bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of Potent Cytotoxic T Lymphocytes Against Castration‐Resistant Prostate Cancer Cells by Dendritic Cells Loaded With Dying Allogeneic Prostate Cancer Cells
Authors: Hwang E. C. , Lim M.‐S. , Im C.‐M. , Kwon D.‐D. , Lee H.‐J. , Nguyen‐Pham T.‐N. , Lee Y.‐K. , Lee J.‐J. 
Published: November 2012

AbstractTo induce a potent cytotoxic T lymphocyte (CTL) response in dendritic cell (DC)‐based immunotherapy against prostate cancer, various tumour antigens should be loaded onto DCs. The aim of this study was to establish a method of immunotherapy for castration‐resistant prostate cancer (CRPC) using prostate cancer–specific CTLs generated in vitro by DCs. Monocyte‐derived DCs from patients with CRPC were induced to mature using a standard cytokine cocktail (in IL‐1β, TNF‐α, IL‐6 and PGE2: standard DCs, sDCs) or using an α‐type 1‐polarized DC (αDC1) cocktail (in IL‐1β, TNF‐α, IFN‐α, IFN‐γ and polyinosinic:polycytidylic acid) and loaded with the UVB‐irradiated CRPC cell line PC‐3. Antigen‐loaded DCs were evaluated by morphological and functional assays. The αDC1s significantly increased the expression of several molecules related to DC maturation, regardless of whether the αDC1s were loaded with tumour antigens or not, compared to sDCs. The αDC1s showed a higher production of interleukin‐12 both during maturation and after subsequent stimulation with CD40L, which was not significantly affected by loading with tumour antigens, as compared to standard DCs (sDCs). Prostate cancer–specific CTLs against autologous CRPC cells were successfully induced by αDC1s loaded with dying PC‐3 cells. Autologous αDC1s loaded with an allogeneic CRPC cell line can generate greater CRPC‐specific CTL responses as compared to sDCs and may provide a novel source of DC‐based vaccines that can be used for the development of immunotherapy in patients with CRPC.
Quinolinic Alkaloids from Galipea longiflora Krause Suppress Production of Proinflammatory Cytokines in vitro and Control Inflammation in vivo upon Leishmania Infection in Mice
Authors: Calla‐Magariños J. , Quispe T. , Giménez A. , Freysdottir J. , Troye‐Blomberg M. , Fernández C. 
Published: November 2012

AbstractAn antileishmanial activity of quinolinic alkaloids from Galipea longiflora Krause, known as Evanta, has been demonstrated. We have previously shown that, apart from its leishmanicidal effect, in vitro pretreatment of spleen cells with an alkaloid extract of Evanta (AEE) interfered with the proliferation and interferon‐γ production in lymphocytes polyclonally activated either with concanavalin A or anti‐CD3. In the present study, we investigated if AEE could interfere with antigen‐specific lymphocyte activation. We found that in vitro and in vivo treatment reduced recall lymphocyte responses, as measured by IFN‐γ production (55% and 63% reduction compared to untreated cells, respectively). Apart from IFN‐γ, the production of IL‐12 and TNF was also suppressed. No effects were observed for meglumine antimoniate (SbV), the conventional drug used to treat leishmaniasis. When mice infected with Leishmania braziliensis promastigotes in the hind footpad were treated with AEE, the dynamics of the infection changed and the footpath thickness was efficiently controlled. The parasite load was also reduced but to a lesser extent than upon treatment with SbV. Combined treatment efficiently controlled both the thickness and parasite load as smaller lesions during the entire course of the infection were seen in the mice treated with AEE plus SbV compared with AEE or SbV alone. We discuss the benefits of combined administration of AEE plus SbV.
Minor Histocompatibility Antigen UTY as Target for Graft‐versus‐Leukemia and Graft‐versus‐Haematopoiesis in the Canine Model
Authors: Bund D. , Buhmann R. , Gökmen F. , Zorn J. , Kolb H.‐J. , Schmetzer H. M. 
Published: November 2012

AbstractMale patients with female‐stem‐cell donors have better prognosis compared to female‐to‐male combinations due to Y‐encoded minor histocompatibility antigens recognized by female‐alloimmune‐effector lymphocytes in the context of a graft‐versus‐leukemia (GvL) effect. We provide data in a dog‐model that the minor histocompatibility antigen UTY might be a promising target to further improve GvL‐immune reactions after allogeneic‐stem‐cell transplantations. Female‐canine‐UTY‐specific T cells (CTLs) were stimulated in vitro using autologous‐DCs loaded with three HLA‐A2‐restricted‐UTY‐derived peptides (3‐fold‐expansion), and specific T cell responses were determined in 3/6 female dogs. CTLs specifically recognized/lysed autologous‐female‐peptide‐loaded DCs, but not naïve‐autologous‐female DCs and monocytes. They mainly recognized bone‐marrow (BM) and to a lower extent DCs, monocytes, PBMCs and B‐cells from DLA‐identical‐male littermates and peptide‐loaded T2‐cells in an MHC‐I‐restricted manner. A UTY‐/male‐specific reactivity was also obtained in vivo after stimulation of a female dog with DLA‐identical‐male PBMCs. In summary, we demonstrated natural UTY processing and presentation in dogs. We showed that female‐dog CTLs were specifically stimulated by HLA‐A2‐restricted‐UTY peptides, thereby enabling recognition of DLA‐identical‐male cells, mainly BM cells. These observations suggest UTY as a promising candidate‐antigen to improve GvL‐reactions in the course of immunotherapy.
Use of real‐time quantitative PCR to document successful treatment of Mycoplasma haemocanis infection with doxycycline in a dog
Authors: Pitorri Francesca , Dell'Orco Marta , Carmichael Nick , Barker Emily N. , Hollywood Mike , Tasker Séverine 
Published: November 2012

AbstractAn 8‐year‐old Jack Russell Terrier was diagnosed with hemolytic anemia caused by hemoplasmosis 4 years following splenectomy. Quantitative real‐time PCR (qPCR) analysis was used initially to confirm infection with Mycoplasma haemocanis and subsequently to monitor and direct medical therapy. Doxycycline was administered beyond resolution of clinical signs until hemoplasma DNA could no longer be detected by qPCR. The dog remained clinically healthy and hemoplasma‐negative 8 months following cessation of therapy. Canine hemoplasmosis should remain as a differential diagnosis for hemolytic anemia in dogs, particularly those that are splenectomized or immunocompromised, even in geographic regions where prevalence of infection is low. Prolonged doxycycline administration has been shown by qPCR to lead to sustained absence of detectable infection and should be considered as a first line treatment for canine hemoplasmosis.
Descending control of the respiratory neuronal network by the midbrain periaqueductal grey in the rat in vivo
Authors: Subramanian Hari H. 
Published: November 2012

Key points
Basic respiratory rhythm is generated and maintained by neurones located in the medulla oblongata.
This basic respiratory rhythm is changed by neurones in the region called the periaqueductal grey (PAG) located in the midbrain, in order to modulate breathing for behaviour and emotional expressivity.
How the PAG converts basic respiratory rhythm into behavioural breathing is not known.
In this study I investigated the influence of the PAG on two important populations of medullary neurones, the late‐inspiratory (late‐I) and post‐inspiratory (post‐I) neurones, which are thought to be involved in mediating rhythmic inspiration to expiration phase transition.
I show that the PAG modulates the activity of the medullary late‐I and post‐I neurones, and this modulation contributes to the conversion of basic breathing into behavioural breathing.
Abstract  Emotional reactions such as vocalization take place during expiration, and thus expression of emotional behaviour requires a switch from inspiration to expiration. I investigated how the midbrain periaqueductal grey (PAG), a known behavioural modulator of breathing, influences the inspiratory‐to‐expiratory phase transition. Contemporary models propose that late inspiratory (late‐I) and post‐inspiratory (post‐I) neurones found in the medulla, which are active during the inspiratory‐to‐expiratory phase transition are involved in converting inspiration to expiration. I examined the effect of excitatory amino acid (d,l‐homocysteic acid; DLH) stimulation of the PAG on the discharge function of late‐I and post‐I neurones. The data show a topographical organization of DLH‐induced late‐I and post‐I neuronal modulation within the PAG. Dorsal PAG stimulation induced tachypnoea and caused excitation of both the late‐I and post‐I neurones. Lateral PAG induced inspiratory prolongation and caused an excitation of late‐I neurones but inhibition of post‐I neurones. Ventrolateral PAG induced expiratory prolongation and caused a persistent activation of post‐I neurones. As well, PAG stimulation modulated both the late‐I and post‐I cells for least two–three breaths even prior to the change in respiratory motor pattern. This indicates that the PAG influences the late‐I and post‐I cells independent of pulmonary or other sensory afferent feedback. I conclude that the PAG modulates the activity of the medullary late‐I and post‐I neurones, and this modulation contributes to the conversion of eupnoea into a behavioural breathing pattern.
A clinically feasible method for the detection of potential collision in proton therapy
Authors: Zou Wei , Lin Haibo , Plastaras John P. , Wang Huanshu , Bui Viet , Vapiwala Neha , McDonough James , Tochner Zelig , Both Stefan 
Published: November 2012

Purpose:Potential collision between the patient/couch and the gantry could delay the start of the treatment and reduce clinical efficiency. The ability to accurately detect possible collisions during the treatment planning phase is desired. Such collision detection should account for the specific proton gantry design, the treatment beam configuration, couch orientation, and the patient specific geometry. In this paper the authors developed an approach to detect possible patient‐machine collisions using patient treatment plan data.Methods:The geometry of the machine and the patient was reconstructed relative to the isocenter of the proton treatment room. The surface contour of the gantry was first captured from the proton computer aided design and reconstructed to account for specific gantry rotation, snout position, collimator rotation, and range compensator dimensions based on the patient treatment plan data. The patient body and couch contours were captured from the patientˈs CT DICOM structure file. They were reconstructed relative to the isocenter taking into account treatment couch rotation. For potential collision that occurs at body portions where no CT images exist, scout images are used to construct the body contour. A software program was developed using a ray casting algorithm that was applied to detect collisions by determining if any of the patient and couch contour points fall into the spatial polygons formed by the proton gantry surfaces.Results:Twenty‐four patient plans with or without potential collisions were retrospectively identified and analyzed using the collision detection software. In addition, five collision cases were artificially generated using an anthropomorphic phantom. The program successfully detected the collisions in all cases. The calculation time for each case was within 20 s. The software program was implemented in the authors’ clinic to detect patient‐gantry or gantry‐couch collisions in the treatment planning phase.Conclusions:The authors developed a fast and clinically feasible patient‐specific collision detection program for proton therapy based on a ray casting algorithm. If incorporated during the treatment planning phase it may lead to improved clinical efficiency. This methodology could also be applied to patient collision detection in photon therapy.
Fast parallel algorithms for the x‐ray transform and its adjoint
Authors: Gao Hao 
Published: November 2012

Purpose:Iterative reconstruction methods often offer better imaging quality and allow for reconstructions with lower imaging dose than classical methods in computed tomography. However, the computational speed is a major concern for these iterative methods, for which the x‐ray transform and its adjoint are two most time‐consuming components. The speed issue becomes even notable for the 3D imaging such as cone beam scans or helical scans, since the x‐ray transform and its adjoint are frequently computed as there is usually not enough computer memory to save the corresponding system matrix. The purpose of this paper is to optimize the algorithm for computing the x‐ray transform and its adjoint, and their parallel computation.Methods:The fast and highly parallelizable algorithms for the x‐ray transform and its adjoint are proposed for the infinitely narrow beam in both 2D and 3D. The extension of these fast algorithms to the finite‐size beam is proposed in 2D and discussed in 3D.Results:The CPU and GPU codes are available athttps://sites.google.com/site/fastxraytransform. The proposed algorithm is faster than Siddonˈs algorithm for computing the x‐ray transform. In particular, the improvement for the parallel computation can be an order of magnitude.Conclusions:The authors have proposed fast and highly parallelizable algorithms for the x‐ray transform and its adjoint, which are extendable for the finite‐size beam. The proposed algorithms are suitable for parallel computing in the sense that the computational cost per parallel thread is O(1).
Emission guided radiation therapy for lung and prostate cancers: A feasibility study on a digital patient
Authors: Fan Qiyong , Nanduri Akshay , Mazin Samuel , Zhu Lei 
Published: November 2012

Purpose:Accurate tumor tracking remains a challenge in current radiation therapy. Many strategies including image guided radiation therapy alleviate the problem to certain extents. The authors propose a new modality called emission guided radiation therapy (EGRT) to accurately and directly track the tumor based on its biological signature. This work is to demonstrate the feasibility of EGRT under two clinical scenarios using a 4D digital patient model.Methods:EGRT uses lines of response (LOR's) from positron emission events to direct beamlets of therapeutic radiation through the emission sites inside a tumor. This is accomplished by a radiation delivery system consisting of a Linac and positron emission tomography (PET) detectors on a fast rotating closed‐ring gantry. During the treatment of radiotracer‐administrated cancer patients, PET detectors collect LORˈs from tumor uptake sites and the Linac responds in nearly real‐time with beamlets of radiation along the same LOR paths. Moving tumors are therefore treated with a high targeting accuracy. Based on the EGRT concept, the authors design a treatment method with additional modulation algorithms including attenuation correction and an integrated boost scheme. Performance is evaluated using simulations of a lung tumor case with 3D motion and a prostate tumor case with setup errors. The emission process is simulated by Geant4 Application for Tomographic Emission package (GATE) and Linac dose delivery is simulated using a voxel‐based Monte Carlo algorithm (VMC++).Results:In the lung case with attenuation correction, compared to a conventional helical treatment, EGRT achieves a 41% relative increase in dose to 95% of the gross tumor volume (GTV) and a 55% increase to 50% of the GTV. All dose distributions are normalized for the same dose to the lung. In the prostate case with the integrated boost and no setup error, EGRT yields a 19% and 55% relative dose increase to 95% and 50% of the GTV, respectively, when all methods are normalized for the same dose to the rectum. In the prostate case with integrated boost where setup error is present, EGRT contributes a 21% and 52% relative dose increase to 95% and 50% of the GTV, respectively.Conclusions:As a new radiation therapy modality with inherent tumor tracking, EGRT has the potential to substantially improve targeting in radiation therapy in the presence of intrafractional and interfractional motion.
Penalization of aperture complexity in inversely planned volumetric modulated arc therapy
Authors: Younge Kelly C. , Matuszak Martha M. , Moran Jean M. , McShan Daniel L. , Fraass Benedick A. , Roberts Donald A. 
Published: November 2012

Purpose:Apertures obtained during volumetric modulated arc therapy (VMAT) planning can be small and irregular, resulting in dosimetric inaccuracies during delivery. Our purpose is to develop and integrate an aperture‐regularization objective function into the optimization process for VMAT, and to quantify the impact of using this objective function on dose delivery accuracy and optimized dose distributions.Methods:An aperture‐based metric (“edge penalty”) was developed that penalizes complex aperture shapes based on the ratio of MLC side edge length and aperture area. To assess the utility of the metric, VMAT plans were created for example paraspinal, brain, and liver SBRT cases with and without incorporating the edge penalty in the cost function. To investigate the dose calculation accuracy, Gafchromic EBT2 film was used to measure the 15 highest weighted apertures individually and as a composite from each of two paraspinal plans: one with and one without the edge penalty applied. Films were analyzed using a triple‐channel nonuniformity correction and measurements were compared directly to calculations.Results:Apertures generated with the edge penalty were larger, more regularly shaped and required up to 30% fewer monitor units than those created without the edge penalty. Dose volume histogram analysis showed that the changes in doses to targets, organs at risk, and normal tissues were negligible. Edge penalty apertures that were measured with film for the paraspinal plan showed a notable decrease in the number of pixels disagreeing with calculation by more than 10%. For a 5% dose passing criterion, the number of pixels passing in the composite dose distributions for the non‐edge penalty and edge penalty plans were 52% and 96%, respectively. Employing gamma with 3% dose/1 mm distance criteria resulted in a 79.5% (without penalty)/95.4% (with penalty) pass rate for the two plans. Gradient compensation of 3%/1 mm resulted in 83.3%/96.2% pass rates.Conclusions:The use of the edge penalty during optimization has the potential to markedly improve dose delivery accuracy for VMAT plans while still maintaining high quality optimized dose distributions. The penalty regularizes aperture shape and improves delivery efficiency.
4(1H)-Quinolones with Liver Stage Activity against Plasmodium berghei
Authors: LaCrue Alexis N. , Sáenz Fabián E. , Cross R. Matthew , Udenze Kenneth O. , Monastyrskyi Andrii , Stein Steven , Mutka Tina S. , Manetsch Roman , Kyle Dennis E. 
Published: November 2012

ABSTRACTWith the exception of primaquine, tafenoquine, and atovaquone, there are very few antimalarials that target liver stage parasites. In this study, a transgenicPlasmodium bergheiparasite (1052Cl1;PbGFP-Luccon) that expresses luciferase was used to assess the anti-liver stage parasite activity of ICI 56,780, a 7-(2-phenoxyethoxy)-4(1H)-quinolone (PEQ), as well as two 3-phenyl-4(1H)-quinolones (P4Q), P4Q-146 and P4Q-158, by using bioluminescent imaging (BLI). Results showed that all of the compounds were active against liver stage parasites; however, ICI 56,780 and P4Q-158 were the most active, with low nanomolar activityin vitroand causal prophylactic activityin vivo. This potent activity makes these compounds ideal candidates for advancement as novel antimalarials.
A Class of Tricyclic Compounds Blocking Malaria Parasite Oocyst Development and Transmission
Authors: Eastman Richard T. , Pattaradilokrat Sittiporn , Raj Dipak K. , Dixit Saurabh , Deng Bingbing , Miura Kazutoyo , Yuan Jing , Tanaka Takeshi Q. , Johnson Ronald L. , Jiang Hongying , Huang Ruili , Williamson Kim C. , Lambert Lynn E. , Long Carole , Austin Christopher P. , Wu Yimin , Su Xin-zhuan 
Published: November 2012

ABSTRACT

Malaria is a deadly infectious disease in many tropical and subtropical countries. Previous efforts to eradicate malaria have failed, largely due to the emergence of drug-resistant parasites, insecticide-resistant mosquitoes and, in particular, the lack of drugs or vaccines to block parasite transmission. ATP-binding cassette (ABC) transporters are known to play a role in drug transport, metabolism, and resistance in many organisms, including malaria parasites. To investigate whether a
Plasmodium falciparum
ABC transporter (Pf14_0244 or PfABCG2) modulates parasite susceptibility to chemical compounds or plays a role in drug resistance, we disrupted the gene encoding PfABCG2, screened the recombinant and the wild-type 3D7 parasites against a library containing 2,816 drugs approved for human or animal use, and identified an antihistamine (ketotifen) that became less active against the PfABCG2-disrupted parasite in culture. In addition to some activity against asexual stages and gametocytes, ketotifen was highly potent in blocking oocyst development of
P. falciparum
and the rodent parasite
Plasmodium yoelii
in mosquitoes. Tests of structurally related tricyclic compounds identified additional compounds with similar activities in inhibiting transmission. Additionally, ketotifen appeared to have some activity against relapse of
Plasmodium cynomolgi
infection in rhesus monkeys. Further clinical evaluation of ketotifen and related compounds, including synthetic new derivatives, in blocking malaria transmission may provide new weapons for the current effort of malaria eradication.
Targeting Organic Anion Transporter 3 with Probenecid as a Novel Anti-Influenza A Virus Strategy
Authors: Perwitasari Olivia , Yan Xiuzhen , Johnson Scott , White Caleb , Brooks Paula , Tompkins S. Mark , Tripp Ralph A. 
Published: November 2012

ABSTRACT

Influenza A virus infection is a major global health concern causing significant mortality, morbidity, and economic loss. Antiviral chemotherapeutics that target influenza A virus are available; however, rapid emergence of drug-resistant strains has been reported. Consequently, there is a burgeoning need to identify novel anti-influenza A drugs, particularly those that target host gene products required for virus replication, to reduce the likelihood of drug resistance. In this study, a small interfering RNA (siRNA) screen was performed to identify host druggable gene targets for anti-influenza A virus therapy. The host organic anion transporter-3 gene (OAT3), a member of the SLC22 family of transporters, was validated as being required to support influenza A virus replication. Probenecid, a prototypical uricosuric agent and chemical inhibitor of organic anion transporters known to target OAT3, was shown to be effective in limiting influenza A virus infection
in vitro
(50% inhibitory concentration [IC
50
] of 5.0 × 10
−5
to 5.0 × 10
−4
μM;
P
< 0.005) and
in vivo
(
P
< 0.05). Probenecid is widely used for treatment of gout and related hyperuricemic disorders, has been extensively studied for pharmacokinetics and safety, and represents an excellent candidate for drug repositioning as a novel anti-influenza A chemotherapeutic.
Clinical Application of a Multiplex Real-Time PCR Assay for Simultaneous Detection of Legionella Species, Legionella pneumophila, and Legionella pneumophila Serogroup 1
Authors: Benitez Alvaro J. , Winchell Jonas M. 
Published: November 2012

ABSTRACT

We developed a single-tube multiplex real-time PCR assay capable of simultaneously detecting and discriminating
Legionella
spp.,
Legionella pneumophila
, and
Legionella pneumophila
serogroup 1 in primary specimens. Evaluation of 21 clinical specimens and 115 clinical isolates demonstrated this assay to be a rapid, high-throughput diagnostic test with 100% specificity that may aid during legionellosis outbreaks and epidemiologic investigations.