gebhart/patrepeval huggingface dataset:
CD19 targeting of chronic lymphocytic leukemia with a novel Fc-domain–engineered monoclonal antibody (2009)

Abstract CD19 is a B cell–specific antigen expressed on chronic lymphocytic leukemia (CLL) cells but to date has not been effectively targeted with therapeutic monoclonal antibodies. XmAb5574 is a novel engineered anti-CD19 monoclonal antibody with a modified constant fragment (Fc)–domain designed to enhance binding of FcγRIIIa. Herein, we demonstrate that XmAb5574 mediates potent antibody-dependent cellular cytotoxicity (ADCC), modest direct cytotoxicity, and antibody-dependent cellular phagocytosis but not complement-mediated cytotoxicity against CLL cells. Interestingly, XmAb5574 mediates significantly higher ADCC compared with both the humanized anti-CD19 nonengineered antibody it is derived from and also rituximab, a therapeutic antibody widely used in the treatment of CLL. The XmAb5574-dependent ADCC is mediated by natural killer (NK) cells through a granzyme B–dependent mechanism. The NK cell–mediated cytolytic and secretory function with XmAb5574 compared with the nonengineered antibody is associated with enhanced NK-cell activation, interferon production, extracellular signal-regulated kinase phosphorylation downstream of Fcγ receptor, and no increased NK-cell apoptosis. Notably, enhanced NK cell–mediated ADCC with XmAb5574 was enhanced further by lenalidomide. These findings provide strong support for further clinical development of XmAb5574 as both a monotherapy and in combination with lenalidomide for the therapy of CLL and related CD19+ B-cell malignancies.
The WaaL O-antigen lipopolysaccharide ligase has features in common with metal ion-independent inverting glycosyltransferases* (2011)

WaaL is a membrane enzyme that catalyzes a key step in lipopolysaccharide (LPS) synthesis: the glycosidic bonding of a sugar at the proximal end of the undecaprenyl-diphosphate (Und-PP) O-antigen with a terminal sugar of the lipid A-core oligosaccharide (OS). Utilizing an in vitro assay, we demonstrate here that ligation with purified Escherichia coli WaaL occurs without adenosine-5'-triphosphate (ATP) and magnesium ions. Furthermore, E. coli and Pseudomonas aeruginosa WaaL proteins cannot catalyze ATP hydrolysis in vitro. We also show that a lysine substitution of the arginine (Arg)-215 residue renders an active protein, whereas WaaL mutants with alanine replacements in the periplasmic-exposed residues Arg-215, Arg-288 and histidine (His)-338 and also the membrane-embedded aspartic acid-389 are nonfunctional. An in silico approach, combining predicted topological information with the analysis of sequence conservation, confirms the importance of a positive charge at the small periplasmic loop of WaaL, since an Arg corresponding to Arg-215 was found at a similar position in all the WaaL homologs. Also, a universally conserved H[NSQ]X(9)GXX[GTY] motif spanning the C-terminal end of the predicted large periplasmic loop and the membrane boundary of the transmembrane helix was identified. The His residue in this motif corresponds to His-338. A survey of LPS structures in which the linkage between O-antigen and lipid A-core OS was elucidated reveals that it is always in the β-configuration, whereas the sugars bound to Und-PP are in the α-configuration. Together, our biochemical and in silico data argue that WaaL proteins use a common reaction mechanism and share features of metal ion-independent inverting glycosyltransferases.
High-Throughput Screens for Small-Molecule Inhibitors of Pseudomonas aeruginosa Biofilm Development (2007)

Pseudomonas aeruginosa is both a model biofilm-forming organism and an opportunistic pathogen responsible for chronic lung infections in cystic fibrosis (CF) patients and infections in burn patients, among other maladies. Here we describe the development of an efficient high-throughput screen to identify small-molecule modulators of biofilm formation. This screen has been run with 66,095 compounds to identify those that prevent biofilm formation without affecting planktonic bacterial growth. The screen is a luminescence-based attachment assay that has been validated with several strains of P. aeruginosa and compared to a well-established but low-throughput crystal violet staining biofilm assay. P. aeruginosa strain PAO1 was selected for use in the screen both because it forms robust biofilms and because genetic information and tools are available for the organism. The attachment-inhibited mutant, strain PAO1 DeltafliC, was used as a screening-positive control. We have also developed and validated a complementary biofilm detachment assay that can be used as an alternative primary screen or secondary screen for the attachment screening-positive compounds. We have determined the potencies of 61 compounds against biofilm attachment and have identified 30 compounds that fall into different structural classes as biofilm attachment inhibitors with 50% effective concentrations of less than 20 microM. These small-molecule inhibitors could lead to the identification of their relevant biofilm targets or potential therapeutics for P. aeruginosa infections.
Role of airway surface liquid and submucosal glands in cystic fibrosis lung disease (2003)

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, an epithelial chloride channel expressed in the airways, pancreas, testis, and other tissues. A central question is how defective CFTR function in CF leads to chronic lung infection and deterioration of lung function. Several mechanisms have been proposed to explain lung disease in CF, including abnormal airway surface liquid (ASL) properties, defective airway submucosal gland function, altered inflammatory response, defective organellar acidification, loss of CFTR regulation of plasma membrane ion transporters, and others. This review focuses on the physiology of the ASL and submucosal glands with regard to their proposed role in CF lung disease. Experimental evidence for defective ASL properties and gland function in CF is reviewed, and deficiencies in understanding ASL/gland physiology are identified as areas for further investigation. New model systems and measurement technologies are being developed to make progress in establishing lung disease mechanisms in CF, which should facilitate mechanism-based design of therapies for CF.
The Treatment of Iron-Deficiency Anemia with Intravenous Iron Dextran (1964)

Abstract Iron-dextran, in doses up to 3000 mg., was administered intravenously by single injection to 37 patients with iron deficiency and to 8 additional patients with acute gastrointestinal bleeding. No serious untoward effects were observed. One patient developed chills and mild abdominal cramps 8 hours after injection. Most of the iron could be accounted for in the circulating blood immediately after the injection. Iron was cleared from the plasma slowly for 3 weeks after the administration. Iron-dextran appears to be a safe and well-tolerated intravenous preparation. It is especially useful in the treatment of iron-deficiency in immobilized patients and individuals with small muscle mass.
Prostate carcinoma knowledge, attitudes, and screening behavior among African-American men in Central Harlem, New York City (2001)

The prevalence of self-reported PSA screening in Central Harlem was lower than that reported for other populations. These findings may be useful in the design of health education campaigns and for counseling innercity, low-income African-American patients appropriately about the disease.
High-Dose-Rate Brachytherapy for Poor-Prognosis, High-Grade Glioma: (Phase II) Preliminary Results (1996)

The short course of brachytherapy provides a good palliation in terms of functional improvement in a high proportion of patients, with low and acceptable toxicity.
Accumulation of ceramide in ischemic human brain of an acute case of cerebral occlusion. (1989)

An increase of ceramide, which is the major component of sphingolipids, was found in the ischemic human brain of an acute case of internal carotid artery occlusion. Amide-linked fatty acids in the ceramide isolated from the ischemic human brain were mostly non-hydroxy fatty acids, such as stearic acid (66.9%) and palmitic acid (20.2%). Other long-chain fatty acids, C24:0 and C21:1, were rare components in the ceramide. The ceramide contained C-20 sphingosine, and the ratio of C-20 to C-18 was 0.13. These findings indicate that an ischemic insult accelerates the degradation of gangliosides and causes an accumulation of ceramide in the ischemic human brain.
Vision and Eating Behavior in Obese Subjects (2003)

The importance of vision in regulating our eating behavior was demonstrated in this study. The obese subjects ate 24% less food blindfolded without feeling less full. Eating blindfolded could be tested as a didactic tool to make obese subjects aware of what factors affect the termination of eating.
Alphaherpesviruses : molecular virology (2011)

This study sought to establish a chronic total occlusion (CTO) model with cell-mediated calcium deposits in rabbit femoral arteries. CTO is the most severe case in atherosclerosis and contains calcium deposits. Previous animal models of CTO do not mimic the gradual occlusion of arteries or have calcium in physiological form. In the present study we tested the strategy of placing tissue-engineering scaffolds preloaded with cells in arteries to develop a novel CTO model. Primary human osteoblasts (HOBs) were first cultured in vitro on polycaprolactone (PCL) scaffolds with 5 ng TGFβ1 loading for 28 days for precalcification. The HOB-PCL construct was then implanted into a rabbit femoral artery for an additional 3, 10 or 28 days. At the time of sacrifice, angiograms and gross histology of arteries were captured to examine the occlusion of arteries. Fluorescent staining of calcium and EDS detection of calcium were used to evaluate the presence and distribution of calcium inside arteries. Rabbit femoral arteries were totally occluded over 28 days. Calcium was presented at CTO sites at 3, 10 and 28 days, with the day 10 specimens showing the maximum calcium. Chronic inflammatory response and recanalization were observed in day 28 CTO sites. A novel CTO model with cell-mediated calcium has been successfully established in a rabbit femoral artery. This model can be used to develop new devices and therapies to treat severe atherosclerotic occlusion.
Blood Pressure and Mortality Among Men With Prior Myocardial Infarction (1995)

In this large cohort of men with prior MI, the association of SBP and DBP with CHD and all-cause mortality varied over the 16-year follow-up period. During early follow-up, in older men only, J- or U-shaped relations were evident. However, after 2 years, these same relations had become positive and graded. Given the substantial excess mortality risk in this cohort associated with high blood pressure, particularly SBP, efforts to gradually lower blood pressure should receive high priority among hypertensive men with prior MI.
Preclinical Development of Oncolytic Immunovirotherapy for Treatment of HPVPOS Cancers (2018)

Immunotherapy for HPV<sup>POS</sup> malignancies is attractive because well-defined, viral, non-self tumor antigens exist as targets. Several approaches to vaccinate therapeutically against HPV E6 and E7 antigens have been adopted, including viral platforms such as VSV. A major advantage of VSV expressing these antigens is that VSV also acts as an oncolytic virus, leading to direct tumor cell killing and induction of effective anti-E6 and anti-E7 T cell responses. We have also shown that addition of immune adjuvant genes, such as IFNβ, further enhances safety and/or efficacy of VSV-based oncolytic immunovirotherapies. However, multiple designs of the viral vector are possible-with respect to levels of immunogen expression and method of virus attenuation-and optimal designs have not previously been tested head-to-head. Here, we tested three different VSV engineered to express a non-oncogenic HPV16 E7/6 fusion protein for their immunotherapeutic and oncolytic properties. We assessed their profiles of efficacy and toxicity against HPV<sup>POS</sup> and HPV<sup>NEG</sup> murine tumor models and determined the optimal route of administration. Our data show that VSV is an excellent platform for the oncolytic immunovirotherapy of tumors expressing HPV target antigens, combining a balance of efficacy and safety suitable for evaluation in a first-in-human clinical trial.
Generation of secretable and nonsecretable interleukin 15 isoforms through alternate usage of signal peptides (1997)

Two isoforms of human interleukin 15 (IL-15) exist. One isoform has a shorter putative signal peptide (21 amino acids) and its transcript shows a tissue distribution pattern that is distinct from that of the alternative IL-15 isoform with a 48-aa signal peptide. The 21-aa signal isoform is preferentially expressed in tissues such as testis and thymus. Experiments using different combinations of signal peptides and mature proteins (IL-2, IL-15, and green fluorescent protein) showed that the short signal peptide regulates the fate of the mature protein by controlling the intracellular trafficking to nonendoplasmic reticulum sites, whereas the long signal peptide both regulates the rate of protein translation and functions as a secretory signal peptide. As a consequence, the IL-15 associated with the short signal peptide is not secreted, but rather is stored intracellularly, appearing in the nucleus and cytoplasmic components. Such production of an intracellular lymphokine is not typical of other soluble interleukin systems, suggesting a biological function for IL-15 as an intracellular molecule.
Requirement for Protein Kinase C θ for Cell Cycle Progression and Formation of Actin Stress Fibers and Filopodia in Vascular Endothelial Cells (1997)

Activation of the protein kinase C (PKC) family with phorbol esters induces endothelial proliferation and angiogenesis, but which of the events that constitute angiogenesis are affected by individual members of the PKC family is unknown. In rat capillary endothelial (RCE) cells, serum stimulation increased expression of a single PKC isoenzyme, PKCtheta, and its translocation to the periphery. Conditional overexpression of a dominant-negative mutant of PKCtheta markedly inhibited RCE proliferation, as well as closure of a "wound" by RCE migration and formation of capillary rings and tubules in vitro. PKCtheta inhibition delayed the endothelial cell cycle at the G2/M phase and prevented formation of actin stress fibers and filopodia but not lamellipodia. The defect in cell morphology and wound closure in PKCtheta-kn cells was reversed by overexpressing kinase-active PKCtheta, indicating that these RCE functions depend upon PKCtheta substrates. Thus, PKCtheta is required for multiple processes essential for angiogenesis and wound repair, including endothelial mitosis, maintenance of a normal actin cytoskeleton, and formation of an enclosed tube.
Tissue glutathione, nutrition, and oxidative stress (1993)

Glutathione, a cysteine-containing tripeptide, is the most abundant nonprotein thiol in mammalian cells. Glutathione plays an important role in the detoxification of xenobiotic compounds and in the antioxidation of reactive oxygen species and free radicals. Because of its multiple functions in various tissues and its involvement in many diseases and malnutrition, a clear understanding of the interrelationships among tissue glutathione, nutrition, and oxidative stress is clinically relevant. The focus of this review is to discuss the regulation of tissue glutathione concentration by diet and nutritional status, and to apply this information to those diseases and malnutrition in which decreased tissue glutathione and increased oxidative stress are implicated. A potential strategy to rapidly restore glutathione for both antioxidant and immune defense systems before therapeutic treatment in malnourished patients is discussed.
Dipeptidyl peptidase IV (DP IV) and superoxide dismutase activity in thymus-derived lymphocytes: effects of inhibitory peptides and Zn2+ in vitro. (1990)

DP IV and superoxide dismutase (SOD) activity in thymus-derived lymphocytes of rats was assayed in vitro. The DP IV activity was measured fluorimetrically by hydrolysis of Leu-Pro-AMC, and the SOD activity by the inhibition of autooxidation of L-adrenaline. In order of their competitive inhibitory potency the following peptides were tested against DP IV and SOD activity: Ile-Pro-Ile (diprotin A), Val-Pro-Leu (diprotin B), Ile-Pro, Leu-Pro, Val-Pro, Tyr-D--Ala-Ala-Pro, Phe-Pro, Tyr-Pro, Ala-Ala-Pro and Gly-Pro. The peptides, in the order of their potency against DP IV, were effective to inhibit the SOD activity in T lymphocytes. Zn2+ ions exerted an inhibition on both DP IV and SOD activity in a near equimolar concentration. The involvement of Zn2+ as well as the peptides liberated by hydrolysis of polypeptides in regulation of cell-mediated immune responses has been discussed.
Optically transparent digitally tunable wavelengthfilter (1995)

A new digital architecture combining a spatial light modulator written dynamic hologram and a fixed diffractive grating has been demonstrated to produce a tunable wavelength filter with a tuning resolution of 2.5 nm over a 160 nm range. Three modes of a broadband 1.45 µm laser diode have been isolated using the filter and selectively coupled into singlemode communications fibre.
Acute Biomarkers of Traumatic Brain Injury: Relationship between Plasma Levels of Ubiquitin C-Terminal Hydrolase-L1 and Glial Fibrillary Acidic Protein (2013)

Biomarkers are important for accurate diagnosis of complex disorders such as traumatic brain injury (TBI). For a complex and multifaceted condition such as TBI, it is likely that a single biomarker will not reflect the full spectrum of the response of brain tissue to injury. Ubiquitin C-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) are among of the most widely studied biomarkers for TBI. Because UCH-L1 and GFAP measure distinct molecular events, we hypothesized that analysis of both biomarkers would be superior to analysis of each alone for the diagnosis and prognosis of TBI. Serum levels of UCH-L1 and GFAP were measured in a cohort of 206 patients with TBI enrolled in a multicenter observational study (Transforming Research and Clinical Knowledge in Traumatic Brain Injury [TRACK-TBI]). Levels of the two biomarkers were weakly correlated to each other (r=0.364). Each biomarker in isolation had good sensitivity and sensitivity for discriminating between TBI patients and healthy controls (area under the curve [AUC] 0.87 and 0.91 for UCH-L1 and GFAP, respectively). When biomarkers were combined, superior sensitivity and specificity for diagnosing TBI was obtained (AUC 0.94). Both biomarkers discriminated between TBI patients with intracranial lesions on CT scan and those without such lesions, but GFAP measures were significantly more sensitive and specific (AUC 0.88 vs. 0.71 for UCH-L1). For association with outcome 3 months after injury, neither biomarker had adequate sensitivity and specificity (AUC 0.65-0.74, for GFAP, and 0.59-0.80 for UCH-L1, depending upon Glasgow Outcome Scale Extended [GOS-E] threshold used). Our results support a role for multiple biomarker measurements in TBI research. ( ClinicalTrials.gov Identifier NCT01565551).
Resonant acoustic radiation force optical coherence elastography (2013)

We report on a resonant acoustic radiation force optical coherence elastography (ARF-OCE) technique that uses mechanical resonant frequency to characterize and identify tissues of different types. The linear dependency of the resonant frequency on the square root of Young's modulus was validated on silicone phantoms. Both the frequency response spectrum and the 3D imaging results from the agar phantoms with hard inclusions confirmed the feasibility of deploying the resonant frequency as a mechanical contrast for tissue imaging. Furthermore, the results of resonant ARF-OCE imaging of a post-mortem human coronary artery with atherosclerosis demonstrate the potential of the resonant ARF-OCE as a non-invasive method for imaging and characterizing vulnerable plaques.
Fabrication of Stretch-Oriented Regioregular Poly(3-Hexylthiophene) film and Its Application to Organic Field-Effect Transistors (2009)

We report a fabrication process for organic field-effect transistors (OFETs) based on stretch-oriented regioregular poly(3-hexylthiophene) (rr-P3HT) film and the anisotropic carrier transport properties in the OFETs. The optical absorption spectra and XRD results indicate that π-conjugated rr-P3HT chains are aligned in the stretching direction with the π-stacking polymer planes parallel to the substrate. The field-effect hole mobility in a current flow parallel to the stretching direction is larger by a factor of 3.4 compared to that perpendicular to the stretching direction. These results indicate that charge transport via the π-conjugated rr-P3HT chains is advantageous in the stretch-oriented rr-P3HT film.
CALCIUM DOBESILATE: PHARMACOLOGICAL PROFILE RELATED TO ITS USE IN DIABETIC RETINOPATHY (1999)

Calcium dobesilate (Doxium) is used in the treatment of diabetic retinopathy. Clinical studies show a slowdown of the progression of the disease after long-term oral treatment. The main action of the drug is related to a reduction of microvascular permeability as measured by different parameters and methods (vitreous fluorophotometry, retinal haemorrhages, skin capillary resistance, blood albumin leakage, blood viscosity) leading to improved visual acuity. The pharmacological activity may be explained in part by the antioxidant properties of calcium dobesilate and its action on endothelium through the synthesis of nitric oxide, increasing the endothelium-dependent relaxation. The antioxidant effect was demonstrated in different in vitro and in vivo models by decreasing the peritoneal permeability in rats induced by pro-oxidant substances. Moreover, vascular leakage was also decreased by calcium dobesilate in a reperfusion model in streptozotocin induced diabetic rats after ischaemia of the central artery of the retina. Doxium may also preserve vascular endothelial function by acting directly as antioxidant to protect lipids from peroxidation.
Gene Variants of VAMP8 and HNRPUL1 Are Associated With Early-Onset Myocardial Infarction (2006)

Variants in 2 genes were associated with early-onset MI: VAMP8, which is involved in platelet degranulation, and HNRPUL1, which encodes a ribonuclear protein. The identification of these variants could improve understanding of disease mechanisms and suggest novel drug targets.
Cigarette smoking and pre-eclampsia: their association and effects on clinical outcomes (2001)

Objective : To determine the effects of smoking on pre-eclampsia in an inner-city, predominantly African-American prenatal population. Methods : We performed a retrospective cohort study of all primigravidas who delivered singletons in our institution between 1980 and 1989. The study population consisted of 1862 smokers and 16 508 non-smokers. Univariate analysis and multiple logistic regression were used to identify relationships between smoking and adverse outcomes. Results : The pre-eclampsia rate was significantly lower among smokers (11.3% vs. 13.0%, OR 0.85, 95% CI 0.73-0.99). Smokers with pre-eclampsia had higher rates of infants with low birth weight (OR 1.44, 95% CI 1.26-1.65) and very low birth weight (OR 1.85, 95% CI 1.55-2.20) and higher rates of placental abruption (OR 3.49, 95% CI 1.65-7.28) compared to non-smoking pre-eclamptics. This relationship persisted after correction for age, race, chronic hypertension and pre-eclampsia as confounding variables. Conclusions : Cigarette smoking was associated with a lower rate of pre-eclampsia among primigravidas independently of other maternal factors. Perinatal outcomes were significantly worsened among pre-eclamptics who smoked.