bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53‐Pathway activity and apoptosis in hydrogen sulfide‐exposed stem cells separated from human gingival epithelium
Authors: Calenic B. , Yaegaki K. , Ishkitiev N. , Kumazawa Y. , Imai T. , Tanaka T. 
Published: October 2012

Background and ObjectiveHydrogen sulfide (
H2S
) is a volatile sulfur compound responsible for physiological halitosis.
H2S
was also reported as having periodontal pathologic activities. Gingival crevicular epithelium is the first barrier against periodontal pathogens and their products; oral keratinocyte stem cells OKSCs play key roles in maintaining this barrier. The p53 pathway is responsible for regulating key biological events. Increased apoptosis and cell‐cycle arrest of DNA repair can affect keratinocyte stem cells, having a direct impact on the architecture of the oral epithelial tissue. However, the link between
H2S
, p53 activity and OKSCs has not yet been fully explored. The main objective of the present study was to explore the implications of the p53 pathway in OKSCs following exposure to
H2S
.Material and MethodsOKSCs were isolated from human gingival epithelium and incubated with physiological levels of
H2S
for 24 and 48 h. Apoptosis and the mitochondrial membrane potential were detected using flow cytometry. Cytochrome c, total p53, phosphorylated p53 and caspase activity were assessed using specific ELISAs. p53 Pathway gene activity was assayed using quantitative RT‐PCR.ResultsThe levels of apoptosis were significantly increased following incubation in the presence of H2S, especially after 48 h (36.95 ± 1.91% vs. 4.77 ± 0.74%). Caspases 9 and 3 were activated, whereas caspase‐8 activity remained low. Total p53 activity and particularly phosphorylated p53 at serine 46, were significantly enhanced compared with controls (47.11 ± 9.84 units/mL vs. 1.5 ± 0 units/mL and 32.22 ± 10.23 units/mL vs. 0.15 ± 0 units/mL, respectively, at 48 h). Among p53 pathway genes, apoptosis‐related genes [i.e. phosphatase and tensin homolog (
PTEN
), B‐cell CLL/lymphoma 2 (
BCL2), sirtuin 3 (
SIRT3) and caspases]) were dramatically increased when compared with controls. Moreover, cell‐cycle progression genes [i.e. E2F transcription factor (E2F) family and histone deacetylase (
HDAC
)] and DNA‐repair genes [i.e. growth arrest and DNA‐damage‐inducible, gamma (
GADD45G
) family and serine/threonine‐protein kinase Chk2 (
CHEK2)] were also increased.ConclusionFollowing incubation with
H2S
, OKSCs express multiple p53‐associated genes, including programmed cell death, cell‐cycle control and DNA‐repair genes.
A holstein cow–calf model for the transfer of ciprofloxacin through milk after a long‐term intravenous infusion
Authors: Chiesa O. A. , Idowu O. R. , Heller D. , Smith M. , Nochetto C. , Chamberlain P. L. , Gehring R. , von Bredow J. 
Published: October 2012

This study is part of an ongoing effort to develop animal models that provide milk and sufficient infant (offspring) plasma samples to fully describe a drug's pharmacokinetics to quantitate the risk to the nursing infant. Ciprofloxacin was administered to six healthy Holstein cows as a constant rate intravenous infusion (flow rate was weight adjusted) to achieve a steady‐state concentration of approximately 300 ng/mL for 7 days. Plasma and milk samples were collected from the cow at regular intervals over the course of the 7 days. The plasma and milk samples were analyzed for ciprofloxacin by high‐performance liquid chromatography. The milk was fed to calves, and calf plasma samples were analyzed to study the lactational transfer of ciprofloxacin from dam to nursing neonate. Remarkably, concentrations of ciprofloxacin in milk were 45 times higher than plasma drug concentrations in the dam. Approximately 6% of the administered dose was transferred to the milk, resulting in an average oral dose of 0.5 mg/kg to the calves with every feeding. The drug did not accumulate in the calves, and plasma concentrations were between one‐tenth and one‐fifth the plasma concentrations of the dam.
Kinematic Analysis of Epicyclic Bevel Gear Trains With Matroid Method
Authors: Talpasanu Ilie , Simionescu P. A. 
Published: October 2012

Abstract
The paper presents a novel technique for the kinematic analysis of bevel gear trains using the incidence matrices of an edge-oriented graph of the mechanism. The kinematic equations are then obtained in matrix form using a cycle basis from a cycle matroid. These equations can be systematically generated, and allow for an efficient computation of the angular velocities of the gears and planet carriers of the mechanism without employing time derivative operations. As illustrated in the paper, the method is applicable to bevel gear trains of any number of gears or degrees of freedom.
Analysis and comparison of two methods for motion correction in PET imaging
Authors: Polycarpou I. , Tsoumpas C. , Marsden P. K. 
Published: October 2012

Purpose:Although there have been various proposed methods for positron emission tomography (PET) motion correction, there is not sufficient evidence to answer which method is better in practice. This investigation aims to characterize the behavior of the two main motion‐correction approaches in terms of convergence and image properties.Methods:For the first method, reconstruct‐transform‐average (RTA), reconstructions of each gate are transformed to a reference gate and averaged. In the second method, motion‐compensated image reconstruction (MCIR), motion information is incorporated within the reconstruction. Both techniques studied were based on the ordered subsets expectation maximization algorithm. Motion information was obtained from a dynamic MR acquisition performed on a human volunteer and concurrent PET data were simulated from the dynamic MR data. The two approaches were assessed statistically using multiple realizations to accurately define the noise properties of the reconstructed images.Results:MCIR successfully recovers the true values of all regions, whereas RTA has high bias due to the limited count‐statistics and interpolation errors during the transformation step. In addition, RTA noise is very small and stabilized, whereas in MCIR noise becomes progressively greater with the number of iterations and therefore MCIR outperforms RTA in terms of MSE only if noise is treated. For example, MCIR with postfiltering results in MSE up to 42% lower than RTA.Conclusions:This study indicates that MCIR may provide superior performance overall to RTA if noise is minimized. However, in applications where quantification is not the main objective RTA can be a practical and simple method to correct for motion.
Definition of parameters for quality assurance of flattening filter free (FFF) photon beams in radiation therapy
Authors: Fogliata A. , Garcia R. , Knöös T. , Nicolini G. , Clivio A. , Vanetti E. , Khamphan C. , Cozzi L. 
Published: October 2012

Purpose: Flattening filter free (FFF) beams generated by medical linear accelerators have recently started to be used in radiotherapy clinical practice. Such beams present fundamental differences with respect to the standard filter flattened (FF) beams, making the generally used dosimetric parameters and definitions not always viable. The present study will propose possible definitions and suggestions for some dosimetric parameters for use in quality assurance of FFF beams generated by medical linacs in radiotherapy.Methods: The main characteristics of the photon beams have been analyzed using specific data generated by a Varian TrueBeam linac having both FFF and FF beams of 6 and 10 MV energy, respectively.Results: Definitions for dose profile parameters are suggested starting from the renormalization of the FFF with respect to the corresponding FF beam. From this point the flatness concept has been translated into one of “unflatness” and other definitions have been proposed, maintaining a strict parallelism between FFF and FF parameter concepts.Conclusions: Ideas for quality controls used in establishing a quality assurance program when introducing FFF beams into the clinical environment are given here, keeping them similar to those used for standard FF beams. By following the suggestions in this report, the authors foresee that the introduction of FFF beams into a clinical radiotherapy environment will be as safe and well controlled as standard beam modalities using the existing guidelines.
Eosinophilic Pneumonias
Authors: Akuthota Praveen , Weller Peter F. 
Published: October 2012

SUMMARY

This review starts with discussions of several infectious causes of eosinophilic pneumonia, which are almost exclusively parasitic in nature. Pulmonary infections due specifically to
Ascaris
, hookworms,
Strongyloides
,
Paragonimus
, filariasis, and
Toxocara
are considered in detail. The discussion then moves to noninfectious causes of eosinophilic pulmonary infiltration, including allergic sensitization to
Aspergillus
, acute and chronic eosinophilic pneumonias, Churg-Strauss syndrome, hypereosinophilic syndromes, and pulmonary eosinophilia due to exposure to specific medications or toxins.
MIC1-MAG1-SAG1 Chimeric Protein, a Most Effective Antigen for Detection of Human Toxoplasmosis
Authors: Holec-Gąsior Lucyna , Ferra Bartłomiej , Drapała Dorota 
Published: October 2012

ABSTRACTThis study describes aToxoplasma gondiiIgG enzyme-linked immunosorbent assay based on a new chimeric antigen containing three immunodominant regions from the MIC1, MAG1, and SAG1 proteins of the parasite and shows that this test is useful for diagnostic purposes and may replace the lysed and whole-cell antigens.
In VitroSusceptibilities of Yeast Species to Fluconazole and Voriconazole as Determined by the 2010 National China Hospital Invasive Fungal Surveillance Net (CHIF-NET) Study
Authors: Wang He , Xiao Meng , Chen Sharon C.-A. , Kong Fanrong , Sun Zi-Yong , Liao Kang , Lu Juan , Shao Hai-Feng , Yan Yan , Fan Hong , Hu Zhi-Dong , Chu Yun-Zhuo , Hu Tie-Shi , Ni Yu-Xing , Zou Gui-Ling , Xu Ying-Chun 
Published: October 2012

ABSTRACTWe conducted active, laboratory-based surveillance for isolates from patients with invasive infections across China from August 2009 to July 2010. DNA sequencing methods were used to define species, and susceptibility to fluconazole and voriconazole was determined by the Clinical and Laboratory Standards Institute M44-A2 disk diffusion method but using up-to-date clinical breakpoints or epidemiological cutoff values.Candidaspp. made up 90.5% of the 814 yeast strains isolated, followed byCryptococcus neoformans(7.7%) and other non-Candidayeast strains (1.7%). Bloodstream isolates made up 42.9% of the strains, isolates from ascitic fluid made up 22.1%, but pus/tissue specimens yielded yeast strains in <5% of the cases. Among theCandidaisolates,Candida albicanswas the most common species from specimens other than blood (50.1%) but made up only 23% of the bloodstream isolates (P< 0.001).C. parapsilosiscomplex species were the most commonCandidaisolates from blood (33.2%). Uncommon bloodstream yeast strains includedTrichosporonspp.,C. pelliculosa, and the novel speciesC. quercitrusa, reported for the first time as a cause of candidemia. Most (>94%) of the isolates ofC. albicans,C. tropicalis, and theC. parapsilosiscomplex were susceptible to fluconazole and voriconazole, as were all of theTrichosporonstrains; however, 12.2% of theC. glabrata sensu strictoisolates were fluconazole resistant and 17.8% had non-wild-type susceptibility to voriconazole. SevenC. tropicalisstrains were cross-resistant to fluconazole and voriconazole; six were from patients in the same institution. Resistance to fluconazole and voriconazole was seen in 31.9% and 13.3% of the uncommonCandidaand non-Candidayeast strains, respectively. Causative species and azole susceptibility varied with the geographic region. This study provided clinically useful data on yeast strains and their antifungal susceptibilities in China.
A Novel Method for Genotyping the
Helicobacter pylori vacA
Intermediate Region Directly in Gastric Biopsy Specimens
Authors: Ferreira Rui M. , Machado Jose C. , Letley Darren , Atherton John C. , Pardo Maria L. , Gonzalez Carlos A. , Carneiro Fatima , Figueiredo Ceu 
Published: October 2012

ABSTRACT

The present report describes a novel method for genotyping the virulence-associated
vacA
intermediate (i) region of
Helicobacter pylori
in archive material.
vacA
i-region genotypes as determined by the novel method were completely concordant with those of sequence analysis and with those of functional vacuolation activity. The method was further validated directly in gastric biopsy specimens of 386
H. pylori
-positive cases, and effective characterization of the
vacA
i region was obtained in 191 of 192 (99.5%) frozen and in 186 of 194 (95.9%) formalin-fixed paraffin-embedded gastric biopsy specimens, respectively. The genotyping method was next used to address the relationship between the
vacA
genotypes and the
cagA
status. The
vacA
i1 genotype was associated with
vacA
s1 (where s indicates signal region),
vacA
m1 (where m indicates middle region), and
cagA
-positive genotypes (
P
< 0.0001), while the
vacA
i2 genotype was closely related with
vacA
s2,
vacA
m2, and
cagA
-negative genotypes (
P
< 0.0001). The relationship between
H. pylori vacA
i-region genotypes and gastric disease development was subsequently evaluated in the Portuguese population. Patients infected with
vacA
i1 strains showed an increased risk for gastric atrophy and for gastric carcinoma, with odds ratios of 8.0 (95% confidence interval [CI], 2.3 to 27) and of 22 (95% CI, 7.9 to 63), respectively. Taken together, the results show that this novel
H. pylori vacA
i-region genotyping method can be applied directly to archive material, providing a fast evaluation of strain virulence determinants without the need of culture. The results further emphasize that the characterization of the
vacA
i region may be useful to identify patients at higher risk of gastric carcinoma development.
Does low-dose acetylsalicylic acid prevent cognitive decline in women with high cardiovascular risk? A 5-year follow-up of a non-demented population-based cohort of Swedish elderly women
Authors: Kern Silke , Skoog Ingmar , Östling Svante , Kern Jürgen , Börjesson-Hanson Anne 
Published: October 2012

ObjectiveThe aim of this study was to examine whether low-dose acetylsalicylic acid (ASA) influences the rate of cognitive change in elderly women.DesignProspective, population-based cohort study.SettingThe city of Gothenburg, Sweden, including those living in private households as well as in residential care.ParticipantsThe sample was derived from the Prospective Population Study of Women and from the H70 Birth Cohort Study in Gothenburg, Sweden. Both samples were obtained from the Swedish Population Register, based on birth date, and included 789 (response rate 71%) women aged 70–92 years. After the exclusion of individuals with dementia and users of warfarin, clopidogrel or heparin at baseline, 681 women were examined. Among all participants, 95.4% (N=601) had a high cardiovascular risk (CVD), defined as 10% or higher 10-year risk of any CVD event according to the Framingham heart study and 129 used low-dose ASA (75–160 mg daily) at baseline. After 5 years a follow-up was completed by 489 women.Primary outcome and secondary outcome measuresCognitive decline and dementia incidence in relation to the use of low-dose ASA and cardiovascular risk factors. Cognition was measured using the Mini Mental State Examination (MMSE), word fluency, naming ability and memory word tests. Dementia was diagnosed according to the DSM-III-R criterion. As secondary outcome incidence of stroke and peptic ulcer in relation to low-dose ASA use was studied.ResultsWomen on regular low-dose ASA declined less on MMSE at follow-up than those not on ASA. This difference was even more pronounced in those who had ASA at both examinations (p=0.004 compared with never users; n=66 vs n=338). All other cognitive tests showed the same trends. There were no differences between the groups regarding short-term risk for dementia (N=41).ConclusionLow-dose ASA treatment may have a neuroprotective effect in elderly women at high cardiovascular risk.
Universal Cancer Peptide-Based Therapeutic Vaccine Breaks Tolerance against Telomerase and Eradicates Established Tumor
Authors: Dosset Magalie , Godet Yann , Vauchy Charline , Beziaud Laurent , Lone Yu Chun , Sedlik Christine , Liard Christelle , Levionnois Emeline , Clerc Bertrand , Sandoval Federico , Daguindau Etienne , Wain-Hobson Simon , Tartour Eric , Langlade-Demoyen Pierre , Borg Christophe , Adotévi Olivier 
Published: October 2012

AbstractPurpose: To evaluate CD4+ helper functions and antitumor effect of promiscuous universal cancer peptides (UCP) derived from telomerase reverse transcriptase (TERT).Experimental Design: To evaluate the widespread immunogenicity of UCPs in humans, spontaneous T-cell responses against UCPs were measured in various types of cancers using T-cell proliferation and ELISPOT assays. The humanized HLA-DRB1*0101/HLA-A*0201 transgenic mice were used to study the CD4+ helper effects of UCPs on antitumor CTL responses. UCP-based antitumor therapeutic vaccine was evaluated using HLA-A*0201–positive B16 melanoma that express TERT.Results: The presence of a high number of UCP-specific CD4+ T cells was found in the blood of patients with various types of cancer. These UCP-specific T cells mainly produce IFN-γ and TNF-α. In HLA transgenic mice, UCP vaccinations induced high avidity CD4+ TH1 cells and activated dendritic cells that produced interleukin-12. UCP-based vaccination breaks self-tolerance against TERT and enhances primary and memory CTL responses. Furthermore, the use of UCP strongly improves the efficacy of therapeutic vaccination against established B16-HLA-A*0201 melanoma and promotes tumor infiltration by TERT-specific CD8+ T cells.Conclusions: Our results showed that UCP-based vaccinations strongly stimulate antitumor immune responses and could be used to design efficient immunotherapies in multiple types of cancers. Clin Cancer Res; 18(22); 6284–95. ©2012 AACR.
In VivoPhosphoantigen Levels in Bisphosphonate-Treated Human Breast Tumors Trigger Vγ9Vδ2 T-cell Antitumor Cytotoxicity through ICAM-1 Engagement
Authors: Benzaïd Ismahène , Mönkkönen Hannu , Bonnelye Edith , Mönkkönen Jukka , Clézardin Philippe 
Published: October 2012

AbstractPurpose: Nitrogen-containing bisphosphonates (N-BP) such as zoledronate and risedronate exhibit antitumor effects. They block the activity of farnesyl pyrophosphate synthase (FPPS) in the mevalonate pathway, leading to intracellular accumulation of mevalonate metabolites (IPP/ApppI), which are recognized as tumor phosphoantigens by Vγ9Vδ2 T cells. However, mechanisms responsible for Vγ9Vδ2 T-cell recognition of N-BP–treated tumors producing IPP/ApppI remain unclear.Experimental Design: The effects of N-BPs on Vγ9Vδ2 T-cell expansion and anticancer activity were evaluated in vitro and in animal models of human breast cancers. The modalities of recognition of breast tumors by Vγ9Vδ2 T cells in N-BP–treated animals were also examined.Results: We found a strong correlation between Vγ9Vδ2 T-cell anticancer activity and intracellular accumulation of IPP/ApppI in risedronate-treated breast cancer cells in vitro. In addition, following risedronate treatment of immunodeficient mice bearing human breast tumors, human Vγ9Vδ2 T cells infiltrated and inhibited growth of tumors that produced high IPP/ApppI levels but not those expressing low IPP/ApppI levels. The combination of doxorubicin with a N-BP improved, however, Vγ9Vδ2 T-cell cytotoxicity against breast tumors expressing low IPP/ApppI levels. Moreover, Vγ9Vδ2 T-cell cytotoxicity in mice treated with risedronate or zoledronate did not only depend on IPP/ApppI accumulation in tumors but also on expression of tumor cell surface receptor intercellular adhesion molecule-1 (ICAM-1), which triggered the recognition of N-BP–treated breast cancer cells by Vγ9Vδ2 T cells in vivo.Conclusion: These findings suggest that N-BPs can have an adjuvant role in cancer therapy by activating Vγ9Vδ2 T-cell cytotoxicity in patients with breast cancer that produces high IPP/ApppI levels after N-BP treatment. Clin Cancer Res; 18(22); 6249–59. ©2012 AACR.
Synthetic miR-34a Mimics as a Novel Therapeutic Agent for Multiple Myeloma:In VitroandIn VivoEvidence
Authors: Di Martino Maria T. , Leone Emanuela , Amodio Nicola , Foresta Umberto , Lionetti Marta , Pitari Maria R. , Cantafio Maria E. Gallo , Gullà Annamaria , Conforti Francesco , Morelli Eugenio , Tomaino Vera , Rossi Marco , Negrini Massimo , Ferrarini Manlio , Caraglia Michele , Shammas Masood A. , Munshi Nikhil C. , Anderson Kenneth C. , Neri Antonino , Tagliaferri Pierosandro , Tassone Pierfrancesco 
Published: October 2012

AbstractPurpose: Deregulated expression of miRNAs has been shown in multiple myeloma (MM). A promising strategy to achieve a therapeutic effect by targeting the miRNA regulatory network is to enforce the expression of miRNAs that act as tumor suppressor genes, such as miR-34a.Experimental Design: Here, we investigated the therapeutic potential of synthetic miR-34a against human MM cells in vitro and in vivo.Results: Either transient expression of miR-34a synthetic mimics or lentivirus-based miR-34a-stable enforced expression triggered growth inhibition and apoptosis in MM cells in vitro. Synthetic miR-34a downregulated canonic targets BCL2, CDK6, and NOTCH1 at both the mRNA and protein level. Lentiviral vector-transduced MM xenografts with constitutive miR-34a expression showed high growth inhibition in severe combined immunodeficient (SCID) mice. The anti-MM activity of lipidic-formulated miR-34a was further shown in vivo in two different experimental settings: (i) SCID mice bearing nontransduced MM xenografts; and (ii) SCID-synth-hu mice implanted with synthetic 3-dimensional scaffolds reconstituted with human bone marrow stromal cells and then engrafted with human MM cells. Relevant tumor growth inhibition and survival improvement were observed in mice bearing TP53-mutated MM xenografts treated with miR-34a mimics in the absence of systemic toxicity.Conclusions: Our findings provide a proof-of-principle that formulated synthetic miR-34a has therapeutic activity in preclinical models and support a framework for development of miR-34a–based treatment strategies in MM patients. Clin Cancer Res; 18(22); 6260–70. ©2012 AACR.