gebhart/patrepeval huggingface dataset:
Pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories and oral syrup to healthy subjects (2000)

The pharmacokinetics of promethazine hydrochloride after administration of rectal suppositories at three dosage strengths and oral syrup were studied. The study had an open-label, randomized, crossover design. At intervals of five to nine days, healthy volunteers were given two 12.5-mg promethazine rectal suppositories, one 25-mg suppository, one 50-mg suppository, or 50 mg (10 mL) of promethazine oral syrup. Blood samples were collected before each dose and at intervals from 0.5 to 48 hours afterward. Promethazine concentration was determined by high-performance liquid chromatography, and pharmacokinetic values were calculated with noncompartmental methods. Thirty-six subjects (18 men and 18 women) completed the study. Absorption was highly variable for all the formulations. On average, absorption was more rapid and the maximum plasma concentration (Cmax) higher for the syrup than for the suppositories. Cmax was significantly lower for the 50-mg suppository (mean, 9.04 ng/mL) than for the syrup (19.3 ng/mL). The time to Cmax (tmax) was significantly shorter for the syrup (mean, 4.4 hours) than for the suppositories (6.7-8.6 hours). There were no significant differences in dose-normalized Cmax among the three suppository treatments. Area under the concentration-versus-time curve (AUC) was comparable between the syrup and the 50-mg suppository and between the treatments with two 12.5-mg suppositories and the 25-mg suppository. Elimination profiles were similar among all treatments (mean half-life [t1/2], 16-19 hours). There were no significant differences in pharmacokinetics on the basis of sex or race. The mean relative bioavailability for the three suppository treatments ranged from 70% to 97%. Individual relative bioavailabilities ranged from 4% to 343%. The pharmacokinetics of promethazine administered in oral syrup and rectal suppositories were highly variable, but, in general, the suppositories produced a lower Cmax and later tmax than the syrup. All formulations were comparable in terms of dose-normalized AUC and t1/2, and the three suppository treatments were comparable in terms of dose-normalized Cmax.
Transcription factors LRF and BCL11A independently repress expression of fetal hemoglobin (2016)

Genes encoding human β-type globin undergo a developmental switch from embryonic to fetal to adult-type expression. Mutations in the adult form cause inherited hemoglobinopathies or globin disorders, including sickle cell disease and thalassemia. Some experimental results have suggested that these diseases could be treated by induction of fetal-type hemoglobin (HbF). However, the mechanisms that repress HbF in adults remain unclear. We found that the LRF/ZBTB7A transcription factor occupies fetal γ-globin genes and maintains the nucleosome density necessary for γ-globin gene silencing in adults, and that LRF confers its repressive activity through a NuRD repressor complex independent of the fetal globin repressor BCL11A. Our study may provide additional opportunities for therapeutic targeting in the treatment of hemoglobinopathies.
N-H Carbazole Synthesis from 2-Chloroanilines via Consecutive Amination and C−H Activation (2006)

N-H carbazoles can be produced from 2-chloroanilines and aryl bromides via consecutive catalytic amination and C-H activation. In many instances, this can be done in a tandem manner in one pot. The methodologies developed can be used in the synthesis of a range of carbazoles, including the natural products Clausine P and glycozolidine and a precursor in the synthesis of Clausines H, K, O, and 7-methoxy-O-methylmukonal, and can be extended to the synthesis of indoles.
Angiogenesis inhibitors in tackling recurrent glioblastoma (2017)

Introduction: Despite aggressive multimodality treatment of glioblastoma, outcome remains poor and patients mostly die of local recurrences. Besides reoperation and occasionally reirradiation, systemic treatment of recurrent glioblastoma consists of alkylating chemotherapy (lomustine, temozolomide), bevacizumab and combinations thereof. Unfortunately, antiangiogenic agents failed to improve survival either as a monotherapy or in combination treatments. This review provides current insights into tumor-derived escape mechanisms and other areas of treatment failure of antiangiogenic agents in glioblastoma.Areas covered: We summarize the current literature on antiangiogenic agents in the treatment of glioblastoma, with a focus on recurrent disease. A literature search was performed using the terms ‘glioblastoma’, ‘bevacizumab’, ‘antiangiogenic’, ‘angiogenesis’, ‘resistance’, ‘radiotherapy’, ‘chemotherapy’ and derivations thereof.Expert commentary: New insights in glioma neoangiogenesis, increasing understanding of vascular pathway escape mechanisms, and upcoming immunotherapy approaches might revitalize the therapeutic potential of antiangiogenic agents against glioblastoma, although with a different treatment intention. The combination of antiangiogenic approaches with or without radiotherapy might still hold promise to complement the therapeutic armamentarium of fighting glioblastoma.
Concepts in in vivo siRNA delivery for cancer therapy (2009)

In vivo gene silencing using RNAi plays an important role in target validation and is advancing towards the development of RNAi-based therapeutics. RNAs were thought to have just two broad functions in cells as messenger RNAs (mRNAs) and ribosomal RNAs, but recently the relevance of microRNAs is becoming more clearly understood. mRNA molecules transmit information between DNA and protein and, as such, are vital intermediaries for gene expression. Ribosomal and transfer RNAs have structural, catalytic, and information-decoding roles in the process of protein synthesis, whereas microRNAs are regulators of gene expression. This review presents the early and intriguing successes of using siRNAs for in vivo gene silencing and its use as a possible cancer therapeutics.
A 9-ns HIT-delay 32-kbyte cache macro for high-speed RISC (1990)

A 32-kB cache macro with an experimental reduced instruction set computer (RISC) is realized. A pipelined cache access to realize a cycle time shorter than the cache access time is proposed. A double-word-line architecture combines single-port cells, dual-port cells, and CAM cells into a memory array to improve silicon area efficiency. The cache macro exhibits 9-ns typical clock-to-HIT delay as a result of several circuit techniques, such as a section word-line selector, a dual transfer gate, and 1.0- mu m CMOS technology. It supports multitask operation with logical addressing by a selective clear circuit. The RISC includes a double-word load/store instruction using a 64-b bus to fully utilize the on-chip cache macro. A test scheme allows measurement of the internal signal delay. The test device design is based on the unified design rules scalable through multigenerations of process technologies down to 0.8 mu m.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Cloning of bovine growth hormone gene and its expression in bacteria (1981)

A hybrid plasmid was constructed containing beta-lactamase gene of plasmid pBR322 and cloned coding sequences of bovine growth hormone (BGH). The constructed plasmid contains all DNA sequences required to encode BGH, and when used as a hybridization probe it detects one growth hormone gene in the bovine genome. The cloned DNA sequences are inserted into the beta-lactamase gene in the correct reading frame for BGH synthesis. The hybrid gene is expressed in bacteria and the product, a fused beta-lactamase-bovine growth hormone protein, is specifically immunoprecipitated with anti-serum to BGH. Unlike beta-lactamase, very little growth hormone containing sequences can be detected in the periplasmic space.
The Ultrasound Macroscope: Initial Studies of Breast Tissue (1984)

A system called the ultrasound macroscope has been developed to measure the ultrasonic properties of tissues. Based on the concept of the scanning acoustic microscope, it is capable of generating quantitative images of ultrasound velocity, attenuation and backscatter for macroscopic slices of tissue. By maintaining high resolution (approximately 120 microns at 13 MHz) the morphology of complex tissues is well delineated. Data from regions of interest in the tissue are transformed into three dimensional probability distributions representative of the tissue's ultrasonic characteristics. Sets of two dimensional projections of these distributions are used to display the information. As an initial study, the properties of breast tissues are analyzed. Examples of both normal and abnormal pathology are presented and the relevance of the results to clinical imaging are discussed.
Principles of Ceramics Processing (2000)

Partial table of contents: Ceramics Processing and Ceramic Products. Surface Chemistry. CERAMIC RAW MATERIALS. Special Inorganic Chemicals. MATERIALS CHARACTERIZATION. Particle Size and Shape. Density, Pore Structure, and Specific Surface Area. PROCESSING ADDITIVES. Liquids and Wetting Agents. Flocculants, Binders, and Bonds. PARTICLE PACKING, CONSISTENCY, AND BATCH CALCULATIONS. Batch Consistency and Formulation. PARTICLE MECHANICS AND RHEOLOGY. Mechanics of Unsaturated Bodies. BENEFICIATION. Comminution. Granulation. FORMING. Pressing. Injection Molding. POSTFORMING PROCESSES. Drying. Firing. Appendices. Index.
A quantitative bioassay for erythropoietin using mouse fetal liver cells. (1975)

The conditions under which mouse fetal liver cells in vitro are most sensitive to erythropoietin have been investigated with the object of establishing a rapid and sensitive bioassay for this hormone. Fetal liver age and incubation times are shown to be relatively unimportant. Of the commercially available media studied, Eagles Minimal Essential Medium plus 5 percent Fetal Calf Serum is superior to other media used to study erythropoiesis in mouse fetal liver cells. The number of cells per 1 ml culture is important since some evidence was obtained for cell cooperation occurring above 10-6 cells per culture. To minimize this possibility 5 x 10-5 cells are used. If (59Fe) ferric citrate is used to assess heme synthesis, no significant advantage is observed by prior binding of the isotope to mouse serum transferrin. Butan-2-one is preferred to cyclohexanone for extracting heme. Using the conditions described in this report the mouse fetal liver cell assay for erythropoietin is capable of detecting erythropoietin concentrations as low as 0.001 unit culture. Preliminary results using normal human sera show that it is sufficiently sensitive to detect erythropoietin over a range of serum concentrations. This allows a full dose-response relationship to the sera to be determined and, by a comparison with an erythropoietin standard, detailed quantitative results can be obtained. Therefore the technique seems to fulfill the need for a rapid and sensitive erythropoietin bioassay for routine clinical use.
Antimitotic Activity of the Potent Tumor Inhibitor Maytansine (1975)

Maytansine, at 6x10(-8)M, irreversibly inhibits cell division in eggs of sea urchins and clams. It causes the disappearance of a mitotic apparatus or prevents one from forming if added at early stages. Maytansine does not affect formation of the mitotic organizing center but does inhibit in vitro polymerization of tubulin. Maytansine and vincristine inhibit in vitro polymerization of tubulin at about the same concentrations, but vincristine is about 100 times less effective as an inhibitor of cleavage in marine eggs.
Alternative treatments for Clostridium difficile disease: what really works? (2005)

Vancomycin and metronidazole have been used for treating Clostridium difficile-associated disease (CDAD) for the past 25 years, but approximately 20 % of patients develop recurrent disease. The increasing incidence of nosocomial outbreaks, cases of recurrent CDAD and other complications (toxic megacolon, ileus, sepsis) has fuelled the search for different types of treatments. As the understanding of the pathogenesis of this disease has matured, newer treatment strategies that take advantage of these mechanisms have been developed. This review will describe such treatments and examine the evidence for each strategy.
The role of oxidative stress in disease progression in individuals infected by the human immunodeficiency virus (1992)

This review describes the potential role of oxidative stress as a cofactor of disease progression from asymptomatic human immunodeficiency virus (HIV) infection to the acquired immunodeficiency syndrome (AIDS). Oxidative stress is a known activator of HIV replication in vitro through the activation of a factor that binds to a DNA-binding protein, NF-kappa B, which in turn stimulates HIV gene expression by acting on the promoter region of the viral long terminal repeat. Tumor necrosis factor alpha (TNF-alpha), an essential cytokine produced by activated macrophages, is also involved in the activation of HIV infection through similar mechanisms. TNF-mediated cytotoxicity of cells exposed to this substance is related to the generation of intracellular hydroxyl radicals. An indirect argument in favor of the role of oxidative stress in HIV-associated disease progression is the consumption of glutathione (GSH), a major intracellular antioxidant, during HIV infection and progression. GSH is known to play a major role in regulation of T cell immune functions. Oxidative stress may also play an important role in the genesis of cellular DNA damage and, in this context, may be related to HIV-associated malignancies and disease progression. Finally, the role of antioxidants as components of therapeutic strategies to combat HIV disease progression is discussed.
Determination of Biotransformation Products of Platinum Drugs in Rat and Human Urine (1997)

Cisplatin is an extremely effective cancer chemotherapeutic agent, but its use is often accompanied by toxicity. Second generation drugs such as carboplatin are becoming more widely used because of reduced toxicity. Since biotransformation products have been implicated in the toxic responses, we have begun to investigate the reactions of cisplatin and carboplatin with potential biological ligands. Reaction products were characterized using HPLC with inductively coupled plasma - mass spectrometry (HPLC-ICP-MS), (1)H and (13)C NMR and fast atom bombardment - mass spectrometry (FAB-MS). Three Pt-creatinine complexes, cis-[Pt(NH(3))(2)Cl(Creat)](+), cis-[Pt(NH(3))(2)(H(2)O)(Creat)](2+) and cis-[Pt(NH(3))(2)(Creat)(2)](2+), were synthesized and the platinum was shown to coordinate to the ring nitrogen, N(3). Human urine samples from patients on cisplatin chemotherapy were shown to contain cisplatin, its hydrolysis product and biotransformation products containing Pt-creatinine, Pt-urea and Pt-uric acid complexes. Urine from carboplatin patients shows fewer biotransformation products. Studies with control and diabetic (protected against cisplatin toxicity) rats showed systematic differences in the biotransformation products formed on administration of cisplatin.
Overproduction of bacterial chaperones improves the solubility of recombinant protein tyrosine kinases in Escherichia coli. (1994)

The production and purification of recombinant proteins from E. coli expression systems is often complicated by the fact that a significant amount of the foreign protein is deposited in the cytoplasm of the bacteria as aggregates or inclusion bodies. Many non-receptor protein tyrosine kinases are typical examples of proteins that are poorly soluble when overproduced in E. coli. Here, we report on the engineering of bacterial strains which overproduce chaperone proteins of the Hsp70 (DnaK, DnaJ and GrpE) and Hsp60 (GroEL and GroES) families. The simultaneous overproduction in E. coli of the chaperones DnaK, DnaJ and GrpE on the one hand, or GroEL and GroES on the other hand, and the human non-receptor protein tyrosine kinases Csk, Fyn or Lck resulted in increased solubility of the recombinant kinases. This provides the basis for future successful production and purification of large quantities of soluble and active non-receptor protein tyrosine kinases from E.coli expression systems and will enable the further characterization of these important enzyme families at the molecular level.
Effects of recombinant human GM-CSF on proliferation of clonogenic cells in acute myeloblastic leukemia (1986)

Proliferation of acute myeloblastic leukemia (AML) cells in vitro is limited in most cases to a small subset of blasts that have several properties of stem cells. These leukemic colony-forming cells (AML-CFU) generally require addition of exogenous growth factors for proliferation in agar or methylcellulose. These factors can be supplied by media conditioned by phytohemagglutinin-stimulated normal leukocytes or by CSF-secreting tumor cell lines. However, the exact factor or factors required for stimulation of AML-CFU growth have not been defined. We compared the AML-CFU stimulatory activity of a human recombinant GM-CSF with that of GCT-CM, Mo-CM, and the PHA-leukocyte feeder system in 15 cases of AML. In each of the 12 cases that required exogenous growth factors for maximum AML-CFU growth, recombinant GM-CSF could replace either GM-CSF or Mo-CM, and could partially replace the PHA-leukocyte feeder system. These results indicate that this GM-CSF is a growth promoter of AML-CFU in these culture systems.
Effects of cannabinoid receptor‐2 activation on accelerated gastrointestinal transit in lipopolysaccharide‐treated rats (2004)

The biological effects of cannabinoids (CB) are mediated by CB(1) and CB(2) receptors. The role of CB(2) receptors in the gastrointestinal tract is uncertain. In this study, we examined whether CB(2) receptor activation is involved in the regulation of gastrointestinal transit in rats. Basal and lipopolysaccharide (LPS)-stimulated gastrointestinal transit was measured after instillation of an Evans blue-gum Arabic suspension into the stomach, in the presence of specific CB(1) and CB(2) agonists and antagonists, or after treatment with inhibitors of mediators implicated in the transit process. In control rats a CB(1) (ACEA; 1 mg kg(-1)), but not a CB(2) (JWH-133; 1 mg kg(-1)), receptor agonist inhibited basal gastrointestinal transit. The effects of the CB(1) agonist were reversed by the CB(1) antagonist AM-251, which alone increased basal transit. LPS treatment increased gastrointestinal transit. This increased transit was reduced to control values by the CB(2), but not the CB(1), agonist. This inhibition by the CB(2) agonist was dose dependent and prevented by a selective CB(2) antagonist (AM-630; 1 mg kg(-1)). By evaluating the inhibition of LPS-enhanced gastrointestinal transit by different antagonists, the effects of the CB(2) agonist (JWH-133; 1 mg kg(-1)) were found to act via cyclooxygenase, and to act independently of inducible nitric oxide synthase (NOS) and platelet-activating factor. Interleukin-1 beta and constitutive NOS isoforms may be involved in the accelerated LPS transit. The activation of CB(2) receptors in response to LPS is a mechanism for the re-establishment of normal gastrointestinal transit after an inflammatory stimulus.
3-D motion estimation using a sequence of noisy stereo images: models, estimation, and uniqueness results (1990)

A kinematic model-based approach for the estimation of 3-D motion parameters from a sequence of noisy stereo images is discussed. The approach is based on representing the constant acceleration translational motion and constant precession rotational motion in the form of a bilinear state-space model using standard rectilinear states for translation and quaternions for rotation. Closed-form solutions of the state transition equations are obtained to propagate the quaternions. The measurements are noisy perturbations of 3-D feature points represented in an inertial coordinate system. It is assumed that the 3-D feature points are extracted from the stereo images and matched over the frames. Owing to the nonlinearity in the state model, nonlinear filters are designed for the estimation of motion parameters. Simulation results are included. The Cramer-Rao performance bounds for motion parameter estimates are computed. A constructive proof for the uniqueness of motion parameters is given. It is shown that with uniform sampling in time, three noncollinear feature points in five consecutive binocular image pairs contain all the spatial and temporal information. Both nondegenerate and degenerate motions are analyzed. A deterministic algorithm to recover motion parameters from a stereo image sequence is summarized from the constructive proof.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Protein kinase C alpha mediates phospholipase D activation by nucleotides and phorbol ester in Madin-Darby canine kidney cells. Stimulation of phospholipase D is independent of activation of polyphosphoinositide-specific phospholipase C and phospholipase A2. (1994)

Protein kinase C (PKC) has been implicated in the activation of phospholipase D (PLD) in a number of systems. By antisense technology, we have "knocked out" alpha and beta isoforms of PKC to study the role of these isoforms in PLD activation in Madin-Darby canine kidney (MDCK) cells. To this end, we have studied PLD activation by phorbol 12-myristate 13-acetate (PMA), ATP, UTP, and 2-methylthio-ATP in cells labeled with [3H]palmitic acid. [3H]Phosphatidylethanol (PEt) production catalyzed by PLD in the presence of ethanol was time- and concentration-dependent in PMA- and nucleotide-stimulated cells. In Ca(2+)-free medium, [3H]PEt accumulation was diminished for all stimuli assayed. Treatment of cells with chelerythrine, an inhibitor of PKC, and phorbol ester down-regulation of PKC inhibited [3H]PEt production by both PMA and nucleotides. In cells transfected with antisense PKC alpha or both PKC alpha and PKC beta, PLD activation was inhibited by both PMA and nucleotides, whereas in cells transfected with antisense PKC beta, PLD activation was similar to that of control cells. Moreover, inhibition of polyphosphoinositide-specific PLC (by neomycin) or of release of arachidonic acid and arachidonic acid metabolites (by nordihydroguaiaretic acid or by indomethacin) failed to decrease [3H]PEt accumulation in PMA- and nucleotide-stimulated MDCK-D1 cells. From these data, we conclude that in MDCK-D1 cells PMA and nucleotide receptors utilize PKC alpha to regulate PLD activity and that PLD activation is independent of the activation of polyphosphoinositide-specific PLC and phospholipase A2-mediated release of arachidonic acid or arachidonic acid metabolites.
In Vitro Propagation of Paradox Walnut Rootstock (1984)

Abstract Apical and lateral meristems of Paradox walnut ( Juglans hindsii x J. regia ) were used to investigate the possibility of accomplishing in vitro propagation of Paradox rootstock. A walnut specific medium, DKW, has been defined supporting optimum multiple shoot development under 4.5 μm benzyladenine (BA) and 5 nm indolebutyric acid (IBA) treatment. The method of analysis to determine the optimum level of constituents in tissue culture medium is discussed. Also reported is the in vivo rooting of tissue culture derived shoots.