bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Specific Targeting of Pancreatic Cancer with Shiga Toxin B-Subunit
Authors: Maak Matthias , Nitsche Ulrich , Keller Larissa , Wolf Petra , Sarr Marianne , Thiebaud Marine , Rosenberg Robert , Langer Rupert , Kleeff Jörg , Friess Helmut , Johannes Ludger , Janssen Klaus-Peter 
Published: July 2011

Abstract
Pancreatic carcinoma is one of the most aggressive tumor entities, and standard chemotherapy provides only modest benefit. Therefore, specific targeting of pancreatic cancer for early diagnosis and therapeutic intervention is of great interest. We have previously shown that the cellular receptor for Shiga toxin B (STxB), the glycosphingolipid globotriaosylceramide (Gb3 or CD77) is strongly increased in colorectal adenocarcinoma and their metastases. Here, we report an upregulation of Gb3 in pancreatic adenocarcinoma (21 of 27 cases) as compared with matched normal tissue (n = 27). The mean expression was highly significantly increased from 30 ± 16 ng Gb3/mg tissue in normal pancreas to 61 ± 41 ng Gb3/mg tissue (mean ± SD, P = 0.0006), as evidenced by thin layer chromatography. Upregulation of Gb3 levels did not depend on tumor stage or grading and showed no correlation with clinical outcome. Tumor cells and endothelial cells were identified as the source of increased Gb3 expression by immunocytochemistry. Pancreatic cancer cell lines showed rapid intracellular uptake of STxB to the Golgi apparatus, following the retrograde pathway. The therapeutic application of STxB was tested by specific delivery of covalently coupled SN38, an active metabolite of the topoisomerase I inhibitor irinotecan. The cytotoxic effect of the STxB-SN38 compound in pancreatic cancer cell lines was increased more than 100-fold compared with irinotecan. Moreover, this effect was effectively blocked by competing incubation with nonlabeled STxB, showing the specificity of the targeting. Thus, STxB constitutes a promising new tool for specific targeting of pancreatic cancer. Mol Cancer Ther; 10(10); 1918–28. ©2011 AACR.
Focal multiple sclerosis lesions abound in ‘normal appearing white matter’
Authors: Mistry Niraj , Tallantyre Emma C , Dixon Jennifer E , Galazis Nicolas , Jaspan Tim , Morgan Paul S , Morris Peter , Evangelou Nikos 
Published: July 2011

Background: The ‘normal appearing white matter’ (NAWM) in multiple sclerosis (MS) is known to be abnormal using quantitative magnetic resonance (MR) techniques. The aetiology of the changes in NAWM remains debatable. Objective: To investigate whether high-field and ultra high-field T1-weighted magnetization prepared rapid acquisition gradient echo (MPRAGE) MRI enables detection of MS white matter lesions in areas defined as NAWM using high-field T2-weighted fluid attenuation inversion recovery (FLAIR) MRI; that is, to ascertain whether undetected lesions are likely contributors to the burden of abnormality in similarly defined NAWM. Methods: Fourteen MS patients underwent MRI scans using 3T FLAIR and MPRAGE and 7 Tesla (7T) MPRAGE sequences. Independent observers identified lesions on 3T FLAIR and (7T and 3T) MPRAGE images. The detection of every individual lesion was then compared for each image type. Results: We identified a total of 812 white matter lesions on 3T FLAIR. Using 3T MPRAGE, 186 additional lesions were detected that were not detected using 3T FLAIR. Using 7T MPRAGE, 231 additional lesions were detected that were not detected using 3T FLAIR. Conclusions: MRI with 3T and 7T MPRAGE enables detection of MS lesions in areas defined as NAWM using 3T FLAIR. Focal MS lesions contribute to the abnormalities known to exist in the NAWM.
A protocol for enumeration of aquatic viruses by epifluorescence microscopy using Anodisc™ 13 membranes
Authors: Budinoff Charles R , Loar Star N , LeCleir Gary R , Wilhelm Steven W , Buchan Alison 
Published: July 2011

Abstract

Background
Epifluorescence microscopy is a common method used to enumerate virus-like particles (VLP) from environmental samples and relies on the use of filter membranes with pore sizes < 0.02 μm; the most commonly used protocols employ 25 mm Anodisc™ membranes with a built-in support ring. Other filters with small pore sizes exist, including the 13 mm Anodisc™ membranes without a support ring. However, the use of these membranes for viral enumeration has not been previously reported.

Results
Here we describe a modified protocol for 13 mm Anodisc membranes that uses a custom filter holder that can be readily constructed in individual investigators' laboratories from commercially available Swinnex® filter holders. We compared VLP concentrations obtained from phage lysates and seawater samples using both Anodisc membranes, as well as Nuclepore™ small pore-size membranes (0.015 or 0.030 μm). The 13 mm Anodisc membranes gave comparable estimates of VLP abundance to those obtained with the 25 mm Anodisc membranes when similar staining methods were employed. Both Nuclepore membranes typically gave an order of magnitude lower VLP abundance values for environmental samples.

Conclusions
The 13 mm Anodisc membranes are less costly and require smaller sample volumes than their 25 mm counterpart making them ideal for large-scale studies and sample replication. This method increases the options of reliable approaches available for quantifying VLP from environmental samples.
Non-specific symptoms as clues to changes in emotional well-being
Authors: Matalon Andre , Kotliroff Andy , Blumberg Gari , Yaphe John , Kitai Eliezer 
Published: July 2011

Abstract

Background -
Somatic symptoms are a common reason for visits to the family physician. The aim of this study was to examine the relation between non-specific symptoms and changes in emotional well-being and the degree to which the physician considers the possibility of mental distress when faced with such patients.

Methods -
Patients who complained of two or more symptoms including headache, dizziness, fatigue or weakness, palpitations and sleep disorders over one year were identified from the medical records of a random sample of 45 primary care physicians. A control group matched for gender and age was selected from the same population. Emotional well-being was assessed using the MOS-SF 36 in both groups.

Results -
The study group and the control group each contained 110 patients. Completed MOS questionnaires were obtained from 92 patients, 48 patients with somatic symptoms and 44 controls. Sixty percent of the patients with somatic symptoms experienced decreased emotional well being compared to 25% in the control group (p = 0.00005). Symptoms of dizziness, fatigue and sleep disturbances were significantly linked with mental health impairments. Primary care physicians identified only 6 of 29 patients (21%) whose responses revealed functional limitations due to emotional problems as suffering from an emotional disorder and only 6 of 23 patients (26%) with a lack of emotional well being were diagnosed with an emotional disorder.

Conclusions -
Non-specific somatic symptoms may be clues to changes in emotional well-being. Improved recognition and recording of mental distress among patients who complain of these symptoms may enable better follow up and treatment.
ATA homozigosity in the IL-10gene promoter is a risk factor for schizophrenia in Spanish females: a case control study
Authors: Almoguera Berta , Riveiro-Alvarez Rosa , Lopez-Castroman Jorge , Dorado Pedro , Lopez-Rodriguez Rosario , Fernandez-Navarro Pablo , Baca-García Enrique , Fernandez-Piqueras Jose , Dal-Ré Rafael , Abad-Santos Francisco , LLerena Adrián , Ayuso Carmen ,   Spanish Consortium of Pharmacogenetics Research in Schizophrenia
Published: July 2011

AbstractBackgroundThreeIL-10gene promoter single nucleotide polymorphisms-1082G > A, -819C > Tand-592C > Aand the haplotypes they define in Caucasians,GCC, ACC, ATA, associated with different IL-10 production rates, have been linked to schizophrenia in some populations with conflicting results. On the basis of the evidence of the sex-dependent effect of certain genes in many complex diseases, we conducted a sex-stratified case-control association study to verify the linkage of theIL-10gene promoter SNPs and haplotypes with schizophrenia and the possible sex-specific genetic effect in a Spanish schizophrenic population.Methods241 DSM-IV diagnosed Spanish schizophrenic patients and 435 ethnically matched controls were genotyped for-1082G > Aand-592C > ASNPs. Chi squared tests were performed to assess for genetic association of alleles, genotypes and haplotypes with the disease.ResultsThe-1082Aallele (p = 0.027),A/A(p = 0.008) andATA/ATA(p = 0.003) genotypes were significantly associated with schizophrenia in females while neither allelic nor genotypic frequencies reached statistical significance in the male population.ConclusionsOur results highlight the hypothesis of an imbalance towards an inflammatory syndrome as the immune abnormality of schizophrenia. Anyway, a better understanding of the involvement of the immune system would imply the search of immune abnormalities in endophenotypes in whose sex and ethnicity might be differential factors. It also reinforces the need of performing complex gene studies based on multiple cytokine SNPs, including anti and pro-inflammatory, to clarify the immune system abnormalities direction in the etiology of schizophrenia.
Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer
Authors: Pértega-Gomes Nelma , Vizcaíno José R , Miranda-Gonçalves Vera , Pinheiro Céline , Silva Joana , Pereira Helena , Monteiro Pedro , Henrique Rui M , Reis Rui M , Lopes Carlos , Baltazar Fátima 
Published: July 2011

Abstract

Background
Monocarboxylate transporters (MCTs) are transmembrane proteins involved in the transport of monocarboxylates across the plasma membrane, which appear to play an important role in solid tumours, however the role of MCTs in prostate cancer is largely unknown. The aim of the present work was to evaluate the clinico-pathological value of monocarboxylate transporters (MCTs) expression, namely MCT1, MCT2 and MCT4, together with CD147 and gp70 as MCT1/4 and MCT2 chaperones, respectively, in prostate carcinoma.

Methods
Prostate tissues were obtained from 171 patients, who performed radical prostatectomy and 14 patients who performed cystoprostatectomy. Samples and clinico-pathological data were retrieved and organized into tissue microarray (TMAs) blocks. Protein expression was evaluated by immunohistochemistry in neoplastic (n = 171), adjacent non-neoplastic tissues (n = 135), PIN lesions (n = 40) and normal prostatic tissue (n = 14). Protein expression was correlated with patients' clinicopathologic characteristics.

Results
In the present study, a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue. All MCT isoforms and CD147 were expressed in PIN lesions. Importantly, for MCT2 and MCT4 the expression levels in PIN lesions were between normal and tumour tissue, which might indicate a role for these MCTs in the malignant transformation. Associations were found between MCT1, MCT4 and CD147 expressions and poor prognosis markers; importantly MCT4 and CD147 overexpression correlated with higher PSA levels, Gleason score and pT stage, as well as with perineural invasion and biochemical recurrence.

Conclusions
Our data provides novel evidence for the involvement of MCTs in prostate cancer. According to our results, we consider that MCT2 should be further explored as tumour marker and both MCT4 and CD147 as markers of poor prognosis in prostate cancer.
Polysaccharides from Agaricus bisporus and Agaricus brasiliensis show similarities in their structures and their immunomodulatory effects on human monocytic THP-1 cells
Authors: Smiderle Fhernanda R , Ruthes Andrea C , van Arkel Jeroen , Chanput Wasaporn , Iacomini Marcello , Wichers Harry J , Van Griensven Leo JLD 
Published: July 2011

AbstractBackgroundMushroom polysaccharides have traditionally been used for the prevention and treatment of a multitude of disorders like infectious illnesses, cancers and various autoimmune diseases. Crude mushroom extracts have been tested without detailed chemical analyses of its polysaccharide content. For the present study we decided to chemically determine the carbohydrate composition of semi-purified extracts from 2 closely related and well known basidiomycete species, i.e.Agaricus bisporusandA. brasiliensisand to study their effects on the innate immune system, in particular on thein vitroinduction of pro-inflammatory cytokines, using THP-1 cells.MethodsMushroom polysaccharide extracts were prepared by hot water extraction and precipitation with ethanol. Their composition was analyzed by GC-MS and NMR spectroscopy. PMA activated THP-1 cells were treated with the extracts under different conditions and the production of pro-inflammatory cytokines was evaluated by qPCR.ResultsSemi-purified polysaccharide extracts ofA. bisporusandA. brasiliensis(=blazei) were found to contain (1→6),(1→4)-linked α-glucan, (1→6)-linked β-glucan, and mannogalactan. Their proportions were determined by integration of1H-NMR signs, and were considerably different for the two species.A. brasiliensisshowed a higher content of β-glucan, whileA. bisporuspresented mannogalactan as its main polysaccharide. The extracts induced a comparable increase of transcription of the pro-inflammatory cytokine genes IL-1β and TNF-α as well as of COX-2 in PMA differentiated THP-1 cells. Pro-inflammatory effects of bacterial LPS in this assay could be reduced significantly by the simultaneous addition ofA. brasiliensisextract.ConclusionsThe polysaccharide preparations from the closely related speciesA. bisporusandA. brasiliensisshow major differences in composition:A. bisporusshows high mannogalactan content whereasA. brasiliensishas mostly β-glucan. Semi-purified polysaccharide extracts from bothAgaricusspecies stimulated the production of pro-inflammatory cytokines and enzymes, while the polysaccharide extract ofA. brasiliensisreduced synthesis of these cytokines induced by LPS, suggesting programmable immunomodulation.
The effects of polyunsaturated fatty acids in alcohol dependence treatment - a double-blind, placebo-controlled pilot study
Authors: Fogaça Marina N , Santos-Galduróz Ruth F , Eserian Jaqueline K , Galduróz José Carlos F 
Published: July 2011

AbstractBackgroundThe lipid fraction of cell membranes consists of polyunsaturated fatty acids (PUFAS), and chronic alcohol use alters it, modifying its permeability, what might contribute for the dysfunctional metabolism observed in the central nervous system of alcohol dependent patients. Therefore, the supplementation of PUFAS can be an important adjuvant in alcoholism treatment.MethodsThis was a placebo controlled, double blind, randomized study where, 80 alcohol dependent patients, according to DSM-IV, were allocated in four groups with 20 patient each: 'PUFAS', 'Naltrexone', 'Naltrexone + PUFAS' and 'Placebo'. Those substances were administered for 90 days and scales were applied to assess patients craving (OCDS) and alcohol dependence severity (SADD) at baseline and after 90 days. PUFAS serum levels were assessed before and after treatment by high performance liquid chromatography assay.ResultsForty-three patients completed the trial. There was a significant improvement over time on drinking days, SADD and OCDS scores in all groups (p < 0.001). The drinking days comparison between groups did not show statistical significant difference. The same effect was observed for compulsion (OCDS) and severity of dependence scale (SADD). The serum levels of PUFAS increased in all the supplemented groups after treatment, although not significantly.ConclusionsThe oral supplementation of 2 g PUFAS for 3 months did not significantly differ from placebo in reducing the amount of alcohol ingestion, or OCDS and SADD scores in a group of alcohol dependent patient.Trial registrationNCT01211769
Effect of α-linolenic acid on endoplasmic reticulum stress-mediated apoptosis of palmitic acid lipotoxicity in primary rat hepatocytes
Authors: Zhang Yong , Yang Xia , Shi Hongyang , Dong Lei , Bai Jian 
Published: July 2011

Abstract

Background
Hepatic inflammation and degeneration induced by lipid depositions may be the major cause of nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the effects of saturated and unsaturated fatty acids (FA) on apoptosis in primary rat hepatocytes.

Methods
The primary rat hepatocytes were treated with palmitic acid and/or α-linolenic acid in vitro. The expression of proteins associated with endoplasmic reticulum (ER) stress, apoptosis, caspase-3 levels were detected after the treatment.

Results
The treatment with palmitic acid produced a significant increase in cell death. The unfolded protein response (UPR)-associated genes CHOP, GRP78, and GRP94 were induced to higher expression levels by palmitic acid. Co-treatment with α-linolenic acid reversed the apoptotic effect and levels of all three indicators of ER stress exerted by palmitic acid. Tunicamycin, which induces ER stress produced similar effects to those obtained using palmitic acid; its effects were also reversed by α-linolenic acid.

Conclusions
α-Linolenic acid may provide a useful strategy to avoid the lipotoxicity of dietary palmitic acid and nutrient overload accompanied with obesity and NAFLD.
Biobanking after robotic-assisted radical prostatectomy: a quality assessment of providing prostate tissue for RNA studies
Authors: Dev Harveer , Rickman David , Sooriakumaran Prasanna , Srivastava Abhishek , Grover Sonal , Leung Robert , Kim Robert , Kitabayashi Naoki , Esqueva Raquel , Park Kyung , Padilla Jessica , Rubin Mark , Tewari Ashutosh 
Published: July 2011

Abstract

Background
RNA quality is believed to decrease with ischaemia time, and therefore open radical prostatectomy has been advantageous in allowing the retrieval of the prostate immediately after its devascularization. In contrast, robotic-assisted laparoscopic radical prostatectomies (RALP) require the completion of several operative steps before the devascularized prostate can be extirpated, casting doubt on the validity of this technique as a source for obtaining prostatic tissue. We seek to establish the integrity of our biobanking process by measuring the RNA quality of specimens derived from robotic-assisted laparoscopic radical prostatectomy.

Methods
We describe our biobanking process and report the RNA quality of prostate specimens using advanced electrophoretic techniques (RNA Integrity Numbers, RIN). Using multivariate regression analysis we consider the impact of various clinicopathological correlates on RNA integrity.

Results
Our biobanking process has been used to acquire 1709 prostates, and allows us to retain approximately 40% of the prostate specimen, without compromising the histopathological evaluation of patients. We collected 186 samples from 142 biobanked prostates, and demonstrated a mean RIN of 7.25 (standard deviation 1.64) in 139 non-stromal samples, 73% of which had a RIN ≥ 7. Multivariate regression analysis revealed cell type - stromal/epithelial and benign/malignant - and prostate volume to be significant predictors of RIN, with unstandardized coefficients of 0.867(p = 0.001), 1.738(p < 0.001) and -0.690(p = 0.009) respectively. A mean warm ischaemia time of 120 min (standard deviation 30 min) was recorded, but multivariate regression analysis did not demonstrate a relationship with RIN within the timeframe of the RALP procedure.

Conclusions
We demonstrate the robustness of our protocol - representing the concerted efforts of dedicated urology and pathology departments - in generating RNA of sufficient concentration and quality, without compromising the histopathological evaluation and diagnosis of patients. The ischaemia time associated with our prostatectomy technique using a robotic platform does not negatively impact on biobanking for RNA studies.
Convergence theorems of solutions of a generalized variational inequality
Authors: Yu Li , Liang Ma 
Published: July 2011

AbstractThe convex feasibility problem (CFP) of finding a point in the nonempty intersection "Equation missing" is considered, where r ≥ 1 is an integer and each C
m
is assumed to be the solution set of a generalized variational inequality. Let C be a nonempty closed and convex subset of a real Hilbert space H. Let A
m
, B
m
: C → H be relaxed cocoercive mappings for each 1 ≤ m ≤ r. It is proved that the sequence {x
n
} generated in the following algorithm:"Equation missing"where u ∈ C is a fixed point, {α
n
}, {β
n
}, {γ
n
}, {δ(1,n)}, ..., and {δ(r,n)} are sequences in (0, 1) and "Equation missing", "Equation missing" are positive sequences, converges strongly to a solution of CFP provided that the control sequences satisfies certain restrictions.2000 AMS Subject Classification: 47H05; 47H09; 47H10.
Common fixed points for some generalized multivalued nonexpansive mappings in uniformly convex metric spaces
Authors: Laowang Worawut , Panyanak Bancha 
Published: July 2011

AbstractAbkar and Eslamian (Nonlinear Anal. TMA,74, 1835-1840, 2011) prove that ifKis a nonempty bounded closed convex subset of a complete CAT(0) spaceX,t:K→Kis a single-valued quasi-nonexpansive mapping andT:K→KC(K) is a multivalued mapping satisfying conditions (E) and (Cλ) for someλ∈ (0, 1) such thattandTcommute weakly, then there exists a pointz∈Ksuch thatz=t(z) ∈T(z). In this paper, we extend this result to the general setting of uniformly convex metric spaces. Nevertheless, condition (E) ofTcan be weakened to the strongly demiclosedness ofI-T.