gebhart/patrepeval huggingface dataset:
Analysis of tumor heterogeneity in a patient with synchronously occurring female genital tract malignancies by DNA flow cytometry, dna fingerprinting, and immunohistochemistry (1988)

A case of a patient with bilateral ovarian cancer and a uterine malignant mesodermal mixed tumor with ascites and metastatic disease is presented. Flow cytometry, DNA fingerprinting, and immunohistochemistry were performed to assess the origin of these malignancies. Ploidy analysis showed that both ovarian tumors had different aneuploid stemlines (DNA index [DI] = 1.64, 1.85, right ovary and DI = 1.73, left ovary) indicating independent origins. One of the stemlines in the right ovary (DI = 1.64) was also present in the ascites cells, whereas omentum metastases showed the same stemline (DI = 1.73) as the left ovarian tumor. The uterine malignancy contained three aneuploid stemlines. The highest stemline was associated with epithelial differentiation, but a metastatic origin from the left ovarian tumor seems unlikely. DNA fingerprinting analysis revealed a common change in restriction fragment length pattern in the DNA from all tumor localizations as compared with the patient's constitutional DNA. These results indicate that DNA flow cytometry can be helpful in discriminating intragenital metastatic disease from multiple primary tumors.
Cell-Mediated Immune Response to Human Papillomavirus Infection (2001)

Acquisition of human papillomavirus (HPV) results in an infection of variable duration which may or may not be associated with clinically apparent lesions. Lesions caused by skintropic HPV types generally manifest as cutaneous warts and most often resolve over a period of months to years. On the other hand, anogenital infections are more likely to remain clinically inapparent. The development of DNA amplificationbased tests has demonstrated that anogenital infections are quite common and generally self-limited. For example, we and others have shown by PCR testing of multiple samples collected at different points in time-that 70 to 90% of sexually active adolescents and young women who develop an incident cervical HPV infection will show clearance of infection within 12 to 30 months (47, 61, 94). The factors influencing the natural history of these infections are not well understood. Given that persistent anogenital infection with oncogenic HPV types is associated with increased risk of neoplasia and invasive cancers (22, 59, 70, 71, 94, 124) and that cervical carcinoma remains a leading cause of death among women in developing countries (129), understanding these factors is of considerable importance. Substantial effort has been directed recently at understanding the role of the host’s immune response in the natural history of HPV, and in particular, anti-viral, cell-mediated immunity. Empirical evidence for the importance of cell-mediated immunity in control of HPV infection comes from an extensive body of literature documenting the increased prevalence of HPV infection and associated disease among immunosuppressed populations, including those with iatrogenic immunosuppression such as renal transplant recipients and individuals with human immunodeficiency virus (HIV) infection. Sillman and coauthors (128) reported in 1984 on 20 immunosuppressed women with various causes of immunosuppression who had lower genital neoplasia, describing evidence of associated HPV infection in all 20. Penn, in 1986, reported a 100-fold increase in cancer of the vulva and anus in renal transplant recipients (111). In the 1990s, as molecular testing for HPV infection came into its own, several reports confirmed increased incidence of HPV infection (50) and associated morbidities, including warts (77) and cervical squamous intraepithelial lesions (SIL) (104), among immunosuppressed renal
Serologic Assay To Quantify Human Immunoglobulin G Antibodies to the Staphylococcus aureus Iron Surface Determinant B Antigen (2009)

A direct binding Luminex assay has been developed and validated for the detection of human immunoglobulin G (IgG) antibodies to the Staphylococcus aureus iron surface determinant B protein (IsdB) in serum following natural infection or immunization with investigational Saccharomyces cerevisiae-derived IsdB-based vaccines. To ensure that IsdB-specific IgG antibodies are measured following immunization with S. cerevisiae-derived IsdB, an Escherichia coli-produced IsdB antigen is used in the assay. The IsdB antigen is covalently conjugated to maleimide microspheres via an engineered carboxy-terminal cysteine residue. Antibody titers are determined in a direct binding format, where the phycoerythrin-labeled monoclonal antibody (HP6043) specific for IgG1 to IgG4 binds to human serum IgG antibodies. Fluorescent signal emitted from bound HP6043 is directly proportional to an individual's antibody levels. A pooled human reference serum from vaccinees with high titers to IsdB is used to generate a 12-point standard curve. The correlation of mean fluorescent intensity (MFI) units to microg/ml of IsdB-specific IgG is made by interpolating the MFI data through a four-parameter curve-fitting algorithm. The assay is sensitive to 1.06 microg/ml with a dynamic range of 2.1 to 10,625 microg/ml. The overall specificity of the assay is >96% and the linearity (parallelism) of the assay is -4% per 10-fold dilution. The total precision of the assay was 16.6% relative standard deviation across three different IsdB antigen lots, three different microsphere lots, two secondary antibody lots, and three different operators. The assay has proven useful for evaluating the immune response following the administration of different dosages and formulations of investigational IsdB-based vaccines.
Detecting arcing downed-wires using fault current flicker and half-cycle asymmetry (1994)

The downed-wires problem, known as high impedance faults, is described. A high voltage laboratory setup was devised to investigate the phenomenon. The laboratory model results agreed with field test results, and previous research efforts. The arcing fault model was justified. The setup was used as a source of fault current signal. A simple approach was taken to design an arcing fault detector. The algorithm utilizes the random behavior of the fault current. It compares the positive and negative current peaks in one cycle to those in the next cycle to measure the flicker in the current signal. The asymmetry of the current is calculated by comparing the positive peak to the negative peak, for each cycle: the moving window length is half a cycle. Both values are used as a signature of arcing. The result is filtered and compared with a suitable detection threshold. The algorithm was tested by traces of normal load, and no-load current disturbed by currents of faults on dry and wet soil, arc welders, computers, and fluorescent light loads, as well as short circuit currents. The algorithm performed well under the test conditions, except for the arc welder load. This load is also a source of insecurity for other algorithms. The detection criterion will be integrated with another detection method to improve the security during arcing load events.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
LY231514, a pyrrolo[2,3-d]pyrimidine-based antifolate that inhibits multiple folate-requiring enzymes. (1997)

N-[4-[2-(2-amino-3,4-dihydro-4-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl ]-benzoyl]-L-glutamic acid (LY231514) is a novel pyrrolo[2,3-d]pyrimidine-based antifolate currently undergoing extensive Phase II clinical trials. Previous studies have established that LY231514 and its synthetic gamma-polyglutamates (glu3 and glu5) exert potent inhibition against thymidylate synthase (TS). We now report that LY231514 and its polyglutamates also markedly inhibit other key folate-requiring enzymes, including dihydrofolate reductase (DHFR) and glycinamide ribonucleotide formyltransferase (GARFT). For example, the Ki values of the pentaglutamate of LY231514 are 1.3, 7.2, and 65 nM for inhibition against TS, DHFR, and GARFT, respectively. In contrast, although a similar high level of inhibitory potency was observed for the parent monoglutamate against DHFR (7.0 nM), the inhibition constants (Ki) for the parent monoglutamate are significantly weaker for TS (109 nM) and GARFT (9,300 nM). The effects of LY231514 and its polyglutamates on aminoimidazole carboxamide ribonucleotide formyltransferase, 5,10-methylenetetrahydrofolate dehydrogenase, and 10-formyltetrahydrofolate synthetase were also evaluated. The end product reversal studies conducted in human cell lines further support the concept that multiple enzyme-inhibitory mechanisms are involved in cytotoxicity. The reversal pattern of LY231514 suggests that although TS may be a major site of action for LY231514 at concentrations near the IC50, higher concentrations can lead to inhibition of DHFR and/or other enzymes along the purine de novo pathway. Studies with mutant cell lines demonstrated that LY231514 requires polyglutamation and transport via the reduced folate carrier for cytotoxic potency. Therefore, our data suggest that LY231514 is a novel classical antifolate, the antitumor activity of which may result from simultaneous and multiple inhibition of several key folate-requiring enzymes via its polyglutamated metabolites.
Role of Egr‐1 in cAMP‐dependent protein kinase regulation of the phenylethanolamine N‐methyltransferase gene (2001)

The molecular mechanism by which cAMP activates the rat phenylethanolamine N-methyltransferase (PNMT) gene was examined by transient transfection of the wild-type rat PNMT promoter-luciferase reporter gene construct pGL3RP893 into PC12 cells. Forskolin treatment (10 microM) of the transfected cells for 3--6 h maximally induced luciferase threefold. Induction by forskolin was mimicked by the cAMP analog, 8-Br-cAMP, and prevented in PC12 cells pretreated with the protein kinase A (PKA) inhibitor H-89 or co-transfected with an expression construct for PKI, a polypeptide inhibitor of PKA. Furthermore, forskolin did not activate the PNMT promoter when the 893 bp PNMT promoter-reporter gene construct was transfected into the PKA-deficient cell line, A126. Detailed examination of the forskolin responsiveness of PNMT constructs harboring > or = 60 bp and < 893 bp of PNMT promoter demonstrated that the cAMP-responsive element(s) lay between < 392 bp and > or =60 bp. Within this region of the promoter lies a functional binding element for Egr-1, a transcriptional activator of the PNMT gene. Forskolin treatment of PC12 cells also rapidly increased nuclear levels of Egr-1 and the catalytic subunit of PKA (PKA-C), with the rise in PKA-C preceding that of Egr-1. Mutation of the --165 bp Egr-1 site markedly decreased forskolin activation of the PNMT promoter. These findings demonstrate that the rat PNMT gene promoter can be activated via the cAMP-PKA signal transduction pathway, mediated by the immediate early gene transcription factor, Egr-1.
Biased T cell receptor usage by Ld-restricted, tum- peptide-specific cytotoxic T lymphocyte clones (1993)

We have investigated the TCR gene usage in a panel of H-2Ld-restricted, tum- peptide-specific CTL clones. These clones possess identical MHC restriction and peptide specificity, yet they vary dramatically in the amount of peptide required to sensitize targets for recognition. We previously demonstrated a precise quantitative correlation between the determinant density requirement of a given clone and the CD8 dependency. In this study we sequenced polymerase chain reaction copies of the TCR mRNA used by these clones, not only to correlate TCR structure with recognition of a specific class I/peptide complex, but also to determine if the functional affinity differences between these clones is reflected in the TCR gene products used. The number of TCR V beta, V alpha, and J alpha region gene segments expressed by these clones is very limited. Twelve of 17 clones express V beta 8 at comparable levels on the cell surface. Using PCR amplification of cDNA templates, cloning, and dideoxy sequencing, we have obtained the nucleotide sequence of the TCR V-(D)-J regions in seven of the V beta 8+ clones. Two of the clones use V beta 8.2 and identical J alpha gene segments. Three of the five V beta 8.3+ clones express identical V alpha and J alpha gene products and the other two use similar V alpha chains and J alpha chains with a shared motif in the predicted CDR3 region. Although no clear correlation between TCR gene usage and CD8 dependency was seen, the range of TCR gene usage in the tum- peptide-specific, Ld-restricted immune response is strikingly narrow and suggests a coselection of the alpha- and beta- chains for recognition of the class I/peptide complex.
Incidental Findings on CT Scans in the Emergency Department (2011)

Objectives. Incidental findings on computed tomography (CT) scans are common. We sought to examine rates of findings and disclosure among discharged patients who received a CT scan in the ED. Methods. Retrospective chart review (Aug-Oct 2009) of 600 patients age 18 and older discharged home from an urban Level 1 trauma center. CT reports were used to identify incidental findings and discharge paperwork was used to determine whether the patient was informed of these findings. Results. There were 682 CT scans among 600 patients: 199 Abdomen & Pelvis, 405 Head, and 78 Thorax. A total of 348 incidental findings were documented in 228/682 (33.4%) of the scans, of which 34 (9.8%) were reported to patients in discharge paperwork. Patients with 1 incidental finding were less likely to receive disclosure than patients with 2 or more (P = .010). Patients age <60 were less likely to have incidental findings (P < .001). There was no significant disclosure or incidental finding difference by gender. Conclusions. While previous research suggests that CT incidental findings are often benign, reporting to patients is recommended but this is rarely happening.
MCT4 Defines a Glycolytic Subtype of Pancreatic Cancer with Poor Prognosis and Unique Metabolic Dependencies (2014)

KRAS mutation, which occurs in ∼ 95% of pancreatic ductal adenocarcinoma (PDA), has been shown to program tumor metabolism. MCT4 is highly upregulated in a subset of PDA with a glycolytic gene expression program and poor survival. Models with high levels of MCT4 preferentially employ glycolytic metabolism. Selectively in such "addicted" models, MCT4 attenuation compromised glycolytic flux with compensatory induction of oxidative phosphorylation and scavenging of metabolites by macropinocytosis and autophagy. In spite of these adaptations, MCT4 depletion induced cell death characterized by elevated reactive oxygen species and metabolic crisis. Cell death induced by MCT4-depletion was augmented by inhibition of compensatory pathways. In xenograft models, MCT4 had a significant impact on tumor metabolism and was required for rapid tumor growth. Together, these findings illustrate the metabolic diversity of PDA described by MCT4, delineate pathways through which this lactate transporter supports cancer growth, and demonstrate that PDA can be rationally targeted based on metabolic addictions.
Cardiac physiology at the cellular level: use of cultured HL-1 cardiomyocytes for studies of cardiac muscle cell structure and function (2004)

HL-1 cells are currently the only cardiomyocyte cell line available that continuously divides and spontaneously contracts while maintaining a differentiated cardiac phenotype. Extensive characterization using microscopic, genetic, immunohistochemical, electrophysiological, and pharmacological techniques has demonstrated how similar HL-1 cells are to primary cardiomyocytes. In the few years that HL-1 cells have been available, they have been used in a variety of model systems designed to answer important questions regarding cardiac biology at the cellular and molecular levels. Whereas HL-1 cells have been used to study normal cardiomyocyte function with regard to signaling, electrical, metabolic, and transcriptional regulation, they have also been used to address pathological conditions such as hypoxia, hyperglycemia-hyperinsulinemia, apoptosis, and ischemia-reperfusion. The availability of an immortalized, contractile cardiac cell line has provided investigators with a tool for probing the intricacies of cardiomyocyte function. In this review, we describe the culture and characterization of HL-1 cardiomyocytes as well as various model systems that have been developed using these cells to gain a better understanding of cardiac biology at the cellular and molecular levels.
Tissue-specific and cell surface expression of human major histocompatibility complex class I heavy (HLA-B7) and light (beta 2-microglobulin) chain genes in transgenic mice. (1988)

We introduced the human genes HLA-B7 and B2M encoding the heavy (HLA-B7) and light [beta 2-microglobulin (beta 2m)] chains of a human major histocompatibility complex class I antigen into separate lines of transgenic mice. The tissue-specific pattern of HLA-B7 RNA expression was similar to that of endogenous class I H-2 genes, although the HLA-B7 gene was about 10-fold underexpressed in liver. Identical patterns of RNA expression were detected whether the HLA-B7 gene contained 12 or 0.66 kilobase(s) (kb) of 5' flanking sequence. The level of expression was copy number dependent and as efficient as that of H-2 genes; gamma interferon enhanced HLA-B7 RNA expression in parallel to that of H-2. In addition to the mechanism(s) responsible for gamma interferon-enhanced expression, there must be at least one other tissue-specific mechanism controlling the constitutive levels of class I RNA. Tissue-specific human beta 2m RNA expression was similar to that of mouse beta 2m, including high-level expression in liver. Cell surface HLA-B7 increased 10- to 17-fold on T cells and on a subset of thymocytes from HLA-B7/B2M doubly transgenic mice compared to HLA-B7 singly transgenic mice. The pattern of expression of HLA-B7 on thymocytes resembled that of H-2K as opposed to H-2D. These results confirm that coexpression of both human chains is required for efficient surface expression and that HLA-B7 may share a regulatory mechanism with H-2K, which distinguishes it from H-2D.
The Actin Cytoskeleton Regulates LFA-1 Ligand Binding through Avidity Rather than Affinity Changes (1999)

To elucidate the role of the cytoskeleton regulating avidity or affinity changes in the leukocyte adhesion receptor lymphocyte function-associated antigen-1 (LFA-1) (alpha(L)beta(2)), we generated mutant cytoplasmic LFA-1 receptors and expressed these into the erythroleukemic cell line K562. We determined whether intercellular adhesion molecule-1 (ICAM-1)-mediated adhesion of LFA-1, lacking parts of its cytoplasmic tails, is regulated through receptor diffusion/clustering and/or by altered ligand binding affinity. All cytoplasmic deletion mutants that lack the complete beta(2) cytoplasmic tail and/or the conserved KVGFFKR sequence in the alpha(L) cytoplasmic tail were constitutively active and expressed high levels of the activation epitopes NKI-L16 and M24. Surprisingly, whereas these mutants showed a clustered cell surface distribution of LFA-1, the ligand-binding affinity as measured by titration of soluble ligand ICAM-1 remained unaltered. The notion that redistribution of LFA-1 does not alter ligand-binding affinity is further supported by the finding that disruption of the cytoskeleton by cytochalasin D did not alter the binding affinity nor adhesion to ICAM-1 of these mutants. Most cytoplasmic deletion mutants that spontaneously bound ICAM-1 were not capable to spread on ICAM-1, demonstrating that on these mutants LFA-1 is not coupled to the actin cytoskeleton. From these data we conclude that LFA-1-mediated cell adhesion to ICAM-1 is predominantly regulated by receptor clustering and that affinity alterations do not necessarily coincide with strong ICAM-1 binding.
Salicylic Acid: A Natural Inducer of Heat Production in Arum Lilies (1987)

For more than 50 years the identity of "calorigen," the agent that triggers pronounced heat production in the flowers and inflorescences of some thermogenic plants, remained obscure. Mass spectroscopic analysis of highly purified calorigen extracted from the male flowers of Sauromatum guttatum Schott (voodoo lily) revealed the presence of 2-hydroxybenzoic (salicylic) acid. Application of salicylic acid at 0.13 microgram per gram (fresh weight) to sections of the upper part of the plant's immature spadix, known as the appendix, led to temperature increases of as much as 12 Celsius degrees. These increases duplicated, in both magnitude and timing, the temperature increases produced by the crude calorigen extract. The sensitivity of appendix tissue to salicylic acid increases daily with the approach of anthesis and is controlled by the photoperiod. Thus, at least in some Arum lilies, salicylic acid functions as an endogenous regulator of heat production.
Gpr125 modulates Dishevelled distribution and planar cell polarity signaling (2013)

During vertebrate gastrulation, Wnt/planar cell polarity (PCP) signaling orchestrates polarized cell behaviors underlying convergence and extension (C&E) movements to narrow embryonic tissues mediolaterally and lengthen them anteroposteriorly. Here, we have identified Gpr125, an adhesion G protein-coupled receptor, as a novel modulator of the Wnt/PCP signaling system. Excess Gpr125 impaired C&E movements and the underlying cell and molecular polarities. Reduced Gpr125 function exacerbated the C&E and facial branchiomotor neuron (FBMN) migration defects of embryos with reduced Wnt/PCP signaling. At the molecular level, Gpr125 recruited Dishevelled to the cell membrane, a prerequisite for Wnt/PCP activation. Moreover, Gpr125 and Dvl mutually clustered one another to form discrete membrane subdomains, and the Gpr125 intracellular domain directly interacted with Dvl in pull-down assays. Intriguingly, Dvl and Gpr125 were able to recruit a subset of PCP components into membrane subdomains, suggesting that Gpr125 may modulate the composition of Wnt/PCP membrane complexes. Our study reveals a role for Gpr125 in PCP-mediated processes and provides mechanistic insight into Wnt/PCP signaling.
Porphyrin-based nanoporous network polymers (2002)

Network polymers exhibiting large surfaces areas (900-1000 m2g-1) are prepared by the highly efficient dibenzodioxane forming reaction between meso-tetrakis(pentafluorophenyl)porphyrin and a rigid bis(catechol) monomer.
Large hydroazaacene diimides: synthesis, tautomerism, halochromism, and redox-switchable NIR optics (2012)

A series of dihydro- and tetrahydro-tetraazaacene diimides containing 6 or 7 laterally fused six-membered rings were synthesized. Halochromic and redox-switchable vis-NIR optical characteristics were exhibited. Quinonoid tautomers of dihydrotetraazaacene derivatives were obtained and characterized, which exhibited adequate stability and existed in equilibrium with the more commonly observed benzenoid tautomer.
Microbial cell surface hydrophobicity (1990)

Microbial cell surface hydrophobicity: history, measurement and significance Nature of the hydrophobic effect Microbial hydrophobicity and fermentation technology Role of hydrophobic interactions in microbial adhesion to plastics used in medical devices Hydrophobicity of proteins and bacterial fimbriae Adhesion of bacteria to plant cells Hydrophobicity in the aquatic environment Changes in bacterial surface hydrophobicity during morphogenesis and differentiation Cell surface hydrophobicity of medically important fungi, especially Candida species Significance of hydrophobicity in the adhesiveness of pathogenic Gram-negative bacteria Hydrophobic characteristics of Staphylococci Relative importance of surface free energy as a hydrophobicity measure in bacterial adhesion to solid surfaces Hydrophobicity of Group A Streptococci to host cells Hydrophobicity of oral bacteria