gebhart/patrepeval huggingface dataset:
Genetic update on inflammatory factors in ulcerative colitis: Review of the current literature (2014)

Ulcerative colitis (UC) is one of the main types of inflammatory bowel disease, which is caused by dysregulated immune responses in genetically predisposed individuals. Several genetic factors, including interleukin and interleukin receptor gene polymorphisms and other inflammation-related genes play central role in mediating and modulating the inflammation in the human body, thereby these can be the main cause of development of the disease. It is clear these data are very important for understanding the base of the disease, especially in terms of clinical utility and validity, but summarized literature is exiguous for challenge health specialist that can used in the clinical practice nowadays. This review summarizes the current literature on inflammation-related genetic polymorphisms which are associated with UC. We performed an electronic search of Pubmed Database among publications of the last 10 years, using the following medical subject heading terms: UC, ulcerative colitis, inflammation, genes, polymorphisms, and susceptibility.
In vivo and in vitro functional examination of a conserved epitope of L- and E-selectin crucial for leukocyte-endothelial cell interactions. (1994)

Selectins constitute a three-member gene family of carbohydrate-binding adhesion proteins found on the surface of leukocytes and endothelial cells that is central to inflammation-associated leukocyte recruitment and lymphocyte recirculation. E- and P-selectin are inducible and expressed on the surface of endothelial cells under inflammatory conditions, whereas L-selectin is constitutively expressed on most circulating leukocytes. Previously, we have characterized a unique mAb (EL-246) that recognizes a common epitope on both E- and L-selectin, which is presented or determined by their short consensus repeat domains. This report defines the functional properties of EL-246 and its cognate epitope. In a novel in vitro physiologic shear system, we show that neutrophil rolling on activated HUVECs and on E-selectin cDNA transfectants is blocked 45 to 120 s after infusion of EL-246. The examination of the binding of neutrophils to E-selectin cDNA transfectants reveals that their adhesion is blocked by EL-246 treatment of either cell type. A unique Ab transfer mechanism is demonstrated in which El-246 is delivered unidirectionally from L- to E-selectin to surpass the adhesion blocked by mAbs that recognize either L- or E-selectin alone. By using flow cytometry and in vivo homing techniques, we show that pretreating bovine lymphocytes with EL-246 blocks their ability to home to mouse peripheral lymph nodes by > 65%. Cumulatively, these results suggest that EL-246 is a uniquely potent pharmacologic inhibitor of leukocyte-endothelial cell interactions that are mediated by either E- or L-selectin.
Cultural Issues and Challenges of the Informed Consent in Older Adults (2007)

Owing to the dramatic increase in an elderly population characterized by cultural diversity and changes in the aging process, performing informed consent in the elderly population can involve complex issues are a challenge for researchers. This article aims to discuss concepts and relevant information concerning informed consent in studies with cognitively intact older adults. A longitudinal study entitled the simplified Tai-Chi exercise program (STEP) was utilized to explain the dilemma and implications of informed consent for research with a cognitively intact elderly population. It is important for researchers to be culturally sensitive to their subjects and establish a trusting relationship during the process of informed consent.
The effect of a biphasic injectable bone substitute on the interface strength in a rabbit knee prosthesis model (2013)

We conclude that early prosthesis-bone interface strength is not influenced by a bone substitute. However, during remodeling, the bone substitute might provide improved mechanical support for the prosthesis. The results support further studies of the use of injectable calcium sulfate/hydroxyapatite in fixation of prosthetic joint implants.
L'année des Nations Unies, questions juridiques - 1982 (1982)

Tavernier Paul. L'année des Nations Unies, questions juridiques - 1982. In: Annuaire français de droit international, volume 28, 1982. pp. 634-671.
Difference in cholesterol-binding and cytolytic activities between listeriolysin O and seeligeriolysin O: a possible role of alanine residue in tryptophan-rich undecapeptide (2001)

We have constructed recombinant listeriolysin O (rLLO) and seeligeriolysin O (rLSO) from Listeria monocytogenes and Listeria seeligeri, respectively. In hemolysis and cholesterol-binding assays, the specific activity of recombinant toxin was lower for LSO as compared to LLO. To understand the molecular basis of this difference, in particular with respect to the conserved Trp-rich undecapeptide, a naturally occurring Ala to Phe substitution in LSO was introduced into rLLO. The rLLO:A488F hemolysin exhibited a reduced activity in both hemolysis and cholesterol-binding. The reverse mutation, inserted into rLSO, also increased the hemolytic activity of this mutant LSO. These results suggested that the natural replacement of Ala to Phe is involved in the weak cytolytic activity of LSO.
Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair. (1989)

Exogenous polypeptide growth factors influence the rate of wound healing and other biological processes, but there is no direct evidence that these peptides have an intrinsic role. To test whether basic fibroblast growth factor is involved in wound repair, rats were implanted with subcutaneous polyvinyl alcohol sponges containing slow-release pellets releasing either a polyclonal neutralizing antiserum directed against basic fibroblast growth factor, preimmune IgG, or nothing. Histological and biochemical evaluation of the granulation tissue that infiltrated the sponges showed anti-basic fibroblast growth factor to cause significant reductions in DNA, protein, and collagen content when compared with either preimmune IgG or placebo at the early stages of wound repair.
Relationship between fallout and trends in infant and fetal mortality. (1970)

Relationship between fallout and trends in infant and fetal mortality. V P BondCopyRight https://doi.org/10.2105/AJPH.60.5.803-a Published Online: August 29, 2011
Clinical Use of Androgens (1984)

The principal clinical use of androgens is the treatment of testosterone deficiency in a male who has primary hypogonadism or who has secondary hypogonadism but is not interested in becoming fertile within the subsequent year. For the treatment of testosterone deficiency in the adult male, one of the two long-acting esters of testosterone, testosterone enanthate or testosterone cypionate, should be administered by intramuscular injection, 200 mg every two weeks or 300 mg every three weeks. The alkylated testosterone derivatives, which can be administered orally, are probably too weak as androgens to be used for the treatment of adult male hypogonadism, but they may have value in situations where full androgenization is not desired, such as adjuvant treatment of breast carcinoma.
Matching biological motion at extreme distances (2014)

The goal of the current paper was to determine the maximum distance at which an actor could be placed so that an observer would still be able to interpret their behavior. Although we know a great deal about the limits of action perception, particularly through studies of biological motion processing, this question of distance has not been previously documented. We began by reviewing the sizes of point-light figures used in 100 previous studies of biological motion. We found that with an average figure height of 6.6° [corrected] visual angle, actors were effectively 15 m from the observer, assuming average physical height of 1.75 m. No previous studies had explicitly examined extreme distances. Here, we introduce a new matching task in which we systematically varied the apparent distance of point-light figures relative to a fixed viewing position by manipulating size. Our results suggest that a variety of human actions could potentially be interpreted up to 1000 m away, a distance at which a human figure would subtend only 0.1° visual angle in height. Dynamic figures could be interpreted at further distances than static figures (Experiment 1), and upright figures were similarly processed more efficiently than inverted figures (Experiment 2). We discuss these findings in the context of the processing mechanisms thought to underlie action perception and suggest that the ability to match actions at extreme distance is another example of the robust nature of biological motion processing.
Total Body Irradiation Causes Residual Bone Marrow Injury by Induction of Persistent Oxidative Stress in Murine Hematopoietic Stem Cells. (2009)

Abstract Abstract 3209 Poster Board III-146 Ionizing radiation (IR) and/or chemotherapy cause not only acute tissue injury but also have late effects including long-term bone marrow (BM) suppression. The induction of residual BM injury is primarily attributable to induction of hematopoietic stem cell (HSC) senescence. However, neither the molecular mechanisms by which IR and/or chemotherapy induce HSC senescence have been clearly defined, nor has an effective treatment been developed to ameliorate the injury, which were investigated in the present study using a total body irradiation (TBI) mouse model. The results showed that exposure of mice to 6.5 Gy TBI induced a persistent increase in reactive oxygen species (ROS) production in HSCs only for up to 8 weeks, primarily via up-regulation of NADPH oxidase 4 (NOX4). This finding provides the foremost direct evidence demonstrating that in vivo exposure to IR causes persistent oxidative stress selectively in a specific population of BM hematopoietic cells (HSCs). The induction of chronic oxidative stress in HSCs was associated with sustained increases in oxidative DNA damage, DNA double strand breaks, inhibition of HSC clonogenic function, and induction of HSC senescence but not apoptosis. Treatment of the irradiated mice with N-acetyl-cysteine (NAC) after TBI significantly attenuated IR-induced inhibition of HSC clonogenic function and reduction of HSC long-term engraftment after transplantation. These findings suggest that selective induction of chronic oxidative stress in HSCs by TBI leads to induction of HSC senescence and residual BM injury and that antioxidant therapy may be used as an effective strategy to mitigate IR- and chemotherapy-induced residual BM injury. Disclosures No relevant conflicts of interest to declare.
TGF-β type I receptor/ALK-5 and Smad proteins mediate epithelial to mesenchymal transdifferentiation in NMuMG breast epithelial cells (1999)

The capacities of different transforming growth factor-(beta) (TGF-(beta)) superfamily members to drive epithelial to mesenchymal transdifferentiation of the murine mammary epithelial cell line NMuMG were investigated. TGF-(beta)1, but not activin A or osteogenic protein-1 (OP-1)/bone morphogenetic protein-7 (BMP-7), was able to induce morphological transformation of NMuMG cells as shown by reorganisation of the actin cytoskeleton and relocalisation/downregulation of E-cadherin and (beta)-catenin, an effect that was abrogated by the more general serine/threonine kinase and protein kinase C inhibitor, staurosporine. TGF-(beta)1 bound to TGF-(beta) type I receptor (T(beta)R-I)/ALK-5 and T(beta)R-II, but not to activin type I receptor (ActR-I)/ALK-2. Activin A bound to ActR-IB/ALK-4 and ActR-II, and BMP-7 bound to ActR-I/ALK-2, BMP type I receptor (BMPR-I)/ALK-3, ActR-II and BMPR-II. TGF-(beta)1 and BMP-7 activated the Smad-binding element (SBE)(4) promoter with equal potency, whereas activin A had no effect. Transfection of constitutively active (CA)-ALK-4 activated the 3TP promoter to the same extent as TGF-(beta)1 and CA-ALK-5 indicating that activin signalling downstream of type I receptors was functional in NMuMG cells. In agreement with this, activin A induced low levels of plasminogen activator inhibitor I expression compared to the high induction by TGF-(beta)1. In contrast to activin A and BMP-7, TGF-(beta)1 strongly induced Smad2 phosphorylation. Consistent with these findings, TGF-(beta)1 induced the nuclear accumulation of Smad2 and/or Smad3. In addition, NMuMG cells transiently infected with adenoviral vectors expressing high level CA-ALK-5 exhibited full transdifferentiation. On the other hand, infections with low level CA-ALK-5, which alone did not result in transdifferentiation, together with Smad2 and Smad4, or with Smad3 and Smad4 led to transdifferentiation. In conclusion, TGF-(beta)1 signals potently and passes the activation threshold to evoke NMuMG cell transdifferentiation. The TGF-(beta) type I receptor (ALK-5) and its effector Smad proteins mediate the epithelial to mesenchymal transition. Activin A does not induce mesenchymal transformation, presumably because the number of activin receptors is limited, while BMP-7-initiated signalling cannot mediate transdifferentiation.
Pharmacokinetic analysis of two-step approaches using bifunctional and enzyme-conjugated antibodies. (1991)

Bifunctional antibodies (BFA) and enzyme-conjugated antibodies (ECA) can be used to preferentially deliver a hapten or drug to tumor sites for diagnosis and therapy. We present here a simple pharmacokinetic model for the above two systems by considering only two compartments, the plasma and tumor. The models predict that the longer the time delay between the BFA and hapten or between the ECA and prodrug injections, the higher the tumor:plasma concentration ratio of the hapten or drug. In addition, multiple injections of the hapten or prodrug is predicted to give a more uniform concentration of the hapten or drug in both the tumor and plasma than bolus injection. We suggest that, initially, the most effective dose of BFA should be selected and then the hapten concentration chosen accordingly. The decrease of the ECA injection dose would increase the tumor:plasma concentration ratio of the drug and yet decrease the tumor concentration of the drug. In clinical application of the ECA system, consideration of ECA dose should be balanced between the tumor concentration and the tumor:plasma concentration ratio of the drug. The dose of the prodrug injection is suggested to be equal to the required toxic concentration of the drug in the tumor. There are several ways to improve the tumor:plasma concentration ratio of the hapten or drug, such as changing the binding kinetics of the antibody to tumor or the hapten to BFA and removing the antibody from the plasma before the injection of the hapten or prodrug. One notable difference between the BFA and ECA approaches is that there is an upper limit for maximum hapten concentration in the former, and hence, from the point of drug delivery alone the latter approach is presumably superior. The limitations of the models and therapeutic implications are also discussed.
Dipeptidyl‐Peptidase IV‐β, a Novel form of Cell‐Surface‐Expressed Protein with Dipeptidyl‐Peptidase IV Activity (1996)

The T-cell activation antigen CD26, is a type II membrane glycoprotein with intrinsic dipeptidyl-peptidase IV (DPP IV) activity, characterized by its capacity to cleave off N-terminal dipeptides containing proline as the penultimate residue. Independent of its catalytic activity, CD26 has also been characterized as adenosine deaminase binding protein. By using CD26 negative human C8166 cells, here we describe the existence of another cell-surface protein which manifests CD26-like DPP IV activity. For convenience, this protein will be referred to as DPP IV-beta. Consistent with the cell-surface expression of DPP IV-beta, intact C8166 cells manifested a high level of DPP IV, whereas, they manifested poor activity against substrates of DPP II known to have an intracellular localization. A partially purified preparation of CD26 from human MOLT4 cells, and the DPP IV-beta expressed on intact cells were found to possess similar catalytic activity and pH optimum. In addition, cell-surface CD26 and DPP IV-beta on intact MOLT4 and C8166 cells, respectively, resisted digestion by proteolytic enzymes such as trypsin and proteinase K. However, adenosine deaminase activity was not detectable on the surface of C8166 cells in contrast to CD26 positive MOLT4 cells. In accord with this, 125I-labeled adenosine deaminase which binds CD26 was found not to bind DPP IV-beta. Gel-filtration experiments using 0.5% Triton X-100 extracts from C8166 and MOLT4 cells, revealed that the apparent molecular mass of DPP IV-beta is 82 kDa, whereas that of CD26 is 110 kDa as expected. Taken together, our results suggest that DPP IV-beta is a CD26-like protein which could be characterized by distinct properties.
Adjuvant Radioimmunotherapy Trial with Iodine-131–Labeled Anti–Carcinoembryonic Antigen Monoclonal Antibody F6 F(ab′)2 after Resection of Liver Metastases from Colorectal Cancer (2008)

RIT is feasible in an adjuvant setting after complete resection of LM from colorectal cancer and should be considered for future trials, possibly in combination with chemotherapy, because of the generally poor prognosis of these patients.
Thermoelectric coolers with small response time (2002)

A method of evaluation of cascade thermoelectric cooler transient response is described. To check the theoretical model, experimental research on a wide range of single-stage and multi-stage TE coolers was carried out. Fast response coolers, providing an achievement of 90% of steady-state temperature difference for times from 1.2 to 6.2 s, have been developed. The limit speed of thermal response for cascade coolers is also predicted.
All-optical image transmission through a single-mode fiber (1992)

All-optical transmission of two-dimensional images through a single single-mode fiber with a two-dimensional multicolor surface-emitting laser array and a volume hologram is described. A preliminary experimental result to prove the concept of the idea is demonstrated by transmitting a simple 2 x 2 image over a distance of 1 mile (1.61 km).
Thalidomide induces γ-globin gene expression through increased reactive oxygen species–mediated p38 MAPK signaling and histone H4 acetylation in adult erythropoiesis (2007)

Although thalidomide has been shown to improve anemia in some patients with myelodysplastic syndromes and stimulates erythropoietin in patients with multiple myeloma, thalidomide's specific effects on gamma-globin gene expression during erythroid differentiation have not been studied. Here, we investigated the effects of thalidomide on gamma-globin gene expression and the involved signaling pathway using an ex vivo culture system of primary human CD34+ cells. We found that thalidomide induced gamma-globin mRNA expression in a dose-dependent manner, but had no effect on beta-globin expression. We also demonstrated that intracellular reactive oxygen species (ROS) levels were increased by treatment with thalidomide for 48 hours (from day 3 to day 5). Western blot analysis demonstrated that thalidomide activated the p38 mitogen-activated protein kinase (MAPK) signaling pathway in a time- and dose-dependent manner and increased histone H4 acetylation. Pretreatment of cells with the antioxidant enzyme catalase and the intracellular hydroxyl scavenger dimethylthiourea (DMTU) abrogated the thalidomide-induced p38 MAPK activation and histone H4 acetylation. Moreover, pretreatment with catalase and DMTU diminished thalidomide-induced gamma-globin gene expression. These data indicate that thalidomide induces increased expression of the gamma-globin gene via ROS-dependent activation of the p38 MAPK signaling pathway and histone H4 acetylation.
Structure-Activity Relationships of Cyclic Pentapeptide Endothelin A Receptor Antagonists (1995)

Analogues of the natural product endothelin A (ETA) receptor antagonists cyclo(-D-Trp1-D-Glu2-Ala3-D-Val4-Leu5-) (1) and cyclo(-D-Trp1-D-Glu2-Ala3-D-alloIle4-Leu5-) (2) were prepared and tested for inhibitory activity against [125I]endothelin (ET-1) binding to protein ETA receptors. The DDLDL chirality sequence of the natural products appeared to be critical for inhibitory activity because conversion of either D-Trp or D-Glu (or both) in 1 to the corresponding L-isomer(s) abolished this property. Systematic modifications at each position of the natural products clarified the structure-activity relationships and led to highly potent and selective ETA receptor antagonists. Most replacements of D-Trp1 and Leu5 with other amino acids caused a significant loss of inhibitory activity. In contrast, replacement of D-Glu2 with D-Asp2 enhanced the activity. With regard to the Ala3 position, all analogues with imino acids, independent of being cyclic or acyclic, showed higher affinities than did the amino acid analogues. In addition, most replacements with amino acids, which had various functional groups in their side chains, did not significantly modify ETA binding affinity. The D-Val4/D-alloIle4 position was very important for inhibitory activity, and a beta-position branched D-amino acid or a D-heteroarylglycine was preferable at this position. Among synthesized cyclic pentapeptides, compound 36 (BQ-518) was the most potent ETA receptor antagonist, with a pA2 of 8.1 against ET-1-induced vasoconstriction in isolated porcine coronary arteries. This compound also showed the greatest selectivity between ETA and ETB receptors (IC50 for human ETA = 1.2 nM, IC50 for human ETB = 55 microM). In contrast, compound 8 (BQ-123) is a highly soluble, potent, and selective ETA receptor antagonist (pA2 = 7.4, IC50 for human ETA = 8.3 nM, IC50 for human ETB = 61 microM). The sodium salt of 8 is practically freely soluble in saline. These compounds are useful tools for not only in vitro but also in vivo pharmacological studies.
Evidence for field cancerization of the prostate (2009)

True carcinogenic field effects should be distinguished from secondary responses of the microenvironment to a developing tumor, although the latter may still lead to useful clinical prediction tools. Prostate 69: 1470-1479, 2009. (c) 2009 Wiley-Liss, Inc.
RNA-Guided Adenosine Deaminases: Advances and Challenges for Therapeutic RNA Editing (2019)

Targeted transcriptome engineering, in contrast to genome engineering, offers a complementary and potentially tunable and reversible strategy for cellular engineering. In this regard, adenosine to inosine (A-to-I) RNA base editing was recently engineered to make programmable base conversions on target RNAs. Similar to the DNA base editing technology, A-to-I RNA editing may offer an attractive alternative in a therapeutic setting, especially for the correction of point mutations. This Perspective introduces five currently characterized RNA editing systems and serves as a reader's guide for implementing an appropriate RNA editing strategy for applications in research or therapeutics.