gebhart/patrepeval huggingface dataset:
Transarterial embolization versus symptomatic treatment in patients with advanced hepatocellular carcinoma: Results of a randomized, controlled trial in a single institution (1998)

This randomized, controlled trial assessed the effect of transarterial embolization (TAE) (without associated chemotherapy) on the survival of patients with nonsurgical hepatocellular carcinoma (HCC). Eighty consecutive patients were randomized to treatment with embolization (Group A, n = 40), or to symptomatic treatment (Group B, n = 40), there being no differences between both groups regarding the degree of liver function impairment and tumor stage. Eighty-two percent of the patients presented a self-limited postembolization syndrome, without treatment-related mortality. Fifty-five percent of the treated cases exhibited a partial response, which resulted in a lower probability of tumor progression during follow-up (57% vs. 77% at 1 year; P < .005). However, after a median follow-up of 24 months (30 deaths in each group), there are no differences in survival (Group A: 49% and 13%; Group B: 50% and 27%, at 2 and 4 years, respectively; P = .72). The absence of differences was maintained even when dividing patients according to Child-Pugh's grade, Okuda stage, or performance status test (PST). Furthermore, there were no differences in the probability of complications or in the need of hospital admissions. In conclusion, TAE has a marked antitumoral effect associated to a slower growth of the tumor, but it does not improve the survival of patients with nonsurgical HCC.
Cross-species complementation of the indispensable Escherichia coli era gene highlights amino acid regions essential for activity (1995)

Era is an essential GTP binding protein in Escherichia coli. Two homologs of this protein, Sgp from Streptococcus mutans and Era from Coxiella burnetii, can substitute for the essential function of Era in E. coli. Site-specific and randomly generated Era mutants which may indicate regions of the protein that are of functional importance are described.
Antibody production in transgenic plants (1994)

Conference Article| November 01 1994 Antibody production in transgenic plants Garry C. Whitelam; Garry C. Whitelam * *To whom correspondence should be addressed. Search for other works by this author on: This Site PubMed Google Scholar William Cockburn; William Cockburn 1Department of Botany, University of Leicester, Leicester LEI 7RH, U.K. Search for other works by this author on: This Site PubMed Google Scholar Meran R. L. Owen Meran R. L. Owen 1Department of Botany, University of Leicester, Leicester LEI 7RH, U.K. Search for other works by this author on: This Site PubMed Google Scholar Biochem Soc Trans (1994) 22 (4): 940–944. https://doi.org/10.1042/bst0220940 Article history Received: June 10 1994 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation Garry C. Whitelam, William Cockburn, Meran R. L. Owen; Antibody production in transgenic plants. Biochem Soc Trans 1 November 1994; 22 (4): 940–944. doi: https://doi.org/10.1042/bst0220940 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Society Transactions Search Advanced Search Keywords: MAb, monoclonal antibody, recAb, recombinant antibody, VH, variable heavy chain, VL, variable light chain This content is only available as a PDF. © 1994 Biochemical Society1994 Article PDF first page preview Close Modal You do not currently have access to this content.
Luminol/H2O2 Chemiluminescence Detector for the Analysis of Nitric Oxide in Exhaled Breath (1999)

A new instrument for the detection of nitric oxide has been developed and applied to the analysis of exhaled breath. The instrument is based on conversion of NO to NO2, using the oxidant chromium trioxide, followed by detection of chemiluminescence in the reaction of NO2 with an alkaline luminol/H2O2 solution. The presence of H2O2 is found to enhance the sensitivity of NO2 detection by a factor of approximately 20. A bundle of porous polypropylene hollow fiber membranes is used to bring the gaseous sample into contact with the luminol solution. Chemiluminescence occurring within the translucent hollow fibers is detected using a miniature photomultiplier tube. The limit of detection for NO is 0.3 ppbv for S/N = 3, and the 1/e response time is 2 s. A large interference resulting from the 4-6% CO2 concentration in exhaled breath is removed by use of an ascarite scrubber in the air stream. Breath measurements of NO were made using a sampling technique developed by Sensor Medics (Yorba Linda, CA) with simultaneous detection using the luminol/H2O2 and NO + O3 chemiluminescence techniques. The two instruments were found to be in excellent agreement. Nitric oxide levels were in the range 6.0-22.0 ppbv for healthy individuals and 40.0-80.0 ppbv for individuals with asthma or a respiratory infection. This new detector offers the advantages of compact size, low cost, and a simple configuration compared to NO detectors based on NO + O3 chemiluminescence.
Diphenolic Monomers Derived from the Natural Amino Acid α-L-Tyrosine: An Evaluation of Peptide Coupling Techniques (1995)

Tlyrosine-derived polycarbonates and polyarylates have recently been recognized as promising biomaterials. In these novel polymers, non-toxic desaminotyrosyl-tyrosine alkyl esters are being used as monomers in place of industrial diphenols such as Bisphenol A. The high cost and limited availability of desaminotyrosyl-tyrosine alkyl esters have prevented the large-scale preparation of these polymers. To address this problem, the following four peptide coupling techniques were explored: dicyclohexylcarbodiimide with 1-hydroxybenzotriazole hydrate (DCC/HOBt), ethyl-3-(3-dimethylamino)propyl carbodiimide hydrochloride salt (EDCI-HCl), N-hydroxysuccinimide (NHS) active ester, and p-nitrophenol (pNP) active ester. Desaminotyrosyl-tyrosine hexyl ester (DTH) was used as a model compound. DCC/HOBt led to a crude product that required column chromatography for purification. The water soluble coupling agent EDCI-HCl made it possible to replace column chromatography by precipitation/extraction in aqueous media. This alleviated possible environmental concerns about the use of organic solvents. Furthermore, EDCI-HC1 did not require the addition of an auxiliary nucleophile such as HOBt in the reaction mixture, The use of the NHS active ester of Dat also produced DTH of sufficient purity, but was less cost effective than EDCI-HCI. The pNP active ester produced YIH which could not be easily purified. Based on these results, the effectiveness of EDCI-HCI was verified by the 100 g synthesis of the ethyl, butyl, hexyl and octyl esters of desaminotrosyl-tyrosine. All of these monomers could be polymerized to high polymers. Overall, the EDCI-HCl mediated coupling of Dat and tyrosine alkyl esters was identified as the best method for the large-scale synthesis of the desaminotyrosyl-tyrosine alkyl esters in a cost efficient and environmentally acceptable manner.
Activation of a vmp pseudogene in Borrella hermsii: an alternate mechanism of antigenic variation during relapsing fever (1994)

The relapsing fever agent, Borrelia hermsii, undergoes multiphasic antigenic variation to evade its host's immune response. A frequently observed switch is serotype 7 to 26. Unlike silent vmp genes previously characterized, the transcriptionally silent vmp26 sequence was a pseudogene in lacking a start codon. In serotype 7 the location of the silent vmp26 sequence just downstream of vmp7 on the expression plasmid, as well as on the silent plasmid, was also unique. The demonstration of a predicted circular recombination product in serotype 7 but not serotype 21 populations indicates that the pseudogene was activated by an intramolecular recombination producing a deletion of DNA between 20-nucleotide direct repeats in vmp7 and psi vmp26.
Activity of novel aminocannabinoids in baboons (1984)

The axial and equatorial isomers of 7-(methylamino)hexahydrocannabinol (1 and 2) and 7-(dimethylamino)hexahydrocannabinol (3 and 4) were prepared by reductive amination of the corresponding cannabinoid aldehydes. The amines caused some tranquility in baboons but did not evoke the typical cannabimimetic syndrome caused by psychoactive cannabinoids. However the axial amines (1 and 3) but not the equatorial ones (2 and 4) caused bouts of scratching and yawning. The latter is a rare pharmacological effect hitherto not observed with other cannabinoids.
Mucosal vaccines based on the use of cholera toxin B subunit as immunogen and antigen carrier. (1994)

Stimulation of strong mucosal IgA immune responses as a basis for vaccine-induced protection against various pathogens has proved difficult. Most soluble protein antigens administered either parenterally or oral-mucosally have given disappointing results. A notable exception in this regard are cholera toxin (CT) and, particularly in humans, its non-toxic B subunit pentamer moiety (CTB) both of which stimulate a strong intestinal IgA antibody response and long-lasting immunological memory. Based on this, CTB has become an important component in recently developed oral vaccines against cholera and diarrhea caused by enterotoxigenic E. coli. The strong immunogenicity of CT and CTB can to a large extent be explained by their ability to bind to receptors on the intestinal mucosal surface. This has promoted much recent interest in the use of CTB as an oral delivery carrier for other vaccine-relevant antigens. Oral administration of antigens coupled to CTB either chemically or genetically has in several systems been found to markedly potentiate both intestinal and extra-intestinal IgA immune responses against the CTB-coupled antigens and to elicit substantial circulating antibody responses. In contrast to CTB, CT also has strong adjuvant properties for stimulating mucosal IgA immune responses to unrelated, non-coupled antigens after oral co-immunization. This adjuvant activity appears to be closely linked to the A subunit-catalyzed ADP-ribosylating action of CT leading to enhanced cyclic AMP formation in the affected cells.
Effect of acute and chronic tramadol on [3H]‐5‐HT uptake in rat cortical synaptosomes (1997)

1. Tramadol hydrochloride is a centrally acting opioid analgesic, the efficacy and potency of which is only five to ten times lower than that of morphine. Opioid, as well as non-opioid mechanisms, may participate in the analgesic activity of tramadol. 2. [3H]-5-hydroxytryptamine (5-HT) uptake in rat isolated cortical synaptosomes was studied in the presence of tramadol, desipramine, fluoxetine, methadone and morphine. Methadone and tramadol inhibited synaptosomal [3H]-5-HT uptake with apparent Kis of 0.27 +/- 0.04 and 0.76 +/- 0.04 microM, respectively. Morphine essentially failed to inhibit [3H]-5-HT uptake (Ki 0.50 +/- 0.30 M). 3. Methadone, morphine and tramadol were active in the hot plate test with ED50s of 3.5, 4.3 and 31 mg kg-1, respectively. At the highest tested dose (80 mg kg-1) tramadol produced only 77 +/- 5.3% of the maximal possible effect. 4. When [3H]-5-HT uptake was examined in synaptosomes prepared from rats 30 min after a single dose of morphine, methadone or tramadol, only tramadol (31 mg kg-1, s.c., equal to the ED50 in the hot plate test) and methadone (35 mg kg-1, s.c., equal to the ED90 in the hot plate test) decreased uptake. 5. Animals were chronically treated for 15 days with increasing doses of tramadol or methadone (5 to 40 mg kg-1 and 15 to 120 mg kg-1, s.c., respectively). Twenty-four hours after the last drug injection, a challenge dose of methadone (35 mg kg-1, s.c.) or tramadol (31 mg kg-1, s.c.) was administered. [3H]-5-HT uptake was not affected in synaptosomes prepared from rats chronically-treated with methadone, whereas chronic tramadol was still able to reduce this parameter by 42%. 6. Rats chronically-treated with methadone showed a significant increase in [3H]-5-HT uptake (190%) 72 h after drug withdrawal. In contrast, [3H]-5-HT uptake in rats chronically-treated with tramadol (110%) did not differ significantly from control animals. 7. These results further support the hypothesis that [3H]-5-HT uptake inhibition may contribute to the antinociceptive effects of tramadol. The lack of tolerance development of [3H]-5-HT uptake, together with the absence of behavioural alterations after chronic tramadol treatment, suggest that tramadol has an advantage over classical opioids in the treatment of pain disorders.
Synthesis, Biochemical Properties and Molecular Modelling Studies of Organometallic Specific Estrogen Receptor Modulators (SERMs), the Ferrocifens and Hydroxyferrocifens: Evidence for an Antiproliferative Effect of Hydroxyferrocifens on both Hormone‐Dependent and Hormone‐Independent Breast Cancer Cell Lines (2003)

Abstract A series of ferrocene derivatives based upon the structure of the antiestrogenic drug tamoxifen or of its active metabolite hydroxytamoxifen has been prepared and named by analogy ferrocifens and hydroxyferrocifens. This series includes 1‐[4‐(O(CH 2 ) n NMe 2 )phenyl]‐1‐phenyl‐2‐ferrocenyl‐but‐1‐ene and 1‐[4‐(O(CH 2 ) n NMe 2 )phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene, with n =2, 3, 5 and 8, and 1‐[4‐(O(CH 2 ) 2 NMe 2 )phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenylethene. Most of these molecules have been synthesised by McMurry cross‐coupling of the appropriate ketones, except for the ethene complexes, which were prepared by a four‐step reaction sequence starting from the ferrocenylacetic acid. All these compounds were obtained as mixtures of Z and E isomers. The isomers were separated in the cases of the ferrocenyl derivatives of tamoxifen and hydroxytamoxifen ( n =2). No isomerisation of the Z and E isomers occurred in DMSO after one day, while a 50:50 mixture of the isomers was obtained within one hour in chloroform. The X‐ray structure of ( E )‐1‐[4‐(O(CH 2 ) 2 NMe 2 )phenyl]‐1‐(4‐hydroxyphenyl)‐2‐ferrocenyl‐but‐1‐ene has been determined. The relative binding affinity (RBA) values of the hydroxyferrocifens for the estrogen receptor alpha (ERα) was good to moderate, with values decreasing progressively with the length of the basic chain. The RBA values found for the estrogen receptor beta (ERβ) are equal to or slightly less than those found for the alpha form. The lipophilicity of the hydroxyferrocifens are superior to the values found for estradiol and increase with lengthening of the chain. The antiproliferative effects of the four hydroxyferrocifens with n =2, 3, 5 and 8 were studied on four breast cancer cell lines (MCF7, MDA‐MB231, RTx6 and TD5) possessing different levels of ERα. On MCF7 cells containing high levels of ERα, hydroxyferrocifens behave as antiestrogens. At a molarity of 1 μ M the effect is close to that of hydroxytamoxifen (used for reference) when n =2 or 5, more marked when n =3, and weaker when n =8. Ferrocene alone has no effect. For the MDA‐MB231 cells, classed as a hormone‐independent breast cancer cell line, on the other hand, the hydroxyferrocifens show remarkable antiproliferative behaviour while the hydroxytamoxifen is completely inactive. Hydroxyferrocifens therefore show the unique property of being active both on hormone‐dependent and on hormone‐independent breast cancer cell lines. The molecular modelling study provides some clues for understanding of the antagonist effect of these molecules, while an additional cytotoxic effect due to the vectorised ferrocenyl unit is revealed in some occasions.
Convenient protection of amines as carbamates using polymer-bound HOBT as catalyst (1998)

A method for the facile protection of primary and secondary amines as carbamate (Cbz, Fmoc and t-Boc) derivatives using polymer bound 1-hydroxybenzotriazole (HOBT) is reported.
Let-7 MicroRNA Family Is Selectively Secreted into the Extracellular Environment via Exosomes in a Metastatic Gastric Cancer Cell Line (2010)

The enrichment of let-7 miRNA family in the extracellular fractions, particularly, in the exosomes from AZ-P7a cells may reflect their oncogenic characteristics including tumorigenesis and metastasis. Since let-7 miRNAs generally play a tumor-suppressive role as targeting oncogenes such as RAS and HMGA2, our results suggest that AZ-P7a cells release let-7 miRNAs via exosomes into the extracellular environment to maintain their oncogenesis.
Synthesis of Stable and Cell-type Selective Analogues of Cyclic ADP−Ribose, a Ca2+-Mobilizing Second Messenger. Structure−Activity Relationship of the N1-Ribose Moiety1 (2005)

We previously developed cyclic ADP-carbocyclic ribose (cADPcR, 2) as a stable mimic of cyclic ADP-ribose (cADPR, 1), a Ca(2+)-mobilizing second messenger. A series of the N1-ribose modified cADPcR analogues, designed as novel stable mimics of cADPR, which were the 2"-deoxy analogue 3, the 3"-deoxy analogue 4, the 3"-deoxy-2"-O-(methoxymethyl) analogue 5, the 3"-O-methyl analogue 6, the 2",3"-dideoxy analogue 7, and the 2",3"-dideoxydidehydro analogue 8, were successfully synthesized using the key intramolecular condensation reaction with phenylthiophosphate-type substrates. We investigated the conformations of these analogues and of cADPR and found that steric repulsion between both the adenine and N9-ribose moieties and between the adenine and N1-ribose moieties was a determinant of the conformation. The Ca(2+)-mobilizing effects were evaluated systematically using three different biological systems, i.e., sea urchin eggs, NG108-15 neuronal cells, and Jurkat T-lymphocytes. The relative potency of Ca(2+)-mobilization by these cADPR analogues varies depending on the cell-type used: e.g., 3"-deoxy-cADPcR (4) > cADPcR (2) > cADPR (1) in sea urchin eggs; cADPR (1) >> cADPcR (2) approximately 3"-deoxy-cADPcR (4) in T-cells; and cADPcR (2) > cADPR (1) > 3"-deoxy-cADPcR (4) in neuronal cells, respectively. These indicated that the target proteins and/or the mechanism of action of cADPR in sea urchin eggs, T-cells, and neuronal cells are different. Thus, this study represents an entry to cell-type selective cADPR analogues, which can be used as biological tools and/or novel drug leads.
Epothilons A and B: Antifungal and Cytotoxic Compounds from Sorangium cellulosum (Myxobacteria). Production, Physico-chemical and Biological Properties. (1996)

An antifungal activity against Mucor hiemalis was detected in the culture broth of Sorangium cellulosum (Myxococcales) strain So ce90. The activity was excreted into the supernatant during the log and early stationary phase. When the adsorber resin XAD-16 was added to the culture, the active metabolites were quantitatively bound to the resin. The epothilons showed a high cytotoxicity for animal cells and mimic the biological effects of taxol (BOLLAG et al., Cancer Res. 55: 2325 approximately 2333, 1995).
Enhancement of neovascularization with cord blood CD133+ cell-derived endothelial progenitor cell transplantation (2004)

The endothelial progenitor cells (EPCs) are responsible for postnatal vasculogenesis in physiological and pathological neovascularization and have been used for attenuating ischemic diseases. However, EPCs from umbilical cord blood (CB) were not well understood and the homing mechanisms of EPCs remain unclear. To determine the potential application of CB-derived EPCs, we established a culture system to induce the differentiation of CB cells into EPCs. Purified CB CD133(+) cells proliferated and, after further vascular endothelial growth factor receptor 2 (VEGFR-2) antibody purification, differentiated into EPCs expressing endothelial markers, such as VE-cadherin, VEGFR-2, CD31, von Willebrand factor (vWF) and Weibel-Palade bodies. These cells could also take up acetylated lower density lipoprotein (Ac-LDL) and bind Ulex europaeus agglutinin-1 (UEA-1). When expanded EPCs were transplanted via tail vein into nude mice, they incorporated into capillary networks in ischemic hindlimb, augmented neovascularization, and improved ischemic limb salvage. In addition, in ischemic tissue, there were elevated expressions of VEGF and stromal derived factor 1 alpha (SDF-1 alpha), both of which had chemotactic effect on EPCs. Moreover, P-/E-selectins was found on mouse ischemic endothelium and P-selectin glycoprotein ligand-1 (PSGL-1) on CB-derived EPCs. Neutralizing antibody against PSGL-1 blocked the homing of EPCs to ischemic area by 61%. These results demonstrate that CB CD133(+) cell-derived EPCs can be applied for therapeutic neovascularization in ischemic diseases, and reveal important roles of chemoattractants and adhesive molecules in the homing of EPCs.
Hydrodynamic properties of bovine cardiac troponin-I and troponin-T. (1983)

Bovine cardiac troponin-I (TN-I) and troponin-T (TN-T) have been examined in solution using ultracentrifugation, gel filtration, and viscosity. A new method of purifying TN-T, employing hydroxylapatite chromatography in 6 M urea, is reported. Cardiac TN-T (Mr = 36,000) undergoes a reversible, concentration-dependent association in nondenaturing buffers, probably to a tetramer. The Stokes radius (Rs) of aggregated TN-T, determined by sedimentation velocity and gel chromatography on Sephacryl S-300, is 80 A and the reduced viscosity of the subunit ranges from 20 to 25 ml/g at protein concentrations between 0.5 and 2.5 mg/ml. These data suggest that TN-T forms highly asymmetric aggregates in solution. Bovine cardiac TN-I also has a tendency toward self-association, but is essentially monomeric (Mr = 23,000) at protein concentrations below 1 mg/ml. The presence of reducing agent is necessary to avoid intermolecular disulfide bond formation. From gel filtration experiments, the value of Rs is 29 A indicating that TN-I is a moderately asymmetric protein (frictional ratio = 1.5). Similar properties are observed when both sulfhydryl groups of TN-I are modified by carboxamidomethylation.
Performance of a multiple-aperture optical system (1996)

Atmospheric turbulence causes intensity and phase disturbances on the wavefront of electromagnetic waves propagation through it that can seriously degrade the reliability of free- space optical communication links. This paper deals with the estimation of the statistics for power fades resulting from the combined effects of distortion of the receiving system instantaneous point-spread function and from the fluctuations of the collected power arising from wavefront intensity fluctuations. Fractal techniques are employed to simulate the turbulence-induced point-spread function distortions, while a log-normal model is assumed for the collected-power fluctuations. The reduction in the cumulative probability of losses due to these two effects through spatial diversity using a multiaperture receiver configuration is assessed.