gebhart/patrepeval huggingface dataset:
Receptor-mediated endocytosis of tissue-type plasminogen activator by low density lipoprotein receptor-related protein on human hepatoma HepG2 cells (1993)

Hepatic parenchymal cells play an essential role in the clearance of circulating tissue-type plasminogen activator (t-PA) in vivo as a major pathway in the regulation of plasma fibrinolytic activity. Previous studies have identified plasminogen activator inhibitor type 1 (PAI-1)-dependent t-PA-binding sites in the human hepatoma cell line HepG2. In this study, we demonstrate that receptor-mediated binding and endocytosis of the t-PA-PAI-1 complex are largely mediated by a recently identified low density lipoprotein receptor-related protein (LRP). A 39-kDa LRP receptor-associated protein that modulates ligand binding to LRP was found to bind specifically to HepG2 cells and to inhibit approximately 70-80% of specific 125I-t-PA.PAI-1 binding. This inhibition by the 39-kDa protein was not due to inhibition of complex formation between 125I-t-PA and PAI-1; instead, the 39-kDa protein inhibited 125I-t-PA.PAI-1 binding to LRP. Polyclonal anti-LRP antibody raised against purified human LRP also inhibited 70-80% of specific 125I-t-PA.PAI-1 binding. A similar extent of inhibition by the 39-kDa protein was also observed for 125I-t-PA.PAI-1 endocytosis and degradation. Chemical cross-linking experiments demonstrated the direct interaction between 125I-t-PA.PAI-1 and LRP on HepG2 cells as anti-LRP antibody, in addition to anti-t-PA and anti-PAI-1 antibodies, was able to immunoprecipitate the 125I-t-PA.PAI-1 complex following binding of 125I-t-PA.PAI-1 to HepG2 cells and cross-linking. This interaction of the t-PA.PAI-1 complex with LRP on HepG2 cells was also observed when the unlabeled t-PA.PAI-1 complex was cross-linked to [35S]methionine-labeled HepG2 cells. In addition, the direct binding of the 39-kDa protein to LRP on HepG2 cells was demonstrated by similar cross-linking experiments. Thus, these data clearly show that LRP is the major cell-surface receptor responsible for t-PA.PAI-1 complex binding and endocytosis on human hepatoma HepG2 cells and extend the multifunctional nature of LRP as an endocytosis receptor for several structurally and functionally distinct ligands.
The evolution of the immune response. VII. Antibody to human "O" cells and properties of the immunoglobulin in lamprey. (1970)

Lamprey produced agglutinins in high titer against Brucella organisms and the H antigens of human “O” cells. The antibody was shown to be labile at room temperature. The lamprey immunoglobulin was purified using Bio-Gel A 1.5 column and DE 52-cellulose column fractionation. Both purified immunoglobulin and antibody activity of serum were shown to have the electrophoretic mobility of an alpha globulin, a sedimentation velocity of 9S and a molecular weight of approximately 300,000. These characteristics indicate that the lamprey immunoglobulin is unique.
Malignant hyperthermia (MH): porcine erythrocyte damage from oxidation and glutathione peroxidase deficiency. (1981)

Malignant hyperthermia (MH) is a severe familial disease in both the pig and the human, with 70% fatality when fully expressed in humans. MH produces rapid elevation of temperature in response to stresses, of which there are two general kinds: Societal or emotional stress, and chemical stressors. The most commonly encountered stressor is halothane, a general anesthetic in wide use. Besides large temperature increases, there occur some twenty symptoms. Much work in other laboratories has been concentrated on elevated CPK i the plasma. However, all the symptoms are consistent with a single disorder, namely oxidative damage, especially in membranes. A deficiency in the glutathione peroxidase (GPX) system is a prime factor, likely the molecular basis allowing abnormal oxidative damage in the MH pig. Catalase activities are normal in MH pigs, but they have only 20-50% normal GPX activities. The deficiency does not cause oxidative damage. It allows failure or protective mechanisms against it. The nonstressed MH animal exhibits less acute symptoms, e.g. enhanced red cell Heinz bodies, but such animals generally mature. Under stress, their inadequate protective mechanisms dependent on GPX are overwhelmed, resulting in gross symptoms and crisis. It is important to concentrate on the GPX system(s) and their adjacent pentose shunt metabolism. We propose that a deficiency in any of these two systems is the molecular basis of the disease. Many tissues are involve in MH, but the red cell obviously provides a convenient means for assay and for screening. This paper mainly pertains to porcine MH. However, preliminary work with humans indicates that human MH has a similar molecular basis.
NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases (2015)

IL-1β production is critically regulated by cytosolic molecular complexes, termed inflammasomes. Different inflammasome complexes have been described to date. While all inflammasomes recognize certain pathogens, it is the distinctive feature of NLRP3 inflammasome to be activated by many and diverse stimuli making NLRP3 the most versatile, and importantly also the most clinically implicated inflammasome. However, NLRP3 activation has remained the most enigmatic. It is not plausible that the intracellular NLRP3 receptor is able to detect all of its many and diverse triggers through direct interactions; instead, it is discussed that NLRP3 is responding to certain generic cellular stress-signals induced by the multitude of molecules that trigger its activation. An ever increasing number of studies link the sensing of cellular stress signals to a direct pathophysiological role of NLRP3 activation in a wide range of autoinflammatory and autoimmune disorders, and thus provide a novel mechanistic rational, on how molecules trigger and support sterile inflammatory diseases. A vast interest has created to unravel how NLRP3 becomes activated, since mechanistic insight is the prerequisite for a knowledge-based development of therapeutic intervention strategies that specifically target the NLRP3 triggered IL-1β production. In this review, we have updated knowledge on NLRP3 inflammasome assembly and activation and on the pyrin domain in NLRP3 that could represent a drug target to treat sterile inflammatory diseases. We have reported mutations in NLRP3 that were found to be associated with certain diseases. In addition, we have reviewed the functional link between NLRP3 inflammasome, the regulator of cellular redox status Trx/TXNIP complex, endoplasmic reticulum stress and the pathogenesis of diseases such as type 2 diabetes. Finally, we have provided data on NLRP3 inflammasome, as a critical regulator involved in the pathogenesis of obesity and cardiovascular diseases.
Clinical Utility of Measuring Infliximab and Human Anti-Chimeric Antibody Concentrations in Patients With Inflammatory Bowel Disease (2010)

Measurement of HACA and infliximab concentration impacts management and is clinically useful. Increasing the infliximab dose in patients who have HACAs is ineffective, whereas in patients with subtherapeutic infliximab concentrations, this strategy may be a good alternative to changing to another anti-TNF agent.
Expression of Bovine Cytochrome P450c17 cDNA in Saccharomyces cerevisiae (1989)

We constructed expression plasmids for bovine adrenal cytochrome P450c17 (P450c17) by inserting the corresponding cDNA between the yeast alcohol dehydrogenase I promoter and terminator of the expression vector pAAH5. Plasmids pA alpha 1 and pA alpha 2 contained the entire coding region for bovine P450c17, whereas pAC alpha 1 included the cDNA coding for chimeric P450c alpha consisting of the amino-terminal 45 amino acid residues of rat P450c and the carboxy-terminal 482 amino acid residues of bovine P450c17. The transformed Saccharomyces cerevisiae AH22/pA alpha 1, AH22/pA alpha 2, and AH22/pAC alpha 1 cells produced about 1 x 10(5), 1 x 10(5), and 2 x 10(4) molecules per cell of the corresponding P450 hemoproteins, respectively. On incubation with the cultures of each of the three strains, progesterone was specifically converted into 17 alpha-hydroxyprogesterone, which was not further converted into androstenedione, indicating that the three strains showed 17 alpha-hydroxylase activity, but almost no C17,20-lyase activity. The microsomal fraction prepared from the AH22/pA alpha 1 cells showed 17 alpha-hydroxylase activity toward progesterone and pregnenolone to higher extents, and exhibited C17,20-lyase activity toward 17 alpha-hydroxypregnenolone to a lesser extent and almost no C17,20-lyase activity toward 17 alpha-hydroxyprogesterone. These results indicated that bovine P450c17 synthesized in S. cerevisiae cells manifests the 17 alpha-hydroxylase activity, but not the C17,20-lyase activity.
A novel protective effect of erythropoietin in the infarcted heart (2003)

Erythropoietin (EPO) has been shown to protect neurons from ischemic stroke, but can also increase thrombotic events and mortality rates in patients with ischemic heart disease. We reasoned that benefits of EPO might be offset by increases in hematocrit and evaluated the direct effects of EPO in the ischemic heart. We show that preconditioning with EPO protects H9c2 myoblasts in vitro and cardiomyocytes in vivo against ischemic injury. EPO treatment leads to significantly improved cardiac function following myocardial infarction. This protection is associated with mitigation of myocyte apoptosis, translating into more viable myocardium and less ventricular dysfunction. EPO-mediated myocyte survival appears to involve Akt activation. Importantly, cardioprotective effects of EPO were seen without an increase in hematocrit (eliminating oxygen delivery as an etiologic factor in myocyte survival and function), demonstrating that EPO can directly protect the ischemic and infarcted heart.
Entrapment of sized emboli by the KMA-Greenfield intracaval filter. (1978)

Clinical studies demonstrating the effectiveness of the Kim-Ray Greenfield vena caval filter in the management of pulmonary emboli have stimulated efforts to accurately define this filter's capability to entrap sized emboli and maintain caval patency. Twenty-three dogs had filters inserted and positioned distal to the renal veins. Radiopaque emboli measuring 2 to 5 mm were introduced via the femoral vein. Cineradiography allowed direct observation of emboli capture and filter flow dynamics. Probability of entrapment was found to be related to (1) emboli size, (2) depth of filling of the conical-shaped filter by prior entrapment of emboli, and (3) absence of distal venous hypertension. The geometric design of the filter, which allows progressive vertical filling while maintaining circumferential blood flow, is thought to be responsible for entrapment of emboli and avoidance of venous thrombosis and hypertension.
QoS-aware elastic cloud brokering for IMS infrastructures (2012)

Cloud computing management supports are becoming more and more important not only in the fields of IT infrastructures for Internet applications and services, but steadily also in the field of telecommunication services and infrastructures. More and more telecommunication service providers have adopted IP Multimedia Subsystems (IMS) to consolidate their service infrastructures towards converged, all-IP, access network independent Next Generation Networks (NGNs). Although modern NGN service environments have the potential to greatly reduce new telecommunication services time-to-market, until now significant upfront investments into computational resources are required, that is still often a risk for the enterprise, with unsure return on invest. The application of cloud computing technologies to IMS-based service infrastructures enables new pay-per-use cost models, so IMS service providers may be charged for what they use only, significantly lowering the risk of bad investments. This work presents the design and implementation of a cloud brokering system for IMS services, capable of simultaneously interworking with multiple cloud infrastructures. We developed a Cloud Broker Engine (CBE) able to dynamically up/down-scale cloud resources across multiple cloud platforms. Our CBE is capable of coping with dynamic load situations and QoS requirements optimizing resource utilization across different cloud infrastructures: it enables QoS assurance and optimizes resource consumption across multiple cloud providers.
Construction of yeast artificial chromosome libraries with large inserts using fractionation by pulsed-field gel electrophoresis (1989)

A method for constructing yeast artificial chromosome (YAC) libraries with large insert sizes is reported. High molecular weight human DNA was partially digested with EcoRI and cloned in the vector pYAC4. When unfractionated DNA was used, the mean YAC size was 120kb. Fractionation by pulsed-field gel electrophoresis using a 'waltzer' apparatus to remove small DNA fragments increased the mean YAC size to congruent to 220kb or congruent to 370kb depending on the fractionation conditions. Ligated DNA prepared by this method was stable at 4 degrees C and routinely yielded transformation efficiencies of greater than 700 colonies/micrograms. It should be possible to extend the method to produce even larger inserts and to use high molecular weight DNA from any source.
Surface modifications of biomaterials vs. biological behaviour (1996)

Tese de mestrado. Engenharia Metalurgica e de Materiais. Faculdade de Engenharia. Universidade do Porto. 1996
Factors affecting drug-induced liver injury: antithyroid drugs as instances (2014)

Methimazole and propylthiouracil have been used in the management of hyperthyroidism for more than half a century. However, hepatotoxicity is one of the most deleterious side effects associated with these medications. The mechanism(s) of hepatic injury induced by antithyroid agents is not fully recognized yet. Furthermore, there are no specific tools for predicting the occurrence of hepatotoxicity induced by these drugs. The purpose of this article is to give an overview on possible susceptibility factors in liver injury induced by antithyroid agents. Age, gender, metabolism characteristics, alcohol consumption, underlying diseases, immunologic mechanisms, and drug interactions are involved in enhancing antithyroid drugs-induced hepatic damage. An outline on the clinically used treatments for antithyroid drugs-induced hepatotoxicity and the potential therapeutic strategies found to be effective against this complication are also discussed.
A chronic carrierlike state is established in nude mice injected with cloned hepatitis B virus DNA (1988)

BALB/c nude mice were injected intrahepatically with hepatitis B virus (HBV) DNA prepared from recombinant plasmids. Hepatitis B surface antigen appeared in the circulation in 19 of 23 mice (82%) 3 to 20 weeks postinjection and persisted for more than 6 months in most animals. Hepatitis B e antigen appeared transiently in the circulation in 12 of the 23 mice (52%) within a few weeks after the appearance of hepatitis B surface antigen. Antibodies to the core, X, and/or polymerase gene products of HBV have also been observed in 14 (61%) of the mice. Histopathological examination of the livers at 7 months postinjection demonstrated that nearly half had characteristics consistent with chronic hepatitis. HBV DNA appeared to be integrated into host liver DNA. No evidence of viral replication was observed in sera or livers from these mice at 7 months postinjection. These results demonstrate that an HBV chronic carrierlike state can be established in mice and that such a model could be used to study host and virus factors important in the establishment and maintenance of HBV-associated chronic liver disease.
Potential of preventing Pseudomonas aeruginosa lung infections in cystic fibrosis patients: Experimental studies in animals (1996)

In patients with cystic fibrosis (CF), respiratory tract infections caused by Staphylococcus aureus and Haemophilus influenzae are followed by Pseudomonas aeruginosa with increasing age. Chronic endobronchial lung infection with P. aeruginosa is the leading cause of morbidity and mortality. In Danish CF patients we noted that both onset of initial colonization and chronic lung infection with P. aeruginosa peaked during the winter months which is the season for respiratory virus infections. Virus may therefore pave the way for P. aeruginosa. We established a chronic P. aeruginosa lung infection in rats by embedding mucoid bacteria in seaweed alginate and installing the beads intratracheally into the lower part of the left lung. Although the rats did not suffer from CF, the antibody responses and the pathologic changes of the lungs mimicked the findings in CF patients. By using this model in normal and athymic rats we showed that the T-cell response during the "natural" course of the infection played no major role. In a model of acute P. aeruginosa pneumonia we found that the macroscopic inflammatory response of the lungs was immense and that the natural capacity to clear P. aeruginosa was very efficient and could not be improved by immunization, although high serum levels of IgM, IgG and IgA antibodies to P. aeruginosa alginate, LPS, exotoxin A and sonicate were induced. We developed a method for collecting and measuring IgA in saliva and noted that mucosal IgA antibodies were induced by vaccination; they did not significantly prevent inflammation, however. In the chronic rat model we succeeded to improve the survival significantly and to change the inflammatory response subsequent to vaccination from an acute type inflammation dominated by polymorphonuclear leukocytes (PMNs) as in CF patients to a chronic type inflammation dominated by mononuclear leukocytes. Furthermore, we found that rats immunized with an alginate containing vaccine had a significantly earlier cellular shift to a chronic type inflammation as well as a significant reduction in the severity of the macroscopic inflammation compared to two other vaccine groups and to nonimmunized controls. Similar results were obtained in rats treated with the TH1 cytokine, interferon-gamma (IFN-gamma). Several authors have shown that the lung tissue damage during chronic infection in CF patients is caused by a type III hypersensitivity reaction leading to release of elastase by PMNs surrounding the bacterial microcolonies. The cellular shift we have induced by vaccination and by IFN-gamma treatment therefore offers a possible new strategy for improving the clinical course in chronically infected CF patients.
Proinflammatory cytokine profiles in sera and pathological tissues of patients with active untreated adult onset Still's disease. (2004)

Significantly higher levels of IL-6, IL-8, IL-18, and TNF-alpha were seen in both sera and pathological tissues of patients with active AOSD. The associations between levels of cytokine profile and distinct clinical manifestations and various patterns of disease course suggest the heterogeneity of pathogenesis in AOSD.
In vivo dissolution behavior of various RF magnetron sputtered Ca‐P coatings (1998)

Radiofrequency magnetron sputter deposition was used to deposit Ca-P sputter coatings on titanium discs, and these coatings were implanted subcutaneously into the backs of rabbits. Half of the as-sputtered coatings were subjected to additional heat treatment for 2 h at 500°C. X-ray diffraction (XRD) demonstrated that annealing at 500°C changed the amorphous sputtered coating into an amorphous-crystalline apatite structure. Scanning electron microscopic (SEM) examination of the sputtered coatings showed excellent coverage of the substrate surface. Annealing of the 4-μm-thick coatings resulted in the appearence of small cracks. SEM demonstrated that until 4 weeks of implantation, all heat-treated coatings were present and all amorphous coatings were completely or mostly dissolved. Fourier transform infrared spectroscopy showed the formation of carbonate apatite (CO3-AP) on these specimens. Furthermore, XRD analysis showed that these CO3-AP precipitated coatings disappeared after 8 weeks of implantation. On the other hand, SEM inspection of these specimens revealed that the 4-μm heat-treated coating was still partially maintained and that small Ca-P crystals were present on the titanium substrate. On the basis of these results, we conclude that apparently 0.1 μm heat-treated Ca-P sputter coating is of sufficient thicknesses to stimulate carbonate apatite deposition under in vivo conditions. © 1998 John Wiley & Sons, Inc. J Biomed Mater Res, 39, 524–530, 1998.
Intervención educativa para el desarrollo de conocimientos sobre salud bucal en la enseñanza primaria. (2008)

Background: There is high prevalence of buccal diseases which could be avoided with appropriate hygienic and alimentary habits that are supposed to be learned since the first stages of life. Objective: To verify the efficacy of an educative strategy on buccal health to develop buccal self-care through its application in girls and boys. Methods: An intervention study was developed with before and after design in 80 children of 5th grade and teachers of the primary school “Armando Mestre Martinez” in Cienfuegos, from September 2005 to March 2006. Initially, learning necessities and buccal hygiene were determined in both groups and later we verified the strategy efficiency. Initial information was obtained through surveys, focal groups, experts’ opinions and observation. Wilcoxon rank test was used for matched samples and Mc Nemar test for variables verification. Findings: Significant differences were obtained between the initial and final knowledge on buccal health and buccal hygiene coefficient. Qualitative methods showed audience approval of this strategy. Conclusions: Educative strategy applications allowed children learning actions of self-care as correct teeth brushing, use of dental floss, appropriate dietary selection and identification of prejudicial habits.
Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone (2016)

ZIKV is a rapidly spreading mosquito-borne pathogen that has been linked to Guillain-Barré syndrome in adults and congenital microcephaly in developing fetuses and infants. ZIKV can also be sexually transmitted. The viral molecular determinants of any of these phenotypes are not well understood. There is no reverse genetics system available for the current epidemic virus that will allow researchers to study ZIKV immunity, develop novel vaccines, or develop antiviral drugs. Here we provide a novel infectious clone system generated from a recent ZIKV isolated from a patient infected in Puerto Rico. This infectious clone produces virus with in vitro and in vivo characteristics similar to those of the primary isolate, providing a critical tool to study ZIKV infection and disease.
Adult issues in phenylketonuria. (2009)

Phenylketonuria (PKU) is a classical example of an inherited metabolic disease, in which mental retardation can be prevented successfully by using a diet. However, in adult PKU new problems occur, such as vitamin deficiencies, osteoporosis and the maternal PKU syndrome. The aim of this review article is to provide guidelines for the clinician to understand and manage PKU in adults.
Pharyngeal Suspension Suture with Repose Bone Screw for Obstructive Sleep Apnea (2000)

A pharyngeal suspension suture changes subjective outcomes. Improvement is incomplete. The procedure is nonexcisional, but significant complications may occur. Further evaluation is required to demonstrate effectiveness.