gebhart/patrepeval huggingface dataset:
Increased Circulating Colony-Stimulating Factor-1 (CSF-1) in SJL/J Mice With Radiation-Induced Acute Myeloid Leukemia (AML) Is Associated With Autocrine Regulation of AML Cells by CSF-1 (1997)

The SJL/J mouse strain has a high spontaneous incidence of a B-cell neoplasm, reticulum cell neoplasm type B (RCN B). In addition, following irradiation, 10% to 30% of these mice develop acute myelomonocytic leukemia (radiation-induced acute myeloid leukemia [RI-AML]), an incidence that can be increased to 50% by treatment of the mice with corticosteroids after irradiation. The role played by the mononuclear phagocyte growth factor, colony-stimulating factor-1 (CSF-1), in the development of RI-AML in SJL/J mice was investigated. Mice dying of RI-AML, but not those dying of RCN B or without disease, possessed elevated concentrations of circulating CSF-1. In addition, in mice developing RI-AML with a more prolonged latency, circulating CSF-1 concentrations were increased before overt expression of RI-AML. First-passage tumors from 14 different RI-AMLs all contained high concentrations of CSF-1, and six of six different first- or second-passage tumors expressed the CSF-1 receptor (CSF-1 R). Furthermore, in vitro colony formation by first- or second-passage tumor cells from 20 of 20 different RI-AMLs was blocked by neutralizing anti-CSF-1 antibody, and four of four of these tumors were inhibited by anti-CSF-1R antibody. The results of these antibody neutralization studies, coupled with the observation of elevated circulating CSF-1 in mice developing RI-AML, show an autocrine role for CSF-1 in RI-AML development in SJL/J mice. Southern blot analysis of tumor DNA from six of six of these tumors failed to reveal any rearrangements in the genes for CSF-1 or the CSF-1R. Studies in humans have shown that patients with AML possess elevated levels of circulating CSF-1 and that AML cells can express CSF-1 and the CSF-1R. Thus, RI-AML in the SJL/J mouse appears to be a useful model for human AML.
Purification and characterization of a tartrate-resistant acid phosphatase from human osteoclastomas (1989)

Tartrate-resistant acid phosphatase is one of the major enzymes produced and secreted by osteoclasts. To obtain sufficient enzyme for biochemical characterization, we have purified this enzyme from human osteoclastomas by sequential chromatography on SP-Sephadex, CM-Sephadex, hydroxylapatite, Sephadex G-150 and concanavalin A-Sepharose. The purification over the original tumour extract was about 2000-fold, with a yield of 10%. The enzyme appeared to be homogeneous when assessed by SDS/polyacrylamide-gel electrophoresis. Both gel filtration and SDS/polyacrylamide-gel electrophoresis indicated an Mr of about 30,000. The reduced and alkylated enzyme consists of two subunits with Mrs of 15,000 and 17,500. The N-terminal amino acid sequence of both subunits indicates that there is a high degree of identity between the osteoclastoma enzyme and similar enzymes purified from spleen and uterus. Using 4-methylumbelliferyl phosphate as substrate, the specific activity of the purified enzyme was 387 units.mg-1, and the Km was 284 microns. The pH optimum was 5.7. Unlike similar enzymes purified from human and bovine bone, osteoclastoma acid phosphatase is not activated by reducing agents (2-mercaptoethanol or ascorbic acid). The enzyme contains 4.8 mol of Fe2+/3+, 0.3 mol of Mn2+ and 1.7 mol of Mg2+ per mol of enzyme. Although the enzyme loses 50% of its activity in the presence of EDTA, it is not inhibited by the iron chelator 1,10-phenanthroline. However, the enzyme is activated to a small extent by Mn2+ and Mg2+. Using a variety of substrates and inhibitors, we demonstrate that there are differences between the osteoclastoma acid phosphatase and the enzyme purified from other sources.
Association of tumor necrosis factor receptor type II polymorphism 196R with systemic lupus erythematosus in the Japanese: Molecular and functional analysis (2001)

These results suggest that 196R TNFRII, which transduces the signals of TNFalpha more effectively than does 196M TNFRII, is involved in the pathogenesis of SLE.
Myeloid leukemic progenitor cells can be specifically targeted by minor histocompatibility antigen LRH-1–reactive cytotoxic T cells (2008)

CD8(+) T cells recognizing minor histocompatibility antigens (MiHAs) on leukemic stem and progenitor cells play a pivotal role in effective graft-versus-leukemia reactivity after allogeneic stem cell transplantation (SCT). Previously, we identified a hematopoiesis-restricted MiHA, designated LRH-1, which is presented by HLA-B7 and encoded by the P2X5 purinergic receptor gene. We found that P2X5 is significantly expressed in CD34(+) leukemic subpopulations from chronic myeloid leukemia (CML) and acute myeloid leukemia (AML) patients. Here, we demonstrate that LRH-1-specific CD8(+) T-cell responses are frequently induced in myeloid leukemia patients following donor lymphocyte infusions. Patients with high percentages of circulating LRH-1-specific CD8(+) T cells had no or only mild graft-versus-host disease. Functional analysis showed that LRH-1-specific cytotoxic T lymphocytes (CTLs) isolated from 2 different patients efficiently target LRH-1-positive leukemic CD34(+) progenitor cells from both CML and AML patients, whereas mature CML cells are only marginally lysed due to down-regulation of P2X5. Furthermore, we observed that relative resistance to LRH-1 CTL-mediated cell death due to elevated levels of antiapoptotic XIAP could be overcome by IFN-gamma prestimulation and increased CTL-target ratios. These findings provide a rationale for use of LRH-1 as immunotherapeutic target antigen to treat residual or persisting myeloid malignancies after allogeneic SCT.
Magnitude of arsenic toxicity in tube-well drinking water in Bangladesh and its adverse effects on human health including cancer: evidence from a review of the literature. (2003)

Only after a decade from 1993, arsenic contamination of groundwater in Bangladesh has been reported as the biggest arsenic catastrophe in the world. It is a burning public health issue in this country. More than 50 percent of the total population is estimated at risk of contamination. Already thousands of people have been affected by the disease arsenicosis. Many more may be on the way to manifest lesions in future. We conducted a review of previous studies and published articles including MEDLINE database on this issue. We found that 59 districts out of 64 have been already affected by arsenic in underground drinking water, where this particular source of drinking water is the main source for 97 percent of the rural people. The water is unfortunately now a great threat for the human being due to high level of arsenic. Continuous arsenic exposure can lead people to develop arsenicosis, which in turn elevates the risk of cancer. Skin lesions are the most common manifestations in arsenicosis patients. Relatively poor rural people and other socio-economically disadvantaged groups are more affected by this exposure. Until now cancer patients have been relatively limited in Bangladesh. One of the reasons may be that several years are needed to show cancer manifestations from the beginning of arsenic exposure. But it is suspected that after some years a large number of patients will appear with cancer in different sites for arsenic exposure in drinking water. Various studies have been conducted in arsenic affected countries - notably in Argentina, Chile, China, Japan, and Taiwan -to find the potential of arsenic exposure to cause development of cancer. Among the arsenic related cancers, liver, lung, skin, bladder and kidney cancers are reported to be prevalent in these countries. Unfortunately no scientific study has been yet conducted in Bangladesh to find the relationship between arsenic exposure and cancers in different sites of the body. So our aim is to conduct an ecological as well as a case-control study in the country in the future.
Detection of tumor messenger RNA in the serum of patients with malignant melanoma. (1999)

Serum RNases are known to be elevated in patients with cancer. Consequently, it is not clear whether human mRNA with sufficient integrity as to permit reverse transcription-PCR (RT-PCR) amplification is detectable in serum. We examined serum from six patients with malignant melanoma for human tyrosinase mRNA using RT-PCR. Serum from 20 normal volunteers served as controls. Tyrosinase mRNA could be demonstrated in serum from four of the six melanoma patients with detection by gel electrophoresis and confirmation by blotting amplified product to a tyrosinase-specific probe. The serum remained tyrosinase mRNA positive, even if passed through a 0.45 microm filter prior to RNA extraction, indicating that the mRNA was extracellular at the time of extraction. Tyrosinase mRNA could not be detected in any control serum (0 of 20 individuals). The presence and integrity of amplifiable RNA was confirmed in all serum specimens (patients and controls) by RT-PCR amplification of c-abl mRNA. Amplifiable RNA could be demonstrated regardless of whether serum was freshly drawn or stored frozen for several years. We conclude that human mRNA can be extracted and amplified from serum. The ability to amplify tumor mRNA from serum may have important utility in cancer diagnostics and monitoring.
Integrins: Emerging Paradigms of Signal Transduction (1995)

Integrins receive signals from other receptors that lead to activation of ligand binding (inside-out signaling) and matrix assembly. Upon binding ligands, they also activate intracellular signaling pathways. These signals converse with pathways that are initiated by soluble ligands to regulate cell functions. In this way, cell adhesion is coordinated with other events to orchestrate complex cellular behavior.
Gene network and canonical pathway analysis in prostate cancer: a microarray study (2008)

The molecular mechanism playing a role in the development of prostate cancer (PCA) is not well defined. We decided to determine the changes in gene expression in PCA tissues and to compare them to those in non-cancerous samples. Prostate tissue samples were collected by needle biopsy from 21 PCA and 10 benign prostate hyperplasic (BPH) patients. Total RNA was isolated, cDNA was synthesized, and gene expression levels were determined by microarray method. In the progression to PCA, 738 up-regulated and 515 down-regulated genes were detected in samples. Analysis using Ingenuity Pathway Analysis (IPA) software revealed that 466 network and 423 functions-pathways eligible genes were up-regulated, and 363 network and 342 functions-pathways eligible genes were down-regulated. Up-regulated networks were identified around IL-1beta and insulin-like growth factor-1 (IGF-1) genes. The NFKB gene was centered around two up- and down-regulated networks. Up-regulated canonical pathways were assigned and four of them were evaluated in detail: acute phase response, hepatic fibrosis, actin cytoskeleton, and coagulation pathways. Axonal guidance signaling was the most significant down-regulated canonical pathway. Our data provide not only networks between the genes for understanding the biologic properties of PCA but also useful pathway maps for future understanding of disease and the construction of new therapeutic targets.
Design and Synthesis of Novel C14-Hydroxyl Substituted Triptolide Derivatives as Potential Selective Antitumor Agents (2009)

It has long been considered that the free beta hydroxyl group at C14 of triptolide (1) is essential to its potent anticancer activity. In this study, we synthesized novel derivatives of 1 with a hydroxyl group substituted by epoxy groups (4-8) or a five-membered ring (11-13). Compounds (4-8) showed significant in vitro anticancer activity although less potent than 1. Although with an alpha oxygen configuration at the C14 position, (14S)-14,21-epoxytriptolide (4) exhibited the highest potency among all these derivatives, clearly challenging the traditional viewpoint on the necessity of C14beta-hydroxyl group of compound 1. Further studies revealed that while displaying broad spectrum in vitro anticancer activity, compound 4 demonstrated prominent selective in vivo anticancer activity, particularly against human ovarian SK-OV-3 and prostate PC-3 cancers with obviously lower toxicity than 1. Noticeably, compound 4 was also highly effective against multidrug resistant cancer cells. Therefore, our study gives new insights into the structure-activity relationship of 1 and also produces a promising anticancer drug candidate with unique anticancer activities.
AGE-RELATED CHANGES IN FREE PLASMA TESTOSTERONE, DIHYDROTESTOSTERONE, AND OESTRADIOL (1975)

Journal Article Age-Related Changes in Free Plasma Testosterone, Dihydrotestosterone, and Oestradiol Get access K M Pirke, K M Pirke Abteilung für Klinische Chemie, Max-Planck-Institut für Psychiatrie, München Search for other works by this author on: Oxford Academic Google Scholar P Doerr P Doerr Abteilung für Klinische Chemie, Max-Planck-Institut für Psychiatrie, München Search for other works by this author on: Oxford Academic Google Scholar Acta Endocrinologica (Norway), Volume 80, Issue 1_Supplement_a, Dec 1975, Page S57, https://doi.org/10.1530/acta.0.080S057 Published: 01 December 1975
Detection of Virtually All Mutations-SSCP (DOVAM-S): A Rapid Method for Mutation Scanning with Virtually 100% Sensitivity (1999)

Dideoxy fingerprinting (ddF) was used as a tool to search for a generic set of conditions with sufficient power to detect virtually all mutations. For each condition tested, a very large sample of mutation-containing, single-stranded segments (about 1500) were analyzed with ddF. Correlation coefficients identified pairs of conditions in which single-strand conformation polymorphism (SSCP) mobilities were poorly correlated. The data strongly suggest that tertiary structure (e.g., base-sugar and sugar-sugar interactions) rather than secondary structure is the predominant determinant of mobility shifts by SSCP. Five conditions were selected with sufficient redundancy to detect all the mutations. The sensitivity of detection of virtually all mutations-SSCP (DOVAM-S) was determined by blinded analyses on samples containing additional mutations scattered throughout the eight exons and splice junctions in the factor IX gene. The factor IX gene sequence (2.5 kb) was scanned in one lane by 15 PCR-amplified segments (125 kb of sequence scanned per gel). All of the 84 single-base substitutions were detected in the blinded analyses, the first consisting of 50 hemizygous mutant and wild-type (WT) samples and the second consisting of 50 heterozygous mutant and WT samples. DOVAM-S is estimated to be five times faster than fluorescent DNA sequencing for the detection of virtually all mutations when the five conditions are applied.
Single-channel speech separation using sparse non-negative matrix factorization (2006)

We apply machine learning techniques to the problem of separating multiple speech sources from a single microphone recording.The method of choice is a sparse non-negative matrix factorization algorithm, which in an unsupervised manner can learn sparse representations of the data.This is applied to the learning of personalized dictionaries from a speech corpus, which in turn are used to separate the audio stream into its components.We show that computational savings can be achieved by segmenting the training data on a phoneme level.To split the data, a conventional speech recognizer is used.The performance of the unsupervised and supervised adaptation schemes result in significant improvements in terms of the target-to-masker ratio.
THE EFFECT OF INHIBITING SCHWANN CELL MITOSIS ON THE RE‐INNERVATION OF ACELLULAR AUTOGRAFTS IN THE PERIPHERAL NERVOUS SYSTEM OF THE MOUSE (1986)

Reactive gliosis in the zone immediately proximal to transection of the sciatic nerve has been inhibited by intraneural injection of mitomycin C, an anti-mitotic agent known to arrest Schwann cell division after transection, crush or demyelination. Mitomycin C-pretreated proximal stumps were subsequently sutured to cellular or acellular autografts (0.5 cm long) and neurite growth into and within the grafts was examined during a 5-week post-operative period. Neurites grew into cellular autografts and became associated with the resident population of Schwann cells within the grafts, to the extent that remyelination was well established in the majority of Schwann cell basal lamina tubes by week 5 post-suture. In marked contrast, very few neurites grew into acellular grafts during this time, and where axons and Schwann cells were seen they tended to be grouped in 'minifascicles'. The results suggest that neurite outgrowth from proximal stumps is dependent upon active Schwann cell participation.
Phenotype of the accessory cell necessary for mitogen-stimulated T and B cell responses in human peripheral blood: delineation by its sensitivity to the lysosomotropic agent, L-leucine methyl ester. (1983)

The lysosomotropic compound L-leucine methyl ester (Leu-OMe) was utilized to delineate the phenotype of the accessory cells involved in human B and T cell activation in vitro. Leu-OMe was shown to cause lysosomal disruption and selective death of human monocytes (M phi). After 30-45 minute incubations with this agent, human peripheral blood mononuclear cells (PBM) were nearly completely depleted of M phi. Associated with this M phi depletion, PBM were rendered unresponsive to a variety of T and B cell mitogens including the plant lectins phytohemagglutinin, concanavalin A, and pokeweed mitogen as well as the oxidative mitogens sodium periodate and neuraminidase plus galactose oxidase. Leu-OMe mediated loss of responsiveness was the result of a selective loss of an accessory cell necessary for each of these responses since reconstitution was accomplished by the addition of a M phi-enriched adherent cell population. While intact adherent cells could reconstitute responsiveness, crude M phi supernatants or highly purified human IL 1 alone were ineffective. Further identification of the Leu-OMe sensitive accessory cell indicated that it was entirely contained within the fraction of the adherent population identified by the monoclonal anti-M phi antibody, 63D3. The mechanism by which Leu-OMe Killed M phi was dependent on the lysosomal content of these cells, since agents that altered lysosomal enzyme activity such as chloroquine or NH4Cl protected M phi from Leu-OMe. Thus, the selective killing of M phi by Leu-OMe appeared to relate to the characteristically rich endowment of lysosomes within these cells. These results support the conclusion that a lysosome-rich, leucine methyl ester-sensitive, intact M phi identified by the monoclonal anti-M phi antibody 63D3 is the circulating accessory cell required for mitogen-triggered human B and T cell activation.
Kinetics and thermodynamics of i-DNA formation: phosphodiester versus modified oligodeoxynucleotides (1998)

At slightly acidic or even neutral pH, oligodeoxynucleotides that include a stretch of cytidines have been shown to form a tetrameric structure in which two parallel-stranded duplexes have their hemiprotonated C.C+base pairs face to face and fully intercalated, in a so-called i-motif. Cytosine-rich pyrimidine oligodeoxynucleotides can form an intramolecular i-motif. We have studied the ability of several DNA analogs to fold into this structure. Evidence for folding was provided by thermal denaturation. We have shown that phosphorothioate and phosphodiester oligodeoxynucleotides, but not methylphosphonate or PNA oligomers, may form the i-motif. Four different PS oligodeoxynucleotides were compared with their PO counterparts. In all cases, the melting temperature (Tm) of the phosphorothioate oligomer was equal or slightly inferior (by 2-3 degreesC) to the Tmof the natural oligodeoxynucleotide. For long oligodeoxynucleotides, a small change of pH leads to a completely different melting profile: the curves are reversible at pH 6.4 or lower, and a hysteresis is obtained at pH 6.8 or higher; cooling and heating curves were not superimposed, allowing us to determine the rate constants of association (kon) and dissociation (koff) as a function of the temperature: these rate constants give linear Arrhenius plots, in agreement with the prediction of the two-state model of association-dissociation. The activation energy Eonis strongly negative and, at neutral pH, the phosphorothioate associates and dissociates nine times faster than the phosphodiester oligodeoxynucleotide of identical sequence.
Ultrahydrophobic Surfaces. Effects of Topography Length Scales on Wettability (2000)

We discuss dynamic hydrophobicity from the perspective of the force required to move a water droplet on a surface and argue that the structure of the three-phase contact line is important. We studied the wettability of a series of silicon surfaces that were prepared by photolithography and hydrophobized using silanization reagents. Hydrocarbon, siloxane, and fluorocarbon surfaces were prepared. The surfaces contain posts of different sizes, shapes, and separations. Surfaces containing square posts with X−Y dimensions of 32 μm and less exhibited ultrahydrophobic behavior with high advancing and receding water contact angles. Water droplets moved very easily on these surfaces and rolled off of slightly tilted surfaces. Contact angles were independent of the post height from 20 to 140 μm and independent of surface chemistry. Water droplets were pinned on surfaces containing square posts with larger dimensions. Increasing the distance between posts and changing the shape of the posts from square to staggered rhombus, star, or indented square caused increases in receding contact angles. We ascribe these contact angle increases to decreases in the contact length and increases in tortuosity of the three-phase contact line. The maximum length scale of roughness that imparts ultrahydrophobicity is ∼32 μm.
Convergence of Acquired Mutations and Alternative Splicing of CD19 Enables Resistance to CART-19 Immunotherapy (2015)

CART-19 yield 70% response rates in patients with B-ALL, but also produce escape variants. We discovered that the underlying mechanism is the selection for preexisting alternatively spliced CD19 isoforms with the compromised CART-19 epitope. This mechanism suggests a possibility of targeting alternative CD19 ectodomains, which could improve survival of patients with B-cell neoplasms.
Characterization of HIV Replication Complexes Early after Cell-to-Cell Infection (1993)

In this study, we have characterized the HIV DNA-containing replication complexes present in cells early after cell-to-cell infection, using sucrose gradient sedimentation and immunoprecipitation. Six hours after cell-to-cell infection, a cytoplasmic HIV replication complex sedimented as a large structure (320S). This replication complex was precipitated by antisera to three virus-coded enzymes (reverse transcriptase, integrase, protease), to the matrix protein (p17), and to cellular histones but not to the major capsid protein (p24). This replication complex was not associated with cell membranes and could not be dissociated into smaller discrete subunits, using detergents. Nuclear extracts from the same cell-to-cell infection contained a smaller (80S) complex that lacked reverse transcriptase and matrix protein (p17). Cytoplasmic replication complexes from a cell-free virus infection sedimented as 160S structures under identical conditions, as previously reported. Our results indicate that, following cell-to-cell transmission of HIV, all the HIV pol gene products, the matrix protein p17, and cellular histones are present in cytoplasmic replication complexes that are taking part in or have completed reverse transcription. Transportation of the cytoplasmic replication complex to the nucleus is associated with structural changes, including a reduction in size and altered protein composition.