gebhart/patrepeval huggingface dataset:
Interpretation of Positive Results of a Methacholine Inhalation Challenge and 1 Week of Inhaled Bronchodilator Use in Diagnosing and Treating Cough-Variant Asthma (1997)

No matter how the results are analyzed, positive MIC results, without observing response to therapy, are only consistent with asthma as the cause of the cough. The results are only diagnostic of asthma when they are followed by a favorable response to asthma therapy. After 1 week of inhaled beta-agonist, only the cough due to cough-variant asthma is significantly better.
Effects of Combination of Nitrate with β1-4 Galacto-oligosaccharides and Yeast (Candida kefyr) on Methane Emission from Sheep (2004)

The objective of the present study was to determine whether 1-4 galacto-oligosaccharides (GOS) and Candida kefyr combined with nitrate as manipulators could suppress rumen methanogenesis without nitrate poisoning in sheep. Four rumen fistulated wethers were allocated to a 44 Latin square design. Nitrate (1.3 g NaNO 3 kg -0.75 body weight) with and without GOS and Candida kefyr were administered into the rumen through fistula as a single dose 30 min after the morning meal. GOS and Candida kefyr were supplemented by sprinkling onto the feed and through rumen fistula, respectively. The four treatments consisted of saline, nitrate, nitrate plus GOS and nitrate plus GOS plus Candida kefyr. Physiological saline was used as the control treatment. Compared to saline treatment, the administration of nitrate alone resulted in a very marked decrease in rumen methanogenesis and an increase in rumen and plasma nitrite production and blood methaemoglobin formation consequently causing a decline in oxygen consumption, carbon dioxide production and metabolic rate. When compared to nitrate alone, the simultaneous administration of nitrate with GOS decreased nitrite accumulation in rumen and plasma and nitrate-induced methaemoglobin, while retaining low methane production. However, GOS could not fully restore metabolic parameters reduced by nitrate. When compared to the simultaneous administration of nitrate with GOS, the simultaneous administration of nitrate with GOS plus Candida kefyr lowered rumen methanogenesis to a negligible level, but did not decrease rumen and plasma nitrite accumulation as well as blood methaemoglobin formation. Thus, these results suggest that combination of nitrate with GOS may be a potent manipulator to suppress rumen methanogenesis with abating the hazards of nitratenitrite toxicity in ruminants. (
ALX-0600 (NPS Allelix Corp). (2001)

NPS Allelix (formerly Allelix Biopharmaceuticals) is developing the glucagon-like peptide 2 (GLP-2) analog ALX-0600 for the potential treatment of gastrointestinal diseases, including short bowel disease. GLP stimulates the growth of the lining of the small intestine, thus increasing the absorptive area of the intestine [214370], [315107]. ALX-0600 also has potential for mucositis associated with cancer chemotherapy and inflammatory bowel disease [331459]. During the third quarter of 1999, a pilot phase II trial began for short bowel syndrome (SBS) [331459]. ALX-0600 began pivotal phase II trials in 2000 following the completion of the pilot trial which was designed to measure the safety, tolerability, and any other drug-related improvements in nutrient absorption and physical changes in the gut of a small number of patients with SBS. Allelix hopes to bring this drug to the market by 2001 [341519]. Allelix filed an application to the FDA for Orphan Drug designation in the third quarter of 1999 [331459]; in August, the designation was approved [377524]. As of November 1998, Allelix was in discussions with a potential marketing partner for worldwide development and marketing [305000]. In August 1998, the USPTO issued a notice of allowance to Allelix for its basic patent containing claims covering the composition and medical uses of ALX-0600 and related GI drug candidate compounds [2946571.
Ultralow-loss, high-density SOI optical waveguide routing for macrochip interconnects (2012)

We report optical waveguides up to one meter long with 0.026 dB/cm loss fabricated in a 300nm thick SOI CMOS process. Combined with tight bends and compact interlayer grating couplers, we demonstrate a complete toolbox for ultralow-loss, high-density waveguide routing for macrochip interconnects.
Effect of the histone deacetylase inhibitor LBH589 against epidermal growth factor receptor–dependent human lung cancer cells (2007)

Activating mutations in the epidermal growth factor receptor (EGFR) selectively activate signal transducers and activators of transcription (STAT) and Akt survival signaling pathways important in lung cancer cell growth and survival. Many kinases, such as EGFR, rely on heat shock protein 90 (Hsp90) chaperone function for conformational maturation and proper function. Histone deacetylase inhibitors (HDACi) have been suggested to regulate signaling protein interactions via modulation of protein chaperone function through Hsp90. For these reasons, we evaluated the effect of a HDACi in lung cancer cells with defined EGFR status. Cell lines with defined EGFR status and sensitivity to EGFR tyrosine kinase inhibitors were exposed to the HDACi LBH589, and the effects on cell survival, proliferation, and downstream signaling were evaluated. LBH589 resulted in increased acetylation of Hsp90 and reduced association of Hsp90 with EGFR, Akt, and STAT3. LBH589 selectively depleted proteins important in signaling cascades in cell lines harboring EGFR kinase mutations, such as EGFR, STAT3, and Akt, and these cells underwent apoptosis following exposure to LBH589. In addition, we found depletion of STAT3-dependent survival proteins, including Bcl-xL, Mcl-1, and Bcl-2. Conversely, LBH589 had little effect on apoptosis in cells not dependent on EGFR for survival, no changes were identified in the expression of EGFR or other survival proteins, and the predominant effect was cell cycle arrest rather than apoptosis. A 10-fold increase in LBH589 was necessary to observe durable depletion of EGFR and Akt in cells not harboring EGFR mutation. Treatment of cells with erlotinib and LBH589 resulted in synergistic effects on lung cancer cells dependent on EGFR for growth and/or survival. Based on these results, LBH589 can acetylate Hsp90, deplete EGFR and other key survival signaling proteins, and trigger apoptosis only in lung cancer cells harboring EGFR mutations. Therefore, EGFR mutation status may be predictive of outcome with LBH589 and possibly other HDACi.
New approaches for the analysis of molecular recognition using the IAsys evanescent wave biosensor (1998)

Trends in the analysis of molecular recognition using the IAsys evanescent wave biosensor are outlined. Diversification of sensor surface chemistry, an open cuvette format and the advent of robotics controlled by intelligent software are widening the range and throughput of applications. Analyses of binding and dissociation are now carried out across a wide spectrum of biomolecules, including protein, nucleic acid, carbohydrate and lipid. Determinations are obtained from a range of experimental formats. These include qualitative 'yes/no' screening assays, through semi quantitative ranking of kinetic association, dissociation and equilibrium constants for a family of binding partners, to deriving constants comparable with those which would be obtained in free solution. A dependence of the initial rate of biomolecular association on concentration allows analyte concentration to be measured--an increasingly common application class. This is often employed in situations where a rapid determination is required The ability to recover bound analyte from the sensor surface in sufficient amounts for subsequent characterization is opening up new routes to the parallel analysis of structure and function.
Intravenous immunoglobulin (IVIg) for the treatment of birdshot retinochoroidopathy (2000)

Intravenous polyclonal immunoglobulin (IVIg) treatment has been successfully used in a number of autoimmune conditions. Birdshot retinochoroidopathy (BRC) is a bilateral autoimmune posterior uveitis which, in its progressive form, frequently requires immunosuppressive therapy. We report a clinical study aimed at determining the tolerance and efficiency of IVIg treatment in patients with active BRC. The study was conducted in an open manner. Eighteen patients were included. The initial visual acuity (VA) was < or =20/30 in 26 eyes, 20/25 in five eyes, and 20/20 in five eyes. IVIg was given as sole treatment at 1.6 g/kg every four weeks for six months, followed by injections of 1.2-1.6 g/kg at six to eight-week intervals. The mean follow-up was 39 months, ranging between 12 and 53 months. The results showed that the final VA of the 26 eyes with an initial VA of < or =20/30 was increased by two lines or more in 14 eyes (53.8%) and decreased in two (7.7%). Of the five eyes with an initial VA of 20/25, four had improved to 20/20 and one remained stable. Of the five eyes with an initial VA of 20/20, four remained stable and one deteriorated to 20/25. When present, macular edema was improved in half of the eyes on fluorescein angiography. Benign side effects were observed in 12 patients: moderate transient arterial hypertension (7), headache (6), eczematous lesions (6), and hyperthermia (4). The results suggest that IVIg may represent a safe alternative therapy for patients with BRC.
Protease‐catalyzed incorporation of 18O into peptide fragments and its application for protein sequencing by electrospray and matrix‐assisted laser desorption/ionization mass spectrometry (1996)

Proteins were digested in normal and highly 18O-enriched water using proteases commonly employed for protein sequencing. The extent of 18O incorporation into the resulting peptide fragments was characterized by electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS). The endoproteinases trypsin, Lys-C and Glu-C incorporate two atoms of 18O, resulting in a mass shift of +4 D for the peptide fragments. This indicates that, following proteolytic cleavage, peptide products continue to interact with these proteases and undergo repeated binding/hydrolysis cycles, resulting in complete equilibration of both oxygens in the carboxy terminus of the fragments with oxygen from solvent water. In contrast, chymotrypsin and Asp-N incorporate only one atom of 18O, resulting in a mass shift of +2 D, indicating that after the cleavage step these proteases do not accept the peptides as substrates. In addition, it was found that the proteases trypsin, Glu-C, and Lys-C exhibit minor or nontypical sequence specificities, resulting in unexpected peptide fragments. These fragments incorporate only one 18O atom, indicating that they do not undergo further binding/hydrolysis cycles with the enzyme. Thus, it is possible to discriminate between enzyme-typical peptide fragments with mass shifts of +4 D and nontypical fragments with mass shifts of only +2 D. Based on these observations, protein digest strategies are described for the generation of 1:1 ion doublets spaced either by 2 or 4 D. In addition, the C-terminus of a protein can be identified by the absence of an ion doublet in the corresponding peptide fragment. In protein sequencing by mass spectrometry, digest protocols generating ion doublets provide the most clear-cut analytical results for the recognition of ion series in ESI-MS/MS and MALDI post-source decay (PSD) product ion spectra. Only the mass spectrometric fragment ions of a C-terminal series show ion doublets spaced either by 2 or 4 D, whereas the fragment ions belonging to an N-terminal series remain unshifted. This assignment unequivocally reveals the direction of the identified sequence.
Inhibitors of the Interaction of a Thyroid Hormone Receptor and Coactivators:  Preliminary Structure−Activity Relationships (2007)

The modulation of gene regulation by blocking the interaction between the thyroid receptor (TR) and obligate coregulators has been reported recently with the discovery of the lead compound 3-(dimethylamino)-1-(4-hexylphenyl)propan-1-one). Herein we report studies aimed at optimization of this initial hit to determine the basic parameters of the structure-activity relationships and clarify the mechanism of action. These studies provided new insights, showing that activity and TRbeta isoform selectivity is highly correlated with the structural composition of these covalent inhibitors.
Lectins--proteins with a sweet tooth: functions in cell recognition. (1995)

Lectins, non-enzymic proteins that bind mono- and oligosaccharides reversibly and with high specificity, occur widely in nature. They come in a variety of sizes and shapes, but can be grouped in families with similar structural features. The combining sites of lectins are also diverse, although they are similar in the same family. The specificities of lectins are determined by the exact shape of the binding sites and the nature of the amino acid residues to which the carbohydrate is linked. Small changes in the structure of the sites, such as the substitution of only one or two amino acids, may result in marked changes in specificity. The carbohydrate is linked to the protein mainly through hydrogen bonds, with added contributions from van der Waals contacts and hydrophobic interactions. Coordination with metal ions may occasionally play a role too. Microbial surface lectins serve as a means of adhesion to host cells of viruses (e.g. influenza virus), bacteria (e.g. E. coli) and protozoa (e.g. amoeba): a prerequisite for the initiation of infection. Blocking the adhesion by carbohydrates that mimic those to which the lectins bind prevents infection by these organisms. The way is thus open for the development of anti-adhesive therapy against microbial diseases. Lectin-carbohydrate mediated interactions between leucocytes and endothelial cells are the first step in the recirculation of lymphocytes and in the migration of neutrophils to sites of inflammation. Such interactions may also feature highly in the formation of metastases. Studies of these processes are expected to lead to the development of carbohydrate-based anti-adhesion drugs for the treatment of inflammatory diseases as well as cancer.
Induced Mutations in the Starch Branching Enzyme II (SBEII) Genes Increase Amylose and Resistant Starch Content in Durum Wheat (2012)

Starch is the largest component of the wheat (<i>Triticum aestivum</i> L.) grain and consists of approximately 70-80% amylopectin and 20-30% amylose. Amylopectin is a highly-branched, readily digested polysaccharide, whereas amylose has few branches and forms complexes that resist digestion and mimic dietary fiber (resistant starch). Down-regulation of the <i>starch branching enzyme II</i> (<i>SBEII</i>) gene by RNA interference (RNAi) was previously shown to increase amylose content in both hexaploid and tetraploid wheat. We generated ethyl methane sulphonate (EMS) mutants for the <i>SBEIIa</i>-A and <i>SBEIIa</i>-B homoeologs in the tetraploid durum wheat variety Kronos (<i>T. turgidum</i> ssp. <i>durum</i> L.). Single-gene mutants showed non-significant increases in amylose and resistant starch content, but a double mutant combining a <i>SBEIIa</i>-A knock-out mutation with a <i>SBEIIa</i>-B splice-site mutation showed a 22% increase in amylose content (<i>P</i><0.0001) and a 115% increase in resistant starch content (<i>P</i><0.0001). In addition, we obtained mutants for the A and B genome copies of the paralogous <i>SBEIIb</i> gene, mapped them 1-2 cM from <i>SBEIIa</i>, and generated double <i>SBEIIa-SBEIIb</i> mutants to study the effect of the <i>SBEIIb</i> gene in the absence of <i>SBEIIa</i>. These mutants are available to those interested in increasing amylose content and resistant starch in durum wheat.
Response of CAPD patients with a high incidence of peritonitis to intraperitoneal immunoglobulin therapy. (1989)

This study has demonstrated that in the majority of high-peritonitis-incidence (PI) CAPD patients the defective opsonic activity levels in the peritoneal dialysis effluent (PDE) are restored for 3 weeks by a 12 g IP injection of immunoglobulins (Ig). Further studies showed that in a minority of high-PI CAPD patients who also had low PDE IgG and opsonic activity levels, IP Ig therapy did not significantly reduce the PI. To evaluate this phenomenon we utilized this therapy in 20 high-PI CAPD patients undergoing IP Ig therapy for an average of 24 months daily for 3 weeks (12 g every 3 weeks) and analyzed: 1) PDE IgG levels; 2) PDE opsonic activity; 3) peritoneal macrophage (PM0) membrane-bound IgG; 4) PDE Interleukin-1 (IL-1) levels; 5) PM0 membrane Fc receptor number. The results showed that in the 15 patients in whom Ig therapy reduced PI, there were long-lasting increases in the PDE IgG, opsonic activity and IL-1 levels, as well as a normal PM0 Fc receptor number and PM0 reversibly bound infused Ig. Conversely, the five patients in whom the IP Ig did not reduce the PI showed only transient increases in PDE IgG and opsonic activity levels, no PDE IL-1 increase, and the PM0 were deficient in Fc receptors and, therefore, unable to take up the infused Ig. We conclude that in high-PI CAPD patients there are different peritoneal immune defense abnormalities and that their identification is, therefore, important for the correct choice of therapy to improve these defects.
Epigenetic changes of tumor suppressor genes, P15, P16, VHL and P53 in oral cancer. (2003)

We performed methylation specific PCR to explore the mechanism of inactivation of tumor suppressor genes P15, P16, P53 and VHL in 48 oral SCC. The frequencies of aberrant methylation on the promoter of the P15, the P16, the P53 and the VHL genes were 0.27 (13/48), 0.42 (20/48), 0.04 (2/48) and none, respectively. Altogether, over 50% of the samples showed the CpG-island methylation modification in at least one of the three tumor suppressor genes, indicating that the frequent inactivation of these genes may be an important step during oral cancer development, and the methylation inactivation of P15 or P16 may occur at pre-cancerous stage.
Assessment of protein kinase C isozymes by two‐site enzyme immunoassay in human brains and changes in Alzheimer's disease (1993)

We assessed the amount of protein kinase C (PKC) in samples from postmortem normal human and Alzheimer's disease (AD) brains by a two-site enzyme immunoassay that quantitatively identified types alpha, beta, and gamma isozymes. In the normal human brain matter, type beta was the main type present, the majority of each isozyme of PKC being present in the membranous fraction of the brain tissues. In AD brains, the amount of type beta PKC was significantly reduced in the membranous fraction of the temporal cortical tissues. The amounts of types alpha and gamma in the membranous fraction and types alpha, beta, and gamma in the cytosolic fraction in AD brains were lower than in the control brains, but the difference was not significant. There was also a significant decrease in the levels of PKC in the membranous fraction of AD brains, as measured by radioactive phorbol ester binding. These results suggest that the type beta PKC isozyme is mainly present in the human temporal cortex and that reduced levels of type beta PKC in the membranous fraction may reflect a biochemical deficit related specifically to the pathogenesis of AD.
Human oral, gut, and plaque microbiota in patients with atherosclerosis (2010)

Periodontal disease has been associated with atherosclerosis, suggesting that bacteria from the oral cavity may contribute to the development of atherosclerosis and cardiovascular disease. Furthermore, the gut microbiota may affect obesity, which is associated with atherosclerosis. Using qPCR, we show that bacterial DNA was present in the atherosclerotic plaque and that the amount of DNA correlated with the amount of leukocytes in the atherosclerotic plaque. To investigate the microbial composition of atherosclerotic plaques and test the hypothesis that the oral or gut microbiota may contribute to atherosclerosis in humans, we used 454 pyrosequencing of 16S rRNA genes to survey the bacterial diversity of atherosclerotic plaque, oral, and gut samples of 15 patients with atherosclerosis, and oral and gut samples of healthy controls. We identified Chryseomonas in all atherosclerotic plaque samples, and Veillonella and Streptococcus in the majority. Interestingly, the combined abundances of Veillonella and Streptococcus in atherosclerotic plaques correlated with their abundance in the oral cavity. Moreover, several additional bacterial phylotypes were common to the atherosclerotic plaque and oral or gut samples within the same individual. Interestingly, several bacterial taxa in the oral cavity and the gut correlated with plasma cholesterol levels. Taken together, our findings suggest that bacteria from the oral cavity, and perhaps even the gut, may correlate with disease markers of atherosclerosis.
Effect of growth rate and substrate limitation on the composition and structure of the cell wall of Saccharomyces cerevisiae (1967)

1. A study was made of the composition and structure of walls isolated from yeast grown in continuous culture at different rates, under three conditions of glucose limitation in which the concentrations of glucose and ammonium sulphate in the medium and the oxygen-transfer rate in the culture were varied, and one condition of NH(4) (+) limitation. 2. The contents of total glucan and total mannan in the walls were relatively little affected by the growth rate under any of the four sets of conditions. The phosphorus and protein contents of walls from yeast grown under each of the four conditions increased as the growth rate was decreased. Walls from yeast grown under NH(4) (+) limitation contained only half as much protein as walls from cells grown under glucose limitation. The proportion of lipid was greatest in walls from yeast grown under NH(4) (+) limitation. 3. A procedure was devised for fractionating isolated walls, based on the ease with which the glucan and mannan were extracted with water and with hot and cold 6% (w/v) potassium hydroxide solution. The percentage of glucan, mannan, protein and phosphorus in each of the fractions was affected by the rate of growth and by the nature of the substrate limitation. 4. The beta-fructofuranosidase activities of yeast grown under glucose limitation increased as the growth rate was lowered, but decreased at very low growth rates. The effects at low growth rates were probably due to repression of enzyme synthesis by residual glucose in the culture filtrate. The beta-fructofuranosidase activities of yeast grown under NH(4) (+) limitation were much lower than those from yeast grown under any of the conditions of glucose limitation. 5. Yeast cells grown at any of the rates under NH(4) (+) limitation were longer and thinner than those grown at the same rate under any of the conditions of glucose limitation. Mean cell volumes were dependent on growth rate but not on the nature of the substrate limitation. 6. Electron micrographs of thin sections of isolated walls showed that cells grown under NH(4) (+) limitation had a more porous structure than those from cells grown under any of the conditions of glucose limitation.