gebhart/patrepeval huggingface dataset:
Purification, partial characterization, and clinical evaluation of a pancreatic oncofetal antigen. (1978)

Abstract This paper describes the purification and partial characterization of a putative pancreatic oncofetal antigen. Pancreatic oncofetal antigen is a glycoprotein with a molecular weight between 800,000 and 900,000, which migrates in the α 2 - to β-region on electrophoresis. It is found in fetal pancreas and pancreatic cancer tissue, but it is not found in normal adult pancreas. Highly purified material migrated as a single band on polyacrylamide gel electrophoresis and immunized rabbits to produce monospecific antibody without absorption. Pancreatic oncofetal antigen is clearly different from carcinoembryonic antigen, other known tumor-associated antigens, acutephase reactants, and normal serum proteins. In addition, a quantitative rocket immunoelectrophoresis assay sensitive enough to detect pancreatic oncofetal antigen in the serum of most patients was developed and used to monitor the purification of pancreatic oncofetal antigen and to evaluate its clinical application. Assays for pancreatic oncofetal antigen were carried out on three panels of sera; one was collected at The University of Chicago, and two were supplied by the Mayo-National Cancer Institute Serum Plasma Bank. The results demonstrate that pancreatic oncofetal antigen is found in the sera of most individuals; however, by far the highest absolute levels and the highest frequency of elevated levels were found in sera of patients with carcinoma of the pancreas. Elevated levels of pancreatic concofetal antigen were also observed in the serum of some patients with carcinoma of the lung, stomach, colon, biliary tract, and breast as well as in the serum of some pregnant women and other individuals with certain benign conditions. The spectrum of patients who have elevated levels of pancreatic oncofetal antigen in their serum is quite different from that found with carcinoembryonic antigen or other known tumor markers. Serial assays were performed on the sera of several patients with cancer of the pancreas; the results suggest that measurement of pancreatic oncofetal antigen may be valuable in monitoring the course of cancer of the pancreas.
Therapeutic applications of transcription factor decoy oligonucleotides (2000)

Nucleic acid
Different photodynamic effects of blue light with and without riboflavin on methicillin-resistant Staphylococcus aureus (MRSA) and human keratinocytes in vitro (2019)

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of infections in humans. Photodynamic therapy using blue light (450 nm) could possibly be used to reduce MRSA on different human tissue surfaces without killing the human cells. It could be less harmful than 300-400 nm light or common disinfectants. We applied blue light ± riboflavin (RF) to MRSA and keratinocytes, in an in vitro liquid layer model, and compared the effect to elimination using common disinfection fluids. MRSA dilutions (8 × 10<sup>5</sup>/mL) in wells were exposed to blue light (450 nm) ± RF at four separate doses (15, 30, 56, and 84 J/cm<sup>2</sup>). Treated samples were cultivated on blood agar plates and the colony forming units (CFU) determined. Adherent human cells were cultivated (1 × 10<sup>4</sup>/mL) and treated in the same way. The cell activity was then measured by Cell Titer Blue assay after 24- and 48-h growth. The tested disinfectants were chlorhexidine and hydrogen peroxide. Blue light alone (84 J/cm<sup>2</sup>) eliminated 70% of MRSA. This dose and riboflavin eradicated 99-100% of MRSA. Keratinocytes were not affected by blue light alone at any dose. A dose of 30 J/cm<sup>2</sup> in riboflavin solution inactivated keratinocytes completely. Disinfectants inactivated all cells. Blue light alone at 450 nm can eliminate MRSA without inactivation of human keratinocytes. Hence, a high dose of blue light could perhaps be used to treat bacterial infections without loss of human skin cells. Photodynamic therapy using riboflavin and blue light should be explored further as it may perhaps be possible to exploit in treatment of skin diseases associated with keratinocyte hyperproliferation.
Leptin modulates β cell expression of IL-1 receptor antagonist and release of IL-1β in human islets (2004)

High concentrations of glucose induce beta cell production of IL-1beta, leading to impaired beta cell function and apoptosis in human pancreatic islets. IL-1 receptor antagonist (IL-1Ra) is a naturally occurring antagonist of IL-1beta and protects cultured human islets from glucotoxicity. Therefore, the balance of IL-1beta and IL-1Ra may play a crucial role in the pathogenesis of diabetes. In the present study, we observed expression of IL-1Ra in human pancreatic beta cells of nondiabetic individuals, which was decreased in tissue sections of type 2 diabetic patients. In vitro, chronic exposure of human islets to leptin, a hormone secreted by adipocytes, decreased beta cell production of IL-1Ra and induced IL-1beta release from the islet preparation, leading to impaired beta cell function, caspase-3 activation, and apoptosis. Exogenous addition of IL-1Ra protected cultured human islets from the deleterious effects of leptin. Antagonizing IL-1Ra by introduction of small interfering RNA to IL-1Ra into human islets led to caspase-3 activation, DNA fragmentation, and impaired beta cell function. Moreover, siIL-1Ra enhanced glucose-induced beta cell apoptosis. These findings demonstrate expression of IL-1Ra in the human beta cell, providing localized protection against leptin- and glucose-induced islet IL-1beta.
Guided-mode resonances in planar dielectric-layer diffraction gratings (1990)

The guided-mode resonance behavior of the evanescent and propagating fields associated with an unslanted, planar diffraction grating is studied by means of the rigorous coupled-wave theory. For weakly modulated gratings, the condition on the guided-mode wave number of the corresponding unmodulated dielectric-layer waveguide may be used to predict the range of the incident angle or wavelength within which the resonances can be excited. Furthermore, the locations of the resonances are predicted approximately by the eigenvalue equation of the waveguide. As the modulation amplitude increases, the location and shape of the resonances are described in detail by the rigorous coupled-wave theory. The results presented demonstrate that the resonances can cause rapid variations in the intensity of the external propagating diffracted waves. © 1990 Optical Society of America.
RNA template-directed RNA synthesis by T7 RNA polymerase. (1994)

In an attempt to synthesize an oligoribonucleotide by run-off transcription by bacteriophage T7 RNA polymerase, a major transcript was produced that was much longer than expected. Analysis of the reaction indicated that the product resulted from initial DNA-directed run-off transcription followed by RNA template-directed RNA synthesis. This reaction occurred because the RNA made from the DNA template displayed self-complementarity at its 3' end and therefore could form an intra- or intermolecular primed template. In reactions containing only an RNA template, the rate of incorporation of NTPs was quite comparable to DNA-dependent transcription. RNA template-directed RNA synthesis has been found to occur with a great number of oligoribonucleotides, even with primed templates that are only marginally stable. In one instance, we observed a multistep extension reaction converting the oligonucleotide into a final product longer than twice its original length. Presumably, such a process could have generated some of the RNAs found to be efficiently replicated by T7 RNA polymerase.
B10 cells and regulatory B cells balance immune responses during inflammation, autoimmunity, and cancer (2010)

The ability of B cells to negatively regulate cellular immune responses and inflammation has only recently been described. Hallmark papers from a number of distinguished laboratories have identified phenotypically diverse B-cell subsets with regulatory functions during distinct autoimmune diseases, including IL-10-producing B cells, CD5+ B-1a cells, CD1d+ marginal zone B cells, and transitional-2-marginal zone precursor B cells. Most recently, a numerically rare and phenotypically unique CD1dhiCD5+CD19hi subset of regulatory B cells has been identified in the spleens of both normal and autoimmune mice. CD1dhiCD5+ B cells with the capacity to produce IL-10 have been named B10 cells as they produce IL-10 exclusively and are the predominant B-cell source of IL-10. Remarkably, B10 cells are potent negative regulators of inflammation and autoimmunity in mouse models of disease in vivo. Herein, our current understanding of B10-cell development and function is reviewed in the context of previous studies that have identified and characterized regulatory B cells, emerging evidence for B10-cell regulation of tumor immunity, and the likelihood that B10 cells exist in humans.
X‐Linked inhibitor of apoptosis protein is involved in mutant SOD1‐mediated neuronal degeneration (2002)

Mutations in the superoxide dismutase 1 (SOD1) gene cause the degeneration of motor neurons in familial amyotrophic lateral sclerosis (FALS). An apoptotic process including caspase-1 and -3 has been shown to participate in the pathogenesis of FALS transgenic (Tg) mouse model. Here we report that IAP proteins, potent inhibitors of apoptosis, are involved in the FALS Tg mouse pathologic process. The levels of X-linked inhibitor of apoptosis protein (XIAP) mRNA and protein were significantly decreased in the spinal cord of symptomatic G93A-SOD1 Tg mice compared with littermates. In contrast, the levels of cIAP-1 mRNA and protein were increased in symptomatic G93A-SOD1 Tg mice, whereas the levels of cIAP-2 mRNA and protein were unchanged. In situ hybridization showed that the expression of XIAP was remarkably reduced in the motor neurons of Tg mice, and the expression of cIAP-1 was strongly increased in the reactive astrocytes of Tg mice. Overexpression of XIAP markedly inhibited the cell death and caspase-3 activity in the neuro2a cells expressing mutant SOD1. Deletional mutant analysis revealed that the N-terminal domain of XIAP, the BIR1-2 domains, was essential for this inhibitory activity. These results suggest that XIAP plays a role in the apoptotic mechanism in the progression of disease in mutant SOD1 Tg mice and holds therapeutic possibilities for FALS.
Locations of High Contact Force During Left Atrial Mapping in Atrial Fibrillation Patients (2013)

High CF often occurs at anterior/rightward roof, where the ascending aorta provides resistance to the LA. Atrial potential amplitude and impedance are poor predictors of CF. Controlling radiofrequency power based on CF seems to prevent steam pop and impedance rise without loss of lesion effectiveness.
A keratinocyte-specific transcription factor, KRF-1, interacts with AP-1 to activate expression of human papillomavirus type 18 in squamous epithelial cells. (1991)

Human papillomavirus type 18 (HPV-18) infects genital squamous epithelium and is an etiological agent of cervical cancer. Cell-type-specific expression of HPV-18 is directed by the region upstream of the viral early genes that contains a transcriptional enhancer whose function is dependent solely on cellular factors. This element directs expression to high levels in squamous epithelial cells but is only weakly active in other cell types. We demonstrate by gel mobility-shift, methylation interference, and mutational analysis that the binding of two distinct factors to the enhancer is necessary for cell-type-specific transcriptional activation. One of these factors is identified as a keratinocyte-specific transcriptional activator, which we call KRF-1, while the other is a member of the AP-1 family. We also find that Oct-1 competes with KRF-1 for binding to enhancer sequences though it does not contribute to transcriptional activation. These results suggest a complex interplay of ubiquitous and cell-type-restricted transcriptional factors in the tissue- and differentiation-specific expression of HPV-18.
Non-steroidal antiandrogens. Design of novel compounds based on an infrared study of the dominant conformation and hydrogen-bonding properties of a series of anilide antiandrogens (1991)

Antiandrogenic activity is observed in anilides containing a tertiary hydroxyl group, and these compounds are used to define a pharmacophore in terms of their physicochemical properties. Infrared spectroscopy shows that these anilides exist in a single conformation, which exerts a powerful influence on the hydrogen-bond donor ability of the hydroxyl group in a model system. Arguments are presented which suggest that hydrogen-bonding ability is an important contributor to biological activity. Compounds were synthesized that reproduced these properties in series not containing an amide bond. Such compounds were found to exhibit good antiandrogen activity. We suggest that quantitative information on hydrogen bonding might also be useful in other systems.
Community Outbreak of Legionnaires' Disease: An Investigation Confirming the Potential for Cooling Towers to Transmit Legionella Species (1996)

In August and September 1993, we investigated an outbreak of legionnaires' disease in Fall River, Massachusetts, that involved 11 persons; the attack rate was highest in Flint, a community of Fall River. All cases were infected with Legionella pneumophila serogroup 1 (Lp-1). A case-control study revealed that cases were more likely than matched controls to have visited sites in neighborhood A of Flint. Environmental sampling in Flint found that four of nine aerosol-producing devices sampled contained legionellae; only two, conjoined cooling towers on building A, contained Lp-1. Three independent methods of subtyping--monoclonal antibody subtyping, arbitrary primer polymerase chain reaction, and pulsed-field gel electrophoresis--revealed that Lp-1 isolates from three cases with culture-positive legionnaires' disease matched those from the cooling towers on building A. Water samples from the homes of cases with culture-positive legionnaires' disease contained no legionellae. The results of this epidemiologic and laboratory investigation indicate that the cooling towers on building A were the source of the outbreak of legionnaires' disease and confirm the importance of cooling towers in the transmission of legionnaires' disease.
Interleukin-5, eosinophils, and disease (1992)

OSINOPHIL production can be induced in vitro by E interleukin-3 (IL-3), granulocyte-macrophage colonystimulating factor (GM-CSF), and IL-5. Both IL-3 and GM-CSF have activities on other hemopoietic lineages, whereas IL-5 is specific for the eosinophil/basophil lineage. The activity of IL-5 on basophils has been reviewed recently' and will not be discussed here. There is now good evidence that IL-5 is the major, and possibly the only, cytokine involved in the production of specific eosinophilia. Classically eosinophilia is observed in a restricted number of diseases, most notably helminth infections and allergic diseases. However, although the increase in eosinophil numbers is less spectacular, there is increasing evidence for an involvement of eosinophils in a wider spectrum of diseases.
Low-Dose Danazol Therapy in Idiopathic Thrombocytopenic Purpura (1987)

Although danazol is effective in the treatment of idiopathic thrombocytopenic purpura, its long-term safety and optimal dosage are not well established. We compared low (50 mg/d) and conventional (400 to 800 mg/d) dosages in 24 patients. Thirteen patients received the low dose 1 to 24 months after conventional doses had been discontinued (group 1). Five patients received low doses immediately after the conventional doses (group 2). Six patients were treated with low doses from the outset (group 3). In group 1, similar responses to either dose were seen in 9 patients, whereas there were better responses to conventional doses in 3 and to the lower dose in 1. All patients in group 2 maintained remissions with low doses. There were two excellent-good responses, one fair, and three poor responses in group 3. Side effects were generally less frequent and severe with the low doses. Low-dose danazol is better tolerated but took longer to obtain remissions, and is useful for maintenance therapy in the management of idiopathic thrombocytopenic purpura.
DksA and ppGpp directly regulate transcription of the Escherichia coli flagellar cascade (2009)

The components of the Escherichia coli flagella apparatus are synthesized in a three-level transcriptional cascade activated by the master regulator FlhDC. The cascade co-ordinates the synthesis rates of a large number of gene products with each other and with nutritional conditions. Recent genome-wide studies have reported that flagellar transcription is altered in cells lacking the transcription regulators DksA or ppGpp, but some or all reported effects could be indirect, and some are contradictory. We report here that the activities of promoters at all three levels of the cascade are much higher in strains lacking dksA, resulting in overproduction of flagellin and hyperflagellated cells. In vitro, DksA/ppGpp inhibits the flhDC promoter and the sigma(70)-dependent fliA promoter transcribing the gene for sigma(28). However, DksA and ppGpp do not affect the sigma(28)-dependent fliA promoter or the sigma(28)-dependent fliC promoter in vitro, suggesting that the dramatic effects on expression of those genes in vivo are mediated indirectly through direct effects of DksA/ppGpp on FlhDC and sigma(28) expression. We conclude that DksA/ppGpp inhibits expression of the flagellar cascade during stationary phase and following starvation, thereby co-ordinating flagella and ribosome assembly and preventing expenditure of scarce energy resources on synthesis of two of the cell's largest macromolecular complexes.
Cell transformation: the role of oncogenes and factors (1986)

An attempt is made to draw together diverse areas of biological research which have recently converged and opened up new experimental approaches to understanding the nature of cancer. In particular, the powerful techniques of molecular biology have been brought to bear on tissue culture systems. The case is made for the continued use of cell transformation in vitro as a real and useful model for cancer development. The hallmark of all cancer cells is loss of control over the cell cycle and the cellular elements involved, growth factors, growth factor receptors and signal transducers have been identified and in some instances shown to be encoded in cellular oncogenes. Moreover, as the molecular mechanisms underlying cell growth control are unravelled, those aspects involved in neoplastic change will be identified and this will lead to the development of definitive short-term tests for the detection of chemical carcinogens.
Allogeneic hematopoietic chimerism in mice treated with sublethal myeloablation and anti-CD154 antibody: absence of graft-versus-host disease, induction of skin allograft tolerance, and prevention of recurrent autoimmunity in islet-allografted NOD/Lt mice (2000)

We describe a tolerance-based stem cell transplantation protocol that combines sublethal radiation with transient blockade of the CD40-CD154 costimulatory pathway using an anti-CD154 antibody. With this protocol, we established hematopoietic chimerism in BALB/c mice transplanted with fully allogeneic C57BL/6 bone marrow. The percentage of donor-origin mononuclear cells in recipients was more than 99%. In addition, all chimeric mice treated with anti-CD154 antibody remained free of graft-versus-host disease (GVHD) and accepted donor-origin but not third-party skin allografts. It was similarly possible to create allogeneic hematopoietic chimerism in NOD/Lt mice with spontaneous autoimmune diabetes. Pancreatic islet allografts transplanted into chimeric NOD/Lt mice were resistant not only to allorejection but also to recurrence of autoimmunity. We conclude that it is possible to establish robust allogeneic hematopoietic chimerism in sublethally irradiated mice without subsequent GVHD by blocking the CD40-CD154 costimulatory pathway using as few as 2 injections of anti-CD154 antibody. We also conclude that chimerism created in this way generates donor-specific allograft tolerance and reverses the predisposition to recurrent autoimmune diabetes in NOD/Lt mice, enabling them to accept curative islet allografts. (Blood. 2000;95:2175-2182)
Stable human immunodeficiency virus type 1 (HIV-1) resistance in transformed CD4+ monocytic cells treated with multitargeting HIV-1 antisense sequences incorporated into U1 snRNA (1997)

We have approached the development of a human immunodeficiency virus type 1 (HIV-1) therapeutic product by producing immune cells stably resistant to HIV-1. Promonocytic CD4+ cells (U937) were made resistant to HIV-1 by the introduction of a DNA construct (pNDU1A,B,C) that contained three independent antisense sequences directed against two functional regions, transactivation response and tat/rev, of the HIV-1 target. Each sequence was incorporated into the transcribed region of a U1 snRNA gene to generate U1/HIV antisense RNA. Stably transfected cells expressed all three U1/HIV antisense transcripts, and these transcripts accumulated in the nucleus. These cells were subjected to two successive challenges with HIV-1 (BAL strain). The surviving cells showed normal growth characteristics and have retained their CD4+ phenotype. In situ hybridization assays showed that essentially all of the surviving cells produced U1/HIV antisense RNA. No detectable p24 antigen was observed, no syncytium formation was observed, and PCR-amplified HIV gag sequences were not detected. Rechallenge with HIV-1 (IIIB strain) similarly yielded no infection at a relatively high multiplicity of infection. As a further demonstration that the antisense RNA directed against HIV-1 was functioning in these transfected immune cells, Tat-activated expression of chloramphenicol acetyltransferase was shown to be specifically inhibited in cells expressing Tat and transactivation response region antisense sequences.
Control of Portal Hypertension by Selective Mesenteric Arterial Drug Infusion (1968)

THE CONTROL of portal hypertension and associated bleeding esophageal and gastric varices continues to be a major problem in emergency situations. Experience with the pharmacologic control of portal hypertension has been an outgrowth of the authors' interest in the preoperative arteriographic demonstration of intraluminal gastrointestinal bleeding<sup>1-4</sup>and the diagnosis of advanced cirrhosis with portal hypertension and varices by selective mesenteric arteriography. Selective infusions of a variety of pharmacologic agents were made into the superior mesenteric artery in a series of dogs with experimentally constructed portal hypertension.<sup>5</sup>These previously reported experimental infusions utilized doses of epinephrine, norepinephrine, angiotensin amide, vasopressin, and vasopressin derivatives at a much lower level than can be employed systemically to produce pharmacologic effects. Epinephrine, norepinephrine, and angiotensin amide caused a significant decrease in the flow in the superior mesenteric artery and thus decreased portal inflow, but the production of a concomitant portal venous outflow block