gebhart/patrepeval huggingface dataset:
Enhancement of Wound Healing by the Alkaloid Taspine Defining Mechanism of Action (1993)

Taspine (mol wt 369,000) is an alkaloid extracted from trees of Croton (family Euphorbiaceae) of the western Amazon region that has been used by natives and others as a vulnerary agent. Taspine was purified from tree sap to test its healing properties using different topical concentrations in the paired rat surgical incision model. Wound tensile strength and histology were evaluated. Samples treated with 250 micrograms, but not those treated with 50 micrograms or 10 micrograms, had significant higher values for MBS than paired controls (26%, P < 0.005, and 30%, P < 0.001, by Days 5 and 7, respectively). Taspine did not modify MBS at Day 12. Sample treated with 250 micrograms had significantly greater mononuclear cellular infiltration at Days 5 and 7 but not at Day 12. To better understand the effect of taspine as an enhancer of wound healing, we conducted in vitro studies in cell cultures. Taspine stimulated chemotaxis for fibroblasts. Taspine did not have an effect on specific assays for macrophage chemotaxis, neutrophil activation, fibroblast proliferation, or matrix assembly. Taken together, the data suggest that taspine promotes early phases of wound healing in a dose-dependent manner with no substantial modification thereafter. Its mechanism of action is probably related to its chemotactic properties on fibroblasts and is not mediated by changes in extracellular matrix.
Platelet Anti-Aggregating Activity and Tolerance of Clopidogrel in Atherosclerotic Patients (1996)

The anti-aggregating activity of five rising doses of clopidogrel has been compared to that of ticlopidine in atherosclerotic patients. The aim of this study was to determine the dose of clopidogrel which should be tested in a large scale clinical trail of secondary prevention of ischemic events in patients suffering from vascular manifestations of atherosclerosis [CAPRIE (Clopidogrel vs Aspirin in Patients at Risk of Ischemic Events) trial]. A multicenter study involving 9 haematological laboratories and 29 clinical centers was set up. One hundred and fifty ambulatory patients were randomized into one of the seven following groups: clopidogrel at doses of 10, 25, 50, 75 or 100 mg OD, ticlopidine 250 mg BID or placebo. ADP and collagen-induced platelet aggregation tests were performed before starting treatment and after 7 and 28 days. Bleeding time was performed on days 0 and 28. Patients were seen on days 0, 7 and 28 to check the clinical and biological tolerability of the treatment. Clopidogrel exerted a dose-related inhibition of ADP-induced platelet aggregation and bleeding time prolongation. In the presence of ADP (5 microM) this inhibition ranged between 29% and 44% in comparison to pretreatment values. The bleeding times were prolonged by 1.5 to 1.7 times. These effects were non significantly different from those produced by ticlopidine. The clinical tolerability was good or fair in 97.5% of the patients. No haematological adverse events were recorded. These results allowed the selection of 75 mg once a day to evaluate and compare the antithrombotic activity of clopidogrel to that of aspirin in the CAPRIE trial.
A novel synthetic lipid A analog with low endotoxicity, DT-5461, prevents lethal endotoxemia (1995)

Bacterial endotoxin (lipopolysaccharide [LPS]) causes severe damage to the host organism as a result of excessive release of inflammatory cytokines, including interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha), from mononuclear phagocytes during gram-negative bacterial infection. We evaluated the ability of a novel synthetic lipid A analog with low endotoxicity, DT-5461, to antagonize LPS-induced IL-1 and TNF-alpha production in cells of monocyte/macrophage lineage and examined the protective effect of DT-5461 against lethal endotoxic shock in mice. The IL-1- or TNF-alpha-inducing activity of DT-5461 is 100,000 to 10,000 times less active than that of Escherichia coli LPS (EcLPS) or synthetic lipid A. DT-5461 significantly inhibited EcLPS-induced IL-1 and TNF-alpha release when murine peritoneal macrophages were incubated with DT-5461 2 h prior to EcLPS stimulation at the same concentration (1 microgram/ml). The antagonistic effect of DT-5461 on the production of IL-1 and TNF-alpha induced by EcLPS occurred in a concentration-dependent manner. DT-5461 also inhibited IL-1 and TNF-alpha induction when murine peritoneal macrophages were stimulated by LPS from Salmonella typhimurium or synthetic lipid A, as well as by EcLPS, but not by muramyl dipeptides. This indicated that DT-5461 specifically antagonized the action of LPS. DT-5461 also antagonized EcLPS-mediated activation of human peripheral blood monocytes. DT-5461 blocked the binding of fluorescein isothiocyanate-labelled LPS to murine peritoneal macrophages as well as it did the binding of EcLPS and synthetic lipid A, i.e., in a concentration-dependent fashion. Injection of DT-5461 2 h before EcLPS challenge prevented the production of serum IL-1 and TNF-alpha in D-galactosamine-treated mice. Furthermore, this treatment modality protected mice against LPS-induced lethal toxicity. This study suggests that DT-5461 possesses a potent LPS antagonistic effect and may be useful in a protective strategy against lethal endotoxemia caused by gram-negative bacterial infection.
A monoclonal antibody to human immunodeficiency virus type 1 which mediates cellular cytotoxicity and neutralization (1990)

Monoclonal antibodies (MAbs) were raised against human immunodeficiency virus type 1 gp120. One MAb, P4/D10, was found to mediate highly efficient antibody-dependent cellular cytotoxicity and virus neutralization. The reactivity was located to a major neutralizing region (amino acids 304 to 323) on gp120. Five other MAbs with a similar epitopic reactivity did not show any antibody-dependent cellulan cytotoxicity activity but had a virus-neutralizing capacity.
Interleukin‐10 functions as an antiinflammatory cytokine in rheumatoid synovium (1996)

These data indicate that endogenously produced IL-10 functions as an immunoregulatory molecule in rheumatoid synovium. Importantly, exogenous IL-10 has potent antiinflammatory effects on SFMC, suggesting that IL-10 may be useful in the treatment of patients with RA.
A simple and reliable turbidimetric and kinetic assay for alpha-amylase that is readily applied to culture supernatants and cell extracts (1990)

A simple, reliable and sensitive assay for alpha-amylase activity is reported, together with its theoretical derivation, that overcomes many of the problems encountered with other assays, especially when attempting to assay alpha-amylase activity in crude cell extracts or culture supernatants. The method relies on the reduction in turbidity that occurs upon digestion of a starch suspension with alpha-amylase. The initial rate of decrease in turbidity is shown to be proportional to a wide range of enzyme concentrations, permitting a rapid spectrophotometric and kinetic determination of alpha-amylase activity.
Freely Dispersible Au@TiO2, Au@ZrO2, Ag@TiO2, and Ag@ZrO2 Core−Shell Nanoparticles:  One-Step Synthesis, Characterization, Spectroscopy, and Optical Limiting Properties (2003)

We report a one-step route for the synthesis of Au@TiO2, Au@ZrO2, Ag@TiO2, and Ag@ZrO2 particles in nanometer dimensions, with controllable shell thickness. This scalable procedure leads to stable and freely dispersible particles, and bulk nanocomposite materials have been made this way. The procedure leads to particles of various morphologies, with a crystalline core in the size range of 30−60 nm diameter and an amorphous shell of ∼3 nm thickness in a typical synthesis. The core diameter and shell thickness (in the range of 1−10 nm) can be varied, leading to different absorption maxima. The material has been characterized with microscopic, diffraction, and spectroscopic techniques. The metal particle growth occurs by the carbamic acid reduction route followed by hydrolysis of the metal oxide precursor, resulting in the oxide cover. The particles could be precipitated and redispersed. The shell, upon thermal treatment, gets converted to crystalline oxides. Cyclic voltammetric studies confirm the core−shell structure. The E1/2 value is 0.250 V (ΔE ≈ 180 mV) for the quasi-reversible Agm/Agm+ couple and 0.320 V (ΔE ≈ 100 mV) for the Aun/Aun+ couple for Ag and Au particles, respectively. Adsorption on the oxide surface blocks electron transfer partially. Nonlinear optical measurements in solutions show that these materials are strong optical limiters with a high laser damage threshold.
Influence of glucose and inflammatory cytokines on TGF-β1 and CTGF mRNA expressions in human peritoneal mesothelial cells (2005)

Peritoneal fibrosis is a major complication of long-term continuous ambulatory peritoneal dialysis (CAPD) treatment. Transforming growth factor-beta (TGF-beta) has been reported to play an important role in the fibrosis of various tissues by stimulating connective tissue growth factor (CTGF) expression. In order to elucidate the mechanism of CAPD-related peritoneal fibrosis, we studied the influence of high glucose concentrations and inflammatory cytokines on mRNA expressions of TGF-beta and CTGF in cultured human peritoneal mesothelial cells (HPMC). HPMC were isolated from normal omentum and cultured with 0.5 or 1.0% glucose or mannitol for 7 days. TGF-beta1 and CTGF mRNA were quantified by one step real-time reverse transcription-polymerase chain reaction (real-time RT-PCR). TGF-beta1 and CTGF mRNA expression levels were significantly increased (p<0.05) by glucose in a dose-dependent manner, but not by mannitol. The expression levels were correlated between TGF-beta1 and CTGF. Effects of inflammatory cytokines were also examined by adding tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) or interleukin-6 (IL-6) to the medium at 0.1 ng/ml for 2 days. TGF-beta1 expression tended to be increased by TNF-alpha and IL-6. On the other hand, CTGF expression was significantly decreased (p<0.01) by IL-1 but not changed by TNF-alpha or IL-6. These results suggest that high glucose concentration may play a central role in peritoneal fibrosis. Responses of TGF-beta1 and CTGF to inflammatory cytokines were not necessarily identical, suggesting that CTGF may be a better therapeutic target for peritoneal fibrosis than TGF-beta1.
Another first for critical care medicine and pediatric critical care medicine (2001)

Luce, John M. MD, FCCM; Kochanek, Patrick M. MD, FCCM; Parrillo, Joseph E. MD, FCCM Author Information
Biochemical properties of CO2-dependent streptococci (1980)

A total of 153 clinical isolates and 10 reference strains were employed in an investigation of CO2-dependent streptococci. Their selection was based on a lactic acid homofermentative end product. This group of organisms grew best in 5 to 10% CO2, and several species, including Streptococcus mutans, S. intermedius, Streptococcus MG, S. anginosus, and S. constellatus, required increased CO2 for primary recovery. A basal medium of thioglycolate with 0.1% Tween 80 and phenol red was prepared and used with selected carbohydrates. This media provided luxuriant growth. Serological testing failed to give any definitive correlation with species identification. A shortened differentiation scheme, combined from previous studies, was proposed.
Tolerance, Danger and the Extended Family (1994)

Exhausted CD8 T (Tex) cells are a distinct cell lineage that arise during chronic infections and cancers in animal models and humans. Tex cells are characterized by progressive loss of effector functions, high and sustained inhibitory receptor expression, ...Read More
Treatment of patients with melanoma of the extremity using hyperthermic isolated limb perfusion with melphalan, tumor necrosis factor, and interferon gamma: results of a tumor necrosis factor dose-escalation study. (1996)

ILP with 4 mg TNF, IFN, and melphalan can lead to complete local responses in the majority of patients with extremity melanoma. Escalating the TNF dose to 6 mg did not increase the complete response rate and increased regional toxicity.
Optimization of a Pipemidic Acid Autotaxin Inhibitor (2009)

Autotaxin (ATX, NPP2) has recently been shown to be the lysophospholipase D responsible for synthesis of the bioactive lipid lysophosphatidic acid (LPA). LPA has a well-established role in cancer, and the production of LPA is consistent with the cancer-promoting actions of ATX. Increased ATX and LPA receptor expression have been found in numerous cancer cell types. The current study has combined ligand-based computational approaches (binary quantitative structure-activity relationship), medicinal chemistry, and experimental enzymatic assays to optimize a previously identified small molecule ATX inhibitor, H2L 7905958 (1). Seventy prospective analogs were analyzed via computational screening, from which 30 promising compounds were synthesized and screened to assess efficacy, potency, and mechanism of inhibition. This approach has identified four analogs as potent as or more potent than the lead. The most potent analog displayed an IC(50) of 900 nM with respect to ATX-mediated FS-3 hydrolysis with a K(i) of 700 nM, making this compound approximately 3-fold more potent than the previously described lead.
Sigma nonopioid intracellular receptor 1 mutations cause frontotemporal lobar degeneration–motor neuron disease (2010)

SIGMAR1 is a causative gene for familial FTLD-MND with a unique neuropathology that differs from other FTLD and MND cases. Our findings also suggest Sigma-1 drugs as potential treatments for the TDP-43/FUS proteinopathies.
Identical genes confer high-level resistance to gentamicin upon Enterococcus faecalis, Enterococcus faecium, and Streptococcus agalactiae (1992)

The structural gene coding for the bifunctional aminoglycoside-modifying 6'-acetyltransferase-2''-phosphotransferase (6'AAC-2''APH) enzyme was specifically amplified by the polymerase chain reaction using template DNA of clinical isolates of enterococci (both Enterococcus faecalis and Enterococcus faecium) and the single high-level gentamicin-resistant Streptococcus agalactiae strain identified thus far. The results of the present study demonstrated that the genes encoding this antibiotic resistance trait are highly homologous in these species. In dot blot hybridization assays using nonradioactively labeled oligonucleotide probes, strains with and without high-level gentamicin resistance could be discerned unequivocally. The gene segment encoding 6'-acetylating activity and the gene segment encoding 2''-phosphorylating activity were simultaneously present in all isolates exhibiting high-level gentamicin resistance.
Output weight optimization for the multi-layer perceptron (2003)

A fast method for designing multilayer perceptron (MLP) neural networks was introduced by S.A. Barton (1991). In this method, linear equations are solved for the output weights. An analysis of the MLP based on polynomial basis functions (PBFs) is used to justify the technique. A conjugate gradient solution to the output weight equations is introduced. A mutation technique that can be used to improve hidden unit weights is described. The output weight optimization (OWO) technique is extended to classification networks, which have nonlinear output unit activations. In several examples, it is seen that OWO is significantly faster than backpropagation (BP).< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Deglycosylated human follitropin: characterization and effects on adenosine cyclic 3',5'-phosphate production in porcine granulosa cells (1986)

Chemical deglycosylation of gonadotropins with hydrogen fluoride (HF) has facilitated the investigation of the structure-function relationship of the individual peptide and oligosaccharide moieties in the mechanism of hormone action. These studies have dealt almost exclusively with lutropin or human choriogonadotropin. We report here the chemical characterization and biological properties of deglycosylated human follitropin (degly hFSH). Results indicate that deglycosylation of hFSH by HF removes 89% of the total carbohydrate without disruption of the peptide chain or significant loss of amino acid residues. However, a change in the conformation of the molecule was observed by measurement of the far-ultraviolet circular dichroic spectrum. The degly hFSH showed a 44% reduction in binding when tested in a FSH radioimmunoassay utilizing a polyclonal antibody. Binding of the degly hFSH to FSH-responsive tissues showed that the altered hormone bound with equal or better avidity than the intact hormone while the association constants were approximately the same for both preparations. The degly hFSH alone did not stimulate the FSH-stimulatable adenylyl cyclase (AC) activity of cellular homogenates of small follicle porcine granulosa cells. Furthermore, degly hFSH was a potent antagonist of hFSH-stimulatable AC activity when coincubated with intact hFSH. In intact granulosa cells, both the hFSH and the degly hFSH stimulated cAMP production and release by these cells. However, the degly hFSH was one-tenth as effective as the intact hormone.(ABSTRACT TRUNCATED AT 250 WORDS)
Magnetically directed poly(lactic acid) 90Y‐microspheres: Novel agents for targeted intracavitary radiotherapy (1994)

High energy beta-emitting radioisotopes like Yttrium-90 have a radiotoxic range of about one centimeter. For cancer treatment they must be brought near the tumor cells and kept there for as long as they are radioactive. We developed as carriers for the ionic form of 90Y a matrix-type polymeric drug delivery system, poly(lactic acid) (PLA) microspheres. This radiopharmaceutical could be selectively delivered to the target site after incorporating 10% Fe3O4 (magnetite) which made the magnetic microspheres (MMS) responsive to an external magnetic field. Furthermore, MMS are biodegradable and slowly hydrolyze into physiologic lactic acid after the radioactivity is completely decayed. Previously prepared 10-40 microns MMS were radiochemically loaded to high specific activity with 90Y at a pH of 5.7. Stability studies showed that approximately 95% of added 90Y is retained within the PLA matrix after 28 days (> 10 half-lives) at 37 degrees C in serum, and electron microscopy showed that the microspheres retained their characteristic morphologic appearance for the same time period. Cytotoxicity studies with SK-N-SH neuroblastoma cells growing in monolayer showed that the radiocytotoxicity of the microspheres could be directed magnetically to either kill or spare specific cell populations, thus making them of great interest for targeted intracavitary tumor therapy. We are currently optimizing this system for use in the treatment of neoplastic meningitis.
Rapid back to back adenosine stress/rest technetium-99m teboroxime myocardial perfusion SPECT using a triple-detector camera. (1993)

Technetium-99m-teboroxime is characterized by a high extraction fraction over a wide range of blood flow rates, rapid myocardial clearance and avid hepatic uptake. This study determined the imaging parameters and examined the clinical efficacy of a rapid back to back adenosine stress/rest teboroxime myocardial perfusion SPECT protocol using a triple-detector camera. Acquisition parameters were determined using cardiac phantom studies which were then applied in SPECT studies of 51 catheterized patients (22 with prior myocardial infarction) and 20 patients with a "low" (7.9% +/- 4.3%) likelihood of coronary artery disease. Technetium-99m-teboroxime (20-25 mCi) was injected at the third minute of adenosine infusion. Teboroxime (20-25 mCi) was also injected at rest, 15 min later. Stress followed by rest SPECT were completed within 25 min using a triple-detector camera and sequential, 1-min continuous rotations in alternating directions. Summed raw data from the first to second (1-2 min), second to third (2-3 min) and second to fifth (2-5 min) minutes of imaging following stress teboroxime injection were reconstructed and compared for image quality, degree of liver interference, and accuracy for diagnostic efficacy. In a subgroup of 30 patients, 2-8-min summed images were also reconstructed to compare this more conventional imaging protocol with our rapid acquisition. Image quality was fair to good in 75% of the 1-2-min, 84% of the 2-3-min and 2-5-min studies and 53% of the 2-8-min scans. The frequency of severe liver interference appeared to increase with the duration of imaging time (1-2 min: 3%; 2-3 min: 7%; 2-5 min: 8%) and was greatest (30%, p = 0.08) with 2-8-min images. Three patients (4%) had uninterpretable studies due to intense hepatic uptake. Overall sensitivity (95%) and specificity (71%) were equal for the 2-3-min and 2-5-min stress images and appeared better than in the 1-2-min images (84% and 57%, respectively). For the 2-8-min scans, vessel sensitivity (69%) and specificity (63%) appeared poorer than with 2-3-min studies (83% and 81%, respectively). Normalcy rates were 89% for the 2-3-min and 2-5-min and 79% for 1-2-min images. The back to back adenosine stress/rest teboroxime SPECT can be performed in 30 min using a triple-detector camera. Although overall high sensitivity and normalcy rates were achieved, the protocol is technically demanding. Interference due to intense liver uptake remains problematic.
Ring contraction of some 1-benzothiepin derivatives to 1-benzothiophens (1981)

Transformations of some 1-benzothiepin derivatives (1) into a 1-benzothiophen derivative (2a) through ring contraction are reported. Similar ring contraction of trans-1,2-dibromo-1,2,3,4-tetrahydronaphtho[2,1-b]thiepin (8) affords the thiophen derivative (9a). Treatment of the bromo-compounds (2a) and (9a) with base in the presence of catalysts provides in excellent yields the dienes (2d) and (9b) respectively.
An Efficient and Highly Diastereoselective Synthesis of GSK1265744, a Potent HIV Integrase Inhibitor (2015)

A novel synthesis of GSK1265744, a potent HIV integrase inhibitor, is described. The synthesis is highlighted by an efficient construction of the densely functionalized pyridinone core as well as a highly diastereoselective formation of the acyl oxazolidine moiety. The latter exploits the target molecule's ability to chelate to Mg(2+), a key feature in the integrase inhibitor's mechanism of action.
Transacylation as a chain-termination mechanism in fatty acid synthesis by mammalian fatty acid synthetase. Synthesis of medium-chain-length (C8-C12) acyl-CoA esters by goat mammary-gland fatty acid synthetase (1982)

1. Ruminant mammary-gland fatty acid synthetases can, in contrast with non-ruminant mammary enzymes, synthesize medium-chain fatty acids. 2. Medium-chain fatty acids are only synthesized in the presence of a fatty acid-removing system such as albumin, beta-lactoglobulin or methylated cyclodextrin. 3. The short- and medium-chain fatty acids synthesized were released as acyl-CoA esters from the fatty acid synthetase.