bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound Molecular Imaging in a Human CD276 Expression–Modulated Murine Ovarian Cancer Model
Authors: Lutz Amelie M. , Bachawal Sunitha V. , Drescher Charles W. , Pysz Marybeth A. , Willmann Jürgen K. , Gambhir Sanjiv Sam 
Published: January 2014

AbstractPurpose: To develop a mouse ovarian cancer model that allows modulating the expression levels of human vascular targets in mouse xenograft tumors and to test whether expression of CD276 during tumor angiogenesis can be visualized by molecularly targeted ultrasound in vivo.Experimental Design: CD276-expressing MILE SVEN 1 (MS1) mouse endothelial cells were engineered and used for coinjection with 2008 human ovarian cancer cells for subcutaneous xenograft tumor induction in 15 nude mice. Fourteen control mice were injected with 2008 cells only. After confirming their binding specificity in flow chamber cell attachment studies, anti-CD276 antibody-functionalized contrast microbubbles were used for in vivo CD276-targeted contrast-enhanced ultrasound imaging.Results: CD276-targeted ultrasound imaging signal was significantly higher (P = 0.006) in mixed MS1/2008 tumors than in control tumors. Compared with control microbubbles, the ultrasound signal using CD276-targeted microbubbles was significantly higher (P = 0.002), and blocking with purified anti-CD276 antibody significantly decreased (P = 0.0096) the signal in mixed MS1/2008 tumors. Immunofluorescence analysis of the tumor tissue confirmed higher quantitative immunofluorescence signal in mixed MS1/2008 tumors than in control 2008 only tumors, but showed not significantly different (P = 0.54) microvessel density.Conclusions: Our novel small animal model allows for modulating the expression of human tumor–associated vascular endothelial imaging targets in a mouse host and these expression differences can be visualized noninvasively by ultrasound molecular imaging. The animal model can be applied to other human vascular targets and may facilitate the preclinical development of new imaging probes such as microbubbles targeted at human vascular markers not expressed in mice. Clin Cancer Res; 20(5); 1313–22. ©2014 AACR.
Gene-Modified Human α/β-T Cells Expressing a Chimeric CD16-CD3ζ Receptor as Adoptively Transferable Effector Cells for Anticancer Monoclonal Antibody Therapy
Authors: Ochi Fumihiro , Fujiwara Hiroshi , Tanimoto Kazushi , Asai Hiroaki , Miyazaki Yukihiro , Okamoto Sachiko , Mineno Junichi , Kuzushima Kiyotaka , Shiku Hiroshi , Barrett John , Ishii Eiichi , Yasukawa Masaki 
Published: January 2014

Abstract
The central tumoricidal activity of anticancer monoclonal antibodies (mAb) is exerted by FcγR IIIa (CD16)–expressing effector cells in vivo via antibody-dependent cell-mediated cytotoxicity (ADCC), as observed for natural killer (NK) cells. In practice, chemotherapy-induced leukopenia and exhaustion of NK cells resulting from ADCC often hamper the clinical efficacy of cancer treatment. To circumvent this drawback, we examined in vivo the feasibility of T cells, gene-modified to express a newly generated affinity-matured (158V/V) chimeric CD16-CD3ζ receptor (cCD16ζ-T cells), as a transferable alternative effector for cancer mAb therapy. cCD16ζ-T cells were readily expandable in ex vivo culture using anti-CD2/CD3/CD28 beads and recombinant human interleukin-2 (rhIL-2), and they successfully displayed ADCC-mediated tumoricidal activity in vitro. During ADCC, ligation of opsonized cancer cells to the introduced cCD16ζ-T cells stimulated the effector cells to produce proinflammatory cytokines and release toxic granules through the activation of the Nuclear factor of activated T cells (NFAT) pathway after phosphorylation of the CD3ζ chain. In parallel, these stimulated cCD16ζ-T cells transiently proliferated and differentiated into effector memory T cells. In contrast, NK cells activated by rhIL-2 displayed similar ADCC activity, but failed to proliferate. Human cCD16ζ-T cells infused concomitantly with anti-CD20 mAb synergistically inhibited the growth of disseminated Raji cells, a CD20+ lymphoma cell line, in immunodeficient mice, whereas similarly infused rhIL-2–treated NK cells survived for a shorter time and displayed less effective tumor suppression. Our findings strongly suggest the clinical feasibility of cCD16ζ-T cells as adoptively transferable ADCC effector cells that could potentially enhance the clinical responses mediated by currently available anticancer mAbs. Cancer Immunol Res; 2(3); 249–62. ©2014 AACR.
Intestinal Lipid Handling
Authors: Veilleux Alain , Grenier Émilie , Marceau Picard , Carpentier André C. , Richard Denis , Levy Emile 
Published: January 2014

Objective—
Animal models have evidenced the role of intestinal triglyceride-rich lipoprotein overproduction in dyslipidemia. However, few studies have confronted this issue in humans and disclosed the intrinsic mechanisms. This work aimed to establish whether intestinal insulin resistance modifies lipid and lipoprotein homeostasis in the intestine of obese subjects.

Approach and Results—
Duodenal specimens obtained from 20 obese subjects undergoing bariatric surgery were paired for age, sex, and body mass index with or without insulin resistance, as defined by the homeostasis model assessment of insulin resistance. Insulin signaling, biomarkers of inflammation and oxidative stress, and lipoprotein assembly were assessed. The intestine of insulin-resistant subjects showed defects in insulin signaling as demonstrated by reduced protein kinase B phosphorylation and increased p38 mitogen-activated protein kinase phosphorylation, likely as the result of high oxidative stress (evidenced by malondialdehyde and conjugated dienes) and inflammation (highlighted by nuclear factor-κB, tumor necrosis factor-α, interleukin-6, intercellular adhesion molecule-1, and cyclooxygenase-2). Enhanced de novo lipogenesis rate and apolipoprotein B-48 biogenesis along with exaggerated triglyceride-rich lipoprotein production were observed, concomitantly with the high expression levels of liver and intestinal fatty acid–binding proteins and microsomal transfer protein. The presence of an aberrant intracellular cholesterol transport/metabolism was also suggested by the reduced expression of ATP-binding cassette A1 transporter and proprotein convertase subtilisin/kexin type 9.

Conclusions—
According to the present data, the small intestine may be classified as an insulin-sensitive tissue. Dysregulation of intestinal insulin signaling, possibly triggered by oxidative stress and inflammation, was associated with exaggerated lipogenesis and lipoprotein synthesis, which may represent a key mechanism for atherogenic dyslipidemia in patients with metabolic syndrome.
ST-Elevation Myocardial Infarction Diagnosed After Hospital Admission
Authors: Garberich Ross F. , Traverse Jay H. , Claussen Michael T. , Rodriguez Gabriel , Poulose Anil K. , Chavez Ivan J. , Rutten-Ramos Stephanie , Hildebrandt David A. , Henry Timothy D. 
Published: January 2014

Background—
Treatment times for ST-elevation myocardial infarction (STEMI) patients presenting to percutaneous coronary intervention hospitals have improved dramatically over the past 10 years, particularly for patients using emergency medical services. Limited data exist regarding treatment times and outcomes for patients who develop STEMI after hospital admission.

Methods and Results—

With the use of a comprehensive prospective regional STEMI program database, we evaluated the characteristics and outcomes for patients who develop STEMI after hospital admission. Of the 3795 consecutive STEMI patients treated by the use of the Minneapolis Heart Institute regional STEMI program from March 2003 to January 2013, 990 (26.1%) presented initially to the percutaneous coronary intervention facility, including 640 arriving via emergency medical services, 267 self/family driven, and 83 already admitted to the hospital. Patients with in-hospital presentation were older with higher body mass indexes, were more likely to have hypertension, and to present with pre–percutaneous coronary intervention cardiac arrest and cardiogenic shock. Door-to-balloon times (diagnostic ECG-to-balloon for in-hospital patients) were longer than for patients using emergency medical services (76 versus 51 minutes;
P
<0.001), but similar to self/family–driven patients (76 versus 66 minutes;
P
=0.13). In-hospital patients had longer lengths of stay (5 versus 3 versus 3 days;
P
<0.001) and higher 1-year mortality (16.9% versus 10.3% versus 7.1%;
P
=0.032). These patients frequently had high-risk and complex reasons for admission, including 30.1% with acute coronary syndrome, 22.9% postsurgery, 13.3% respiratory failure, and 8.4% ventricular fibrillation.

Conclusions—
Patients who develop STEMI while in-hospital represent a unique, high-risk subset of patients. They have increased treatment time and lengths of stay and higher mortality rates than the patients presenting via emergency medical services or who are self/family driven.
Role of Extracellular RNA and TLR3‐Trif Signaling in Myocardial Ischemia–Reperfusion Injury
Authors: Chen Chan , Feng Yan , Zou Lin , Wang Larry , Chen Howard H. , Cai Jia‐Yan , Xu Jun‐Mei , Sosnovik David E. , Chao Wei 
Published: January 2014

Background

Toll‐like receptor 3 (
TLR
3) was originally identified as the receptor for viral
RNA
and represents a major host antiviral defense mechanism.
TLR
3 may also recognize extracellular
RNA
(ex
RNA
) released from injured tissues under certain stress conditions. However, a role for ex
RNA
and
TLR
3 in the pathogenesis of myocardial ischemic injury has not been tested. This study examined the role of ex
RNA
and
TLR
3 signaling in myocardial infarction (MI), apoptosis, inflammation, and cardiac dysfunction during ischemia‐reperfusion (I/R) injury.

Methods and Results

Wild‐type (
WT
),
TLR
3
−/−
, Trif
−/−
, and interferon (
IFN
) α/β receptor‐1 deficient (
IFNAR
1
−/−
) mice were subjected to 45 minutes of coronary artery occlusion and 24 hours of reperfusion. Compared with
WT
,
TLR
3
−/−
or Trif
−/−
mice had smaller MI and better preserved cardiac function. Surprisingly, unlike
TLR
(2/4)‐MyD88 signaling, lack of
TLR
3‐Trif signaling had no impact on myocardial cytokines or neutrophil recruitment after I/R, but myocardial apoptosis was significantly attenuated in Trif
−/−
mice. Deletion of the downstream
IFNAR
1 had no effect on infarct size. Importantly, hypoxia and I/R led to release of
RNA
including micro
RNA
from injured cardiomyocytes and ischemic heart, respectively. Necrotic cardiomyocytes induced a robust and dose‐dependent cytokine response in cultured cardiomyocytes, which was markedly reduced by RNase but not DNase, and partially blocked in
TLR
3‐deficient cardiomyocytes. In vivo, RNase administration reduced serum
RNA
level, attenuated myocardial cytokine production, leukocytes infiltration and apoptosis, and conferred cardiac protection against I/R injury.

Conclusion

TLR
3‐Trif signaling represents an injurious pathway during I/R. Extracellular
RNA
released during I/R may contribute to myocardial inflammation and infarction.
How specific are venous symptoms for diagnosis of chronic venous disease?
Authors: Van der Velden SK , Shadid NH , Nelemans PJ , Sommer A 
Published: January 2014

Objective The objective of this study is to evaluate whether and which ‘venous’ symptoms are characteristic for patients affected with chronic venous disease compared to patients with other diseases of the lower limbs (e.g. arthrosis, peripheral arterial disease, spinal disc herniation). Methods A cross-sectional study was performed to compare the frequency of venous symptoms among 76 patients with chronic venous disease and reflux and 74 patients with other diseases of the legs without reflux. The VEINES-Sym of the VEINES-QOL/Sym questionnaire was used to evaluate the frequency of symptoms. Demographic, clinical classification and ultrasound findings were also noted. Results A total of 122 patients were included for analysis (response rate of 87%). Presence of venous symptoms was slightly more often reported in the chronic venous disease group than in the non-chronic venous disease group, but differences were small and statistically non-significant. Severity of chronic venous disease as classified by the CEAP classification was not associated with higher proportions of patients reporting symptoms than in non-chronic venous disease patients, except for swelling ( p = .016) and itching ( p = .007) in C3-C6 patients. The largest difference between the chronic venous disease and non-chronic venous disease group was observed for the time of the day at which symptoms were most intense; patients with chronic venous disease were more likely to experience symptoms at the end of the day ( p < .001). Conclusions The small differences in prevalence of reported ‘venous’ symptoms between chronic venous disease patients and patients with other diseases of the legs suggest that these symptoms may be less specific for patients with chronic venous disease and refluxing veins than is usually assumed.
Transurethral seminal vesiculoscopy in the diagnosis and treatment of intractable seminal vesiculitis
Authors: Liu Bianjiang , Li Jie , Li Pengchao , Zhang Jiexiu , Song Ninghong , Wang Zengjun , Yin Changjun 
Published: January 2014

Objective To investigate the efficacy and safety of transurethral seminal vesiculoscopy in the diagnosis and treatment of intractable seminal vesiculitis. Methods This prospective observational study enrolled patients with intractable seminal vesiculitis. The transurethral seminal vesiculoscope was inserted into the bilateral ejaculatory ducts and seminal vesicles, via the urethra. The ejaculatory ducts and seminal vesicles were visualized to confirm the diagnosis of seminal vesiculitis and to determine the cause of the disease. The seminal vesicles were washed repeatedly using 0.90% (w/v) sodium chloride before a 0.50% (w/v) levofloxacin solution was injected into the seminal vesicles. Results A total of 114 patients participated in the study and 106 patients underwent bilateral seminal vesiculoscopy. Six patients with postoperative painful ejaculation were treated successfully with oral antibiotics and α-blockers. Two patients with postoperative epididymitis were treated successfully with a 1-week course of antibiotics. Haematospermia was alleviated in 94 of 106 patients (89%), and their pain and discomfort had either disappeared or had been obviously relieved, following treatment. Conclusion Transurethral seminal vesiculoscopy is effective for diagnosing and treating intractable seminal vesiculitis.
Identification of RNA silencing components in soybean and sorghum
Authors: Liu Xiang , Lu Tao , Dou Yongchao , Yu Bin , Zhang Chi 
Published: January 2014

Abstract

Background
RNA silencing is a process triggered by 21–24 small RNAs to repress gene expression. Many organisms including plants use RNA silencing to regulate development and physiology, and to maintain genome stability. Plants possess two classes of small RNAs: microRNAs (miRNAs) and small interfering RNAs (siRNAs). The frameworks of miRNA and siRNA pathways have been established in the model plant, Arabidopsis thaliana (Arabidopsis).

Results
Here we report the identification of putative genes that are required for the generation and function of miRNAs and siRNAs in soybean and sorghum, based on knowledge obtained from Arabidopsis. The gene families, including DCL, HEN1, SE, HYL1, HST, RDR, NRPD1, NRPD2/NRPE2, NRPE1, and AGO, were analyzed for gene structures, phylogenetic relationships, and protein motifs. The gene expression was validated using RNA-seq, expressed sequence tags (EST), and reverse transcription PCR (RT-PCR).

Conclusions
The identification of these components could provide not only insight into RNA silencing mechanism in soybean and sorghum but also basis for further investigation. All data are available at http://sysbio.unl.edu/.
Substrate-dependent gene regulation of self-assembled human MSC spheroids on chitosan membranes
Authors: Yeh Hsi-Yi , Liu Bing-Hsien , Sieber Martin , Hsu Shan-hui 
Published: January 2014

AbstractBackgroundThree-dimensional (3D) multicellular spheroids of mesenchymal stem cells (MSCs) are generally regarded to have beneficial properties over MSCs in monolayer. Recent literatures have documented that MSCs can self-assemble into 3D spheroids with a greater capacity for differentiation into various cell types when grown on chitosan (CS), a biopolymer. The genomic modulation occurring in these MSC spheroids is thus of essential importance for understanding their uniqueness and therapeutic potentials. In this study, 3D spheroids self-assembled from human umbilical cord MSCs grown on CS membranes were analyzed by mRNA as well as microRNA microarrays, which helped identify the critical signaling events that may alter the cellular functions during the spheroid forming process.ResultsGenes screened from mRNA and microRNA cross-correlation analyses were further confirmed with the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) analysis. Results revealed the regulation of a significant number of calcium-associated genes, which suggested the crucial role of calcium signaling in CS-derived MSC spheroids. In addition, many genes associated with the multilineage differentiation capacities and those associated with the antiinflammatory and antitumor properties of MSCs were upregulated. The genetic modulation was significantly more remarkable and endured longer for MSC spheroids derived on CS substrates compared to those derived on a non-adherent (polyvinyl alcohol) substrate.ConclusionsBased on the study, the culture substrates used to prepare 3D MSC spheroids may predefine their properties through cell-substrate interaction.
Loss of molars early in life develops behavioral lateralization and impairs hippocampus-dependent recognition memory
Authors: Kawahata Masatsuna , Ono Yumie , Ohno Akinori , Kawamoto Shoichi , Kimoto Katsuhiko , Onozuka Minoru 
Published: January 2014

Abstract

Background
Using senescence-accelerated mouse prone 8 (SAMP8), we examined whether reduced mastication from a young age affects hippocampal-dependent cognitive function. We anesthetized male SAMP8 mice at 8 weeks of age and extracted all maxillary molar teeth of half the animals. The other animals were treated similarly, except that molar teeth were not extracted. At 12 and 24 weeks of age, their general behavior and their ability to recognize novel objects were tested using the open-field test (OFT) and the object-recognition test (ORT), respectively.

Results
The body weight of molarless mice was reduced significantly compared to that of molar-intact mice after the extraction and did not recover to the weight of age-matched molar-intact mice throughout the experimental period. At 12 weeks of age, molarless mice showed significantly greater locomotor activity in the OFT than molar-intact mice. However, the ability of molarless mice to discriminate a novel object in the ORT was impaired compared to that of molar-intact mice. The ability of both molarless and molar-intact SAMP8 mice to recognize objects was impaired at 24 weeks of age. These results suggest that molarless SAMP8 mice develop a deficit of cognitive function earlier than molar-intact SAMP8 mice. Interestingly, both at 12 and 24 weeks of age, molarless mice showed a lateralized preference of object location in the encoding session of the ORT, in which two identical objects were presented. Their lateralized preference of object location was positively correlated with the rightward turning-direction preference, which reached statistical significance at 24 weeks of age.

Conclusions
Loss of masticatory function in early life causes malnutrition and chronic stress and impairs the ability to recognize novel objects. Hyperactivation and lateralized rotational behavior are commonly observed with dysfunction of the dopaminergic system, therefore, reduced masticatory function may deplete the mesolimbic and mesocorticolimbic dopaminergic systems to impair the cognitive functions of selective attention and recognition memory in the prefrontal cortex and the hippocampus.
Renal nerve ultrastructural alterations in short term and long term experimental diabetes
Authors: Sato Karina Laurenti , Sanada Luciana Sayuri , Ferreira Renata da Silva , de Marco Maria Carolina del Bem de Barros Ol , Castania Jaci Airton , Salgado Helio Cesar , Nessler Randy Alan , Fazan Valeria Paula Sassoli 
Published: January 2014

Abstract

Background
Despite the evidence that renal hemodynamics is impaired in experimental diabetes, associated with glomeruli structural alterations, renal nerves were not yet investigated in experimental models of diabetes and the contribution of nerve alterations to the diabetic nephropathy remains to be investigated. We aimed to determine if ultrastructural morphometric parameters of the renal nerves are affected by short term and/or long term experimental diabetes and if insulin treatment reverses these alterations. Left renal nerves were evaluated 15 days or 12 weeks (N = 10 in each group) after induction of diabetes, with a single injection of streptozotocin (STZ). Control rats (N = 10 in each group) were injected with vehicle (citrate buffer). Treated animals (N = 10 in each group) received a single subcutaneous injection of insulin on a daily basis. Arterial pressure, together with the renal nerves activity, was recorded 15 days (short-term) or 12 weeks (long-term) after STZ injection. After the recordings, the renal nerves were dissected, prepared for light and transmission electron microscopy, and fascicle and fibers morphometry were carried out with computer software.

Results
The major diabetic alteration on the renal nerves was a small myelinated fibers loss since their number was smaller on chronic diabetic animals, the average morphometric parameters of the myelinated fibers were larger on chronic diabetic animals and distribution histograms of fiber diameter was significantly shifted to the right on chronic diabetic animals. These alterations began early, after 15 days of diabetes induction, associated with a severe mitochondrial damage, and were not prevented by conventional insulin treatment.

Conclusions
The experimental diabetes, induced by a single intravenous injection of STZ, in adult male Wistar rats, caused small fiber loss in the renal nerves, probably due to the early mitochondrial damage. Conventional treatment with insulin was able to correct the weight gain and metabolic changes in diabetic animals, without, however, correcting and / or preventing damage to the thin fibers caused by STZ-induced diabetes. The kidney innervation is impaired in this diabetic model suggesting that alterations of the renal nerves may play a role in the development of the diabetic nephropathy.