gebhart/patrepeval huggingface dataset:
Expression of interleukin 8 and not parathyroid hormone-related protein by human breast cancer cells correlates with bone metastasis in vivo. (2002)

Metastasis is the process by which tumor cells spread from their site of origin to distant sites after gaining access to the circulatory system. An understanding of the factors contributing to the metastatic potential of breast cancer cells to bone will enhance the prospect of developing new therapies that impede metastasis. In this study, we have used an in vivo selection scheme involving left cardiac ventricle injection into nude mice to identify a highly metastatic human breast cancer cell line (MDA-MET) from a less metastatic (MDA-231) parental cell line. In this model, tumor-bearing mice exhibit features similar to those associated with human metastatic bone disease such as osteolytic bone destruction. After inoculation, MDA-MET cells form devastating lesions within 4 weeks, whereas the parental cells do not, even after 10 weeks. In vitro, the MDA-MET cells have a similar growth rate to the parental MDA-231 cells yet demonstrate distinct adhesive and invasive phenotypes. MDA-MET cells show increased early adhesion to type IV collagen and are significantly more invasive through Matrigel than MDA-231 cells. Analysis of the gene expression profile in the metastatic MDA-MET versus poorly metastatic MDA-231 cells identified relatively few genes whose expression was altered >2-fold. Of particular interest was the lack of parathyroid hormone-related protein (PTHrP) mRNA expression, which was supported at the protein level by immunoradiometric assay. These data support the idea that PTHrP is not predictive of the metastasis of human breast cancer to bone. Another important difference between the two cell lines was the elevated expression by MDA-MET cells of the cytokine IL-8. Reverse transcriptase-PCR and ELISA confirmed the increased expression of IL-8 in MDA-MET cells. In addition, IL-8 mRNA expression is also elevated in a variety of human cancer cell lines with different metastatic potential in vivo. These experiments suggest that the elevated expression of IL-8 (and not PTHrP) by MDA-MET cells is a phenotypic change that may be related to their enhanced ability to metastasize to the skeleton.
Reciprocal Regulation of Endothelial Nitric-oxide Synthase by Ca2+-Calmodulin and Caveolin (1997)

The endothelial nitric-oxide synthase (eNOS) is a key determinant of vascular homeostasis. Like all known nitric-oxide synthases, eNOS enzyme activity is dependent on Ca2+-calmodulin. eNOS is dynamically targeted to specialized cell surface signal-transducing domains termed plasmalemmal caveolae and interacts with caveolin, an integral membrane protein that comprises a key structural component of caveolae. We have previously reported that the association between eNOS and caveolin is quantitative and tissue-specific (Feron, O., Belhassen, L., Kobzick, L., Smith, T. W., Kelly, R. A., and Michel, T. (1996) J. Biol. Chem. 271, 22810-22814). We now report that in endothelial cells the interaction between eNOS and caveolin is importantly regulated by Ca2+-calmodulin. Addition of calmodulin disrupts the heteromeric complex formed between eNOS and caveolin in a Ca2+-dependent fashion. In addition, overexpression of caveolin markedly attenuates eNOS enzyme activity, but this inhibition is reversed by purified calmodulin. Caveolin overexpression does not affect the activity of the other NOS isoforms, suggesting eNOS-specific inhibition of NO synthase by caveolin. We propose a model of reciprocal regulation of eNOS in endothelial cells wherein the inhibitory eNOS-caveolin complex is disrupted by binding of Ca2+-calmodulin to eNOS, leading to enzyme activation. These findings may have broad implications for the regulation of Ca2+-dependent signal transduction in plasmalemmal caveolae.
ANTITUMORAL ACTIVITY OF FLAVONE L-86-8275 (1995)

L 86-8275, a flavone of novel structure, was shown to be a kinase inhibitor and to possess surprising potent antiproliferative potency (IC50=0.1-0.15 mu M) on various tumor cell lines after long period of incubation. Short period of incubation was significantly less effective (IC50=133 mu M). In vitro L 86-8275 showed almost no cross-resistance on L 1210 mouse leukemia tumor cell line 110-fold resistant to doxorubicin. In vivo significant antitumoral effects were seen with xenografted lung, colon, mammary and ovarian tumors as well as glioblastoma. T/C values ranged from 29 to 86% and were comparable to standard chemotherapeutic treatment. Optimal schedule required daily oral application of L 86-8275.
Improved nucleic acid descriptors for siRNA efficacy prediction (2012)

Although considerable progress has been made recently in understanding how gene silencing is mediated by the RNAi pathway, the rational design of effective sequences is still a challenging task. In this article, we demonstrate that including three-dimensional descriptors improved the discrimination between active and inactive small interfering RNAs (siRNAs) in a statistical model. Five descriptor types were used: (i) nucleotide position along the siRNA sequence, (ii) nucleotide composition in terms of presence/absence of specific combinations of di- and trinucleotides, (iii) nucleotide interactions by means of a modified auto- and cross-covariance function, (iv) nucleotide thermodynamic stability derived by the nearest neighbor model representation and (v) nucleic acid structure flexibility. The duplex flexibility descriptors are derived from extended molecular dynamics simulations, which are able to describe the sequence-dependent elastic properties of RNA duplexes, even for non-standard oligonucleotides. The matrix of descriptors was analysed using three statistical packages in R (partial least squares, random forest, and support vector machine), and the most predictive model was implemented in a modeling tool we have made publicly available through SourceForge. Our implementation of new RNA descriptors coupled with appropriate statistical algorithms resulted in improved model performance for the selection of siRNA candidates when compared with publicly available siRNA prediction tools and previously published test sets. Additional validation studies based on in-house RNA interference projects confirmed the robustness of the scoring procedure in prospective studies.
Bone Morphogenetic Protein Excipients: Comparative Observations on Poloxamer (2000)

Clinicians await the availability of synthetic bioimplants that will replace the need for autogeneic bone grafts in bone reconstructive surgery. For more than a decade, researchers have evaluated delivery vehicles for the tissue morphogen bone morphogenetic protein. The object of this investigation was to measure induced bone development when bone morphogenetic protein was delivered by human tendon collagen, human demineralized bone matrix, hydroxyapatite, a composite of human tendon collagen and human demineralized bone matrix (tendon collagen + demineralized bone matrix), Poloxamer 407, and a composite of human demineralized bone matrix and Poloxamer 407. Sixty-three adult male Swiss Webster mice (Harlan Sprague-Dawley, Indianapolis, Ind.) received 126 implants. The animals were divided into seven groups of nine animals, depending on carrier (six carriers plus the positive control group) used. Each animal received a bone morphogenetic protein-enhanced carrier in one hindquarter muscle mass, with the contralateral leg being implanted with the carrier alone. Implants were evaluated by quantitative radiomorphometry validated by histologic methods. Radiographically, no significant differences were identified among any of the implants evaluated (p > 0.05). Histomorphometric analysis demonstrated that Poloxamer 407 was significantly (p < 0.05) better at delivering bone morphogenetic protein than the other carriers involved in this investigation. The new bone developed in a tubular or spherical shape. Interaction of endogenous and exogenous delivery systems seems to be essential for optimal transmission of bone morphogenetic protein. The importance of the excipient to deliver bone morphogenetic protein and develop a bone morphogenetic protein concentration gradient has been emphasized by other investigators and confirmed by our research on poloxamer. With further research on the physicochemical mechanisms of localization and transmission of bone morphogenetic protein, it may be possible to avoid hazardous operations with autogeneic bone.
A high-speed and high-precision Winner-Select-Output (WSO) ASIC (1998)

The design and performance characteristics of a 16-channel Winner-Select-Output (WSO) ASIC are presented. The WSO ASIC does a fast comparison of 16 analog input voltages, outputs the maximum signal, the "second" maximum (partner) signal, and their addresses. The WSO ASIC chip is a key component of an analog electronics system being developed for a depth of interaction (DOI) PET detector module. The basic cell of the WSO ASIC is a "winner take all" (WTA) circuit. The precision of the WSO ASIC is enhanced by using a cascade structure WTA cell. The chip requires a single +5 V supply and consumes 35 mW of power. The WSO ASIC is sensitive to voltage differences as small as 10 mV. The propagation delay of the chip is less than 30 nsec for voltage differences of >50 mW (typical for proposed application).
Feline hyperthyroidism: Pretreatment clinical and laboratory evaluation of 131 cases (1983)

Hyperthyroidism was diagnosed in 131 cats during a 3 1/2-year period. The cats ranged in age from 6 to 20 years; there was no breed or sex predilection. The most frequent clinical signs included weight loss, polyphagia, increased activity, polydipsia, polyuria, and vomiting. Common serum biochemical abnormalities included high values for alkaline phosphatase activity (75%), lactate dehydrogenase activity (66%), aspartate transaminase activity (66%), and alanine transaminase activity (54%). Electrocardiographic changes included tachycardia (greater than or equal to 240 beats/min) and increased R-wave amplitude in lead II (greater than or equal to 0.9 mV) in 66% and 29% of the 131 cats, respectively. Thoracic radiography in 82 cats revealed cardiomegaly in 40 (49%) of these cats; 16 cats with congestive heart failure also had pulmonary edema or pleural effusion. In 5 cats with markedly increased fecal volume, mean 48-hour fecal fat content was significantly greater than normal, with daily fat excretion 2 to 15 times the upper limit of normal. Base-line serum thyroxine concentrations were increased above normal range in all cats, whereas triiodothyronine concentrations were increased in 127 (97%) of the 131 cats. In 11 cats tested, mean thyroxine concentration did not increase significantly after thyroid-stimulating hormone administration. Mean 24-hour percentage of thyroid radioiodine uptake in 32 hyperthyroid cats was significantly higher (39.1%) than normal (9.2%). Thyroid scans, performed on 126 cats, showed enlargement and increased radionuclide accumulation in 1 thyroid lobe in 36 (29%) and both lobes in 90 (71%) of the cats.
Role of capsule endoscopy as a screening tool for colorectal cancer (2012)

SUMMARY Colon capsule endoscopy is currently under evaluation to become a noninvasive colorectal cancer screening test. The sensitivity and specificity of colon capsule endoscopy for colorectal polyps and cancer are improving with ongoing technical refinements to the capsule and recording device, with sensitivity as high as 84% for polyps greater than 1 mm in size. Specificity for smaller polyps, however, remains suboptimal. Colon capsule endoscopy requires extensive bowel preparation to ensure adequate colon cleansing and complete colonic evaluation. The complication rate for colon capsule endoscopy is unclear, but may be lower than that for small bowel capsule endoscopy. The role of colon capsule endoscopy in colorectal cancer screening has not been fully defined, as technical, logistical and implementation issues remain.
Application of immobilized heparins for isolation of human antithrombin III (1986)

Immobilized heparins were prepared by six different methods, and these were utilized for affinity purification of human antithrombin III (AT-III). Affinity support capacities (mg AT-III/g support) were strongly influenced by immobilized active heparin concentrations. In the temperature range 5-37 degrees C, colder temperatures favored affinity adsorption of AT-III as well as nonspecific interactions of all proteins. For representative human-plasma-derived feed solutions the selectivity for AT-III on the affinity support was dependent on relative concentrations of non-AT-III proteins as well as the specific mode of adsorption and elution (batch/continuous).
Effects of Amylopectin Branch Chain Length and Amylose Content on the Gelatinization and Pasting Properties of Starch (1999)

ABSTRACT Structures and properties of starches isolated from different botanical sources were investigated. Apparent and absolute amylose contents of starches were determined by measuring the iodine affinity of defatted whole starch and of fractionated and purified amylopectin. Branch chain‐length distributions of amylopectins were analyzed quantitatively using a high‐performance anion‐exchange chromatography system equipped with a postcolumn enzyme reactor and a pulsed amperometric detector. Thermal and pasting properties were measured using differential scanning calorimetry and a rapid viscoanalyzer, respectively. Absolute amylose contents of most of the starches studied were lower than their apparent amylose contents. This difference correlated with the number of very long branch chains of amylopectin. Studies of amylopectin structures showed that each starch had a distinct branch chain‐length distribution profile. Average degrees of polymerization (dp) of amylopectin branch chain length ranged from 18.8 for waxy rice to 30.7 for high‐amylose maize VII. Compared with X‐ray A‐type starches, B‐type starches had longer chains. A shoulder of dp 18–21 (chain length of 6.3–7.4 nm) was found in many starches; the chain length of 6.3–7.4 nm was in the proximity of the length of the amylopectin crystalline region. Starches with short average amylopectin branch chain lengths (e.g., waxy rice and sweet rice starch), with large proportions of short branch chains (dp 11–16) relative to the shoulder of dp 18–21 (e.g., wheat and barley starch), and with high starch phosphate monoester content (e.g., potato starch) displayed low gelatinization temperatures. Amylose contents and amylopectin branch chain‐length distributions predominantly affected the pasting properties of starch.
The molecular cloning and characterisation of cDNA coding for the α subunit of the acetyl-choline receptor (1982)

A rare cDNA coding for most of the alpha subunit of the Torpedo nicotinic acetylcholine receptor has been cloned into bacteria. The use of a mismatched oligonucleotide primer of reverse transcriptase facilitated the design of an efficient, specific probe for recombinant bacteria. DNA sequence analysis has enabled the elucidation of a large part of the polypeptide primary sequence which is discussed in relation to its acetylcholine binding activity and the location of receptor within the plasma membrane. When used as a radioactive probe, the cloned cDNA binds specifically to a single Torpedo mRNA species of about 2350 nucleotides in length but fails to show significant cross-hybridisation with alpha subunit mRNA extracted from cat muscle.
3D Bioprinting of Tissue/Organ Models (2016)

In vitro tissue/organ models are useful platforms that can facilitate systematic, repetitive, and quantitative investigations of drugs/chemicals. The primary objective when developing tissue/organ models is to reproduce physiologically relevant functions that typically require complex culture systems. Bioprinting offers exciting prospects for constructing 3D tissue/organ models, as it enables the reproducible, automated production of complex living tissues. Bioprinted tissues/organs may prove useful for screening novel compounds or predicting toxicity, as the spatial and chemical complexity inherent to native tissues/organs can be recreated. In this Review, we highlight the importance of developing 3D in vitro tissue/organ models by 3D bioprinting techniques, characterization of these models for evaluating their resemblance to native tissue, and their application in the prioritization of lead candidates, toxicity testing, and as disease/tumor models.
DIFFERENTIALIN SITU EXPRESSION OF THE GENES ENCODING THE CHEMOKINES MCP-1 AND RANTES IN HUMAN INFLAMMATORY BOWEL DISEASE (1996)

Two chemotactic cytokines, monocyte chemoattractant protein-1 (MCP-1) and RANTES, possibly contribute to the recruitment and activation of leukocytes in inflamed tissues. The expression of these cytokine genes was evaluated in tissue sections from resected bowel segments of 14 patients with inflammatory bowel disease (IBD) and seven control patients by use of 35S-labelled antisense RNA probes. MCP-1 and RANTES transcripts were generally increased in the intestinal mucosa of patients with IBD, compared with controls. Whereas MCP-1 gene expression in the mucosa was restricted to the lamina propria, the gene coding for RANTES was expressed in intraepithelial lymphocytes and in the subepithelial lamina propria. Furthermore, MCP-1 mRNA, but not RANTES mRNA, was abundant in vessel-associated cells, such as endothelial cells, medial smooth muscle cells, and intraluminal cells; in smooth muscle cells of the intestinal tunica muscularis; and in cells of the myenteric plexus. Compared with controls, a significant increase of MCP-1-expressing cells was observed in tissue specimens from patients with IBD, in endothelial cells of venules, and in cells present in the lumen of intestinal vessels. Conversely, the expression of MCP-1 mRNA in smooth muscle cells and myenteric plexus cells appeared to be comparable in control and diseased intestines. The increased number of MCP-1 and RANTES mRNA-expressing cells in mucosa from patients with IBD suggests that these cytokines play a role in the pathogenesis of mucosal inflammation. Furthermore, the expression of the MCP-1 gene in vessel-associated cells may indicate its involvement in mechanisms regulating the adhesion of blood monocytes to endothelial cells.
IL-25 augments type 2 immune responses by enhancing the expansion and functions of TSLP-DC–activated Th2 memory cells (2007)

Interleukin (IL) 25 (IL-17E), a distinct member of the IL-17 cytokine family, plays important roles in evoking T helper type 2 (Th2) cell-mediated inflammation that features the infiltrations of eosinophils and Th2 memory cells. However, the cellular sources, target cells, and underlying mechanisms remain elusive in humans. We demonstrate that human Th2 memory cells expressing distinctive levels of IL-25 receptor (R) are one of the responding cell types. IL-25 promotes cell expansion and Th2 cytokine production when Th2 central memory cells are stimulated with thymic stromal lymphopoietin (TSLP)-activated dendritic cells (DCs), homeostatic cytokines, or T cell receptor for antigen triggering. The enhanced functions of Th2 memory cells induced by IL-25 are associated with sustained expression of GATA-3, c-MAF, and JunB in an IL-4-independent manner. Although keratinocytes, mast cells, eosinophils, and basophils express IL-25 transcripts, activated eosinophils and basophils from normal and atopic subjects were found to secrete bioactive IL-25 protein, which augments the functions of Th2 memory cells. Elevated expression of IL-25 and IL-25R transcripts was observed in asthmatic lung tissues and atopic dermatitis skin lesions, linking their possible roles with exacerbated allergic disorders. Our results provide a plausible explanation that IL-25 produced by innate effector eosinophils and basophils may augment the allergic inflammation by enhancing the maintenance and functions of adaptive Th2 memory cells.
소비자의 병원 선택 및 만족도에 영향을 미치는 용인 (2010)

Understanding consumers` perception and attitude to hospitals is a fundamental basis for efficient and effective hospital management, especially in very competitive industries such as large hospitals in Korea. This study aimed to examine hospital factors influencing consumer`s hospital choice, their satisfaction, and their intention to revisit. A survey was conducted to collect information of patients` perception to the hospital in which patient or family member are visiting, using a structured questionnaire. Top five hospitals in Seoul, Korea were selected according to their volume of outpatients, and 200 outpatients were contacted and interviewed. Five hospitals were compared in terms of hospital choice and satisfaction factors using correlation analysis and graphical presentation. Factors influencing patient`s satisfaction and intention to revisit were analyzed using multiple regression and logistic regression, respectively. The results showed high correlation between hospital choice and satisfaction in accessibility and kindness and significant differences across five hospitals. Hospital choice factors were significantly influencing patient`s satisfaction in three factors: accessibility, kindness, and expenditure. Among seven factors, kindness and expenditure were only factors influencing patient`s intention to revisit. The findings identified significant differences in relationship between hospital choice and satisfaction and factors influencing patient satisfaction and intention to revisit across five big hospitals. For effective hospital management, each hospital needs to develop the customized strategy increasing their customer`s loyalty through continuous customer management.
Reliable surrogate outcome measures in multicenter clinical trials of Duchenne muscular dystrophy (2006)

We studied the reliability of a series of endpoints in an evaluation of subjects with Duchenne muscular dystrophy (DMD). The endpoints included quantitative muscle tests (QMTs), timed function tests, forced vital capacity (FVC), and manual muscle tests (MMT). Thirty-one ambulatory subjects with DMD (mean age 8.9 years; range 5-16 years) were evaluated at eight sites by 15 newly trained evaluators as a test of interrater reliability of outcome measures. Both total QMT score [intraclass correlation coefficient (ICC) 0.96] and individual QMT assessments (ICC 0.85-0.96) were highly reliable. Forced vital capacity and all timed function tests were also highly reliable (ICC 0.97-0.99). MMT was the least reliable assessment method (ICC 0.61). These data suggest that primary surrogate outcome measures in large multicenter clinical trials in DMD should use QMT, FVC, or time function tests to obtain maximum power and greatest sensitivity.
Polymyositis, Pulmonary Fibrosis and Autoantibodies to Aminoacyl-tRNA Synthetase Enzymes (1990)

The clinical and laboratory features of 29 patients who had one of three anti-aminoacyl-tRNA synthetase autoantibodies, anti-Jo1 (histidyl-tRNA synthetase), anti-PL12 (alanyl-tRNA synthetase) or anti-PL7 (threonyl-tRNA synthetase) were analysed and compared with the findings of other published reports. These autoantibodies were found to be associated with a syndrome delineated by inflammatory myositis (24 patients) and pulmonary fibrosis (23 of 29), but also including inflammatory arthritis (26/29), keratoconjunctivitis sicca (17/29), sclerodactyly (21/29), Raynaud's phenomenon (27/29), hepatitis (8/29) and subcutaneous calcinosis (7/29). The most important clinical determinant of outcome in this group of patients was the severity of the interstitial pulmonary disease. No patient fulfilled the classification criteria for systemic lupus erythematosus, although 10 had autoantibodies to extractable nuclear antigens including Ro, La, RNP, and Sm, and two patients had anti-dsDNA antibodies. Although it seems unlikely that anti-aminoacyl-tRNA synthetase antibodies are directly responsible for causing disease, they may provide an important clue to the aetiology of this unusual syndrome.