gebhart/patrepeval huggingface dataset:
β-Amyloid Stimulation of Inducible Nitric-oxide Synthase in Astrocytes Is Interleukin-1β- and Tumor Necrosis Factor-α (TNFα)-dependent, and Involves a TNFα Receptor-associated Factor- and NFκB-inducing Kinase-dependent Signaling Mechanism (2000)

In Alzheimer's disease, beta-amyloid (Abeta) plaques are surrounded by activated astrocytes and microglia. A growing body of evidence suggests that these activated glia contribute to neurotoxicity through the induction of inflammatory cytokines such as interleukin (IL)-1beta and tumor necrosis factor-alpha (TNFalpha) and the production of neurotoxic free radicals, mediated in part by the expression of inducible nitric-oxide synthase (iNOS). Here, we address the possibility that Abeta-stimulated iNOS expression might result from an initial induction of IL-1beta and TNFalpha. We find that in Abeta-stimulated astrocyte cultures, IL-1beta and TNFalpha production occur before iNOS production, new protein synthesis is required for increased iNOS mRNA levels, and the IL-1 receptor antagonist IL-1ra can inhibit nitrite accumulation. Likewise, dominant-negative mutants of tumor necrosis factor-alpha receptor-associated factor (TRAF) 6, TRAF2, and NFkappaB-inducing kinase (NIK), intracellular proteins involved in IL-1 and TNFalpha receptor signaling cascades, inhibit Abeta-stimulated iNOS promoter activity. Our data suggest that Abeta stimulation of astrocyte iNOS is mediated in part by IL-1beta and TNFalpha, and involves a TRAF6-, TRAF2-, and NIK-dependent signaling mechanism.
An Anti-Idiotype Vaccine Elicits a Specific Response to N-Glycolyl Sialic Acid Residues of Glycoconjugates in Melanoma Patients (2002)

We generated the 1E10 gamma-type anti-idiotype mAb (Ab2) specific to an Ab1 mAb able to react specifically with N-glycolyl-containing gangliosides and with Ags expressed on human melanoma and breast carcinoma cells. This Ab2 mAb induced an Ab response in animal models sharing immunochemically defined idiotopes with the Ab1. The treatment of tumor-bearing mice with 1E10 mAb induced a strong antitumor activity. A clinical trial was conducted in 20 patients with advanced malignant melanoma. Patients were treated with six intradermal injections of aluminum hydroxide-precipitated 1E10 anti-Id mAb given at 2-wk intervals. Sixteen of the 17 patients who received at least four doses of the anti-Id vaccine develop Ab3 Abs capable of inhibiting Ab2 binding to Ab1 (Ab3Id+). In contrast to the incapacity of 1E10 mAb to generate Ab3 Abs with the same antigenic specificity as the Ab1 mAb in mice, a very specific and strong Ab3 response against N-glycolyl-containing gangliosides was induced in 16 patients (Ab3Ag+). No evidence of serious or unexpected adverse effects has been observed in this clinical trial. 1E10 anti-Id vaccine was safe, well tolerated, and immunologically effective, with most patients being able to generate a specific immune response against 1E10 and Neu-glycolyl-GM(3) ganglioside.
Antithrombin: structure and function. (1991)

This review will summarize our knowledge of the physical properties of AT, the mechanism of proteinase inhibition, and the mechanism whereby heparin augments the activity of AT. In addition, we will summarize the results of chemical modification studies and recent discoveries of AT mutations that have illuminated features of the structure and function of AT
In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads (1997)

Antibiotic-impregnated beads are used in the dead bone space following debridement surgery to deliver local, high concentrations of antibiotics. Polymethylmethacrylate (PMMA), 2,000-molecular-weight (MW) polylactic acid (PLA), Poly(DL-lactide)-coglycolide (PL:CG; 90:10, 80:20, and 70:30), and the combination 2,000-MW PLA-70:20 PL:CG were individually mixed with clindamycin, tobramycin, or vancomycin. Beads were placed in 1 ml of phosphate-buffered saline (PBS) and incubated at 37 degrees C. The PBS was changed daily, and the removed PBS samples were stored at -70 degrees C until the antibiotic in each sample was determined by microbiological disk diffusion assay. Nondissolving PMMA beads with tobramycin and clindamycin had concentrations well above breakpoint sensitivity concentrations (i.e., the antibiotic concentrations at the transition point between bacterial killing and resistance to the antibiotic) for more than 90 days, but vancomycin concentrations dropped by day 12. ALl PLA, PL:CG, and the 2,000-MW PLA-70:30 PL:CG biodegradable beads release high concentrations of all the antibiotics in vitro for the period of time needed to treat bone infections (i.e., 4 to 8 weeks). Antibiotic-loaded PLA and PL:CG beads have the advantage of better antibiotic elution and the ability to biodegradable (thereby averting the need for secondary surgery for bead removal) compared to the PMMA beads presently used in the clinical setting.
The economic burden of psoriasis with high comorbidity among privately insured patients in the United States (2018)

HRU and cost burden of psoriasis are substantial, and increase with the development of psoriasis-related comorbidities.
Staphylococcal Enterotoxin H Displays Unique MHC Class II-Binding Properties (1999)

Staphylococcal enterotoxin H (SEH) has been described as a superantigen by sequence homology with the SEA subfamily and briefly characterized for its in vivo activity. In this study, we demonstrate that SEH is a potent T cell mitogen and inducer of T cell cytotoxicity that possesses unique MHC class II-binding properties. The apparent affinity of SEH for MHC class II molecules is the highest affinity ever measured for a staphylococcal enterotoxin (Bmax1/2 approximately 0.5 nM for MHC class II expressed on Raji cells). An excess of SEA or SEAF47A, which has reduced binding to the MHC class II alpha-chain, is able to compete for binding of SEH to MHC class II, indicating an overlap in the binding sites at the MHC class II beta-chain. The binding of SEH to MHC class II is like SEA, SED, and SEE dependent on the presence of zinc ions. However, SEH, in contrast to SEA, binds to the alanine-substituted DR1 molecule, betaH81A, believed to have impaired zinc-bridging capacity. Furthermore, alanine substitution of residues D167, D203, and D208 in SEH decreases the affinity for MHC class II as well as its in vitro potency. Together, this indicates an MHC class II binding site on SEH with a different topology as compared with SEA. These unique binding properties will be beneficial for SEH to overcome MHC class II isotype variability and polymorphism as well as to allow an effective presentation on APCs also at low MHC class II surface expression.
Intermittent dosing of the farnesyl transferase inhibitor tipifarnib (R115777) in advanced malignant solid tumors: a phase I California Cancer Consortium Trial (2005)

Tipifarnib (R115777) inhibits farnesylation of key proteins that modulate signaling pathways implicated in cell growth and proliferation, including members of the Ras and Rho families. It has broad-spectrum antiproliferative activity in vitro and in vivo. Clinical trials employing a continuous administration schedule have demonstrated dose-limiting neurotoxicity and myelosuppression. Preclinical studies have shown that intermittent oral administration can suppress tumor growth comparable to continuous administration. We conducted a National Cancer Institute-sponsored phase I trial to determine the feasibility of an intermittent dosing schedule of R115777 given orally twice daily on weeks 1 and 3 of a 28-day cycle in patients with malignant solid tumors. Starting dose was 300 mg twice daily (b.i.d.) with escalation by 300 mg b.i.d. increments over six dose levels to a maximum of 1800 mg b.i.d. Dose-limiting toxicity (DLT) was defined as any grade 3 or 4 non-hematologic toxicity, grade 4 thrombocytopenia, grade 4 neutropenia (ANC) with fever (38.3 degrees C or above) or a documented infection. Twenty-one patients with advanced solid tumors, all of whom had prior systemic therapy, were accrued. Grade 3 fatigue was dose limiting for two of three patients at the 900 mg b.i.d. dose level. Although no responses were seen, four of six patients with stable disease remained on study for at least a year (16, 17, 13 and 12 months) before developing progressive disease. Three of these prolonged stable disease patients had non-small cell lung cancer. We conclude that intermittent dosing of R115777 is feasible and tolerable. The recommended phase II dose is 600 mg orally b.i.d. on alternate weeks.
Control of Surface State Emission via Phosphonic Acid Modulation in Ultrasmall CdSe Nanocrystals: The Role of Ligand Electronegativity (2009)

Pinned emission from ultrasmall (<1.7 nm) CdSe nanocrystals is dominated by surface trap state emission. In sharp contrast to bulk defect emission, optical properties of the nanocrystal can be tuned through surface chemistry. We demonstrate the ability to alter this pinned emission from 2.79 to 2.91 eV by varying the phosphonic acid ligand. The blue shifting emission is attributed to the increased electronegativity of shorter chain length ligands. Further, the quantum yield of these nanocrystals can be enhanced by increasing the chain length of the ligand. These results indicate that for ultrasmall nanocrystals, the surface ligands play the dominant role in the emission properties.
Role of ATP dependent potassium channels in myocardial ischaemia (1992)

Recently, a class of potassium (K) channels has been discovered which are regulated by the intracellular level of ATP. These channels have been termed ATP dependent K channels (KATP) and have been found to exist in the heart, skeletal muscle, pancreatic beta cells, brain, and smooth muscle. In this article, we discuss the function of the KATP channel in the ischaemic myocardium and present evidence to suggest that activation of these channels may, on the one hand, result in a marked cardioprotective effect from reversible or irreversible electrical, functional or biochemical damage or, on the other hand, have the potential to produce electrical instability and a proarrhythmic effect. The therapeutic potential of potassium channel modulators is also discussed.
Generation of a serum free CHO DG44 cell line stably producing a broadly protective anti-influenza virus monoclonal antibody (2017)

Because of the broad neutralization and in vivo protection across influenza A and influenza B virus strains, monoclonal antibody CR9114 is widely used in influenza virus research as a positive control in many experiments. To produce amounts sufficient for the demand requires regular transient transfections, resulting in varying yield as well as differing batch to batch quality. Here, we report the development of a serum-free CHO DG44 cell line, stably producing a CR9114-like antibody with a potential to become a useful influenza virus research tool.
Blood platelets and sepsis pathophysiology: A new therapeutic prospect in critical ill patients? (2017)

Beyond haemostasis, platelets have emerged as versatile effectors of the immune response. The contribution of platelets in inflammation, tissue integrity and defence against infections has considerably widened the spectrum of their role in health and disease. Here, we propose a narrative review that first describes these new platelet attributes. We then examine their relevance to microcirculatory alterations in multi-organ dysfunction, a major sepsis complication. Rapid progresses that are made on the knowledge of novel platelet functions should improve the understanding of thrombocytopenia, a common condition and a predictor of adverse outcome in sepsis, and may provide potential avenues for management and therapy.
Molecular Biomarkers for Cancer Detection in Blood and Bodily Fluids (2006)

Cancer is a major and increasing public health problem worldwide. Traditionally, the diagnosis and staging of cancer, as well as the evaluation of response to therapy have been primarily based on morphology, with relatively few cancer biomarkers currently in use. Conventional biomarker studies have been focused on single genes or discrete pathways, but this approach has had limited success because of the complex and heterogeneous nature of many cancers. The completion of the human genome project and the development of new technologies have greatly facilitated the identification of biomarkers for assessment of cancer risk, early detection of primary cancers, monitoring cancer treatment, and detection of recurrence. This article reviews the various approaches used for development of such markers and describes markers of potential clinical interest in major types of cancer. Finally, we discuss the reasons why so few cancer biomarkers are currently available for clinical use.
Rescue of the Pseudo-Vitamin D Deficiency Rickets Phenotype of CYP27B1-Deficient Mice by Treatment With 1,25-Dihydroxyvitamin D3: Biochemical, Histomorphometric, and Biomechanical Analyses (2003)

The treatment of choice for pseudo-vitamin D deficiency rickets (PDDR), caused by mutations in the 25-hydroxyvitamin D-1alpha-hydroxylase (CYP27B1; 1alpha-OHase) gene, is replacement therapy with 1,25(OH)2D3. We have previously engineered an animal model of PDDR by targeted inactivation of the 1alpha-OHase gene in mice. Replacement therapy was performed in this model. The 1alpha-OHase-/- mice and heterozygote controls were treated with 500 pg of 1,25(OH)2D/g body weight/day for 2 weeks, followed by 100 pg of 1,25(OH)2D3/g body weight/day for an additional 3 weeks before death at 8 weeks of age. Blood biochemistry analysis revealed that the rescue treatment corrected the hypocalcemia and secondary hyperparathyroidism. The daily injections of 1,25(OH)2D3 induced strong expression of CYP24, the 25-hydroxyvitamin D 24-hydroxylase gene. Bone histology and histomorphometry confirmed that the rickets and osteomalacia were cured. The rescue regimen also restored the biomechanical properties of the bone tissue within normal parameters. These results show that chronic treatment with the active 1,25(OH)2D3 metabolite is effective to rescue the PDDR phenotype of 1alpha-OHase mutant mice.
Feasibility of an Epidemiologic Study of Submariners Who Received Radium Irradiation Treatment (1996)

Thousands of World War II veterans reportedly received nasopharyngeal irradiation with radium-tipped applicators for treatment of middle ear pressure problems known as aerotitis media. Because of concerns about adverse health effects of radiation exposure, including the increased risk of head and neck cancer, the feasibility of identification of a large number of veterans with documented exposure for an epidemiologic study was investigated. The irradiation treatments were found to have occurred at the New London Naval Medical Research Department, at several Naval Hospitals, and aboard ships during the period from 1945 to 1952. Documentation of the treatment on veterans' medical records was sparse and inconsistent. Only 8 of 668 records reviewed were found to have evidence of the radium treatment: 7 from 33 self-reported veterans and 1 from 635 names on submarine school class rosters and submarine muster rolls. There appears to be no practical way to identify from military service and medical records a large number of submariners who received the treatment.
Structure and Conformational Changes in the C-terminal Domain of the β2-Adrenoceptor (2007)

The C terminus of the beta(2)-adrenoceptor (AR) interacts with G protein-coupled receptor kinases and arrestins in an agonist-dependent manner, suggesting that conformational changes induced by ligands in the transmembrane domains are transmitted to the C terminus. We used fluorescence resonance energy transfer (FRET) to examine ligand-induced structural changes in the distance between two positions on the beta(2)-AR C terminus and cysteine 265 (Cys-265) at the cytoplasmic end of transmembrane domain 6. The donor fluorophore FlAsH (Fluorescein Arsenical Helix binder) was attached to a CCPGCC motif introduced at position 351-356 in the proximal C terminus or at the distal C terminus. An acceptor fluorophore, Alexa Fluor 568, was attached to Cys-265. FRET analyses revealed that the average distances between Cys-265 and the proximal and distal FlAsH sites were 57 and 62A(,) respectively. These relatively large distances suggest that the C terminus is in an extended, relatively unstructured conformation. Nevertheless, we observed ligand-specific changes in FRET. All ligands induced an increase in FRET between the proximal C-terminal FlAsH site and Cys-265. Ligands that have been shown to induce arrestin-dependent ERK activation, including the catecholamine agonists and the inverse agonist ICI118551, led to a decrease in FRET between the distal FlAsH site and Cys-265, whereas other ligands had no effect or induced a small increase in FRET. Taken together the results provide new insight into the structure of the C terminus of the beta(2)-AR as well as ligand-induced conformational changes that may be relevant to arrestin-dependent regulation and signaling.
Back Cover: Ceria Nanoparticles that can Protect against Ischemic Stroke (Angew. Chem. Int. Ed. 44/2012) (2012)

Ceria nanoparticles are known to exhibit free-radical scavenging activity by reversibly binding oxygen. In their Communication on page 11039 ff., S.-H. Lee, T. Hyeon, et al. show that discrete, uniform 3 nm PEGylated ceria nanoparticles can protect against ischemic stroke by scavenging reactive oxygen species and reducing apoptosis. Optimal doses of ceria nanoparticles reduce infarct volumes and the rate of ischemic cell death, and target the infarct site in vivo.
The Replicative Helicases of Bacteria, Archaea, and Eukarya Can Unwind RNA-DNA Hybrid Substrates (2006)

Replicative helicases are hexameric enzymes that unwind DNA during chromosomal replication. They use energy from nucleoside triphosphate hydrolysis to translocate along one strand of the duplex DNA and displace the complementary strand. Here, the ability of a replicative helicase from each of the three domains, bacteria, archaea, and eukarya, to unwind RNA-containing substrate was determined. It is shown that all three helicases can unwind DNA-RNA hybrids while translocating along the single-stranded DNA. No unwinding could be observed when the helicases were provided with a single-stranded RNA overhang. Using DNA, RNA, and DNA-RNA chimeric oligonucleotides it was found that whereas the enzymes can bind both DNA and RNA, they could translocate only along DNA and only DNA stimulates the ATPase activity of the enzymes. Recent observations suggest that helicases may interact with enzymes participating in RNA metabolism and that RNA-DNA hybrids may be present on the chromosomes. Thus, the results presented here may suggest a new role for the replicative helicases during chromosomal replication or in other cellular processes.
Heparan Sulfate Biosynthesis (2012)

Nearly all vertebrate cells have been shown to express heparan sulfate proteoglycans (HSPGs) at the cell surface. The HSPGs bind to many secreted signaling proteins, including numerous growth factors, cytokines, and morphogens, to affect their tissue distribution and signaling. The heparan sulfate (HS) chains may have variable length and may differ with regard to both degree and pattern of sulfation. As the sulfation pattern of HS chains in most cases will determine if an interaction with a potential ligand will take place, as well as the affinity of the interaction, a key to understanding the function of HSPGs is to clarify how HS biosynthesis is regulated in different biological contexts. This review provides an introduction to the current understanding of HS biosynthesis and its regulation, and identifies research areas where more knowledge is needed to better understand how the HS biosynthetic machinery works.
Cellular levels and activity of the flagellar sigma factor FliA of Escherichia coli are controlled by FlgM‐modulated proteolysis (2007)

In Escherichia coli the flagellar regulon consists of more than 60 genes organized in three hierarchically and temporally regulated transcriptional classes. The flagellar sigma factor FliA (sigma(28)) is responsible for class 3 expression and, in the early phase of flagellar assembly, is inhibited by its anti-sigma factor FlgM. The flagellar hook basal body forms a type III secretion system capable of secreting both flagellar subunits and FlgM. This results in release and therefore activation of FliA and class 3 expression. Here we demonstrate that FliA is also subject to proteolysis which mainly depends on Lon protease. FlgM not only acts as an anti-sigma factor but also protects FliA from being degraded. Based on quantitative measurements over time upon experimental induction of the flagellar cascade as well as during the growth cycle of a motile strain, we show that FliA proteolysis increases in parallel to class 3 expression, i.e. correlates with FlgM secretion and the phase of highest activity of FliA. Thus, when FlgM is not available due to secretion or mutation, and with RNA polymerase interaction being only transient during the transcription initiation cycle, the proteases can degrade FliA. Experiments with a lon mutant indicate that Lon protease and FliA degradation maintain appropriate FliA : FlgM stoichiometry upon induction of the flagellar system and thereby contribute to timely shut-off of this system.
A rare allele of a microsatellite located in the tyrosine hydroxylase gene found in schizophrenic patients. (1995)

We investigated the frequency of a rare variant of a common microsatellite tetrarepeat allele in the tyrosine hydroxylase gene in 2 independent ethnic groups of schizophrenic patients and their matched controls. In a French population we found the rare variant allele in 5 of 94 (5%) unrelated chronic schizophrenic patients and in none of 145 unaffected controls, thus yielding a significant association (p < 0.01) between schizophrenia and the tyrosine hydroxylase gene. Similarly, in a replication study, we found the rare allele in 4 of 44 (9%) unrelated chronic schizophrenic patients and in none of 44 unaffected controls in a Tunisian population. Albeit the reason of this association is at the moment unknown, it is possible that this polymorphism in the tyrosine hydroxylase gene may be involved in the regulation of its activity.
Topical antibiotic ear drops: are they safe? (2006)

A discharging ear is a very common condition for the general practitioner and the ENT surgeon. Oral and intravenous antibiotics have potential complications, are costly, and exhibit increasing resistance. This study explores the advantages and disadvantages of all common otic preparations and compares effectiveness, safety, cost and complication rates. In chronic otitis media (chronic discharging ears), topical antibiotics seem to be the treatment of choice by comparison with oral or intravenous antibiotics. Cultures and antibiograms do not correspond directly to clinical efficacy, as laboratory determination of resistance does not take into account the high concentration of antibiotics in local preparations. It is safer to use quinolone drops as a first-line treatment, but it is still possible to use short courses of other drops if quinolones are either unavailable or contraindicated (e.g. allergy), or when bacteria are resistant to them. However, in such a situation, a round window membrane involved in an established inflammatory process and therefore less permeable to the passage of topical preparations is the preferred setting, as ototoxicity is a potential complication, especially in the case of gentamicin, in which case patients should be warned accordingly.