gebhart/patrepeval huggingface dataset:
Safety and Tolerance of Methylnaltrexone in Healthy Humans: A Randomized, Placebo‐Controlled, Intravenous, Ascending‐Dose, Pharmacokinetic Study (1997)

N-methylnaltrexone bromide (methylnaltrexone) is a quaternary opioid antagonist with a limited ability to cross the blood-brain barrier. In animal models it reverses at peripheral receptors such side effects of opioids as decreased gastrointestinal motility, emesis, and cough suppression without affecting the desired analgesic effect mediated by central nervous system receptors. Methylnaltrexone thus may be a clinically useful compound for the prevention and treatment of opioid-induced side effects. This study was designed to examine the safety and tolerance of methylnaltrexone in healthy human participants over a range of doses and to identify any adverse effects or toxicity associated with methylnaltrexone and the doses at which these adverse effects occur. Healthy male volunteers received intravenous methylnaltrexone in six ascending doses with a placebo randomly inserted into the sequence. Each participant was observed for subjective and hemodynamic changes. Electrocardiogram and laboratory studies were also performed. The dose-limiting adverse effect of methylnaltrexone was orthostatic hypotension at 0.64 mg/kg (n = 3) or 1.25 mg/kg (n = 5), which was transient and self-limiting. Plasma levels of methylnaltrexone in excess of 1,400 ng/mL were observed to be associated with orthostatic hypotension. There were no significant subjective changes, no release of histamine, and no changes in physical examination or laboratory studies during the course of the study. Pharmacokinetic analysis revealed an elimination half-life of 117.5 minutes (+/-53.2), and a clearance of 38.8 L/hr (+/-17.4) with a methylnaltrexone dose of 0.64 mg/kg. Our results indicate that methylnaltrexone is well tolerated at doses of 0.32 mg/kg in healthy humans.
<title>Time-gated fluorescence spectroscopy and imaging of porphyrins and phthalocyanines</title> (1991)

Time-gated fluorescence spectroscopy provides a very useful tool to evaluate the photophysical properties and the incorporation mechanisms of drugs interacting with biological substrates. In particular, taking into account that different fluorophores, even if overlapped in fluorescence spectrum, present different fluorescence lifetimes, it is possible to evidence the emission of a single molecular species by choosing a suitable observation window in the time domain. Using this technique, the effect of systemic administration on the uptake of Hematoporphyrin Derivative (HpD), its tumor localizing fraction (TLF), and disulphonated Aluminum Phthalocyanine (AlS2Pc) at the cellular level was evaluated on a murine ascitic tumor. The results obtained indicate that the TLF is the part of HpD actually retained by the cells and that AlS2Pc is incorporated more rapidly with respect to porphyrins. The observation of the gated spectra of HpD also evidenced the possibility of improving the contrast between the fluorescence of the cells and that of the drug. Thus, an imaging system has been developed which utilizes a gated, intensified, CCD camera synchronized with a subnanosecond laser- pulse excitation. The gate can be set to a minimum width of 5 ns and arbitrarily delayed with respect to the laser pulse. By optimization of the gate parameters, porphyrin fluorescence images in single cells and microscopy sections of tumor were obtained with a valuable signal- to-noise ratio.
In vitro induction of chronic myeloid leukemia associated immune reactivity in normal human lymphocytes by xenogeneic immune RNA. (1983)

Peripheral blood lymphocytes from normal human donors were treated with immune RNA (IRNA) prepared from lymphoid tissues of guinea pigs immunized with chronic myeloid leukemia (CML) cells, normal leukocytes (WBCs) and normal bone marrow (BM) cells, in order to study whether IRNA can confer specific immunoreactivity on normal lymphocytes. The IRNA treated lymphocytes were further exposed to solubilized membrane antigens from CML cells, normal WBCs and BM cells in a criss-cross fashion. The migration inhibition factor produced by these lymphocytes was tested in an in vitro leukocyte migration inhibition assay using normal leukocytes. The results indicated that IRNA prepared from guinea pigs immunized with all the three cell types could transfer the immune reactivity to normal cells in response to the respective antigens. The WBC IRNA incubated lymphocytes did not react with BM cell and CML cell antigens. A potent transfer of specific reactivity was shown by CML IRNA. IRNA produced against BM cells and CML cells demonstrated considerable cross reactivity perhaps due to shared immature cell antigens.
Randomized trial of an inhibitor of secretory phospholipase A2 on atherogenic lipoprotein subclasses in statin-treated patients with coronary heart disease (2010)

Reductions in atherogenic lipoproteins suggest that varespladib methyl 500 mg once daily may be an effective anti-atherosclerotic agent. Trial registered at ClinicalTrials.gov, identifier: NCT00525954.
A microlens-array-based optical neural network application (1997)

We have designed and are currently constructing a recurrent neural network with 16 × 16 fully interconnected channels and an optical feedback loop. We have mainly used diffractive microlens arrays instead of bulk achromats for illumination, imaging and fan-in. We report on the advantages of this approach, design considerations and first experimental results with various original and replicated microlens arrays.
Aspirin to Prevent Gentamicin-Induced Hearing Loss (2006)

To the Editor: The use of aminoglycosides as powerful broad-spectrum, bactericidal, and nonallergenic antibiotics is limited by serious side effects, including irreversible hearing loss. Nevertheless, the drugs are commonly prescribed in some situations, including as part of the regimen against multidrug-resistant tuberculosis recommended by the World Health Organization.1 The incidence of gentamicin-induced hearing loss averages 8 percent for a short course of therapy2 but may be higher in developing countries, where aminoglycosides are frequently the only affordable antibiotics and are sold over the counter. No therapy presently exists to prevent ototoxicity. Animal models suggest that ototoxicity is caused by reactive . . .
Plant Cell Electroporation And Electrofusion Protocols (1995)

Gene transfer is an essential technology for improving our under standing of gene structure and function. Although there are many meth ods by which DNA may be introduced into cells—including heat and
Growth inhibition of the intestinal parasite Giardia lamblia by a dietary lectin is associated with arrest of the cell cycle. (1994)

Giardia lamblia, a cause of diarrheal disease throughout the world, is a protozoan parasite that thrives in the small intestine. It is shown here that wheat germ agglutinin (WGA), a naturally occurring lectin widely consumed in normal human diets, reversibly inhibits the growth of G. lamblia trophozoites in vitro, and reduces infection by G. muris in the adult mouse model of giardiasis. The inhibitory effect was dose related, not associated with cytotoxicity and reversed by N-acetyl-D-glucosamine in accordance with the known specificity of the lectin and in agreement with the presence of GlcNAc residues on the surface membrane of G. lamblia trophozoites. Cell cycle analysis revealed that parasites grown in the presence of WGA are arrested in the G2/M phase, providing an explanation for the lectin-induced inhibition of cell proliferation. Comparison of electrophoretic profiles by lectin blot analysis revealed both glycoprotein induction and suppression in growth-arrested organisms. Our findings raise the possibility that blocking trophozoite growth with naturally occurring dietary lectins may influence the course of giardiasis. In addition, the study of cell cycle arrest by WGA may provide a model to study the regulation of cell division in lower eukaryotes.
Amphiphilic Block Copolymers in Structure-Controlled Nanomaterial Hybrids (1998)

Amphiphilic block copolymers (ABCs) are important in interface and particle stabilization. Following consideration of the various methods of synthesis of ABCs, mesophases and micelles of block copolymers and the solubilization and adhesion of ABCs are considered. The Figure shows micelles formed by a polystyrene-poly(vinylpyridine) copolymer. Nanoparticles and ABC/nanoparticle hybrid systems are also reviewed.
Nerve growth factor potentiates the neurotoxicity of beta amyloid. (1990)

The role of growth factors in the pathogenesis of Alzheimer disease is unknown. The beta-amyloid protein accumulates abnormally in the brain in Alzheimer disease and is neurotoxic to differentiated hippocampal neurons in culture. Nerve growth factor (NGF) increased the neurotoxic potency of a beta-amyloid polypeptide by a factor of approximately 100,000, which resulted in a reduction of the beta-amyloid neurotoxic EC50 from 0.1 microM to 1 pM. This potentiating effect of NGF was reversed by a monoclonal antibody against NGF and was not observed for a variety of other neurotrophic growth factors. Exposure of hippocampal neurons to very low concentrations of beta amyloid alone resulted in a marked induction of immunoreactive NGF receptors. Addition of NGF with beta amyloid resulted in the appearance of neurodegenerative changes in NGF receptor-positive neurons. The early and profound degeneration of hippocampal and basal forebrain cholinergic neurons that occurs in Alzheimer disease may result from a neurotoxic interaction of beta amyloid with NGF.
Sphingosine kinase-1 enhances endothelial cell survival through a PECAM-1–dependent activation of PI-3K/Akt and regulation of Bcl-2 family members (2005)

Sphingosine-1-phosphate (S1P), the bioactive product of sphingosine kinase (SK) activation, is a survival factor for endothelial cells. The mechanism of SK-mediated survival was investigated in endothelial cells with moderately raised intracellular SK activity. Overexpression of SK mediated survival primarily through the activation of the phosphatidyl inositol 3-kinase (PI-3K)/protein kinase B (Akt/PKB) pathway and an associated up-regulation of the antiapoptotic protein B cell lymphoma gene 2 (Bcl-2) and down-regulation of the proapoptotic protein bisindolylmaleimide (Bcl-2 interacting mediator of cell death; Bim). In addition there was an up-regulation and dephosphorylation of the junctional molecule platelet endothelial cell adhesion molecule-1 (PECAM-1), which was obligatory for activation of the PI-3K/Akt pathway, for SK-induced cell survival, and for the changes in the apoptosis-related proteins. Thus, raised intracellular SK activity induced a molecule involved in cell-cell interactions to augment cell survival through a PI-3K/Akt-dependent pathway. This is distinct from the activation of both PI-3K/Akt and mitogen-activated protein kinase (MAPK) pathways seen with exogenously added S1P. Cells overexpressing SK showed enhanced survival under conditions of serum deprivation and absence of attachment to extracellular matrix, suggesting a role for SK in the regulation of vascular phenomena that occur under conditions of stress, such as angiogenesis and survival in unattached states, as would be required for a circulating endothelial cell.
Human fibroblast interferon. An improved purification. (1981)

Human fibroblast interferon has been purified 2,900-fold to homogeneity. The purification is achieved in two steps by chromatography on blue Sepharose. The specific activity of the homogeneous interferon is 5 X 10(8) units/mg and the yield of biological activity has ranged from 20-40%. The interferon can exist as a monomer (Mr = 20,000) and as a dimer (Mr - 40,000). The dimer can be converted to the monomer by heating in sodium dodecyl sulfate and thioglycolic acid.
Using ionic liquids in whole-cell biocatalysis for the nucleoside acylation (2014)

The use of biocatalysts has become an increasingly attractive alternative to traditional chemical methods, due to the high selectivity, mild reaction conditions and environmentally-friendly processes in nonaqueous catalysis of nucleosids. However, the extensive use of organic solvents may generally suffer from sever drawbacks such as volatileness and toxicity to the environment and lower activity of the biocatalyst. Recently, ionic liquids are considered promising solvents for nonaqueous biocatalysis of polyhydroxyl compounds as ILs are environmental-friendly. In this research, we developed new IL-containing reaction systems for synthesis of long chain nucleoside ester catalyzed by Pseudomonas fluorescens whole-cells. Various ILs exerted significant but different effects on the bio-reaction. And their effects were closely related with both the anions and cations of the ILs. Use of 10% [BMI][PF6]/THF gave high reaction efficiency of arabinocytosine laurate synthesis, in which the initial rate, product yield and 5′-regioselectivity reached 2.34 mmol/L·h, 81.1% and >99%, respectively. Furthermore, SEM analysis revealed that ILs can alter the cell surface morphology, improve the permeability of cell envelopes and thus facilitate the mass transfer of substrates to the active sites of cell-bound enzymes. Our research demonstrated the potential of ILs as promising reaction medium for achieving highly efficient and regioselective whole-cell catalysis.
Soluble group- and type-specific antigens from type III group B Streptococcus (1980)

Two soluble polysaccharide antigens of a type III group B Streptoccus were isolated from the culture medium after growth of strain M732 in a chemically defined broth supplemented with acid-hydrolyzed casein. The type- and group- specific antigens were isolated from the culture supernatant by anion-exchange chromatography with diethylaminoethyl-Sephacel. Two carbohydrate-containing peaks, which had serological reactivity with group B or type III antiserum, respectively, were eluted with a linear NaCl gradient and further purified by gel filtration. The type III polysaccharide was found to contain glucose, galactose, glucosamine, and sialic acid, whereas the group B polysaccharide contained galactose, glucosamine, and rhamnose. For the type III polysaccharide, sialic acid was shown to be the major immunodeterminant, and for the group B polysaccharide, rhamnose was the immunodominant sugar. Both the type III and group B polysaccharides were obtained in high yields without employing harsh physical or chemical treatment and both were immunologically distinct. By immunoelectrophoresis or counterimmunoelectrophoresis, type III antigen failed to react with group-specific antiserum and the group B antigen failed to react with type III antiserum.
NF-κB activation provides the potential link between inflammation and hyperplasia in the arthritic joint (1998)

The transcription factor NF-kappaB is a pivotal regulator of inflammatory responses. While the activation of NF-kappaB in the arthritic joint has been associated with rheumatoid arthritis (RA), its significance is poorly understood. Here, we examine the role of NF-kappaB in animal models of RA. We demonstrate that in vitro, NF-kappaB controlled expression of numerous inflammatory molecules in synoviocytes and protected cells against tumor necrosis factor alpha (TNFalpha) and Fas ligand (FasL) cytotoxicity. Similar to that observed in human RA, NF-kappaB was found to be activated in the synovium of rats with streptococcal cell wall (SCW)-induced arthritis. In vivo suppression of NF-kappaB by either proteasomal inhibitors or intraarticular adenoviral gene transfer of super-repressor IkappaBalpha profoundly enhanced apoptosis in the synovium of rats with SCW- and pristane-induced arthritis. This indicated that the activation of NF-kappaB protected the cells in the synovium against apoptosis and thus provided the potential link between inflammation and hyperplasia. Intraarticular administration of NF-kB decoys prevented the recurrence of SCW arthritis in treated joints. Unexpectedly, the severity of arthritis also was inhibited significantly in the contralateral, untreated joints, indicating beneficial systemic effects of local suppression of NF-kappaB. These results establish a mechanism regulating apoptosis in the arthritic joint and indicate the feasibility of therapeutic approaches to RA based on the specific suppression of NF-kappaB.
Applying Dynamic Parameters to Predict Hemodynamic Response to Volume Expansion in Spontaneously Breathing Patients With Septic Shock (2013)

Volume expansion is a mainstay of therapy in septic shock, although its effect is difficult to predict using conventional measurements. Dynamic parameters, which vary with respiratory changes, appear to predict hemodynamic response to fluid challenge in mechanically ventilated, paralyzed patients. Whether they predict response in patients who are free from mechanical ventilation is unknown. We hypothesized that dynamic parameters would be predictive in patients not receiving mechanical ventilation. This is a prospective, observational, pilot study. Patients with early septic shock and who were not receiving mechanical ventilation received 10-mL/kg volume expansion (VE) at their treating physician's discretion after initial resuscitation in the emergency department. We used transthoracic echocardiography to measure vena cava collapsibility index and aortic velocity variation before VE. We used a pulse contour analysis device to measure stroke volume variation (SVV). Cardiac index was measured immediately before and after VE using transthoracic echocardiography. Hemodynamic response was defined as an increase in cardiac index 15% or greater. Fourteen patients received VE, five of whom demonstrated a hemodynamic response. Vena cava collapsibility index and SVV were predictive (area under the curve = 0.83, 0.92, respectively). Optimal thresholds were calculated: vena cava collapsibility index, 15% or greater (positive predictive value, 62%; negative predictive value, 100%; P = 0.03); SVV, 17% or greater (positive predictive value 100%, negative predictive value 82%, P = 0.03). Aortic velocity variation was not predictive. Vena cava collapsibility index and SVV predict hemodynamic response to fluid challenge patients with septic shock who are not mechanically ventilated. Optimal thresholds differ from those described in mechanically ventilated patients.
A Yeast Replicative Helicase, Dna2 Helicase, Interacts with Yeast FEN-1 Nuclease in Carrying Out Its Essential Function (1997)

We have recently described a new helicase, the Dna2 helicase, that is essential for yeast DNA replication. We now show that the yeast FEN-1 (yFEN-1) nuclease interacts genetically and biochemically with Dna2 helicase. FEN-1 is implicated in DNA replication and repair in yeast, and the mammalian homolog of yFEN-1 (DNase IV, FEN-1, or MF1) participates in Okazaki fragment maturation. Overproduction of yFEN-1, encoded by RAD27/RTH1, suppresses the temperature-sensitive growth of dna2-1 mutants. Overproduction of Dna2 suppresses the rad27/rth1 delta temperature-sensitive growth defect. dna2-1 rad27/rth1 delta double mutants are inviable, indicating that the mutations are synthetically lethal. The genetic interactions are likely due to direct physical interaction between the two proteins, since both epitope-tagged yFEN-1 and endogenous yFEN-1 coimmunopurify with tagged Dna2. The simplest interpretation of these data is that one of the roles of Dna2 helicase is associated with processing of Okazaki fragments.
Precision and broadband frequency swept laser source based on high-order modulation-sideband injection-locking (2015)

A precision and broadband laser frequency swept technique is experimentally demonstrated. Using synchronous current compensation, a slave diode laser is dynamically injection-locked to a specific high-order modulation-sideband of a narrow-linewidth master laser modulated by an electro-optic modulator (EOM), whose driven radio frequency (RF) signal can be agilely, precisely controlled by a frequency synthesizer, and the high-order modulation-sideband enables multiplied sweep range and tuning rate. By using 5th order sideband injection-locking, the original tuning range of 3 GHz and tuning rate of 0.5 THz/s is multiplied by 5 times to 15 GHz and 2.5 THz/s respectively. The slave laser has a 3 dB-linewidth of 2.5 kHz which is the same to the master laser. The settling time response of a 10 MHz frequency switching is 2.5 µs. By using higher-order modulation-sideband and optimized experiment parameters, an extended sweep range and rate could be expected.
Immune Recognition and Rejection of Allogeneic Skin Grafts (2011)

The transplantation of allogeneic skin grafts is associated with a potent inflammatory immune response leading to the destruction of donor cells and the rejection of the graft. Shortly after transplantation, skin dendritic cells (DCs) migrate out of the graft through lymphatic vessels and infiltrate the recipient's draining lymph nodes where they present donor antigens via two mechanisms: the direct pathway, in which T cells recognize intact donor MHC antigens on donor DCs; and the indirect pathway, involving T-cell recognition of donor peptides bound to self-MHC molecules on recipient DCs. Some recent studies have suggested that T cells can become activated via recognition of donor MHC molecules transferred on recipient antigen-presenting cells (semidirect pathway). Activation of T cells via direct or indirect allorecognition is sufficient to trigger acute rejection of allogeneic skin grafts. In addition, allospecific antibodies contribute to the rejection process either by killing allogeneic targets in a complement-dependent fashion or by opsonizing donor cells and forming immune complexes. Finally, several studies demonstrate that NK cells, activated due to missing self-MHC class I molecules on allogeneic cells, are involved in allogeneic skin graft rejection via direct killing of donor cells and through the production of proinflammatory cytokines including IFN-γ and TNF-α.
Etiolation aids rooting of Protea cynaroides cuttings (2006)

The role that starch content and blanching play in the rooting of Protea cynaroides cuttings was studied.P. cynaroides stems were blanched on the motherplant in the field, which resulted in a higher starch concentration in the cuttings.The relationship between starch content and rooting was also established, whereby the ability of the blanched cuttings to maintain a consistent starch level throughout the rooting period, resulted in the acceleration of the rooting process.The blanched cuttings had a higher dry root mass than the control at day 90 when the cuttings were ready to be transplanted.The untreated cuttings were only suitable for transplanting after 120 days.Blanching the cuttings also resulted in a higher rooting percentage (100%) than the control (60%).