gebhart/patrepeval huggingface dataset:
Increased Cellular Free Cholesterol in Macrophage-specific Abca1 Knock-out Mice Enhances Pro-inflammatory Response of Macrophages (2008)

Macrophage-specific Abca1 knock-out (Abca1(-)(M)(/-)(M)) mice were generated to determine the role of macrophage ABCA1 expression in plasma lipoprotein concentrations and the innate immune response of macrophages. Plasma lipid and lipoprotein concentrations in chow-fed Abca1(-)(M)(/-)(M) and wild-type (WT) mice were indistinguishable. Compared with WT macrophages, Abca1(-)(M)(/-)(M) macrophages had a >95% reduction in ABCA1 protein, failed to efflux lipid to apoA-I, and had a significant increase in free cholesterol (FC) and membrane lipid rafts without induction of endoplasmic reticulum stress. Lipopolysaccharide (LPS)-treated Abca1(-)(M)(/-)(M) macrophages exhibited enhanced expression of pro-inflammatory cytokines and increased activation of the NF-kappaB and MAPK pathways, which could be diminished by silencing MyD88 or by chemical inhibition of NF-kappaB or MAPK. In vivo LPS injection also resulted in a higher pro-inflammatory response in Abca1(-)(M)(/-)(M) mice compared with WT mice. Furthermore, cholesterol depletion of macrophages with methyl-beta-cyclodextrin normalized FC content between the two genotypes and their response to LPS; cholesterol repletion of macrophages resulted in increased cellular FC accumulation and enhanced cellular response to LPS. Our results suggest that macrophage ABCA1 expression may protect against atherosclerosis by facilitating the net removal of excess lipid from macrophages and dampening pro-inflammatory MyD88-dependent signaling pathways by reduction of cell membrane FC and lipid raft content.
STUDIES ON PROSTATIC CANCER (1941)

The thesis of this work may be briefly summarized. In many instances a malignant prostatic tumor is an overgrowth of adult epithelial cells. All known types of adult prostatic epithelium undergo atrophy when androgenic hormones are greatly reduced in amount or inactivated. In this paper evidence is presented that significant improvement often occurs in the clinical condition of patients with far advanced cancer of the prostate after they have been subjected to castration. Conversely, the symptoms are aggravated when androgens are injected. We believe that this work provides a new concept of prostatic carcinoma. The evidence that prostatic carcinoma is often composed of an adult type of epithelium derives from a study of such tissue with respect to the phosphatase which manifests optimum activity at<i>p</i>H5. An important advance in the technic of investigation of the prostate gland was made by Kutscher and Wolbergs,<sup>1</sup>who found that
In vitro activity of dactimicin, a novel pseudodisaccharide aminoglycoside, compared with activities of other aminoglycosides (1989)

The in vitro activity of dactimicin, a new pseudodisaccharide aminoglycoside which possesses a formimidoyl group, was compared with those of gentamicin, tobramycin, and amikacin against 500 isolates. Dactimicin inhibited 90% of isolates from the family Enterobacteriaceae at a concentration of less than or equal to 4 micrograms/ml. It was more active than amikacin against Klebsiella pneumoniae, Serratia marcescens, Citrobacter diversus, Enterobacter agglomerans, Yersinia species, and Salmonella species, with an MIC for 90% of the strains (MIC90) of less than or equal to 4 micrograms/ml. The MIC90s for the Pseudomonas aeruginosa isolates were greater than 128 micrograms/ml. Dactimicin did not inhibit most methicillin-resistant Staphylococcus aureus isolates and coagulase-negative staphylococci but had an MIC50 (MIC for 50% of strains tested) of 2 micrograms/ml against methicillin-susceptible S. aureus isolates and coagulase-negative staphylococci. Dactimicin in combination with piperacillin acted synergistically against 75% of Escherichia coli, K. pneumoniae, S. marcescens, and S. aureus isolates. It exhibited an excellent postantibiotic suppressive effect on E. coli. Dactimicin was active against organisms possessing aminoglycoside-modifying enzymes including AAC(2')-b, AAC(3)-III, -IV, and -V, and AAC(6')-Ia, -Ib, Ic, -II, and -IV but was not active against isolates which contained AAC(3)-I and the bifunctional APH(2")-AAC(6')-I. Its lack of activity against P. aeruginosa appeared to be permeability related since in the presence of EDTA P. aeruginosa was susceptible, as were mutant isolates resistant because of permeability barriers.
Detection of K-ras mutations in the stool of patients with pancreatic adenocarcinoma and pancreatic ductal hyperplasia. (1994)

Pancreatic adenocarcinoma is the fifth leading cause of cancer death in the United States. Mutations in the K-ras oncogene occur in 85% of pancreatic adenocarcinomas and have also been identified in 75% of pancreatic ducts with mucinous cell hyperplasia seen in association with chronic pancreatitis. We identified K-ras mutations in 65% of duct lesions associated not only with chronic pancreatitis but also with pancreatic adenocarcinoma and distal common bile duct carcinoma (cholangiocarcinoma). These observations make K-ras a potential candidate for a gene-based diagnostic test. Indeed, K-ras mutations have been demonstrated in the pancreatic secretions of patients with pancreatic carcinoma and pancreatic intraductal neoplasia. We analyzed stool specimens for mutated K-ras sequences using a plaque hybridization assay in patients with pancreatic adenocarcinoma, cholangiocarcinoma, and chronic pancreatitis. K-ras mutations were detected in stool specimens from 6 of 11 patients with pancreatic adenocarcinoma, from 2 of 3 patients with cholangiocarcinoma, and from 1 of 3 patients with chronic pancreatitis. The K-ras mutations found in stool specimens from patients with pancreatic carcinoma were identical to those in the primary cancer in five cases. Mutations found in the stool specimens from one patient with pancreatic cancer, one patient with chronic pancreatitis, and two patients with cholangiocarcinoma were the same as those identified in pancreatic ductal mucinous cell hyperplasia lesions present in the resected pancreas specimens. Our data suggest that the K-ras mutations originating from cells of pancreatic adenocarcinomas and from cells shed by abnormal pancreatic duct epithelium can be detected in the stool. These results support the further exploration of stool K-ras analysis as a potential screening assay for the early detection of pancreatic adenocarcinoma and precursor lesions such as pancreatic ductal mucinous cell hyperplasia.
Imiquimod to Treat Different Cancers of the Epidermis (2003)

BACKGROUND Topical immunomodulatory therapy with imiquimod has been recently used for the treatment of actinic keratoses, intraepithelial carcinoma, and small basal cell carcinoma (BCC) besides the licensed indication of extragenital warts (condyloma). METHODS We treated several patients with particular epidermal neoplasias such as squamous cell cancer (SCC) and basal cell cancer of sclerodermiform type three times per week for 4 to 12 weeks. RESULTS We report several novel aspects of the treatment of epidermal cancers with self-applied, nonpainful, immunomodulatory therapy. First, we treated—for the first time—two immunosuppressed renal transplant patients for invasive SCC with imiquimod. Interestingly, systemic immunosuppression did not adversely affect the response to therapy. Second, one patient with the high-risk and aggressive growth pattern of basal cell cancer (sclerodermiform histology) was cured from his disease at a particular location in the face, suggesting sufficient penetration despite scarring. No recurrence was detected in another patient who suffered from 29 BCCs until almost 2-years follow-up. Third, the treatment of actinic keratoses in the face is substantially shorter (in the order of 4 to 6 weeks) as opposed to other skin cancers. Immunomodulatory treatment with imiquimod led to the demarcation of in situ actinic keratosis lesions that could not be identified using the dermatologist's experience, probably because of the existence of exclusive alterations on the molecular level. CONCLUSION Several novel aspects of immunomodulatory treatment with imiquimod and new indications such as selected cases of sclerodermiform BCC and SCC have been described. The texture of the skin at various different body locations may explain the varying sensitivities to imiquimod when facial skin is compared with skin on the extremities.
A system for effortless content annotation to unfold the semantics in videos (2000)

We propose and investigate a new but simple and natural extension of the way people record video. This extension allows one to unfold the semantics of video clips and thus enables a completely new set of applications for raw video footage. Two microphones are connected to a camcorder: a headworn speech input microphone and an environmental microphone. During recording the cameraman speaks out loud content-descriptive annotations and/or editing commands. Due to the two-microphones setup the sound of annotations and editing commands can be removed from the environmental audio by adaptive filtering enabling people to play back the video as if there had been no annotations. Simultaneously, these annotations are transcribed to ASCII by means of a standard speech recognition engine. The viability of this approach is demonstrated by means of an important application for video libraries: the automatic abstraction of raw video footage.
Experiences on bio-medical sensing using ultra wideband communications and radar technology (2010)

The aim of this work is to study and report some experimental results on the application of ultra wideband (UWB) technology to perform bio-medical sensing and vital signs monitoring in humans. Among the numerous signals that can be measured, the heart rate (HR) was chosen as the first objective due to its importance. The research is pointed towards the development of a technique that can allow both, radar sensing and communications using the same UWB transceiver. Such a sensor could use UWB radar principles to measure the heart beat rate and UWB communication standards to transmit these measurements. A readily available commercial transceiver with no hardware adaptations was used to solve for the physical layer. Wavelets and super-resolution techniques were used for signal processing the echo response achieving a sensing range of 84 cm. Having sensors with such 'duo' properties can make them ideal nodes for wearable computing, as well as sensor and body area networks.
Dérivés de la dihydro‐2,4 triazole‐1,2,4 thione‐3 et de l'amino‐2 thiadiazole‐1,3,4 à partir de nouvelles thiosemicarbazones d'esters (1984)

Abstract Une nouvelle synthèse générale des dihydro‐2,4 triazole‐1,2,4 thiones‐3 disubstituées en position 4 et 5 est proposée. Ces hétérocycles sont obtenus par action d'amines primaires, d'arylhydrazines ou d'aroylhydrazines sur les thiosemicarbazones d'esters. Celles‐ci sont préparées par action de chlorhydrates d'iminoéthers sur la thiosemicarbazide dans le diméthylformamide. Les thiosemicarbazones se prêtent à d'autres réactions avec les acides forts, les anhydrides et chlorures d'acides; par thermolyse, ils donnent des dérivés de l'amino‐2 thiadiazole‐1,3,4. Enfin, deux dérivés du [1,2,4triazolo][3,4‐ b ]thiadiazole‐1,3,4 ont été préparés.
Sickle cell vaso-occlusion: multistep and multicellular paradigm (2002)

Sickle cell disease is characterized by recurrent, painful episodes and organ damage resulting from microvascular occlusion. Seminal studies performed 20 years ago revealed increased adherence of sickle erythrocytes to vascular endothelial cells. Subsequent work showed that these interactions were mediated by multiple adhesion pathways, but the relevance of these interactions has not been evaluated in vivo. Clinical data suggest that leukocytes may play a role, because leukocytosis correlates with clinical severity and early death, and administration of myeloid growth factors to patients can precipitate sickle cell crises. In addition, recent experimental data using intravital microscopy indicate that sickle erythrocytes can interact with adherent leukocytes in inflamed postcapillary and collecting venules. A novel multistep model for sickle cell vaso-occlusion is proposed in which endothelial activation is induced by sickle cells or secondary inflammatory stimuli and leads to the recruitment of adherent leukocytes. The resulting adherent leukocytes interact with circulating sickle erythrocytes, and this interaction impedes microvascular blood flow. Finally, irregularly shaped sickle cells become nonspecifically trapped, resulting in vaso-occlusion. The molecular mechanisms and requirements for the heterotypic interactions between erythrocytes and leukocytes are currently unknown and may involve further activation of adherent leukocytes or circulating erythrocytes. This model offers exciting new opportunities for therapeutic intervention and suggests a critical participation of adherent leukocytes in sickle cell vaso-occlusion.
Antagonizing cAMP-dependent protein kinase A in the dorsal CNS activates a conserved Sonic hedgehog signaling pathway (1996)

Hedgehog (Hh) signaling plays a significant role in defining the polarity of a variety of tissue types along the anterior/posterior and dorsal/ventral axes in both vertebrate and invertebrate organisms. The pathway through which Hh transduces its signal is still obscure, however, recent data have implicated the cyclic AMP-dependent protein kinase A as a negative regulator of the Hh signal transduction pathway. One of the vertebrate Hh family members, Sonic hedgehog (Shh), can induce ventral neural cell types both in vivo and in vitro; high concentrations induce floor plate and lower concentrations motor neurons. To investigate whether PKA plays an active role in the suppression of ventral neural differentiation, we generated transgenic embryos expressing a dominant negative form of PKA (dnPKA) in primarily dorsal aspects of the mouse CNS. Similar to our earlier results with Shh, we observed the induction of floor plate and motor neuron markers in embryos expressing the dominant negative PKA transgene and the loss of dorsal gene expression at rostral levels. Thus suppression of PKA activity is sufficient to activate targets of the Shh signaling pathway in the vertebrate CNS suggesting that induction of ventral cell types occurs via the antagonistic action of Shh on PKA activity. Two mammalian target genes that are strongly expressed in ectopic dorsal locations in response to dnPKA are Ptc and Gli. As both of these are targets of Drosophila Hh signaling, our data point to an evolutionary conservation in both the mechanisms of signaling and the effectors of the signaling pathway.
Genetic abnormalities in hereditary hemorrhagic telangiectasia (1998)

Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber disease, is an autosomal dominant disorder of localized angiodysplasia, although it is sometimes mistakenly identified as a hemostatic disorder due to its associated characteristic bleeding. The vascular lesions that develop consist of direct arteriovenous connections without an intervening capillary bed. Germline mutations in one of two different genes, endoglin or ALK-1, can cause HHT. Both are members of the transforming growth factor (TGF)-beta receptor family of proteins, and are expressed primarily on the surface of endothelial cells. They are associated together in a receptor complex on the cell surface. Biochemical studies suggest that endoglin modulates TGF-beta signaling through ALK-1 and the type I TGF-beta receptor. Most mutations identified in endoglin and ALK-1 create null alleles, which lead to reduced message or protein levels. A model of haploinsufficiency is proposed, in which inheritance of a mutation predisposes an individual to develop HHT-associated vascular lesions. The factors that initiate lesion formation are unknown, but disruption of these genes in mice should provide animal models to address these and other important questions about the pathogenesis of HHT.
Herpes simplex virus type 1 glycoprotein H binds to αvβ3 integrins (2004)

Glycoprotein H (gH) homologues are found in all members of the herpes virus family, and gH is one of the virion envelope glycoproteins that is essential for virus entry. In this study, a recombinant soluble form of Herpes simplex virus type 1 (HSV-1) gH, in which the ectodomain is fused to the Fc-binding region of IgG, has been generated. This was expressed in mammalian cells together with gL and the resulting gHFc-gL heterodimer was purified using Protein A Sepharose. Low-affinity cell binding assays showed that gHFc-gL bound specifically to Vero cells and mutation of a potential integrin-binding motif, Arg-Gly-Asp (RGD), in gH abolished binding. CHO cells failed to bind in this assay. However, CHO cells expressing the human alphavbeta3 integrin bound efficiently to gHFc-gL, suggesting that HSV-1 gH can bind to cells using alphavbeta3 integrins and that this binding is mediated by the RGD motif in the gH ectodomain.
ChemInform Abstract: 1‐(4‐Cyclopentylphenyl)piperazine and Its 4‐Substituted Derivatives: Synthesis and Biological Screening. (1987)

Abstract The title compound (III) and its derivatives (VI) show some antimicrobial and in the case of (VIa) and (VIe) anthelmintic activity.
Conquering the complex world of human septins: implications for health and disease (2010)

Septins are highly conserved filamentous proteins first characterized in budding yeast and subsequently identified in must eukaryotes. Septins can bind and hydrolyze GTP, which is intrinsically related to their formation of septin hexamers and functional protein interactions. The human septin family is composed of 14 loci, SEPT1-SEPT14, which encode dozens of different septin proteins. Their central GTPase and polybasic domain regions are highly conserved but they diverge in their N-terminus and/or C-terminus. The mechanism by which the different isoforms are generated is not yet well understood, but one can hypothesize that the use of different promoters and/or alternative splicing could give rise to these variants. Septins perform diverse cellular functions according to tissue expression and their interacting partners. Functions identified to date include cell division, chromosome segregation, protein scaffolding, cellular polarity, motility, membrane dynamics, vesicle trafficking, exocytosis, apoptosis, and DNA damage response. Their expression is tightly regulated to maintain proper filament assembly and normal cellular functions. Alterations of these proteins, by mutation or expression changes, have been associated with a variety of cancers and neurological diseases. The association of septins with cancer results from alterations of expression in solid tumors or translocations in leukemias [mixed lineage leukemia (MLL)]. Expression changes in septins have also been associated with neurological conditions such as Alzheimer's and Parkinson's disease, as well as retinopathies, hepatitis C, spermatogenesis and Listeria infection. Pathogenic mutations of SEPT9 were identified in the autosomal dominant neurological disorder hereditary neuralgic amyotrophy (HNA). Human septin research over the past decade has established their importance in cell biology and human disease. Further functional characterization of septins is crucial to our understanding of their possible diagnostic, prognostic, and therapeutic applications.
78-kilodalton glucose-regulated protein is induced in Rous sarcoma virus-transformed cells independently of glucose deprivation. (1988)

To identify mRNAs with altered expression in Rous sarcoma virus (RSV)-transformed cells, we screened a chicken embryo fibroblast (CEF) cDNA library by differential hybridization. One clone, designated R1H, showed markedly elevated mRNA expression in RSV-transformed cells. Nucleotide sequence analysis indicated that R1H mRNA encodes 78-kilodalton glucose-regulated protein (GRP78). Chicken GRP78 was found to be very highly conserved in comparison with rat GRP78 (96% identity between chicken and rat amino acid sequences). In contrast to previous observations, we found that GRP78 was induced in RSV-transformed cells in the absence of glucose deprivation. When cells were grown in glucose-supplemented medium, the level of GRP78 mRNA was approximately fivefold higher in RSV-transformed CEF than in transformation-defective virus-infected or uninfected CEF. Similar changes in GRP78 protein content were also found. Using a temperature-sensitive mutant of RSV and supplemental glucose, we found a gradual increase in the level of GRP78 mRNA beginning at 4 h after shiftdown to permissive temperature. Uridine supplementation did not block the induction seen in CEF infected with a temperature-sensitive mutant. These results indicate that GRP78 is induced by p60v-src in the absence of glucose deprivation.
A putative protein of a growth specific cDNA from BALB/C‐3T3 cells is highly similar to the extracellular portion of mouse interleukin 1 receptor (1989)

A cDNA clone, which represents a species of mRNA that is expressed in growth-stimulated BALB/c-3T3 cells but not in resting cells, was found to encode a protein remarkably similar in sequence to the members of the immunoglobulin superfamily, especially to the extracellular portion of the mouse interleukin 1 receptor. The immunoglobulin superfamily is believed to be involved in cell adhesion and cell-to-cell interaction. The evidence that a member of this family is induced in the course of the initiation of cell proliferation is intriguing.
Investigating Protein−Ligand Interactions with a Mutant FKBP Possessing a Designed Specificity Pocket (2000)

Using structure-based design and protein mutagenesis we have remodeled the FKBP12 ligand binding site to include a sizable, hydrophobic specificity pocket. This mutant (F36V-FKBP) is capable of binding, with low or subnanomolar affinities, novel synthetic ligands possessing designed substituents that sterically prevent binding to the wild-type protein. Using binding and structural analysis of bumped compounds, we show here that the pocket is highly promiscuous-capable of binding a range of hydrophobic alkyl and aryl moieties with comparable affinity. Ligand affinity therefore appears largely insensitive to the degree of occupancy or quality of packing of the pocket. NMR spectroscopic analysis indicates that similar ligands can adopt radically different binding modes, thus complicating the interpretation of structure-activity relationships.
1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents (1962)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXT1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic AgentsGeorge Y. Lesher, Ernest J. Froelich, Monte D. Gruett, John Hays. Bailey, and R. Pauline. BrundageCite this: J. Med. Chem. 1962, 5, 5, 1063–1065Publication Date (Print):September 1, 1962Publication History Published online1 May 2002Published inissue 1 September 1962https://pubs.acs.org/doi/10.1021/jm01240a021https://doi.org/10.1021/jm01240a021research-articleACS PublicationsRequest reuse permissionsArticle Views2124Altmetric-Citations567LEARN 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 options Get e-Alerts