the inhibition of Treg induction at low Ag doses. These studies indicate that the strength of Akt/mTOR signaling, a critical T cell-intrinsic determinant for Treg vs Th induction, can be controlled by adjusting the dose of antigenic peptide. Furthermore, this operates in a dominant fashion over DC phenotype and cytokine production.
TCR Down-Regulation Controls T Cell Homeostasis
Authors: Boding Lasse , Bonefeld Charlotte Menné , Nielsen Bodil L. , Lauritsen Jens Peter H. , von Essen Marina Rode , Hansen Ann Kathrine , Larsen Jeppe Madura , Nielsen Morten Milek , Ødum Niels , Geisler Carsten
Published: October 2009

TCR and cytokine receptor signaling play key roles in the complex homeostatic mechanisms that maintain a relative stable number of T cells throughout life. Despite the homeostatic mechanisms, a slow decline in naive T cells is typically observed with age. The CD3γ di-leucine-based motif controls TCR down-regulation and plays a central role in fine-tuning TCR expression and signaling in T cells. In this study, we show that the age-associated decline of naive T cells is strongly accelerated in CD3γLLAA knock-in mice homozygous for a double leucine to alanine mutation in the CD3γ di-leucine-based motif, whereas the number of memory T cells is unaffected by the mutation. This results in premature T cell population senescence with a severe dominance of memory T cells and very few naive T cells in middle-aged to old CD3γ mutant mice. The reduced number of naive T cells in CD3γ mutant mice was caused by the combination of reduced thymic output, decreased T cell apoptosis, and increased transition of naive T cells to memory T cells. Experiments with bone marrow chimeric mice confirmed that the CD3γLLAA mutation exerted a T cell intrinsic effect on T cell homeostasis that resulted in an increased transition of CD3γLLAA naive T cells to memory T cells and a survival advantage of CD3γLLAA T cells compared with wild-type T cells. The experimental observations were further supported by mathematical modeling of T cell homeostasis. Our study thus identifies an important role of CD3γ-mediated TCR down-regulation in T cell homeostasis.
Acquisition of T Regulatory Function in Cathepsin L-Inhibited T Cells by Eye-Derived CTLA-2α during Inflammatory Conditions
Authors: Sugita Sunao , Horie Shintaro , Nakamura Orie , Maruyama Kazuichi , Takase Hiroshi , Usui Yoshihiko , Takeuchi Masaru , Ishidoh Kazumi , Koike Masato , Uchiyama Yasuo , Peters Christoph , Yamamoto Yoshimi , Mochizuki Manabu
Published: October 2009

Pigment epithelium isolated from the eye possesses immunosuppressive properties such as regulatory T (Treg) cell induction; e.g., cultured retinal pigment epithelium (RPE) converts CD4+ T cells into Treg cells in vitro. RPE constitutively expresses a novel immunosuppressive factor, CTLA-2α, which is a cathepsin L (CathL) inhibitor, and this molecule acts via RPE to induce Treg cells. To clarify CTLA-2α’s role in the T cell response to RPE in ocular inflammation, we used the experimental autoimmune uveitis (EAU) animal model to examine this new immunosuppressive property of RPE. In EAU models, TGF-β, but not IFN-γ inflammatory cytokines, promotes the up-regulation of the expression of CTLA-2α in RPE. Similarly, CTLA-2α via RPE was able to promote TGF-β production by the CD4+ T cells. The RPE-exposed T cells (RPE-induced Treg cells) greatly produced TGF-β and suppressed bystander effector T cells. There was less expression of CathL by the RPE-exposed T cells, and CathL-inhibited T cells were able to acquire the Treg phenotype. Moreover, CathL-deficient mice spontaneously produced Treg cells, with the increase in T cells potentially providing protection against ocular inflammation. More importantly, CD4+ T cells from EAU in CathL knockout mice or rCTLA-2α from EAU animals were found to contain a high population of forkhead box p3+ T cells. In both EAU models, there was significant suppression of the ocular inflammation. These results indicate that RPE secretes CTLA-2α, thereby enabling the bystander T cells to be converted into Treg cells via TGF-β promotion.
Recombination Signal Sequence-Associated Restriction on TCRδ Gene Rearrangement Affects the Development of Tissue-Specific γδ T Cells
Authors: Uche Uzodinma N. , Huber Christopher R. , Raulet David H. , Xiong Na
Published: October 2009

Assembly of TCRα and TCRδ genes from the TCRα/δ locus is tightly controlled for the proper generation of αβ and γδ T cells. Of >100 shared variable gene segments in the TCRα/δ locus, only a few are predominantly used for the TCRδ gene assembly, while most are for TCRα. However, the importance and mechanisms of the selective variable gene rearrangement for T cell development are not fully understood. We report herein that the development of a tissue-specific γδ T cell population is critically affected by recombination signal sequence-associated restriction on the variable gene usage for TCRδ assembly. We found that the development of substitute skin γδ T cells in mice deficient of the TCRγ3 gene, which is used in wild-type skin γδ T cells, was drastically affected by the strain background. A Vγ2+ skin γδ T cell population developed in mice of the B6 but not the 129 strain backgrounds, due to a difference in the rearrangement of endogenous Vδ7+ TCRδ genes, which paired with the Vγ2+ TCRγ gene to generate the Vγ2/Vδ7+ skin γδ T cell precursors in fetal thymi of the B6 background mice. The defective TCRδ rearrangement of the 129-“Vδ7” gene was associated with specific variations in its recombination signal sequence, which renders it poorly compatible for rearrangement to Dδ genes. These findings provide the first direct evidence that recombination signal sequence-associated restriction on the variable gene usage for TCRα/δ gene assembly plays an important role in T cell development.
Langerhans Cells Suppress Contact Hypersensitivity Responses Via Cognate CD4 Interaction and Langerhans Cell-Derived IL-10
Authors: Igyarto Botond Z. , Jenison Matthew C. , Dudda Jan C. , Roers Axel , Müller Werner , Koni Pandelakis A. , Campbell Daniel J. , Shlomchik Mark J. , Kaplan Daniel H.
Published: October 2009

Mice lacking epidermal Langerhans cells (LC) develop exaggerated contact-hypersensitivity (CHS) responses due to the absence of LC during sensitization/initiation. Examination of T cell responses reveals that the absence of LC leads to increased numbers of hapten-specific CD4 and CD8 T cells but does not alter cytokine expression or development of T regulatory cells. CHS responses and Ag-specific T cells are increased in mice in which MHC class II is ablated specifically in LC suggesting that direct cognate interaction between LC and CD4 cells is required for suppression. LC-derived IL-10 is also required for optimal inhibition of CHS. Both LC-derived IL-10-mediated suppression and full LC activation require LC expression of MHC class II. These data support a model in which cognate interaction of LC with CD4 T cells enables LC to inhibit expansion of Ag-specific responses via elaboration of IL-10.
Cutting Edge: Extracellular Signal-Related Kinase Is Not Required for Negative Selection of Developing T Cells
Authors: McGargill Maureen A. , Ch'en Irene L. , Katayama Carol D. , Pagès Gilles , Pouysségur Jacques , Hedrick Stephen M.
Published: October 2009

Signals initiated through the TCR during development can result in either survival and differentiation or cell death. High affinity signals that induce death elicit a robust yet transient activation of signaling pathways, including Erk, whereas low affinity ligands, which promote survival, generate a gradual and weaker activation of the same pathways. It was recently demonstrated that Erk localizes to distinct cellular locations in response to high and low affinity ligands. Although a requirement for Erk in positive selection is well established, its role in negative selection is controversial and, thus, the importance of Erk relocalization during development is not understood. In this study, we examined the role of Erk in negative selection using mice that are genetically deficient in both Erk1 and Erk2 in T cells. Results from three different models reveal that thymocyte deletion remains intact in the absence of Erk.
Tumors and tumor-like lesions of the heart valves
Authors: Yuan Shi-Min , Jing Hua , Lavee Jacob
Published: October 2009

Valvular tumors and tumor-like lesions may have similar morphological and clinical characteristics, and may place the patients at a high risk of stroke in different ways. From January 2004 to June 2008, 11 patients underwent surgery for a suspected valvular tumor. Valvular tumor and tumor-like lesions accounted for 0.32% of adult cardiac operations. Five (45.5%) valvular lesions were papillary fibroelastomas, one (9.1%) was myxoma, 2 (18.2%) were organized thrombi, and 3 (27.3%) were calcification lesions. There was a total of 5 (45.5%) atrioventricular valve lesions, 4 arising from the atrial side of the leaflets, and one from the ventricular side. All 5 (45.5%) semilunar valvular lesions were from the aortic valve. One (9.1%) lesion originated from the chorda tendinea of the mitral valve. All leaflet lesions were resected by a simple shave technique, and all the patients recovered favorably. Valvular tumor and tumor-like lesions are rare. Pre-operative differential diagnoses among these valvular lesions pose important clinical implications for appropriate treatment for the underlying diseases. Prompt therapeutic measures in view of the underlying diseases of the valvular lesions are essential to prevent potential embolic events.
Multilayer Hybrid Films Consisting of Alternating Graphene and Titania Nanosheets with Ultrafast Electron Transfer and Photoconversion Properties
Authors: Manga Kiran Kumar , Zhou Yong , Yan Yongli , Loh Kian Ping
Published: October 2009

Alternating graphene (G) and titania (Ti0.91O2) multilayered nanosheets are fabricated using layer‐by‐layer electrostatic deposition followed by UV irradiation. Successful assemblies of graphene oxide (GO) and titania nanosheets in sequence with polyethylenimine as a linker is confirmed by UV–vis absorption and X‐ray diffraction. Photocatalytic reduction of GO into G can be achieved upon UV irradiation. Ultrafast photocatalytic electron transfer between the titania and graphene is demonstrated using femtosecond transient absorption spectroscopy. Efficient exciton dissociation at the interfaces coupled with cross‐surface charge percolation allows efficient photocurrent conversion in the multilayered Ti0.91O2/G films.
Preferential recruitment of interferon‐γ–expressing TH17 cells in multiple sclerosis
Authors: Kebir Hania , Ifergan Igal , Alvarez Jorge Ivan , Bernard Monique , Poirier Josée , Arbour Nathalie , Duquette Pierre , Prat Alexandre
Published: October 2009

Objective

There is substantial evidence supporting the role of interferon (IFN)‐γ–producing T helper (TH) 1 and interleukin (IL)‐17–expressing TH17 lymphocytes in multiple sclerosis (MS) and its animal model, experimental allergic encephalomyelitis (EAE). However, to date little is known about the potential cooperative interplay between these 2 cytokines. In the current study, we sought to evaluate the frequency of IFN‐γ–expressing TH17 lymphocytes in MS and EAE, and study their recruitment into the central nervous system (CNS).

Methods

Human TH17 lymphocytes were expanded in vitro from the blood of healthy controls and relapsing MS patients using IL‐23. Immune cell migration to the CNS was assessed in vitro with primary cultures of human blood–brain barrier (BBB)‐derived endothelial cells, and in vivo in EAE mice.

Results

We demonstrate that in response to IL‐23, human memory lymphocytes expand into a TH17 phenotype, with a subpopulation of cells simultaneously expressing IFN‐γ and IL‐17. We note that lymphocytes obtained from the blood of relapsing MS patients have an increased propensity to expand into IFN‐γ–producing TH17 cells and identify numerous T lymphocytes coexpressing IL‐17 and IFN‐γ in brain tissue of MS patients. We also find lymphocytes expressing both the TH1‐ and the TH17‐associated transcription factors RORγt and T‐bet, in situ and in vitro. We further provide in vitro and in vivo evidence that IFN‐γ+ TH17 lymphocytes preferentially cross the human BBB and accumulate in the CNS of mice during the effector phase of EAE.

Interpretation

Our data underscore the involvement of IFN‐γ+ TH17 lymphocytes in the pathology of MS and EAE and their preferential recruitment into the CNS during inflammatory events. Ann Neurol 2009;66:390–402
Student laboratory presentations as a learning tool in anatomy education
Authors: Chollet Madeleine B. , Teaford Mark F. , Garofalo Evan M. , DeLeon Valerie B.
Published: October 2009

Previous studies have shown that anatomy students who complete oral laboratory presentations believe they understand the material better and retain it longer than they otherwise would if they only took examinations on the material; however, we have found no studies that empirically test such outcomes. The purpose of this study was to assess the effectiveness of oral presentations through comparisons with other methods of assessment, most notably, examination performance. Specifically, we tested whether students (n = 256) performed better on examination questions on topics covered by their oral presentations than on other topics. Each student completed two graded, 12‐minute laboratory presentations on two different assigned topics during the course and took three examinations, each of which covered a third of the course material. Examination questions were characterized by type (memorization, pathway, analytical, spatial). A two‐way repeated measures analysis of variance revealed that students performed better on topics covered by their presentations than on topics not covered by their presentations (P < 0.005), regardless of presentation grade (P > 0.05) and question type (P > 0.05). These results demonstrate empirically that oral presentations are an effective learning tool. Anat Sci Educ 2: 260–264, 2009. © 2009 American Association of Anatomists.
Demonstrating and eliminating the aggregation effect in physical skill tasks
Authors: Stone Eric R. , Rittmayer Ashley D. , Murray Nicole T. , McNiel J. Murray
Published: October 2009

Confidence judgments can be elicited in multiple ways. One of these procedures is to provide confidence judgments regarding each of a number of cases (individual judgments). A second procedure is to provide confidence judgments about a set of items (an aggregate judgment). Much research has demonstrated an aggregation effect—that individual judgments are more confident than aggregate judgments—within the cognitive knowledge domain. However, this effect has not previously been investigated with physical performance skill tasks. In three experiments, participants gave individual and aggregate judgments regarding the number of successful tosses they would make in either a ring toss, ping‐pong toss, or basketball toss task. In keeping with the aggregation effect, individual judgments were more confident than were aggregate judgments of success. Additionally, we eliminated the aggregation effect in Experiments 2 and 3 by employing a case‐specific base rate manipulation. Consistent with previous research with cognitive tasks, these results suggest that individual confidence judgments for physical skill tasks are determined primarily by characteristics associated with the individual case to be judged, whereas aggregate confidence judgments are determined by a more general evaluation of one's ability in the domain. Copyright © 2009 John Wiley & Sons, Ltd.