gebhart/patrepeval huggingface dataset:
Catalytic Activity and Inhibition of Human Histone Deacetylase 8 Is Dependent on the Identity of the Active Site Metal Ion (2006)

Histone deacetylases play a key role in regulating transcription and other cellular processes by catalyzing the hydrolysis of epsilon-acetyl-lysine residues. For this reason, inhibitors of histone deacetylases are potential targets for the treatment of cancer. A subset of these enzymes has previously been shown to require divalent metal ions for catalysis. Here we demonstrate that histone deacetylase 8 (HDAC8) is catalytically active with a number of divalent metal ions in a 1:1 stoichiometry with the following order of specific activity: Co(II) > Fe(II) > Zn(II) > Ni(II). The identity of the catalytic metal ion influences both the affinity of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) and the Michaelis constant, with Fe(II)- and Co(II)-HDAC8 having K(M) values that are over 5-fold lower than that of Zn(II)-HDAC8. These data suggest that Fe(II), rather than Zn(II), may be the in vivo catalytic metal. In further support of this hypothesis, recombinant HDAC8 purified from E. coli contains 8-fold more iron than zinc before dialysis, and the HDAC8 activity in cell lysates is oxygen-sensitive. Identification of the in vivo metal ion of HDAC8 is essential for understanding the biological function and regulation of HDAC8 and for the development of improved inhibitors of this class of enzymes.
Partial purification and properties of L-phenylalanine ammonia-lyase from Streptomyces verticillatus (1970)

Phenylalanine ammonia-lyase (EC 4.3.1.5) was purified 40-fold from a cell homogenate of Streptomyces verticillatus. In many respects the enzyme was similar to phenylalanine ammonia-lyases isolated from plants and fungi. It was most active at pH 9.0 and the K m for L-phenylalanine was 1.6 × 10 −4 M. It showed no requirement for metal ions but was inhibited by heavy metals, some sulfhydryl reagents, and carbonyl reagents. The Stokes' radius was estimated by gel filtration to be 5.45 nm. Sucrose gradient centrifugation gave an s 20,w of 10.0, leading to calculated values of 226 000 and 1.61 for the molecular weight and frictional ratio, respectively, if a partial specific volume of 0.725 ml/g is assumed. The enzyme deaminated o-, m-, and p-fluoro-, p-chloro-, and p-methyl-phenylalanine but was without action on L-tyrosine. It was inhibited by trans-cinnamic acid and certain phenylalanine derivatives, as well as by some less closely related aromatic compounds, but not by trans-cinnamamide.
Adverse reactions in patients transfused with cryopreserved marrow (1991)

Marrow is cryopreserved for use in autologous bone marrow transplants, but little is known of the incidence of reactions in patients transfused with these cryopreserved marrows. Reactions in patients transfused during a 4-year period with 134 autologous marrows cryopreserved in dimethyl sulfoxide (DMSO) were compared with those in patients transfused with marrow that had been collected from HLA-compatible donors and that had not been cryopreserved. Patients transfused with cryopreserved marrow had significantly more nausea (44.8 vs. 14.1%; p less than 0.0005), vomiting (23.9 vs. 8.5%; p less than 0.01), chills (31.3 vs. 1.4%; p less than 0.0005), and fever (17.9 vs. 0%; p less than 0.005) than patients transfused with fresh allogeneic marrow. The incidence of emesis correlated with the dose of DMSO received, but that of nausea did not. All cryopreserved marrows were cultured for bacteria at the time of transfusion and 17 (12.7%) were found to be positive. Only 1 of the 17 patients transfused with culture-positive marrow developed sepsis during the transplant course with the same organism that was present in the transfused marrow. Although the reactions in donors transfused with cryopreserved marrow were readily treated, this study suggests that the incidence of some reactions might be decreased by reducing the dose of DMSO transfused. Bacterial contamination of transfused marrow was a worrisome complication, and efforts should be made to improve marrow collection and processing techniques to minimize that risk.
Scanning Electrochemical Microscopy of Quinoprotein Glucose Dehydrogenase (2004)

The activity of immobilized glucose dehydrogenase (GDH), a typical PQQ-dependent quinoprotein, was studied qualitatively and quantitatively by scanning electrochemical microscopy (SECM). PQQ-dependent GDH is of interest because of its high activity and independence of dissolved oxygen in catalyzing the transfer of electrons from glucose to an electron mediator. Biotinylated glucose dehydrogenase was bound to streptavidin-coated paramagnetic beads (surface concentration > or = 1.8 x 10(-11) mol cm(-2)) which were deposited as microscopic microspots on a hydrophobic surface. The catalytic activity of immobilized GDH was mapped in SECM feedback mode and generation-collection mode using ferrocenemethanol, ferrocenecarboxylic acid, p-aminophenol, and ferricyanide as electron mediators, respectively. The apparent steady-state kinetics of catalysis were measured under conditions of high d-glucose concentration using the theory developed for the SECM feedback and generation collection (GC) modes. In feedback mode, curves of the kinetically controlled substrate current against normalized distance were plotted, and it was found that GDH catalysis follows pseudo-first-order kinetics. In GC mode detection, the catalysis follows zero-order kinetics in the presence of high concentration of both substrates for GDH. The turnover rate obtained for immobilized GDH is lower than that of native GDH but much higher than that generally observed for glucose oxidase.
Effect of Light on the Phytotoxicity of Fluridone in American Pondweed (Potamogeton nodosus) and Sago Pondweed (P. pectinatus) (1981)

The effect of 1.0 ppmw fluridone {1-methyl-3-phenyl-5-[3-trifluoromethyl)phenyl]-4(1 H )-pyridinone} on growth of American pondweed ( Potamogeton nodosus Poir.) and sago pondweed ( Potamogeton pectinatus L.) was examined in plants kept in darkness or under various numbers of 12-h photoperiods. When plants were exposed to 1.0 ppmw fluridone for 1 to 10 12-h days, no stunting of American pondweed occurred until 21 days after treatment. Thirtythree days after treatment, plants that had received 4 to 10 days' exposure were most stunted. Sago pondweed was slightly more susceptible than American pondweed (87% and 50% reduction in length, respectively) 37 days after a 10-day exposure. Chlorophylls a and b were significantly lower in both species 14 days after all fluridone treatments. American pondweed plants exposed to fluridone continuously (1.0 ppmw) for 15 days, but given 0, 3, 6, 9, 12, or 15 12-h days were stunted only after having received at least six photoperiods. Stunting in sago pondweed was only slightly light-dependent. Neither species absorbed significantly more 14 C-labeled fluridone after 2, 4, or 14 photoperiods compared to plants kept in darkness for the same time.
Unusual patterns of alloimmunity evoked by allogeneic liver parenchymal cells (2000)

Despite the widely accepted view of the liver as an immunoprivileged tissue, purified allogeneic liver parenchymal cells delivered to the liver of a recipient mouse are highly antigenic. A functional transgenic model of hepatocyte transplantation in mice is used to explore host immune responses to allogeneic hepatocytes. Transplanted hepatocytes expressing human alpha-1-antitrypsin (hA1AT) are monitored for survival by the secretion of the transgene product hA1AT. Transplantation of transgenic hepatocytes into syngeneic or immunoincompetent severe combined immunodeficiency disease (SCID) mice results in indefinite hepatocellular allograft survival. However, transplantation of transgenic hepatocytes into allogeneic hosts results in rapid hepatocyte rejection. This rejection response is associated with prominent delayed type hypersensitivity responses to cellular alloantigen but minimal donor-reactive humoral immunity. Hepatocyte rejection is not controlled by host treatment with anti-CD4 mAb despite the ability of the same treatment regimen to produce indefinite survival of donor-matched heart allografts. Host immune responses to allogeneic hepatocytes utilize CD40L/CD40 but not CD28/B7 co-stimulation, unlike the activation of both of these systems in responses to other allografts. Furthermore, C57BL/6 mice which have been induced by anti-CD4 mAb or gallium nitrate treatment to accept heart allografts promptly reject donor-matched transgenic hepatocytes. Studies in reconstituted SCID, CD4 knockout (KO), and CD8 KO mice demonstrate that hepatocyte rejection can be initiated independently by either CD4+ T cells or CD8+ T cells, which again diverges from what has been observed for most other types of allografts. This may account for the relative resistance to immunoprotection for hepatocellular allografts with conventional immunosuppressive agents and to immunoregulatory states induced by other allografts. Three models of hepatocyte rejection are discussed.
Evaluation of the safety, recovery, half-life, and clinical efficacy of antithrombin III (human) in patients with hereditary antithrombin III deficiency. Cooperative Study Group [see comments] (1990)

Antithrombin III (Human) (AT III) was administered to 18 patients with documented hereditary AT III deficiency. In eight patients with no ongoing clinical symptoms of thrombosis, the percent increase per unit AT III infused per kilogram of body weight ranged from 1.56% to 2.74%, and the half-life from 43.3 to 77.0 hours. No significant difference was noted between patients receiving and those not receiving coumarin therapy. In clinically ill patients, the in vivo recovery was significantly lower and ranged from 0.64% to 1.90% increase per unit AT III infused/kg. Efficacy of AT III was evaluated in 13 patients for the prevention or treatment of thrombosis. AT III was efficacious as assessed by the absence of thrombotic complications after surgery and/or parturition, and the nonextension and nonrecurrence of thrombosis in patients exhibiting an acute thrombotic episode. No side effects were noted. Follow-up studies indicated no hepatitis B seroconversion and no alanine aminotransferase elevations in patients who were not transfused with other blood products.
Reduced Placental 11 -Hydroxysteroid Dehydrogenase Type 2 mRNA Levels in Human Pregnancies Complicated by Intrauterine Growth Restriction: An Analysis of Possible Mechanisms (2001)

11 beta -Hydroxysteroid dehydrogenase type 2 (11 beta -HSD2) inactivates cortisol to cortisone. In the placenta 11 beta -HSD2 activity is thought to protect the fetus from the deleterious effects of maternal glucocorticoids. Patients with apparent mineralocorticoid excess owing to mutations in the 11 beta -HSD2 gene invariably have reduced birth weight, and we have recently shown reduced placental 11 beta -HSD2 activity in pregnancies complicated by intrauterine growth restriction. This is reflected in the literature by evidence of hypercortisolemia in the fetal circulation of small babies. In this study we have determined the levels of placental 11 beta -HSD2 mRNA expression across normal gestation (n = 86 placentae) and in pregnancies complicated by intrauterine growth restriction (n = 19) and evaluated the underlying mechanism for any aberrant 11 beta -HSD2 mRNA expression in intrauterine growth restriction. 11 beta -HSD2 mRNA expression increased more than 50-fold across gestation, peaking at term. Placental 11 beta -HSD2 mRNA levels were significantly decreased in intrauterine growth restriction pregnancies when compared with gestationally matched, appropriately grown placentae [e.g. at term Delta Ct (11 beta -hydroxysteroid dehydrogenase type 2/18S) 12.8 +/- 0.8 (mean +/- SE) vs. 10.2 +/- 0.2, respectively, P &lt;0.001]. These differences were not attributable to changes in trophoblast mass in intrauterine growth restriction placentae, as assessed by parallel analyses of cytokeratin-8 mRNA expression. No mutations were found in the 11-HSD2 gene in the intrauterine growth restriction cohort, and imprinting analysis revealed that the 11 beta -HSD2 gene was not imprinted. Although the underlying cause is unknown, 11 beta -HSD2 gene expression is reduced in intrauterine growth restriction pregnancies. These data highlight the important role of 11 beta -HSD2 in regulating fetal growth, a known factor in determining fetal morbidity but also the subsequent development of cardiovascular disease in adulthood.
Cancer Radioimmunotherapy: Present and Future (1998)

This book represents an update of investigations devoted to the utilization of new biological probes, conjugated to suitable radioisotopes, for the treatment of different solid and hematological tumors. Much progress has been made since the original findings of monoclonal antibodies, but several problems have to be resolved before this particular therapeutic approach can be applied extensively.
Improved Acid, Flavor and Volatile Compound Production in a High Protein and Fiber Soymilk Yogurt‐like Product (1996)

ABSTRACT The effects of added caseinate (CAS), casein hydrolyzate (CASHY) and whey protein hydrolyzate (WPHY) on acid, flavor and volatile compound production in a high protein and fiber soymilk yogurt‐like product were studied. High protein and fiber soymilk, produced by blending soaked, boiled and dehulled soybeans with Swiss cheese whey ultrafiltration permeate, was fermented with a mixed S. thermophilus and L. bulgaricus yogurt culture. The concentrations of lactic acid, key volatile compounds, i.e., acetaldehyde, acetone, and diacetyl, and the flavor and texture of the resulting soymilk based yogurt formulated with added CAS or CASHY were comparable to those in a milk yogurt control.
Experimental Evaluation of a Metal Mesh Bearing Damper (2000)

Metal mesh is a commercially available material used in many applications including seals, heat shields, filters, gaskets, aircraft engine mounts, and vibration absorbers. This material has been tested by the authors as a bearing damper in a rotordynamic test rig. The test facility was originally used to support the design of a turboprop engine, developing squirrel cages and squeeze film dampers for both the gas generator and power turbine rotors. To design the metal mesh damper, static stiffness and dynamic rap test measurements were first made on metal mesh samples in a specially designed nonrotating test fixture. These property tests were performed on samples of various densities and press fits. One sample was also tested in an Instron machine as an ancillary and redundant way to determine the stiffness. Using the stiffness test results and equations derived by a previous investigator, a spreadsheet program was written and used to size metal mesh donuts that have the radial stiffness value required to replace the squirrel cage in the power turbine. The squirrel cage and squeeze film bearing damper developed for the power turbine rotor was then replaced by a metal mesh donut sized by the computer code. Coast down tests were conducted through the first critical speed of the power turbine. The results of the metal mesh tests are compared with those obtained from previous testing with the squeeze film damper and show that the metal mesh damper has the same damping as the squeeze film at room temperature but does not lose its damping at elevated temperatures up to 103°C. Experiments were run under several different conditions, including balanced rotor, unbalanced rotor, heated metal mesh, and wet (with oil) metal mesh. The creep, or sag, of the metal mesh supporting the rotor weight was also measured over a period of several weeks and found to be very small. Based on these tests, metal mesh dampers appear to be a viable and attractive substitute for squeeze film dampers in gas turbine engines. The advantages shown by these tests include less variation of damping with temperature, ability to handle large rotor unbalance, and the ability (if required) to operate effectively in an oil free environment. Additional testing is required to determine the endurance properties, the effect of high impact or maneuver loads, and the ability to sustain blade loss loads (which squeeze films cannot handle). [S0742-4795(00)01002-4]
A New Multi-clade DNA Prime/Recombinant MVA Boost Vaccine Induces Broad and High Levels of HIV-1-specific CD8+ T-cell and Humoral Responses in Mice (2007)

The results presented here are from the preclinical evaluation in BALB/c mice of a DNA prime/modified vaccinia virus Ankara (MVA) boost multi-gene multi-subtype human immunodeficiency virus-1 (HIV-1) vaccine intended for use in humans. The plasmid DNA vaccine was delivered intradermally using a Biojector, and the MVA was delivered intramuscularly by needle. This combination of recombinant DNA and MVA proved to induce extraordinarily strong cellular responses, with more than 80% of the CD8(+) T cells specific for HIV-1 antigens. Furthermore, we show that the DNA priming increases the number of T-cell epitopes recognized after the MVA boost. In the prime/boost-immunized animals, a significant proportion of CD8(+) T cells were stained positive for both interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), a feature that has been associated with control of HIV-1 infection in long-term non-progressors. The HIV-1-specific antibody levels were moderate after the plasmid DNA immunizations but increased dramatically after the MVA boost. Although the initial injection of MVA induced significant levels of vaccinia-neutralizing antibodies, the HIV-specific responses were still significantly boosted by the second MVA immunization. The results from this study demonstrate the potency of this combination of DNA plasmids and MVA construct to induce broad and high levels of immune responses against several HIV-1 proteins of different subtypes.
Identification of Mouse ZP3 Protein in Mammalian Oocytes with Antisera against Synthetic ZP3 Peptides1 (1994)

The mouse zona pellucida (ZP) protein ZP3 plays an important role in the process of fertilization by mediating sperm binding and the acrosome reaction. ZP3 primary structures are highly conserved, as revealed by cDNA cloning. We raised antisera against synthetic peptides that are either conserved in the structure of ZP3 from different mammalian species (AS ZP3-5 and AS ZP3-6) or specific for mouse ZP3 (AS ZP3-2). In ovary sections, AS ZP3-2 revealed immunoreactivity only to mouse ZP. AS ZP3-5 and AS ZP3-6 reacted with mouse, human, rat, hamster, porcine, and bovine ZP proteins. In porcine oocytes, immunoreactive material was highly abundant in the ooplasm. Immunoblots showed that antiserum AS ZP3-5 recognized the mouse ZP3 protein. In porcine ZP preparations, AS ZP3-5 recognized a 53-kDa ZP protein. No reaction was observed with purified porcine ZP3 alpha or with ZP3 beta. Immunofluorescence studies revealed that AS ZP3-5 and AS ZP3-6 antibodies react with ZP of isolated porcine and human oocytes. Our results show that antisera against synthetic mouse ZP3 peptides can be used as markers for the identification of ZP3-like proteins in mammalian oocytes and might be useful tools for the evaluation of ZP integrity and ZP3 function.
The NCGC Pharmaceutical Collection: A Comprehensive Resource of Clinically Approved Drugs Enabling Repurposing and Chemical Genomics (2011)

Small-molecule compounds approved for use as drugs may be "repurposed" for new indications and studied to determine the mechanisms of their beneficial and adverse effects. A comprehensive collection of all small-molecule drugs approved for human use would be invaluable for systematic repurposing across human diseases, particularly for rare and neglected diseases, for which the cost and time required for development of a new chemical entity are often prohibitive. Previous efforts to build such a comprehensive collection have been limited by the complexities, redundancies, and semantic inconsistencies of drug naming within and among regulatory agencies worldwide; a lack of clear conceptualization of what constitutes a drug; and a lack of access to physical samples. We report here the creation of a definitive, complete, and nonredundant list of all approved molecular entities as a freely available electronic resource and a physical collection of small molecules amenable to high-throughput screening.
Identification of an isoprenylated cysteine methyl ester hydrolase activity in bovine rod outer segment membranes (1992)

Proteins from eucaryotic cells which have a carboxyl-terminal CAAX motif are posttranslationally modified by isoprenylation. The pathway involves the linkage of an all-trans-farnesyl (C15) or an all-trans-geranylgeranyl (C20) moiety to the cysteine residue followed by proteolysis which generates the modified cysteine as the carboxyl-terminal residue. Carboxylmethylation of the modified cysteine residue completes the pathway. This latter methylation reaction is the only potentially reversible reaction in the pathway and thus of possible regulatory significance. A specific esterase is required to reverse the methylation. It is demonstrated here that simple isoprenylated cysteine derivatives, such as N-acetyl-S-farnesyl-L-cysteine methyl ester (L-AFCM) and N-acetyl-S-geranylgeranyl-L-cysteine methyl ester (L-AGGCM), are substrates for a rod outer segment (ROS) membrane esterase activity. The KM and Vmax values for L-AFCM and L-AGGCM are 186 microM and 2.2 nmol mg-1 min-1 and 435 microM and 4.8 nmol mg-1 min-1, respectively. The enzyme(s) is stereoselective rather than stereospecific because D-AFCM is enzymatically hydrolyzed with KM and Vmax values of 157 microM and 0.46 nmol mg-1 min-1, respectively. The enzyme(s) does not process N-acetyl-L-cysteine methyl ester, demonstrating that the isoprenyl moiety is required for substrate activity. Ebelactone B is a potent mechanism-based inactivator of the enzyme with a KI = 42 microM and a kinh = 3.7 x 10(-3) s-1. Importantly, L-AFCM, L-AGGCM, and ebelactone B all inhibit the demethylation of the endogenous ROS substrates, showing that the same enzymatic activity is involved in the processing of the synthetic and physiological substrates.
Aetiology of respiratory tract infections: clinical assessment versus serological tests. (2001)

Two hundred and fifty ambulatory patients with febrile respiratory tract infections were included in a prospective study, aimed at determining the reliability of physicians judgements relating to the aetiology of the infection. Compared with advanced serological testing, physicians' judgements for a bacterial/atypical, rather than viral, aetiology had a negative predictive value of 60% and a positive predictive value of only 50%. We conclude that physicians' ability to assess whether the infectious aetiology of RTI is viral or bacterial/atypical is low and no more reliable than tossing a coin.
Resistance development over 144 weeks in treatment‐naive patients receiving tenofovir disoproxil fumarate or stavudine with lamivudine and efavirenz in Study 903* (2006)

Treatment of HIV-1 with TDF, 3TC and EFV was highly effective, with <3% of patients developing resistance to TDF over 144 weeks.