gebhart/patrepeval huggingface dataset:
Tumor Cell Expression of CD59 Is Associated With Resistance to CD20 Serotherapy in Patients With B-Cell Malignancies (2001)

SUMMARY: The anti-CD20 chimeric monoclonal antibody rituximab (Rituxan) is used to treat patients with various B-cell tumors, including patients with plasma cell dyscrasias who have CD20+ disease. Many patients with CD20+ disease have either primary unresponsive disease or progress after initially responding to rituximab; therefore, understanding how tumor cells are, or become, resistant to rituximab is of clinical relevance. In this report, we determined whether tumor cells express antigens that block complement-mediated lysis or antibody-dependent cell-mediated cytotoxicity (ADCC) and thereby contribute to rituximab resistance. We demonstrate that expression of the complement regulator CD59 is associated with resistance to rituximab-mediated complement lysis of multiple myeloma (MM) and non-Hodgkin's lymphoma (NHL) cell lines. Moreover, neutralization of CD59 using a blocking monoclonal antibody reversed resistance to rituximab-mediated complement lysis of CD20++ CD59++ ARH-77 MM cells. In addition, we demonstrate the presence of CD59 and rituximab binding on viable tumor cells from patients with MM and Waldenstrom's macroglobulinemia with progressive disease despite rituximab therapy. Last, we also examined MM and NHL B-cell lines, as well as patient tumor cells, for the expression of other antigens that may have a role in blocking ADCC activity, such as Fas ligand (FasL), MUC1, or TRAIL. FasL, MUC1, and/or TRAIL were coexpressed with complement regulators on many of these cells. These studies therefore show that complement regulators, particularly CD59 and antigens that may block ADCC, are present on various B-cell tumors and associated with rituximab resistance in patients. A prospective, clinical study is assessing the role of these antigens in mediating rituximab resistance.
Identification of Clusterin Domain Involved in NF-κB Pathway Regulation (2009)

Clusterin (CLU) is a ubiquitous protein that has been implicated in tumorigenesis, apoptosis, inflammation, and cell proliferation. We and others have previously shown that CLU is an inhibitor of the NF-kappaB pathway. However, the exact form of CLU and the region(s) of CLU involved in this effect were unknown. Using newly generated molecular constructs encoding for CLU and various regions of the molecule, we demonstrated that the presecretory form of CLU (psCLU) form bears the NF-kappaB regulatory activity. Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation. These homologies were localized in the disulfide constraint region of CLU. We generated a specific molecular construct of this region, named DeltaCLU, and showed that it has the same NF-kappaB regulatory activity as CLU. Neither the alpha-chain nor the beta-chain of CLU had any NF-kappaB regulatory activity. Furthermore, we showed that following tumor necrosis factor-alpha stimulation of transfected cells, we could co-immunoprecipitate phospho-IkappaB-alpha with DeltaCLU. Moreover, we showed that DeltaCLU could localize both in the cytoplasm and in the nucleus. These results demonstrate the identification of a new CLU activity site involved in NF-kappaB pathway regulation.
ESCHERICHIA COLI LIPOPOLYSACCHARIDE POTENTIATION AND INHIBITION OF RAT NEONATAL MICROGLIA SUPEROXIDE ANION GENERATION (1999)

The effects of lipopolysaccharide (LPS) on the central nervous system, one of the first organs to be affected by sepsis, are still incompletely understood. Rat microglia (BMphi) constitute the main leukocyte-dependent source of reactive oxygen species in the central nervous system. The in vitro effect of LPS on agonist-stimulated superoxide (O2-) generation from BMphi appears controversial. Our purpose was to determine the time- and concentration-dependent effect of Escherichia coil LPS on phorbol-12 myristate 13-acetate-stimulated O2- generation from BMphi. Our results demonstrate that BMphi O2- generation in vitro peaked 17 h after stimulation of with .3 ng/mL LPS. Furthermore, stimulation of BMphi with LPS for 17 h resulted in the following concentration-dependent responses: .1-1 ng/mL LPS induced no prior mediator generation but potently enhanced subsequent phorbol-12 myristate 13-acetate-stimulated O2- generation; 3-10 ng/mL LPS caused nitric oxide, tumor necrosis factor-alpha (TNF-alpha), thromboxane B2 and matrix metalloproteinase-9 release although partially inhibiting ensuing phorbol-12 myristate 13-acetate-stimulated O2- generation; 30-100 ng/mL LPS, maximized nitric oxide, TNF-alpha, thromboxane B2, matrix metalloproteinase-9 generation with concomitant lactic dehydrogenase release although strongly deactivating successive phorbol-12 myristate 13-acetate-stimulated O2 production. Our in vitro studies suggest that enhanced release of these four mediators (nitric oxide, TNF-alpha, thromboxane B2, and matrix metalloproteinase-9) during stimulation of BMphi with LPS might play a critical role in the subsequent ability of BMphi to generate O2- in vivo. Potential clinical implications of our findings are suggested by the fact that LPS levels similar to the ones used in this study have been observed in cerebrospinal fluid both in Gram-negative meningitis and sepsis.
Rhodotorula mucilaginosa Catheter-related Fungemia in a Patient with Sickle Cell Disease: Case Presentation and Literature Review (2007)

Rhodotorula mucilaginosa (formerly Rhodotorula rubra) is a ubiquitous, environmental, urease-positive yeast that does not ferment sugars and can assimilate various carbohydrates. Characterized by the salmon-pink to coral-red color of its colonies, Rhodotorula mucilaginosa can disseminate and cause significant disease. We present a case of sustained Rhodotorula mucilaginosa catheter-related fungemia in a patient with sickle cell anemia who refused removal of the implanted port. The patient remained clinically stable, with blood cultures persistently growing Rhodotorula mucilaginosa, despite appropriate antifungal therapy. An extensive literature review revealed a wide range of clinical manifestations in immunocompromised patients. Susceptibility patterns to different antifungal agents and therapeutic considerations are thoroughly discussed. Rhodotorula mucilaginosa can be a significant, recalcitrant pathogen in immunocompromised patients and prompt treatment should be instituted.
FGF19 as a Postprandial, Insulin-Independent Activator of Hepatic Protein and Glycogen Synthesis (2011)

Fibroblast growth factor (FGF) 19 is an enterokine synthesized and released when bile acids are taken up into the ileum. We show that FGF19 stimulates hepatic protein and glycogen synthesis but does not induce lipogenesis. The effects of FGF19 are independent of the activity of either insulin or the protein kinase Akt and, instead, are mediated through a mitogen-activated protein kinase signaling pathway that activates components of the protein translation machinery and stimulates glycogen synthase activity. Mice lacking FGF15 (the mouse FGF19 ortholog) fail to properly maintain blood concentrations of glucose and normal postprandial amounts of liver glycogen. FGF19 treatment restored the loss of glycogen in diabetic animals lacking insulin. Thus, FGF19 activates a physiologically important, insulin-independent endocrine pathway that regulates hepatic protein and glycogen metabolism.
Pulmonary vasodilator therapy in the failing Fontan circulation: rationale and efficacy (2015)

The Fontan operation is the final step of palliation for patients with a functionally single ventricle. Since its introduction in the 1970s, the Fontan surgery has become part of a successful surgical strategy that has improved single ventricle mortality. In recent years, we have become more aware of the limitations and long-term consequences of the Fontan physiology. Pulmonary vascular resistance plays an important role in total cavopulmonary circulation, and has been identified as a potential therapeutic target to mitigate Fontan sequelae. In this review, we will discuss the results of different pulmonary vasodilator trials and the use of pulmonary vasodilators as a treatment strategy for Fontan patients.
Polyoxometalates in Medicine (1998)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPolyoxometalates in MedicineJeffrey T. Rhule, Craig L. Hill, Deborah A. Judd, and Raymond F. SchinaziView Author Information Department of Chemistry, Emory University, Atlanta, Georgia 30322 Veterans Affairs Medical Center, and Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine, Decatur, Georgia 30033 Cite this: Chem. Rev. 1998, 98, 1, 327–358Publication Date (Web):February 5, 1998Publication History Received27 September 1997Revised3 November 1997Published online5 February 1998Published inissue 1 February 1998https://pubs.acs.org/doi/10.1021/cr960396qhttps://doi.org/10.1021/cr960396qresearch-articleACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views7930Altmetric-Citations1655LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Anions,Antimicrobial agents,Inhibition,Peptides and proteins,Viruses Get e-Alerts
Pa, a Novel Combination of Delayed Release (DR) Aspirin (ASA) and Immediate-Release (IR) Omeprazole, Is Associated with a Decreased Risk of Gastroduodenal Mucosal Injury (2008)

Purpose: To evaluate via endoscopy the gastroduodenal effects of the fixed combination tablet of DR ASA 325 mg and IR omeprazole (20 or 40 mg). Methods: We conducted 3 Phase I, single-blind, randomized, controlled trials in healthy volunteers (>50 yrs) with normal baseline endoscopy (Lanza score 0). Two studies evaluated PA32520 (DR ASA 325 mg + IR omeprazole 20 mg) vs. either enteric-coated (EC)-ASA 81 mg or 325 mg. The third study compared PA32540 (DR ASA 325 mg + IR omeprazole 40 mg) with EC-ASA 325 mg. All medications were dosed once daily for 4 weeks. The primary endpoint was the proportion of subjects with Grade 3 or Grade 4 Lanza scores at Week 4. Additional assessments included incidence of gastric or duodenal ulcers (GU/DU) at 4 weeks and pharmacokinetics. Data were pooled across the 3 studies. Results: A total of 240 subjects participated. As shown in the Figure, Grade 3 or 4 Lanza scores and the incidences of GU/DU for the PA products were lower than for EC-ASA. With regard to Grade 3 or 4 Lanza scores: PA32520 vs. EC-ASA 81 mg (9.9 vs. 20.5%, P= 0.151); PA32520 vs. EC-ASA 325 mg (9.9% vs. 42.5%, P < 0.001); PA32540 vs. EC-ASA 81 mg (2.5% vs. 20.5%, P= 0.014); PA32540 vs. EC-ASA 325 mg (2.5% vs. 42.5%, P < 0.001). With regard to the incidence of GU/DU: PA32520 vs. EC-ASA 81 mg (2.5% vs. 5.1%, P= 0.595); PA32520 vs. EC-ASA 325 mg (2.5% vs.13.8%, P= 0.009); PA32540 2.5% vs. EC-ASA 81 mg (2.5% vs. 5.1%, P= 0.615); PA32540 vs. EC-ASA 325 mg (2.5% vs. 13.8%, P= 0.059). Plasma salicylic acid pharmacokinetics was similar following dosing with PA32520 or PA32540 and EC-ASA 325 mg following both single-dose and repeat-dose administration.FigureConclusion: Gastroduodenal Grade 3 or 4 Lanza scores and incidence of GU/DU for EC-ASA were dose-related. The fixed dose combination of DR ASA and IR omeprazole was associated with a significant reduction in gastroduodenal Grade 3 or 4 Lanza scores and GU/DU that were dose-related to the proton pump inhibitor. PA32540 demonstrated the least gastroduodenal damage and may provide an important option for at-risk patients who require long-term ASA therapy.
Tertiary lymphoid structures, drivers of the anti‐tumor responses in human cancers (2016)

The characterization of the microenvironment of human tumors led to the description of tertiary lymphoid structures (TLS) characterized by mature dendritic cells in a T-cell zone adjacent to B-cell follicle including a germinal center. TLS represent sites of lymphoid neogenesis that develop in most solid cancers. Analysis of the current literature shows that the TLS presence is associated with a favorable clinical outcome for cancer patients, regardless of the approach used to quantify TLS and the stage of the disease. Using several approaches that combine immunohistochemistry, gene expression assays, and flow cytometry on large series of lung tumors, our work demonstrated that TLS are important sites for the initiation and/or maintenance of the local and systemic T- and B-cell responses against tumors. Surrounded by high endothelial venules, they represent a privileged area for the recruitment of lymphocytes into tumors and generation of central-memory T and B cells that circulate and limit cancer progression. TLS can be considered as a novel biomarker to stratify the overall survival risk of untreated cancer patients and as a marker of efficient immunotherapies. The induction and manipulation of cancer-associated TLS using drug agonists and/or biotherapies should open new avenues to treat cancer patients.
Sound-source recognition: a theory and computational model (1999)

The ability of a normal human listener to recognize objects in the environment from only the sounds they produce is extraordinarily robust with regard to characteristics of the acoustic environment and of other competing sound sources. In contrast, computer systems designed to recognize sound sources function precariously, breaking down whenever the target sound is degraded by reverberation, noise, or competing sounds. Robust listening requires extensive contextual knowledge, but the potential contribution of sound-source recognition to the process of auditory scene analysis has largely been neglected by researchers building computational models of the scene analysis process. This thesis proposes a theory of sound-source recognition, casting recognition as a process of gathering information to enable the listener to make inferences about
Nucleophile Substitution von Nitrit in Nitrobenzolen, Nitrobiphenylen und Nitronaphthalinen (1991)

Nucleophilic Substitution of Nitrite in Nitrobenzenes, Nitrobiphenyls, and Nitronaphthalenes Aromatic compounds, accessible only by multistep procedures, can be synthesized easily by nucleophilic substitution of nitrite in nitrobenzenes, nitrobiphenyls, and nitronaphthalenes. Thus, meta ‐substituted phenols 3, 4 , and 7 are obtained from 1,3‐dinitrobenzene ( 1 ) and meta ‐substituted nitrobenzenes 6 , as well as 3,5‐disubstituted phenols 10 and 5‐substituted resorcinol derivatives 11 from 3,5‐disubstituted nitrobenzenes 9 . The unsymmetrically substituted nitrobiphenyls 13, 15, 17, 19, 21, 23, 24 , and 26 are also available by nitrite exchange from the corresponding easily accessible dinitrobiphenyls 16, 18, 20, 22 , and 25 . A nitrite exchange with nucleophiles is easily possible in the 1,5‐disubstituted naphthalenes 29, 34 , while in the case of the 1,8‐disubstituted naphthalenes 31, 36 only the chloro derivative 36 undergoes this exchange under much stronger conditions in low yield.
Electroretinographic Effects of an Intravitreal Injection of Triamcinolone in Rabbit Retina (2005)

Intravitreal injection of 4 mg of triamcinolone acetonide does not cause a toxic reaction in the rabbit retina after 7 days. Triamcinolone therapy may augment the rod-driven electroretinographic responses, suggesting a mechanism by which visual function may improve. Clinical Relevance Evaluation of the toxic effects of triamcinolone is useful because of increased applications of intravitreal injection.
Middle Cerebral Artery Occlusion in the Rat by Intraluminal Suture (1996)

Reversible MCAo in which a poly-L-lysine-coated intraluminal suture was used proved to be a reliable and effective modification of this technique, yielding consistently larger infarcts and greatly reduced interanimal variability.
Edge effects on water droplet condensation (2014)

In this study we investigate the effect of geometrical or thermal discontinuities on the growth of water droplets condensing on a cooled substrate. Edges, corners, and cooled and noncooled boundaries can have a strong effect on the vapor concentration profile and mass diffusion around the drops. In comparison to growth in a pattern where droplets have to compete to catch vapor, which results in a linear water concentration profile directed perpendicularly to the substrate, droplets near discontinuities can get more vapor (outer edges, corners), resulting in faster growth or less vapor (inner edges), giving lower growth. When the cooling heat flux limits growth instead of mass diffusion (substrate with low thermal conductivity, strong heat exchange with air), edge effects can be canceled. In certain cases, growth enhancement can reach nearly 500% on edges or corners.
A single polypeptide possesses the binding and transcription activities of the adenovirus major late transcription factor. (1986)

A simple approach has been developed for the unambiguous identification and purification of sequence-specific DNA-binding proteins solely on the basis of their ability to bind selectively to their target sequences. Four independent methods were used to identify the promoter-specific RNA polymerase II transcription factor MLTF as a 46-kilodalton (kDa) polypeptide. First, a 46-kDa protein was specifically cross-linked by UV irradiation to a body-labeled DNA fragment containing the MLTF binding site. Second, MLTF sedimented through glycerol gradients at a rate corresponding to a protein of native molecular weight 45,000 to 50,000. Third, a 46-kDa protein was specifically retained on a biotin-streptavidin matrix only when the DNA fragment coupled to the matrix contained the MLTF binding site. Finally, proteins from the most highly purified fraction which were eluted and renatured from the 44- to 48-kDa region of a sodium dodecyl sulfate-polyacrylamide gel exhibited both binding and transcription-stimulatory activities. The DNA-binding activity was purified 100,000-fold by chromatography through three conventional columns plus a DNA affinity column. Purified MLTF was characterized with respect to the kinetic and thermodynamic properties of DNA binding. These parameters indicate a high degree of occupancy of MLTF binding sites in vivo.
Bone morphogenetic protein (BMP) signaling controls hair pigmentation by means of cross-talk with the melanocortin receptor-1 pathway (2004)

Hair pigmentation is controlled by tightly coordinated programs of melanin synthesis and involves signaling through the melanocortin type 1 receptor (MC-1R) that regulates the switch between pheomelanogenesis and eumelanogenesis. However, the involvement of other signaling systems, including the bone morphogenetic protein (BMP) pathway, in the control of hair pigmentation remains to be elucidated. To assess the effects of BMP signaling on hair pigmentation, transgenic mice overexpressing the BMP antagonist noggin (promoter: keratin 5) were generated. Whereas wild-type C3H/HeJ mice have a subapical yellow band on otherwise black dorsal hairs, K5-Noggin mice are characterized by the absence of a yellow band and near-black pigment in dorsal coat. Noggin overexpression is accompanied by strongly reduced levels of Agouti signal protein and enhanced expression of microphthalmia transcription factor in the midphase of the hair-growth cycle. Wild-type color in K5-Noggin mice is restored by administration of a synthetic MC-1R antagonist resulting in the reappearance of a subapical yellow band. BMP-4 stimulates the expression of Agouti transcripts and protein in primary epidermal keratinocytes, and BMP signaling positively regulates dermal papilla-specific enhancer of the Agouti gene in primary dermal fibroblasts. Taken together, these data suggests that BMP signaling controls the expression of Agouti protein in the hair follicle and provide evidence for interaction between BMP and MC-1R signaling pathways to modulate the balance between pheomelanogenesis and eumelanogenesis during hair growth.
Renal Failure (2009)

Creatinine- and cystatin C-based equations for the estimation of GFR are valuable tools for the early diagnosis of chronic renal disease and for disease staging according to the US National Kidney Foundation criteria.
Splicing analysis of rare/novel synonymous or intronic variants identified in ABCB11 heterozygotes presenting as progressive intrahepatic cholestasis with low γ‐glutamyltransferase (2018)

We successfully identified five pathogenic synonymous or intronic variants with some common features. These features might help to choose the right variant for further functional assay.
Technical Notes - Synthesis of a Lipid/Peptide/Drug Conjugate: N4(Acylpeptidyl)-Ara-C (1994)

A lipid/peptide/drug conjugate, N4-(acylpeptidyl)-ara-C, is synthesized under mild conditions to give an ara-C prodrug protected against cytidine deaminase-catalyzed deactivation. The compounds can be bound, via their hydrocarbon tails, to phospholipid membranes and examined for chymotrypsin-induced drug release. A tripeptide is too short to permit efficient enzyme/membrane contact and subsequent freeing of the drug. Faster rates can, presumably, be achieved by "fine tuning" the length and polarity of the peptide spacer attached to the drug.
A Cellular Protein Binds Vaccinia Virus Late Promoters and Activates Transcription In Vitro (1998)

ABSTRACT Available evidence indicates that the transcription of the late class of vaccinia virus genes requires the participation of several virus-encoded proteins in addition to the viral RNA polymerase. In this report we describe the identification of a protein present in extracts of uninfected HeLa cells that binds avidly to viral late promoter DNA. The protein bound specifically to several different vaccinia virus late promoters but not an early nor an intermediate promoter. DNase I footprinting localized the protein’s binding site to nucleotides surrounding the transcriptional start site of the I1L promoter. Optimal promoter binding required sequences in the highly conserved TAAAT motif at the transcriptional start site as well as sequences immediately upstream; however, one variation on the motif’s sequence did not affect promoter binding by the protein. Partially purified late promoter binding protein (LPBP) was capable of stimulating the transcription activity of extracts depleted of LPBP on a late promoter-driven template, establishing LPBP as a transcription activator in vitro. These results suggest that a cellular protein is responsible for targeting vaccinia virus late promoters for initiation of transcription.