gebhart/patrepeval huggingface dataset:
Strength and tissue specificity of chimeric promoters derived from the octopine and mannopine synthase genes (1995)

Summary To investigate promoter strength and the tissue‐specific patterns of expression, chimeric promoters incorporating subdomains of mannopine synthase ( mas 2′) and octopine synthase ( ocs ) promoter and activator regions were affixed to a β‐glucuronidase reporter gene and the constructions introduced into tobacco plants. Addition of a trimer of the ocs upstream activating sequence (UAS) to a mas promoter/activator region resulted in highly elevated levels of GUS activity in all tissues examined. In leaf tissue, this chimeric promoter is approximately 156‐fold and 26‐fold stronger than are the CaMV 35S and the ‘enhanced’ double CaMV 35S promoters, respectively. Expression of GUS activity directed by the mas and ocs promoters/activators is limited to specific cell types. Addition of the ocs or mas UAS to the mas or ocs promoter/activator regions modulated these expression patterns. The addition of a trimer of the ocs UAS to the mas promoter/activator region resulted in a transcriptional control element that directed GUS expression in most cell types. In addition to the strong expression in transgenic tobacco plants, this novel promoter directed higher levels of GUS expression than did the CaMV 35S promoter in transiently transformed tobacco leaf discs and suspension culture cells, as well as in cassava and cowpea explants. It is proposed that the strong promoter containing a trimer of the ocs UAS affixed to the mas promoter/activator will be useful for the very high level constitutive expression of linked genes in a wide variety of plant species.
Immunotherapy based on bispecific T‐cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma (2015)

Bispecific antibodies play an important role in immunotherapy. They have received intense interest from pharmaceutical enterprises. The first antibody drug, OKT3 (muromonab-CD3), showed great performance in clinical treatment. We have successfully developed a single-chain variable fragment (ScFv) combination of anti-CD3 ScFv and anti-CD138 ScFv with the hIgG1 Fc (hIgFc) sequence. The novel bispecific T-cell engager (BiTE) with an additional hIgFc (BiTE-hIgFc, STL001) can target T cells, natural killer cells, and multiple myeloma cells (RPMI-8226 or U266). In addition, BiTE-hIgFc (STL001) has nanomolar-level affinity to recombinant human CD138 protein and shows more potent antitumor activity against RPMI-8226 cells than that of separate aCD3-ScFv-hIgFc and aCD138-ScFv-hIgFc, or the isotype mAb in vitro or in vivo.
Analysis of Rates of Multiple Enzymes in Cell Lysates by Electrospray Ionization Mass Spectrometry (1999)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTADDITION / CORRECTIONThis article has been corrected. View the notice.Analysis of Rates of Multiple Enzymes in Cell Lysates by Electrospray Ionization Mass SpectrometryScott A. Gerber, C. Ronald Scott, Frantisek Turecek, and Michael H. GelbView Author Information Departments of Chemistry, Pediatrics, and Biochemistry University of Washington Box 351700, Seattle, Washington 98195 Cite this: J. Am. Chem. Soc. 1999, 121, 5, 1102–1103Publication Date (Web):January 26, 1999Publication History Received11 August 1998Published online26 January 1999Published inissue 1 February 1999https://pubs.acs.org/doi/10.1021/ja982878khttps://doi.org/10.1021/ja982878krapid-communicationACS PublicationsCopyright © 1999 American Chemical SocietyRequest reuse permissionsArticle Views226Altmetric-Citations38LEARN 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:Assays,Conjugate acid-base pairs,Nutrition,Organic compounds,Peptides and proteins Get e-Alerts
Activation of apoptosis pathways in peripheral blood lymphocytes by in vivo chemotherapy (2001)

In addition to myelosuppression, anticancer drugs cause rapid and persistent depletion of lymphocytes, possibly by direct apoptosis induction in mature T and B cells. Induction of apoptosis regulators was analyzed in peripheral blood lymphocytes from pediatric patients undergoing first-cycle chemotherapy for solid tumors. In vivo chemotherapy induced a significant increase in lymphocyte apoptosis ex vivo. The activation of initiator caspase-8 and effector caspase-3 and the cleavage of caspase substrates was detected 12 to 48 hours after the onset of therapy. Caspase inhibition by Z-VAD-fmk did not reduce ex vivo lymphocyte apoptosis in all patients, indicating the additional involvement of caspase-independent cell death. No evidence for the involvement of activation-induced cell death was found in the acute phase of lymphocyte depletion as analyzed by activation marker expression and sensitivity for CD95 signaling. Lymphocyte apoptosis in vivo appeared to be predominantly mediated by the mitochondrial pathway because a marked decrease of mitochondrial membrane potential (DeltaPsi(M)) was detected after 24 to 72 hours of treatment, preceded by the increased expression of Bax. Interestingly, despite the use of DNA-damaging agents, p53 remained completely undetectable throughout treatment. In contrast, in vitro treatment with cytarabine and etoposide induced p53 protein, CD95 receptor expression, CD95 sensitivity, and CD95 receptor-ligand interaction in stimulated cycling lymphocytes, but no such induction was seen in resting cells. These data suggest that chemotherapy-induced lymphocyte depletion involves distinct mechanisms of apoptosis induction, such as direct mitochondrial and caspase-dependent pathways in resting cells and p53-dependent pathways in cycling lymphocytes.
Expression and immunogenicity of a tumor‐associated antigen, 90K/Mac‐2 binding protein, in lung carcinoma (2002)

M2BP is highly expressed in lung carcinoma cells and is sufficiently immunogenic to elicit specific immunity to this molecule in patients with lung carcinoma. M2BP is expected to be useful as a tumor marker and a target antigen in cancer immunotherapy.
Virus-Induced Neuronal Apoptosis Blocked by the Herpes Simplex Virus Latency-Associated Transcript (2000)

Latent infections with periodic reactivation are a common outcome after acute infection with many viruses. The latency-associated transcript (LAT) gene is required for wild-type reactivation of herpes simplex virus (HSV). However, the underlying mechanisms remain unclear. In rabbit trigeminal ganglia, extensive apoptosis occurred with LAT(-) virus but not with LAT(+) viruses. In addition, a plasmid expressing LAT blocked apoptosis in cultured cells. Thus, LAT promotes neuronal survival after HSV-1 infection by reducing apoptosis.
Expression of TNF-superfamily members BAFF and APRIL in breast cancer: Immunohistochemical study in 52 invasive ductal breast carcinomas (2008)

Our data show, for the first time, an autocrine secretion of BAFF and APRIL from breast cancer cells, offering new perspectives for their role in neoplastic and normal breast cell biology and offering new perspectives for possible selective intervention in breast cancer.
Constrictive Bronchiolitis and Ulcerative Colitis (1999)

Pulmonary complications occur in an estimated 0.21% of patients with inflammatory bowel disease. The most common presentation of pulmonary manifestations is large airway disease, such as tracheobronchitis, chronic bronchitis or bronchiectasis. Small airway disease, such as constrictive bronchiolitis or bronchiolitis obliterans with organizing pneumonia, is less frequently reported, and is described as occurring in isolation from large airway disease. A case of a postcolectomy ulcerative colitis in a patient who has both large airway involvement, tracheobronchitis and bronchiectasis, and constrictive bronchiolitis is presented.
Thalidomide Analogues Suppress Lipopolysaccharide-Induced Synthesis of TNF-α and Nitrite, an Intermediate of Nitric Oxide, in a Cellular Model of Inflammation (2011)

An unregulated neuroinflammation accompanies numerous chronic and acute neurodegenerative disorders and it is postulated that such a neuroinflammatory component likely exacerbates disease progression. A key player in brain inflammation is the microglial cell; a vital soluble factor synthesized by activated microglial cells is the key cytokine, tumor necrosis factor-alpha (TNF-α). Additionally, microglial cells release IL-1α/β, reactive oxygen species (ROS), such as superoxide (O(2) (-)) and reactive nitrogen species (RNS) like nitric oxide (NO). Nitric oxide reactive oxygen species can undergo various forms of interactions in cells whereby the synthesis of RNS / ROS intermediates are generated that can damage cell membranes. The presence of oxidative damaged cells is implicated with the abnormal cellular activity in brain or in the spinal cord, and is a classical feature of neurodegenerative disorders. To aid characterize this process, a quantitative analysis of nitrite generation was undertaken on agents developed to lower TNF-α levels in cell culture. Nitrite is a stable end product of nitric oxide metabolism and, thereby, acts as a surrogate measure of the highly unstable nitric oxide. Utilizing a RAW 264.7 cellular model of lipopolysaccharide-induced inflammation that induces high levels of TNF-α protein accompanied by a robust generation of nitrite, the properties of a series of thalidomide-based TNF-α synthesis inhibitors were evaluated to reduce the levels of both. Specific analogues of thalidomide effectively suppressed the generation of both TNF-α and nitrite at well-tolerated doses.
Optical Methods for Measurements of Skin Penetration (2008)

Fourier transform infrared photoacoustic (PAS), photothermal deflection (PDS) and Raman spectroscopy belong to the modern innovative noninvasive analytical tools that are beginning to be recognized as highly potential techniques for the noninvasive study of biological tissues and human skin under in vivo conditions. They can be applied to obtain information regarding the molecular composition of the skin down to several hundred micrometers below the skin surface. All three methods allow depth-resolved investigations. While PAS and PDS use a frequency modulation of the excitation beam to reach deeper regions in the sample, the principle of confocal Raman microspectroscopy (CRM) is a movement of the specimen in the focal plane. In consideration of depth measurements PAS and PDS complete the applicable spectrum of CRM, since Raman microscopy requires particular transparent materials.
Clinical Effects of a Topically Applied Toll-like Receptor 9 Agonist in Active Moderate-to-Severe Ulcerative Colitis (2016)

Therapy with the topically applied TLR-9 agonist DIMS0150 is a promising and well-tolerated novel therapeutic option for treatment-refractory, chronic active UC patients, warranting further clinical trials.
Structure of the human gene for monoamine oxidase type A (1991)

Monoamine oxidases, type A and type B, are principal enzymes for the degradation of biogenic amines, including catecholamines and serotonin. These isozymes have been implicated in neuropsychiatric disorders. Previously, cDNA clones for both MAO-A and MAO-B have been sequenced and the genes encoding them have been localized to human chromosome Xp11.23-Xp11.4. In this work, we isolated human genomic clones spanning almost all the MAOA gene from cosmid and phage libraries using a cDNA probe for MAO-A. Restriction mapping and sequencing show that the human MAOA gene extends over 70 kb and is composed of 15 exons. The exon structure of human MAOA is similar to that described by others for human MAOB. Exon 12 (bearing the codon for cysteine, which carries the covalently bound FAD cofactor) and exon 13 are highly conserved between human MAOA and MAOB genes (92% at the amino acid level). Earlier work revealed two species of MAO-A mRNA, 2.1 kb and 4.5-5.5 kb. We now report on further cDNA isolation and sequencing, which demonstrates that the longer message has an extension of 2.2 kb in the 3' noncoding region. This extended region is contained entirely within exon 15. The two messages therefore appear to be generated by the use of two alternative polyadenylation sites. Results from the present work should facilitate the mutational analysis of functional domains of MAO-A and MAO-B. Knowledge of the gene structure will also help in evaluating the role of genetic variations in MAO-A in human disease through the use of genomic DNA, which is more accessible than the RNA, as a template for PCR-amplification and sequencing.
Infection initiated by the RNA pregenome of a DNA virus (1991)

We describe experiments demonstrating that after transfection into permissive cells, the RNA pregenome of an avian hepadnavirus, the duck hepatitis B virus, is infectious. Using a Sindbis virus expression vector, we showed that cytoplasmic synthesis of the pregenome resulted in hepadnaviral DNA synthesis. Moreover, complete infectious virus was produced from cells transfected with hepadnaviral pregenomic RNA. We conclude that the pregenome of hepadnaviruses can express all the proteins required for DNA synthesis as well as serve as a template for reverse transcription and that DNA resulting from pregenome expression can be utilized to establish a productive infection in pregenome-transfected cells.
Immunotherapy for Human Renal Cell Carcinoma by Adoptive Transfer of Autologous Transforming Growth Factor β–Insensitive CD8+ T Cells (2009)

The one-to-one adoptive transfer strategy is an ideal in vivo murine model for studying the relationship between TGF-beta and immunosurveillance in RCC in vivo. Furthermore, this technique may offer the promise of a novel therapeutic option for the treatment of human patients with RCC.
Conversion of p-coumarate into caffeate by Streptomyces nigrifaciens. Purification and properties of the hydroxylating enzyme (1972)

1. An enzyme responsible for the conversion of p-coumarate into caffeate was purified 97-fold from Streptomyces nigrifaciens. The enzyme had a molecular weight of 18000 as determined by Sephadex G-100 gel filtration and was homogeneous on polyacrylamide-gel electrophoresis. 2. The preparation exhibited both p-coumarate hydroxylase and caffeate oxidase activities. 3. Stoicheiometry of the reaction indicated a mono-oxygenase-mediated catalysis consuming 1mol of O(2)/mol of substrate hydroxylated. 4. NADH, NADPH, tetrahydropteroylglutamate or ascorbate act as electron donors for the reaction, ascorbate being inhibitory at higher concentrations. 5. The optimum enzyme activity was at about pH7.7 and 40 degrees C, with an activation energy of 39kJ/mol. 6. Monophenols such as p-hydroxyphenylpropionate, p-hydroxyphenylacetate, l-tyrosine and dl-p-hydroxyphenyl-lactate were also hydroxylated by the preparation, in addition to p-coumarate. 7. The enzyme was a copper protein having 0.38% copper in a bound form. 8. Thiol-group inhibitors did not affect the reaction. 9. The relationship of the enzyme to other hydroxylases is discussed.
Chemoselective Alcoholysis of Acylureas (1994)

Two methods for the chemoselective alcoholysis of acylureas were developed to generate esters and amides, respectively. In alcoholysis using sodium methoxide in methanol, methoxide attacked the acyl carbonyl to give the corresponding methyl ester. While in alcoholysis using lithium benzyloxide in diethyl ether, benzyloxide attacked the urea carbonyl to give the amide. The chemoselectivity originates in the different chelating abilities of the metals and the polarity of the solvents.
Robust Detection of DNA Hypermethylation of ZNF154 as a Pan-Cancer Locus with in Silico Modeling for Blood-Based Diagnostic Development (2016)

Sites that display recurrent, aberrant DNA methylation in cancer represent potential biomarkers for screening and diagnostics. Previously, we identified hypermethylation at the ZNF154 CpG island in 15 solid epithelial tumor types from 13 different organs. In this study, we measure the magnitude and pattern of differential methylation of this region across colon, lung, breast, stomach, and endometrial tumor samples using next-generation bisulfite amplicon sequencing. We found that all tumor types and subtypes are hypermethylated at this locus compared with normal tissue. To evaluate this site as a possible pan-cancer marker, we compare the ability of several sequence analysis methods to distinguish the five tumor types (184 tumor samples) from normal tissue samples (n = 34). The classification performance for the strongest method, measured by the area under (the receiver operating characteristic) curve (AUC), is 0.96, close to a perfect value of 1. Furthermore, in a computational simulation of circulating tumor DNA, we were able to detect limited amounts of tumor DNA diluted with normal DNA: 1% tumor DNA in 99% normal DNA yields AUCs of up to 0.79. Our findings suggest that hypermethylation of the ZNF154 CpG island is a relevant biomarker for identifying solid tumor DNA and may have utility as a generalizable biomarker for circulating tumor DNA.
Reexamination of gene targeting frequency as a function of the extent of homology between the targeting vector and the target locus. (1992)

Mutations were targeted to the Hprt locus of mouse embryo-derived stem cells by using 22 different sequence replacement and sequence insertion vectors. The targeting frequency was examined at two sites within the Hprt locus as a function of the extent of homology between the targeting vector and the target locus. The targeting frequency was also compared by using vectors prepared from isogenic and nonisogenic DNA sources. With one exception, all of the vectors showed the same exponential dependence of targeting efficiency on the extent of homology between the targeting vector and the target locus. This was true regardless of whether they were sequence replacement or sequence insertion vectors, whether they were directed toward either of the two different sites within the Hprt locus, or whether they were prepared from isogenic or nonisogenic DNA sources. Vectors prepared from isogenic DNA targeted four to five times more efficiently than did the corresponding vectors prepared from nonisogenic DNA. The single case of unexpectedly low targeting efficiency involved one of the vectors prepared from nonisogenic DNA and could be attributed to an unfavorable distribution of heterology between the Hprt sequences present in the targeting vector and the endogenous Hprt gene.
HAVcR-1 expression in human colorectal cancer and its effects on colorectal cancer cells in vitro. (2013)

HAVcR-1 overexpression may be a diagnostic biomarker for colorectal cancer and a prognostic marker for a longer disease-free interval after surgery for colorectal cancer. HAVcR-1 overexpression can reduce cell adhesion and invasion and could thus be involved in the metastatic cascade.
Artificial Immune System against Viral Infection Involving Antisense RNA Targeted to the 5'-Terminal Noncoding Region of Coliphage SP RNA1 (1989)

We previously reported the utilization of antisense RNA in the development of a novel immune system against RNA coliphage SP proliferation (Hirashima et al. [1986] Proc. Natl. Acad. Sci. U.S. 83, 7726-7730). We attempted to determine the most effective (i.e., those eliciting antiviral activity) sequences for targeting micRNAs within the 5'-terminal noncoding region of 54 nucleotides (nt). It was found that a 30-nt micRNA against the sequence from base 32 to 61 exhibited nearly complete inhibition of phage production. Upon further dissection of this sequence, it was concluded that the most effective micRNA against phage SP production should contain the sequences complementary to the Shine-Dalgarno (SD) sequence of the first gene and its 13-nt upstream sequence. The addition of downstream sequences had little effect. These results suggest that the micRNA functions by preventing the binding of ribosomes to the SD sequence of the first gene. The addition of further upstream sequences had a significant negative effect on the micRNA function, indicating that the removal of such impeditive sequences from a micRNA is an important strategy for the development of a potent micRNA immune system.
B lymphocyte-specific, Cre-mediated mutagenesis in mice (1997)

Adaptation of the P1 phage-derived Cre /loxP site- specific recombination system to the gene targeting technique allows for the conditional deletion of genes in mice. To selectively modify genes in B lymphocytes, we have generated mice (designated CD19-Cre) which express cre under the transcriptional control of the B lineage-restricted CD19 gene. In a model system involving the cross of CD19-Cre mice with mice bearing a loxP -flanked substrate, we find a deletion efficiency of 75-80% in bone marrow-derived pre-B cells that increases to 90-95% in splenic B cells.
PIK3CA mutation in Chinese patients with lung squamous cell carcinoma. (2013)

The frequency of PIK3CA mutation is low in Chinese patients with LSCC. The mutational status of PIK3CA is not mutually exclusive to EGFR mutation.
Engineering human hematopoietic stem/progenitor cells to produce a broadly neutralizing anti-HIV antibody after in vitro maturation to human B lymphocytes. (2008)

Broadly neutralizing anti-HIV antibodies are rare and have proved hard to elicit with any immunogen. We have tested in vitro the notion that such antibodies or other antiviral proteins could be made by lentivirus-mediated gene transfer into human hematopoietic stem/progenitor cells (HSPCs), followed by differentiation of the transduced cells into B cells, the most potent antibody-producing cells. To do this, we have developed a highly efficient system for in vitro maturation of secreting B lymphocytes and plasma cells from CD34(+) HSPCs. It is a 3-stage, in vitro culture system that supports normal human B-lineage development from HSPCs to antibody-secreting plasmablasts (approximately 36%) and plasma cells (approximately 20%). By transducing human cord blood CD34(+) cells with lentiviral vectors encoding a secretory monoclonal anti-HIV antibody, b12 (IgG(1)), we were able to program human B cells to produce in vitro up to 1.5 microg/mL of this broadly neutralizing antibody. Our results suggest that an HIV vaccine might be delivered by autologous transplantation of in vitro-programmed HSPCs, which would develop into antibody-secreting B cells in vivo and provide a continuous supply of anti-HIV neutralizing antibodies.