gebhart/patrepeval huggingface dataset:
Interpretation of Genetic Test Results for Hereditary Nonpolyposis Colorectal Cancer (1999)

The identification of pathogenic mutations in a significant subset of families for whom the results may have marked clinical importance makes genetic testing an important option for HNPCC and HNPCC-like kindreds. However, for the majority of individuals in whom sequence analysis of hMSH2 and hMLH1 does not give a definitive result, intensive follow-up is still warranted.
Overexpression of MUC15 activates extracellular signal-regulated kinase 1/2 and promotes the oncogenic potential of human colon cancer cells (2009)

Mucins play a key role in tumorigenesis. MUC15 is a membrane-bound mucin and the MUC15 messenger RNA (mRNA) has been detected in various organs. However, its role in tumor malignancy is still unclear. This study was to investigate the MUC15 expression in colorectal tumors and the role of MUC15 in colon cancer cells. We found that the mRNA expression of MUC15 was significantly higher in 70.8% (51/72) of colorectal tumors compared with their normal counterparts by real-time reverse transcription-polymerase chain reaction. Immunohistochemistry showed that MUC15 expression was increased in 82.6% (43/52) of colorectal tumors. MUC15 overexpression in HCT116 cells enhanced cell proliferation, cell-extracellular matrix adhesion, colony-forming ability and invasion. Furthermore, these effects were significantly reversed by knockdown of MUC15 with short-hairpin RNA. In nude mice models, MUC15 overexpression significantly (P < 0.01) enhanced tumor growth. In addition, treatment of PD98059 significantly (P < 0.01) inhibited MUC15-enhanced invasion, suggesting that the invasion induced by MUC15 in HCT116 cells was primarily mediated through activation of extracellular signal-regulated kinase 1/2. In conclusion, these results suggest that MUC15 is upregulated in colorectal tumors and its expression enhances the oncogenic potential of colon cancer cells.
Identification of mutations in the coding sequence of the proto-oncogene c-kit in a human mast cell leukemia cell line causing ligand-independent activation of c-kit product. (1993)

The c-kit proto-oncogene encodes a receptor tyrosine kinase. Binding of c-kit ligand, stem cell factor (SCF) to c-kit receptor (c-kitR) is known to activate c-kitR tyrosine kinase, thereby leading to autophosphorylation of c-kitR on tyrosine and to association of c-kitR with substrates such as phosphatidylinositol 3-kinase (PI3K). In a human mast cell leukemia cell line HMC-1, c-kitR was found to be constitutively phosphorylated on tyrosine, activated, and associated with PI3K without the addition of SCF. The expression of SCF mRNA transcript in HMC-1 cells was not detectable by means of PCR after reverse transcription (RT-PCR) analysis, suggesting that the constitutive activation of c-kitR was ligand independent. Sequencing of whole coding region of c-kit cDNA revealed that c-kit genes of HMC-1 cells were composed of a normal, wild-type allele and a mutant allele with two point mutations resulting in intracellular amino acid substitutions of Gly-560 for Val and Val-816 for Asp. Amino acid sequences in the regions of the two mutations are completely conserved in all of mouse, rat, and human c-kit. In order to determine the causal role of these mutations in the constitutive activation, murine c-kit mutants encoding Gly-559 and/or Val-814, corresponding to human Gly-560 and/or Val-816, were constructed by site-directed mutagenesis and expressed in a human embryonic kidney cell line, 293T cells. In the transfected cells, both c-kitR (Gly-559, Val-814) and c-kitR (Val-814) were abundantly phosphorylated on tyrosine and activated in immune complex kinase reaction in the absence of SCF, whereas tyrosine phosphorylation and activation of c-kitR (Gly-559) or wild-type c-kitR was modest or little, respectively. These results suggest that conversion of Asp-816 to Val in human c-kitR may be an activating mutation and responsible for the constitutive activation of c-kitR in HMC-1 cells.
Pruritus in Elderly Patients—Eruptions of Senescence (2011)

Geriatric patients are frequently afflicted by pruritic dermatoses. Most pruritic elderly patients present with a skin eruption. The high prevalence of pruritic inflammatory skin disorders in elderly patients is a consequence of three physiological changes that occur with aging: (1) the epidermal barrier repair is diminished; (2) the immune systems of elderly patients are activated and have defective Th1 function along with enhanced Th2 function (immunosenescense); and (3) neurodegenerative disorders may lead to pruritus by their central or peripheral effects. These consequences of aging may all afflict the same patient, explaining why elderly people often have multiple overlapping skin conditions. The following article outlines the pathogenesis of the most common forms of pruritic skin disease in elderly patients and the hallmarks that allow the dermatologist to establish an accurate diagnosis and also suggests a management strategy for each common type of pruritic skin disease in the elderly patient.
In vivo assembly of yeast mitochondrial alpha-ketoglutarate dehydrogenase complex. (1991)

The assembly of alpha-ketoglutarate dehydrogenase complex (KGDC) has been studied in wild-type Saccharomyces cerevisiae and in respiratory-deficient strains (pet) with mutations in KGD1 and KGD2, the structural genes for alpha-ketoglutarate dehydrogenase (KE1) and dihydrolipoyl transsuccinylase (KE2) components, respectively. Mutants unable to express KE1 or KE2 form partial complexes similar to those reported in earlier studies on the resolution and reconstitution of bacterial and mammalian KGDC. Thus mutants lacking KE1 assemble a high-molecular-weight subcomplex consisting of a KE2 core particle with bound dihydrolipoyl dehydrogenase (E3). Similarly, mitochondrial extracts of mutants lacking KE2 contain dimeric KE1 and E3. These components, however, are not associated with each other. The partial complexes detected in the mutants are capable of reconstituting normal KGDC when supplied with the missing subunit. Complete restoration of overall alpha-ketoglutarate dehydrogenase activity is achieved by mixing appropriate ratios of mitochondrial extracts from mutants deficient in KE1 and KE2. The reconstitution of enzymatic activity correlates with binding of KE1 to the KE2-E3 particle to form a complex with the same sedimentation properties as wild-type KGDC. Overexpression of KE2 relative to KE1 results in a preponderance of incompletely assembled complexes with substoichiometric contents of KE1. Formation of a complex with a full complement of KE1 therefore depends on a balanced output of KE1 and KE2 from their respective genes. Biochemical screens of a pet mutant collection have led to the identification of a new gene required for the expression of enzymatically active KGDC. Mitochondria of the mutant have all of the catalytic subunits of KGDC. Sedimentation analysis of these components indicates that while the mutant has a stable KE2-E3 subcomplex, the interaction of KE1 with KE2 core is much weaker in the mutant than in the wild type. The gene product responsible for this phenotype, therefore, appears to function at a late stage of assembly of KGDC, most likely by posttranslational modification of one of the subunits.
Tenascin distribution in articular cartilage from normal subjects and from patients with osteoarthritis and rheumatoid arthritis (1994)

Tenascin is increased in arthritic cartilage and is weakly expressed in normal cartilage.
Role for Caspase-Mediated Cleavage of Rad51 in Induction of Apoptosis by DNA Damage (1999)

We report here that the Rad51 recombinase is cleaved in mammalian cells during the induction of apoptosis by ionizing radiation (IR) exposure. The results demonstrate that IR induces Rad51 cleavage by a caspase-dependent mechanism. Further support for involvement of caspases is provided by the finding that IR-induced proteolysis of Rad51 is inhibited by Ac-DEVD-CHO. In vitro studies show that Rad51 is cleaved by caspase 3 at a DVLD/N site. Stable expression of a Rad51 mutant in which the aspartic acid residues were mutated to alanines (AVLA/N) confirmed that the DVLD/N site is responsible for the cleavage of Rad51 in IR-induced apoptosis. The functional significance of Rad51 proteolysis is supported by the finding that, unlike intact Rad51, the N- and C-terminal cleavage products fail to exhibit recombinase activity. In cells, overexpression of the Rad51(D-A) mutant had no effect on activation of caspase 3 but did abrogate in part the apoptotic response to IR exposure. We conclude that proteolytic inactivation of Rad51 by a caspase-mediated mechanism contributes to the cell death response induced by DNA damage.
Signaling via CD7 molecules on human NK cells. Induction of tyrosine phosphorylation and beta 1 integrin-mediated adhesion to fibronectin. (1994)

We have previously reported that CD7 expressed on resting human NK cells is a signal-transducing molecule, which upon ligation with mAb induces a rapid increase in cytoplasmic free calcium, secretion of IFN-gamma, and augmented NK activity against K562 targets. We now demonstrate that Ab-mediated clustering of CD7 molecules on NK cells results in enhanced phosphorylation on tyrosine residues of intracellular proteins of 60, 70, 80, 97, and 120 kDa. In the presence of genistein, a specific inhibitor of protein tyrosine kinase, the enhanced level of tyrosine phosphorylation was blocked, indicating that CD7 may induce signaling via activation of tyrosine kinases. Cross-linking of CD7 or CD16 molecules with primary and secondary Abs, as well as stimulation of NK cells with phorbol ester (PMA) or with calcium ionophore A23187 also induced beta 1 integrin-mediated adhesion of these cells to fibronectin (FN)-coated plastic surfaces. In contrast, cross-linking of CD2 expressed on the surface of NK cells had no significant effect on NK cell adhesion to FN. This adhesion was not associated with up-regulation of expression of alpha 4 beta 1 or alpha 5 beta 1 FN receptors on NK cells, but it required an intact cytoskeleton. The CD7-induced adhesion to FN was mediated by alpha 4 beta 1 and alpha 5 beta 1 integrins, as it was partially blocked by FN connective segment-1 peptide (EILDVPST), the alpha 4 beta 1-binding domain, as well as by RGD-containing peptides, the alpha 5 beta 1-binding domain, but not by EILEVPST or RGE control peptides. NK cell binding to FN was also partially inhibited by mAb to alpha 4, alpha 5, and beta 1 integrins. The mechanism by which cross-linking of CD7 or CD16 on NK cells induced adhesion to FN appeared to involve both protein tyrosine kinase and protein kinase C, because this adhesion was blocked in the presence of either genistein or a protein kinase C inhibitor, staurosporin. Our data demonstrate that signals transduced via triggering of either CD7 or CD16 molecules are involved in the regulation of the functional activity of beta 1 integrins on NK cells.
Bacterial direct-fed microbials in ruminant diets: Performance response and mode of action (2003)

Direct-fed microbials (DFM) have been shown to increase daily gain and feed efficiency in feed- lot cattle, enhance milk production in dairy cows, and improve health and performance of young calves. How- ever, their effects on performance have been mixed, and the mode of action remains unclear. Bacteria used as DFM have been defined as single or mixed cultures of live organisms, which, when fed to animals, beneficially affect the host. The original concept of feeding DFM to man and livestock was based primarily on the potential for beneficial intestinal effects, including the establish- ment of a desirable gut microflora and/or prevention of the establishment of pathogenic organisms. More re- cently, however, there has been some indication that certain bacterial DFM might have beneficial effects in the rumen, such as decreasing the potential for ruminal acidosis. In several experiments, supplementing feedlot cattle with lactate-utilizing and/or lactate-producing bacteria has been shown to improve feed efficiency and daily gain (approximately 2.5%), with little change in DMI. In addition, increased milk yield (0.75 to 2.0 kg/
High Internal Phase Emulsions Stabilized Solely by Functionalized Silica Particles (2008)

Small but mighty: Oleic acid functionalized silica particles possess adequate hydrophobicity to stabilize water/oil Pickering high internal phase emulsions. The particles adsorb irreversibly at the aqueous/organic interface and prevent droplet coalescence and phase inversion. Polymerization of the emulsions produced highly porous polymer foams. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2008/z802244_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Continuous flow real-time PCR device using multi-channel fluorescence excitation and detection (2013)

High throughput automation is greatly enhanced using techniques that employ conveyor belt strategies with un-interrupted streams of flow. We have developed a 'conveyor belt' analog for high throughput real-time quantitative Polymerase Chain Reaction (qPCR) using droplet emulsion technology. We developed a low power, portable device that employs LED and fiber optic fluorescence excitation in conjunction with a continuous flow thermal cycler to achieve multi-channel fluorescence detection for real-time fluorescence measurements. Continuously streaming fluid plugs or droplets pass through tubing wrapped around a two-temperature zone thermal block with each wrap of tubing fluorescently coupled to a 64-channel multi-anode PMT. This work demonstrates real-time qPCR of 0.1-10 μL droplets or fluid plugs over a range of 7 orders of magnitude concentration from 1 × 10(1) to 1 × 10(7). The real-time qPCR analysis allows dynamic range quantification as high as 1 × 10(7) copies per 10 μL reaction, with PCR efficiencies within the range of 90-110% based on serial dilution assays and a limit of detection of 10 copies per rxn. The combined functionality of continuous flow, low power thermal cycling, high throughput sample processing, and real-time qPCR improves the rates at which biological or environmental samples can be continuously sampled and analyzed.
Recent Developments and Trends in 18F-Radiochemistry: Syntheses and Applications (2007)

In this short review we describe recent methods and novel trends for the introduction of fluorine-18 into molecules which in turn are intended to serve as imaging agents for the in vivo imaging modality positron emission tomography (PET). These 18F-labeling schemes are based on enzymatic fluorination, the use of ionic liquids, protic solvents acting as catalysts, application of “click chemistry”, thiol-reactive labeling agents for peptide and protein labeling and the most recent introduction of “non-classical” radiochemistry based on organo-phosphorous, organo-boron and organo-silicon radiochemistry. The latter approach for the first time introduced an 18F-chemistry characterized by high selectivity and unique efficiency making complicated work-up procedures obsolete. Keywords: Fluorine-18, positron emission tomography (PET), labeling chemistry
Tethered-bilayer lipid membranes as a support for membrane-active peptides (2001)

An immunosensing device, comprising a lipid membrane incorporating ion channels tethered to the surface of a gold electrode, has been reported [Cornell, Braach-Maksvytis, King, Osman, Raguse, Wieczorek and Pace (1997) Nature (London) 387, 580-583]. The present article describes key steps in the assembly of the device and provides further evidence for its proposed sensing mechanism.
Relative Safety of Selected Acarieides to Three Hemipteran Natural Enemies of Planthoppers in Rice Ecosystem (2006)

Greenhouse studies on the toxicity of twelve selected acarieides to hemipteran predators of planthoppers in rice viz. , green mirid bug ( Cyrtorhitnus lividipennis) ; brown mirid bug ( Tytthus parviceps ) and veliid bug ( Microvelia douglasi atrolineata ) revealed that fenpropathrin at ISO ppm and diafenthiuron at 450 ppm were highly toxic to these predators and need to be avoided in mite pest management programmes in rice. Spiromesifen at 72 ppm, pyriproxifen at 75 ppm, milbemectin at 2.5 ppm and dicofol at 500 ppm were less toxic to these predators and can be preferred. Other acaricides like profenophos (500 ppm), ethion (500 ppm), propargite (570 ppm), abamectin (10 ppm) and fenazaquin (125 ppm) were moderately toxic to these predators and can be selectively used depending on their potential toxicity to the mite species to be tackled in rice ecosystem.
Activation of bovine factor VII (proconvertin) by factor XIIa (activated Hageman factor) (1977)

Bovine factor VII (proconvertin) is a plasma glycoprotein that participates in the extrinsic pathway of blood coagulation. It has a molecular weight of 45 500 and is composed of a single polypeptide chain with an amino-terminal alanine residue. Factor VII is readily converted to factor VIIa by factor XIIa (activated Hageman factor) employing an enzyme to substrate weight ratio of 1:50. Factor VIIa is composed of a light and a heavy chain held together by a disulfide bond(s). The heavy chain, which is formed from the carboxyl-terminal region of the precursor, contains an amino-terminal sequence of Ile-Val-Gly-Gly-. The heavy chain also contains the active-site sequence of -Phe-Cys-Ala-Gly-Tyr-Thr-Asp-Gly-Thr-Lys-Asp-Ala-Cys-Lys-Gly-Asp-Ser-Gly-Gly-Pro-His-. This sequence is homologous with the active-site region of a number of plasma serine proteases. These data indicate that factor VII is a typical precursor of a serine protease which is converted to an enzyme by factor XIIa by the cleavage of a single, internal peptide bond.
Bleomycin-induced pulmonary fibrosis in transgenic mice that either lack or overexpress the murine plasminogen activator inhibitor-1 gene. (1996)

Impaired fibrinolytic activity within the lung is a common manifestation of acute and chronic inflammatory lung diseases. Because the fibrinolytic system is active during repair processes that restore injured tissues to normal, reduced fibrinolytic activity may contribute to the subsequent development of pulmonary fibrosis. To examine the relationship between the fibrinolytic system and pulmonary fibrosis, lung inflammation was induced by bleomycin in transgenic mice that either overexpressed or were completely deficient in murine plasminogen activator inhibitor-1 (PAI-1). 2 wk after 0.075 U of bleomycin, the lungs of transgenic mice overexpressing PAI-1 contained significantly more hydroxyproline (118 +/- 8 micrograms) than littermate controls (70.5 +/- 8 micrograms, P < 0.005). 3 wk after administration of a higher dose of bleomycin (0.15 U), the lung hydroxyproline content of mice completely deficient in PAI-1 (49 +/- 8 micrograms) was not significantly different (P = 0.63) than that of control animals receiving saline (37 +/- 1 micrograms), while hydroxyproline content was significantly increased in heterozygote (77 +/- 12 micrograms, P = 0.06) and wild-type (124 +/- 19 micrograms, P < 0.001) littermates. These data demonstrate a direct correlation between the genetically determined level of PAI-1 expression and the extent of collagen accumulation that follows inflammatory lung injury. These results strongly support the hypothesis that alterations in fibrinolytic activity influence the extent of pulmonary fibrosis that occurs after inflammatory injury.
Neuromodulation of perineally transposed antropylorus with pudendal nerve anastomosis following total anorectal reconstruction in humans (2014)

Spontaneous rhythm, its generation after electrical stimulation, and response to voluntary contraction demonstrates the viability and functional reinnervation of the perineally transposed antropyloric segment. Rise in pressure on electrical stimulation shows evidence for its neuromodulation.
Characteristics and applications of high performance, tunable, fiber Fabry-Perot filters (2002)

The unique characteristics (stable optical performance, inherently pigtailed, insertion loss <2 dB, finesse >100) of tunable, fiber Fabry-Perot (FFP) filters allow diverse optical signal processing necessary for third-generation wavelength division multiplex (WDM) systems and wavelength division multiple access (WDMA) networks. After describing the FFP characteristics, the author discusses the WDM long-haul field experiment and the prototype IBM Rainbow WDMA network. Other applications for this filter technology are EDFA noise filters, channel switches, and signal processors for extremely broadband ISDN (integrated services digital network) and digital high-definition TV distribution systems.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Asymmetric Synthesis of (+)-(S,S)-Reboxetine via a New (S)-2-(Hydroxymethyl)morpholine Preparation (2005)

(S,S)-Reboxetine was synthesized stereospecifically in 30% overall yield and 99% ee in eight steps. Key steps were selective oxidation of an N-protected hydroxymethylmorpholine and aryl-chromium-mediated aromatic nucleophilic substitution. [structure: see text]
Macromolecular beta-adrenergic antagonists discriminating between receptor and antibody. (1980)

The beta-adrenergic antagonist, alprenolol, was attached in an irreversible manner to macromolecular dextran via side arms that differed in length. The ability of these macromolecules to bind to the beta-adrenergic receptor of frog erythrocytes and to catecholamine-binding antibodies raised against partially purified receptors was studied. Compared to the parent drug the potency of binding of macromolecular alprenolol to the receptor decreased about 1/10, 1/600, and 1/8000 when the length of the arm separating alprenolol from the dextran moiety was 13, 8, and 4 atoms, respectively. In contrast, the binding potencies of the parent drug and of all its macromolecular derivatives for the antibody were within the same order of magnitude. Thus, conversion of a drug to a macromolecular form may not only sustain its binding activity but may also lead in a higher selectivity. The macromolecular derivatives described here may be suitable probes for investigation of the location and of the molecular properties of the binding sites for beta-adrenergic drugs.
Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate. (1988)

Two anti-tumor monoclonal antibodies, L6 (anticarcinoma) and 1F5 (anti-B lymphoma), were covalently linked to alkaline phosphatase (AP), forming conjugates that could bind to the surface of antigen-positive tumor cells. The conjugates were capable of converting a relatively noncytotoxic prodrug, etoposide phosphate (EP), into etoposide--a drug with significant antitumor activity. In vitro studies with a human colon carcinoma cell line, H3347, demonstrated that while EP was less toxic than etoposide by a factor of greater than 100, it was equally toxic when the cells were pretreated with L6-AP, a conjugate that bound to the surface of H3347 cells. The L6-AP conjugate localized in H3347 tumor xenografts in nude mice and histological evaluation indicated that the targeted enzyme (AP) was distributed throughout the tumor mass. A strong antitumor response was observed in H3347-bearing mice that were treated with L6-AP followed 18-24 hr later by EP. This response, which included the rejection of established tumors, was superior to that of EP (P less than 0.005) or etoposide (P less than 0.001) given alone. The IF5-AP conjugate did not bind to H3347 cells and did not enhance the toxicity of EP on these cells in vitro. In addition, IF5-AP did not localize to H3347 tumors in nude mice and did not demonstrate enhanced antitumor activity in combination with the prodrug.