gebhart/patrepeval huggingface dataset:
Activation of Expressed KCNQ Potassium Currents and Native Neuronal M-Type Potassium Currents by the Anti-Convulsant Drug Retigabine (2001)

Retigabine [D-23129;<i>N</i>-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester] is a novel anticonvulsant compound that is now in clinical phase II development. It has previously been shown to enhance currents generated by KCNQ2/3 K<sup>+</sup> channels when expressed in Chinese hamster ovary (CHO) cells (Main et al., 2000;Wickenden et al., 2000). In the present study, we have compared the actions of retigabine on KCNQ2/3 currents with those on currents generated by other members of the KCNQ family (homomeric KCNQ1, KCNQ2, KCNQ3, and KCNQ4 channels) expressed in CHO cells and on the native M current in rat sympathetic neurons [thought to be generated by KCNQ2/3 channels (Wang et al., 1998)]. Retigabine produced a hyperpolarizing shift of the activation curves for KCNQ2/3, KCNQ2, KCNQ3, and KCNQ4 currents with differential potencies in the following order: KCNQ3 &gt; KCNQ2/3 &gt; KCNQ2 &gt; KCNQ4, as measured either by the maximum hyperpolarizing shift in the activation curves or by the EC<sub>50</sub> values. In contrast, retigabine did not enhance cardiac KCNQ1 currents. Retigabine also produced a hyperpolarizing shift in the activation curve for native M channels in rat sympathetic neurons. The retigabine-induced current was inhibited by muscarinic receptor stimulation, with similar agonist potency but 25% reduced maximum effect. In unclamped neurons, retigabine produced a hyperpolarization and reduced the number of action potentials produced by depolarizing current injections, without change in action potential configuration.
Carbonates, Thiocarbonates, and the Corresponding Monoalkyl Derivatives. 1. Their Preparation and Isotropic 13C NMR Chemical Shifts (2001)

Three series of potassium carbonate and thiocarbonate salts were synthesized, and the corresponding (13)C isotropic solid-state NMR and the aqueous solution (13)C and (1)H NMR data were collected. The series of compounds that were studied consists of (1) the parent compounds, i.e., potassium carbonate, K(2)CO(3), potassium hydrogen carbonate, KHCO(3), potassium monothiocarbonate, K(2)CO(2)S, potassium dithiocarbonate, K(2)COS(2), and potassium trithiocarbonate, K(2)CS(3), (2) the oxygen monoalkyl substituted derivatives of the parent compounds (OR series), i.e., three potassium O-alkylcarbonates, KO(2)COR, three potassium O-alkylmonothiocarbonates, KOSCOR, and three potassium O-alkyldithiocarbonates, KS(2)COR, all with R = CH(3), CH(2)CH(3), CH(CH(3))(2), and (3) the sulfur monoalkyl substituted derivatives of the parent compounds (SR series), i.e., two potassium S-alkylmonothiocarbonates, KO(2)CSR; two potassium S-alkyldithiocarbonates, KOSCSR, and two potassium S-alkyltrithiocarbonates, KS(2)CSR, all with R = CH(3) or CH(2)CH(3). The preparation and proper characterization of KO(2)CSR and KOSCSR with R = CH(3) and CH(2)CH(3) along with new IR and X-ray powder diffraction data for several other compounds in the series are reported for the first time in this study. Solution NMR data for KO(2)CSR (R = CH(3), CH(2)CH(3)) and KOSCSR (R = CH(3)) and solid-state NMR data for K(2)CO(2)S and K(2)COS(2) could not be obtained because they are unstable under the corresponding measurement conditions. The isotropic chemical shift values of the central carbon atoms obtained from solid-state MAS (magic angle spinning) NMR experiments deviate at most by 3 ppm from the corresponding solution values. Two major trends in the (13)C chemical shift values of the central carbon atoms were found. First, if an oxygen atom in a parent compound or in an alkyl-substituted derivative is replaced by a sulfur atom, a significantly higher chemical shift value is observed. This trend is discussed in terms of the paramagnetic contribution to the chemical shielding constant. Second, the size of the alkyl group in the monoalkyl derivatives has a very small effect on the chemical shift values of the central carbon atoms. This observation is explained using the concept of varying inductive effects produced by alkyl groups. The trends observed for the (13)C and (1)H chemical shift values of the alkyl groups follow common concepts on the structure dependency of chemical shifts.
Sensitization of human breast cancer cells to cyclophosphamide and ifosfamide by transfer of a liver cytochrome P450 gene. (1996)

The cancer chemotherapeutic agent cyclophosphamide (CPA) and its isomer ifosfamide (IFA) are alkylating agent prodrugs that require metabolism by liver cytochrome P450 (P450) enzymes for antitumor activity. The therapeutic effectiveness of these oxazaphosphorines is limited by the hematopoietic, renal, and cardiac toxicity that accompanies the systemic distribution of liver-derived activated drug metabolites. Transfer of a liver cytochrome P450 gene, CYP2B1, into human breast MCF-7 cancer cells is presently shown to greatly sensitize these cells to oxazaphosphorine toxicity as a consequence of the acquired capacity for intratumoral CPA and IFA activation. Thus, CPA and IFA were highly cytotoxic to MCF-7 cells following stable transfection of CYP2B1 but exhibited no toxicity to parental tumor cells or to a beta-galactosidase-expressing MCF-7 transfectant. This cytotoxicity could be appreciably blocked by the CYP2B1 inhibitor metyrapone. Cell cycle analysis revealed that CPA arrested the CYP2B1-expressing cells, but not CYP2B1-negative cells, at G(2)-M phase. A strong bystander cytotoxicity effect that does not require direct cell-cell contact was mediated by CYP2B1-expressing MCF-7 cells on non-CYP2B1 cells. Intratumoral CYP2B1 expression conferred a distinct therapeutic advantage when treating MCF-7 tumors grown in nude mice with CPA, as revealed by a 15-20-fold greater in vivo cytotoxicity, determined by tumor excision/colony formation assay, and by the substantially enhanced antitumor activity, monitored by tumor growth delay, for CYP2B1-e xpressing MCF-7 tumors as compared to CYP2B1-negative control tumors. These enhanced therapeutic effects were obtained without any apparent increase in host toxicity. To evaluate the extent to which a CPA/P450 gene therapy strategy may be generally applicable to other tumor cell types, a replication-defective recombinant adenovirus carrying the CYP2B1 gene driven by the cytomegalovirus (CMV) promotor ad.CMV-2B1 was constructed and used to infect a panel of human tumor cell lines. Ad.CMV-2B1 infection rendered each of the cell lines highly sensitive to CPA and IFA cytotoxicity, with substantial chemosensitization seen at multiplicities of infection as low as 10. The CPA/P450 prodrug activation system may thus serve as a useful paradigm for further development of novel cancer gene therapy strategies that utilize drug susceptibility genes to significantly potentiate the antitumor activity of conventional cancer chemotherapeutic agents.
Cardiac Stem Cells Possess Growth Factor-Receptor Systems That After Activation Regenerate the Infarcted Myocardium, Improving Ventricular Function and Long-Term Survival (2005)

Cardiac stem cells and early committed cells (CSCs-ECCs) express c-Met and insulin-like growth factor-1 (IGF-1) receptors and synthesize and secrete the corresponding ligands, hepatocyte growth factor (HGF) and IGF-1. HGF mobilizes CSCs-ECCs and IGF-1 promotes their survival and proliferation. Therefore, HGF and IGF-1 were injected in the hearts of infarcted mice to favor, respectively, the translocation of CSCs-ECCs from the surrounding myocardium to the dead tissue and the viability and growth of these cells within the damaged area. To facilitate migration and homing of CSCs-ECCs to the infarct, a growth factor gradient was introduced between the site of storage of primitive cells in the atria and the region bordering the infarct. The newly-formed myocardium contained arterioles, capillaries, and functionally competent myocytes that with time increased in size, improving ventricular performance at healing and long thereafter. The volume of regenerated myocytes was 2200 microm3 at 16 days after treatment and reached 5100 microm3 at 4 months. In this interval, nearly 20% of myocytes reached the adult phenotype, varying in size from 10,000 to 20,000 microm3. Moreover, there were 43+/-13 arterioles and 155+/-48 capillaries/mm2 myocardium at 16 days, and 31+/-6 arterioles and 390+/-56 capillaries at 4 months. Myocardial regeneration induced increased survival and rescued animals with infarcts that were up to 86% of the ventricle, which are commonly fatal. In conclusion, the heart has an endogenous reserve of CSCs-ECCs that can be activated to reconstitute dead myocardium and recover cardiac function.
On the concept of linear modified retro-peptide structures (1979)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOn the concept of linear modified retro-peptide structuresMurray Goodman and Michael ChorevCite this: Acc. Chem. Res. 1979, 12, 1, 1–7Publication Date (Print):January 1, 1979Publication History Published online1 May 2002Published inissue 1 January 1979https://pubs.acs.org/doi/10.1021/ar50133a001https://doi.org/10.1021/ar50133a001research-articleACS PublicationsRequest reuse permissionsArticle Views823Altmetric-Citations225LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose Get e-Alerts
The promise of plasmonics (2007)

Light is a wonderful medium for carrying information. Optical fibers now span the globe, guiding light signals that convey voluminous streams of voice communications and vast amounts of data. This gargantuan capacity has led some researchers to prophesy that photonic devices--which channel and manipulate visible light and other electromagnetic waves--could someday replace electronic circuits in microprocessors and other computer chips. Unfortunately, the size and performance of photonic devices are constrained by the diffraction limit; because of interference between closely spaced light waves, the width of an optical fiber carrying them must be at least half the light's wavelength inside the material. For chip-based optical signals, which will most likely employ near-infrared wavelengths of about 1,500 nanometers (billionths of a meter), the minimum width is much larger than the smallest electronic devices currently in use; some transistors in silicon integrated circuits, for instance, have features smaller than 100 nanometers.
Reduction of UDP-N-acetylglucosamine 2-Epimerase/N-Acetylmannosamine Kinase Activity and Sialylation in Distal Myopathy with Rimmed Vacuoles (2004)

Distal myopathy with rimmed vacuoles is an autosomal recessive muscle disease with preferential involvement of the tibialis anterior that spares the quadriceps muscles in young adulthood. In a Japanese patient with distal myopathy with rimmed vacuoles, we identified pathogenic mutations in the gene encoding the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase, which catalyzes the initial two steps in the biosynthesis of sialic acid. In this study, we demonstrated the relationship between the genetic mutations and enzymatic activities using an in vitro expression assay system. Furthermore, we also showed that the levels of sialic acid in muscle and primary cultured cells from DMRV patients were reduced to 60-75% of control. The reactivities to lectins were also variable in some myofibers, suggesting that hyposialylation and abnormal glycosylation in muscles may contribute to the focal accumulations of autophagic vacuoles, amyloid deposits, or both in patient muscle tissue. The addition of ManNAc and NeuAc to primary cultured cells normalized sialylation levels, thus demonstrating the therapeutic potential of these compounds for this disease.
Identification of 1,25-Dihydroxycholecalciferol, a Form of Vitamin D 3 Metabolically Active in the Intestine (1971)

A biologically active vitamin D(3) metabolite ("peak V metabolite") more polar than 25-hydroxycholecalciferol has been isolated from chicken intestines in pure form as a mono(trimethylsilyl)ether derivative. The molecule has been identified as 1,25-dihydroxycholecalciferol by means of mass spectrometry, ultraviolet absorption spectrophotometry, and specific chemical reactions.
Chromosome 8 Allelic Loss and the Outcome of Patients With Squamous Cell Carcinoma of the Supraglottic Larynx (1996)

Allelic loss in the p23 region of chromosome 8 appears to be a statistically significant, independent predictor of poor prognosis in patients with supraglottic squamous cell carcinoma.
Monitoring techniques for the detection of flow failure in the postoperative period (1993)

Free tissue transfer is now a commonly used reconstructive tool. Vascular compromise is still a common complication and salvage rates of compromised flaps have been in the region of 50%. Numerous monitoring techniques have been tried but there is yet no single technique which has enjoyed universal acceptance. This paper reviews the available techniques and indicates where current trends are leading.
Peptide YY Levels Are Elevated After Gastric Bypass Surgery (2006)

Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut-derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY(3-36) replacement could represent an effective therapy for obesity.
Dimerization of Transcobalamin II Receptor (1996)

Transcobalamin II receptor (TC II-R) exists as a monomer and a dimer of molecular masses of 62 and 124 kDa in the microsomal and plasma membranes, respectively, and in vitro, pure TC II-R monomer dimerizes upon insertion into egg PC/cholesterol (molar ratio, 4:1) liposomes (Bose, S., Seetharam, S., and Seetharam, B. (1995) J. Biol Chem. 270, 8152-8157 and Bose, S., Seetharam, S., Hammond, T., and Seetharam, B. (1995) Biochem. J. 310, 923-929). The current studies were carried out to define the mechanism of TC II-R dimerization. Both the mature TC II-R (62 kDa) and the enzymatically deglycosylated TC II-R (45-47 kDa) demonstrated optimal association and formed dimers of molecular masses of 95 and 124 kDa, respectively, at 22 degrees C when bound to egg PC vesicles containing at least 10 mol % of cholesterol. Mature TC II-R dimerized upon insertion into synthetic phosphatidylcholine vesicles of different fatty acyl chain length (dimyristoyl, dipalmitoyl, and disteroyl phosphatidylcholine) in the absence or the presence of cholesterol at temperatures below or above their transition temperatures, respectively. Dimerization of TC II-R also occurred with vesicles prepared using lipid extract from the plasma but not microsomal membranes. Cholesterol depletion of native intestinal plasma membranes or its enrichment in the microsomal membranes resulted in the in situ conversion of the 124-kDa dimer to the 62-kDa monomer or of the monomer into the dimer form, respectively. Treatment of plasma membranes with phospholipase A2 resulted in the conversion of the dimer form of the receptor to the monomer form and spin label studies using 1-palmitoyl, 12 doxylsteroyl phosphatidylcholine revealed that interactions of TC II-R with PC vesicles increased order around the probe. Based on these results we suggest that dimerization of TC II-R is mediated by its interactions with a rigid more ordered lipid bilayer membrane, is regulated in plasma membranes by cholesterol levels, and is independent of glycosylation-mediated folding.
Studies on Escherichia coli Enzymes Involved in the Synthesis of Uridine Diphosphate- N -Acetyl-Muramyl-Pentapeptide (1972)

The specific activities of l-alanine:d-alanine racemase, d-alanine:d-alanine ligase, and the l-alanine, d-glutamic acid, meso-diaminopimelic acid, and d-alanyl-d-alanine adding enzymes were followed during growth of Escherichia coli. The specific activities were nearly independent of the growth phase. d-Alanine:d-alanine ligase was inhibited by d-alanyl-d-alanine, d-cycloserine, glycine, and glycyl-glycine. l-Alanine:d-alanine racemase was found to be sensitive to d-cycloserine, glycine, and glycyl-glycine. The l-alanine adding enzyme was inhibited by glycine and glycyl-glycine.
Comparison of Pilot-Scale and Rapid Visco Analyzer Process Cheese Manufacture (2004)

Numerous formulation and processing parameters influence the functionality of process cheese. A small-scale manufacturing and analysis method could be used to evaluate the influence of formulation parameters and processing conditions on the functionality of process cheese. The objective of this study was to compare process cheese produced on a small-scale (25 g) in a Rapid Visco Analyzer (RVA) to process cheese produced on a pilot-scale (4.5 kg) in a Blentech twin-screw pilot-scale cooker (BTS). Three replicates of pasteurized process cheese (PC) and pasteurized process cheese food (PCF) were produced in an RVA and in a BTS. Texture profile analysis (TPA) and the RVA melt test were performed on all PC and PCF produced. There was a significant replication effect on TPA-hardness and hot apparent viscosity of the PC and PCF produced in the RVA and the BTS. The PC and PCF produced in the RVA had significantly higher TPA-hardness and hot apparent viscosity compared with PC and PCF produced in the BTS. The RVA manufacturing time (short vs. long) did not have a significant effect on TPA-hardness values for PC or PCF. However, the long manufacturing time significantly increased hot apparent viscosity for PC and PCF. The RVA was successfully used to manufacture process cheeses; however, differences in the manufacturing profiles and type of cooker influenced the functional properties of the process cheese.
Patterns of Acute Rhesus Cytomegalovirus (RhCMV) Infection Predict Long-Term RhCMV Infection (2012)

We previously reported that long-term rhesus cytomegalovirus (RhCMV) excretion in infected macaques was related to UL/b' coding content. Acute biopsy specimens of the inoculation sites from the previous study have now been analyzed to determine whether there were acute phenotypic predictors of long-term RhCMV infection. Only in animals displaying acute endothelial tropism and neutrophilic inflammation was RhCMV excretion detected. The results imply that vaccinating against these early viral determinants would significantly impede long-term RhCMV infection.
Podocyte Detachment and Reduced Glomerular Capillary Endothelial Fenestration in Human Type 1 Diabetic Nephropathy (2007)

The aim of this study was to investigate the structural characteristics of podocytes and endothelial cells in diabetic nephropathy. We studied 18 patients with type 1 diabetes (seven normoalbuminuric, six microalbuminuric, and five proteinuric), and six normal control subjects. Groups were not different for age. Type 1 diabetic groups were not different for diabetes duration or age at diabetes onset. Podocyte foot process width (FPW), fraction of glomerular basement membrane (GBM) surface with intact nondetached foot processes (IFP), fraction of glomerular capillary luminal surface covered by fenestrated endothelium [S(S)(Fenestrated/cap)] and classic diabetic glomerulopathy lesions were morphometrically measured. Albumin excretion (AER) and glomerular filtration (GFR) rates were also measured. GFR correlated inversely and AER directly with GBM and mesangial measurements in diabetic patients. FPW correlated inversely with GFR (r = -0.71, P = 0.001) and directly with AER (r = 0.66, P = 0.003), GBM, and mesangial parameters. The GBM fraction covered by IFP was decreased in proteinuric versus control subjects (P = 0.001), normoalbuminuric patients (P = 0.0002) and microalbuminuric patients (P = 0.04) and correlated with renal structural and functional parameters, including AER (r = -0.52, P = 0.03). Only 78% of GBM was covered by IFP in proteinuric patients. S(S)(Fenestrated/cap) was reduced in normoalbuminuric (P = 0.03), microalbuminuric (P = 0.03), and proteinuric (P = 0.002) patients versus control subjects. S(S)(Fenestrated/cap) correlated with mesangial fractional volume per glomerulus (r = -0.57, P = 0.01), IFP (r = 0.61, P = 0.007), and FPW (r = -0.58, P = 0.01). These novel studies document that podocyte detachment and diminished endothelial cell fenestration are related to classical diabetic nephropathy lesions and renal function in type 1 diabetic patients and support a need for further studies of podocyte/GBM adherence and podocyte/endothelial cell functional interactions in diabetic nephropathy.
Dendritic oligoguanidines as intracellular translocators (2004)

A series of polyguanidylated dendritic structures that can be used as molecular translocators have been designed and synthesized based on nonpeptide units. The dendritic oligoguanidines conjugated with fluorescein or with a green fluorescent protein (GFP) mutant as cargos were isolated and characterized. Quantification and time-course analyses of the cellular uptake of the conjugates using HeLa S3 and human cervical carcinoma cells reveal that the polyguanidylated dendrimers have comparable translocation efficiency to the Tat(49-57) peptide. Furthermore, the deconvolution microscopy image analysis shows that they are located inside the cells. These results clearly show that nonlinear, branched dendritic oligoguanidines are capable of translocation through the cell membrane. This work also demonstrates the potential of these nonpeptidic dendritic oligoguanidines as carriers for intracellular delivery of small molecule drugs, bioactive peptides, and proteins.
A Model Recognition Approach to the Prediction of All-Helical Membrane Protein Structure and Topology (1994)

This paper describes a new method for the prediction of the secondary structure and topology of integral membrane proteins based on the recognition of topological models. The method employs a set of statistical tables (log likelihoods) complied from well-characterized membrane protein data, and a novel dynamic programming algorithm to recognize membrane topology models by expectation maximization. The statistical tables show definite biases toward certain amino acid species on the inside, middle, and outside of a cellular membrane. Using a set of 83 integral membrane protein sequences taken from a variety of bacterial, plant, and animal species, and a strict jackknifing procedure, where each protein (along with any detectable homologues) is removed from the training set used to calculate the tables before prediction, the method successfully predicted 64 of the 83 topologies, and of the 37 complex multispanning topologies 34 were predicted correctly.