gebhart/patrepeval huggingface dataset:
Indirect Cytotoxicity of Flucloxacillin toward Human Biliary Epithelium via Metabolite Formation in Hepatocytes (2001)

Flucloxacillin, an isoxazolyl-penicillin, causes cholestasis and biliary epithelium injury. The aim of the study was to determine whether flucloxacillin, either directly or through metabolite formation, may induce cytotoxicity in hepatic or biliary cells. Cytotoxicity was assessed by lactate dehydrogenase release in primary cultures of human hepatocytes and of gallbladder-derived biliary epithelial cells (BEC). Metabolite production in microsome and cell preparations was analyzed by chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry. While flucloxacillin induced no direct cytotoxicity in any of the hepatocyte (n = 12) and BEC (n = 19) preparations, the conditioned media from cultured hepatocytes preincubated with flucloxacillin (50-500 mg/L) triggered a significant increase in lactate dehydrogenase release over controls in approximately 50% of BEC preparations (7/12), and this effect depended upon flucloxacillin concentration. Remaining BEC preparations exhibited no toxic response. Cytotoxicity in BEC preparations (9/13) was also induced by the supernatants of human liver microsomes and of recombinant human cytochrome P450 (CYP)3A4 preincubated with flucloxacillin (500 mg/L). Supernatants from both liver microsome and CYP3A4 preparations contained one major metabolite which was identified as 5'-hydroxymethylflucloxacillin. The production of this metabolite was inhibited following CYP3A4 inhibition by troleandomycin in human liver microsomes, and markedly enhanced following CYP3A induction by dexamethasone in rat liver microsomes. As opposed to BEC, cultured hepatocytes displayed significant CYP3A activity and produced low amounts of this metabolite. The purified metabolite (0.01-5 mg/L) exerted toxic effects in BEC but not in hepatocytes. In conclusion, hepatocytes mainly via CYP3A4 activity, generate flucloxacillin metabolite(s) including 5'-hydroxymethylflucloxacillin that may induce cytotoxicity in susceptible BEC. These metabolic events may contribute to the pathogenesis of drug-induced cholangiopathies.
Increased Soluble Form of P-Selectin in Patients With Unstable Angina (1995)

Plasma P-selectin levels after angina increased significantly in patients with unstable angina but did not in patients with stable effort angina. These findings may contribute to understanding of the pathophysiology of the acute coronary syndrome of unstable angina.
Continuous proliferation of murine antigen-specific helper T lymphocytes in culture. (1979)

Murine helper T cells activated to sheep or horse erythrocyte antigens in vivo have been established as continuous cell lines in culture. T cells require the presence of a T-cell growth factor (TCGF) for continuous proliferation. TCGF purified from murine, rat, or human sources all stimulate murine T-cell growth. The T-cell mitogens concanavalin A and phytohemagglutinin do not stimulate cell proliferation in continuous T-cell lines. All cells that grow in the presence of TCGF express Thy-1 antigens. Helper activity of T-cell lines is both antigen specific and effective for syngeneic or F1 B cells. Supernates from T-cell lines do not contain antigen-specific or nonspecific helper factors. Although several T-cell lines have shown stable helper activity for greater than 50 wk in culture, other cell lines have shown a gradual decline in effector function. The procedure used to establish and maintain proliferation of T cells in culture should be suitable for the selection and growth of antigen-specific effector T cells from each subclass.
Epratuzumab, a Humanized Anti-CD22 Antibody, in Aggressive Non-Hodgkin’s Lymphoma (2004)

These data demonstrate that epratuzumab has a good safety profile and exerts antitumor activity in aggressive non-Hodgkin's lymphoma at doses of > or =240 mg/m2, thus warranting further evaluation in this clinical setting.
Correlating animal and human phase Ia/Ib clinical data with CALAA-01, a targeted, polymer-based nanoparticle containing siRNA (2014)

Nanoparticle-based experimental therapeutics are currently being investigated in numerous human clinical trials. CALAA-01 is a targeted, polymer-based nanoparticle containing small interfering RNA (siRNA) and, to our knowledge, was the first RNA interference (RNAi)-based, experimental therapeutic to be administered to cancer patients. Here, we report the results from the initial phase I clinical trial where 24 patients with different cancers were treated with CALAA-01 and compare those results to data obtained from multispecies animal studies to provide a detailed example of translating this class of nanoparticles from animals to humans. The pharmacokinetics of CALAA-01 in mice, rats, monkeys, and humans show fast elimination and reveal that the maximum concentration obtained in the blood after i.v. administration correlates with body weight across all species. The safety profile of CALAA-01 in animals is similarly obtained in humans except that animal kidney toxicities are not observed in humans; this could be due to the use of a predosing hydration protocol used in the clinic. Taken in total, the animal models do appear to predict the behavior of CALAA-01 in humans.
Flexible, All-Organic Chemiresistor for Detecting Chemically Aggressive Vapors (2012)

Chemiresistors made of thin films of single-walled carbon nanotube (CNT) bundles on cellulosics (paper and cloth) can detect aggressive oxidizing vapors such as nitrogen dioxide and chlorine at 250 and 500 ppb, respectively, at room temperature in ambient air without the aid of a vapor concentrator. Inkjet-printed films of CNTs on 100% acid-free paper are significantly more robust than dip-coated films on plastic substrates. Performance attributes include low sensor-to-sensor variation, spontaneous signal recovery, negligible baseline drift, and the ability to bend the sensors to a crease without loss of sensor performance.
Poly(Amidoamine) Dendrimer-Templated Nanocomposites. 1. Synthesis of Zerovalent Copper Nanoclusters (1998)

ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTPoly(Amidoamine) Dendrimer-Templated Nanocomposites. 1. Synthesis of Zerovalent Copper NanoclustersLajos Balogh and Donald A. TomaliaView Author Information Michigan Molecular Institute, 1910 W. St. Andrews Road Midland, Michigan 48640 Cite this: J. Am. Chem. Soc. 1998, 120, 29, 7355–7356Publication Date (Web):July 9, 1998Publication History Received16 March 1998Published online9 July 1998Published inissue 1 July 1998https://pubs.acs.org/doi/10.1021/ja980861whttps://doi.org/10.1021/ja980861wrapid-communicationACS PublicationsCopyright © 1998 American Chemical SocietyRequest reuse permissionsArticle Views3874Altmetric-Citations640LEARN 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-AlertscloseSupporting Info (1)»Supporting Information Supporting Information SUBJECTS:Copper,Dendrons,Metals,Nanocomposites,Solution chemistry Get e-Alerts
Interaction of human thyroid hormone receptor beta with transcription factor TFIIB may mediate target gene derepression and activation by thyroid hormone. (1993)

The human thyroid hormone receptor beta (hTR beta) is capable of both transcriptional silencing and hormone-dependent activation. However, the detailed mechanism of this transcriptional regulation remains to be elucidated. One possibility is that hTR beta interacts directly with factors of the basal transcriptional machinery, thereby modulating basal promoter activity in a direct manner, as has been shown for other transcription factors. Here, we show that hTR beta interacts specifically with the human basal transcription factor TFIIB. Deletion analysis revealed two contact sites in the receptor: one is located in the N terminus, while the other is part of the ligand-binding domain (LBD) and is located at the C terminus. Interestingly, each receptor contact site interacts with different sites in TFIIB. Cotransfection experiments revealed that, when fused to the DNA-binding domain of yeast transcription factor GAL4, the C-terminal interaction site of hTR beta was transcriptionally inactive; however, when it was cotransfected with the remaining part of the LBD on a separate molecule, silencing function was restored. In agreement with that, we show that thyroid hormone is able to significantly decrease the interaction of its receptor LBD with TFIIB. Our data suggest that hTR beta acts as a transcriptional silencer by interacting with TFIIB and that thyroid hormone may act in part by preventing transcriptional repression at this level.
Autonomic Influences in Atrial Tachyarrhythmias (1996)

The electrophysiologic characteristics of atrial cells (action potential duration and refractoriness, conduction speed) are modulated differently by vagal and sympathetic influences. The former tend to favor macroreentry phenomena, whereas the latter favor abnormal automaticity and triggered activity. In normal hearts, vagal influences are predominant, thus explaining why the clinical pattern of vagally mediated paroxysmal atrial fibrillation is preferentially observed in the absence of detectable heart disease, in young male adults, with an ECG pattern of common flutter alternating with fibrillation. Sympathetically mediated atrial fibrillation is observed in the presence of any heart disease, the first effect of which is to provoke a vagal withdrawal. The clinical history is a reliable guide for determining which type of physiologic autonomic predominance contributes to destabilization of the arrhythmogenic substrate, but observing the behavior of sinus rate variability just preceding the onset of the arrhythmia only permits documentation of the mechanism. The role of autonomic influences should be taken into consideration every time conventional antiarrhythmic treatment is insufficient. Beta blockers as well as digitalis may be either beneficial or detrimental, depending on the causal mechanism, so the choice of their use as a single or a combined therapy should be appropriate.
Direct methods for transient stability analysis of power systems: Recent results (1985)

Transient stability analysis of a power system is concerned with the system's ability to remain in synchronism following a disturbance. In utility planning, transient stability is studied by numerical simulation. The long CPU run times for simulation preclude their use for on-line security analysis. Interest has therefore shifted toward the Lyapunov direct method of stability analysis. This paper provides a critical review of research on direct methods since 1970. Considerable progress has been made on both theoretical properties of energy functions and on criteria suitable for on-line implementation. Current theory provides a satisfactory treatment of voltage-dependent reactive power demand, transfer conductances, and flux decay. However, it cannot incorporate the exciter control Proposed on-line criteria appear to work very well on sample examples; but, they still lack rigorous justification. Finally, recent work has shown that power systems can exhibit chaotic behavior. This surprising fact demonstrates that our understanding of the dynamics of power systems remains incomplete.
Inflammatory bowel disease and irritable bowel syndrome (2003)

Both irritable bowel syndrome and inflammatory bowel diseases share symptoms of altered bowel habits associated with abdominal pain or discomfort. Irritable bowel syndrome has been referred to as a functional bowel disorder, which is diagnosed by a characteristic cluster of symptoms in the absence of detectable structural abnormalities. Inflammatory bowel disease is a heterogeneous group of disorders characterized by various forms of chronic mucosal and/or transmural inflammation of the intestine. In this review, the authors discuss recent evidence suggesting several potential mechanisms that might play a pathophysiologic role in both syndromes. Possible shared pathophysiologic mechanisms include altered mucosal permeability, an altered interaction of luminal flora with the mucosal immune system, persistent mucosal immune activation, alterations in gut motility, and a role of severe, sustained life stressors in symptom modulation. It is proposed that similarities and differences between the two syndromes can best be addressed within the framework of interactions between the central nervous system and the gut immune system. Based on recent reports of low-grade mucosal inflammation in subpopulations of patients meeting current diagnostic criteria for irritable bowel syndrome, therapeutic approaches shown to be effective in inflammatory bowel disease, such as probiotics, antibiotics, and antiinflammatory agents, have been suggested as possible therapies for certain patients with irritable bowel syndrome.
Non-Random Chromosomal Rearrangements and Their Implications in Clinical Features and Outcome of Multiple Myeloma and Plasma Cell Leukemia (1996)

Rearrangements of bands 14q32.3 and 19p13.3 and preferential deletion of the short arm of chromosome 1 were nonrandom chromosomal abnormalities in MM and PCL, warranting further investigation at the molecular level. From the viewpoint of clinical relevance, chromosome 14q32 translocation seems to be associated with leukemic manifestation, level of LDH, and shorter survival period from the time of chromosomal analysis. However, these results were obtained from patients with advanced disease, most of whom had already been treated with alkylating agents prior to cytogenetic analysis. To investigate the karyotypes of MM in the early stage and to determine correlations with clinical features, non-dividing cells should be analyzed. For this purpose, interphase FISH and/or comparative genomic hybridization are promising procedures to detect genomic alterations in early multiple myeloma.
Synthesis of C-glycosyl compounds. Part 1. Reaction of ethyl isocyanoacetate with 2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone (1977)

Formylaminomethylenation of 2,3:5,6-di-O-isopropylidene-D-mannono-1,4-lactone (1) with ethyl isocyanoacetate (2) gave, as the major product, (E)-ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-D-manno-oct-2-enonate (3)(58%), which on hydrogenation gave ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-D-erythro-L-gluco-octonate (17), in almost quantitative yield. Base-catalysed equilibration of the D-erythro-L-gluco-octonate (17) gave a mixture of the L-allo-, L-altro-, L-gluco-, and L-manno-epimers [(23), (22), (17), and (19), respectively]. The configurations at C-2 and C-3 of these epimers were established by chemical and physical methods.The D-erythro-L-gluco-epimer (17) and the D-erythro-L-manno-epimer (19) were degraded to ethyl 3,6-anhydro-2-deoxy-2-formylamino-4,5-O-isopropylidene-D-glycero-L-gluco-heptonate (37) and its D-glycero-L-manno-epimer (39), respectively. Acidic hydrolysis of compounds (17), (19), (37), and (39) gave the free amino-acids, L-2-(β-D-mannofuranosyl)-glycine (41), the analogous D-amino-acid (42), L-2-(β-D-lyxofuranosyl)-glycine (43), and the analogous D-amino-acid (44), in moderate yields.In the presence of base, alcohols and thiols readily attacked the double bond of the oct-2-enonate (3) to give, for example, ethyl (ethyl 2-deoxy-2-formylamino-4,5:7,8-di-O-isopropylidene-α-D-manno-D-glycero-oct-3-ulo-3,6-furanosid)onate and its D-manno-L-glycero-epimer [(9) and (10)].
FHIT gene alterations in head and neck squamous cell carcinomas. (1996)

To determine whether the FHIT gene at 3p14.2 is altered in head and neck squamous cell carcinomas (HNSCC), we examined 26 HNSCC cell lines for deletions within the FHIT locus by Southern analysis, for allelic losses of specific exons FHIT by fluorescence in situ hybridization (FISH) and for integrity of FHIT transcripts. Three cell lines exhibited homozygous deletions within the FHIT gene, 55% (15/25) showed the presence of aberrant transcripts, and 65% (13/20) showed the presence of multiple cell populations with losses of different portions of FHIT alleles by FISH of FHIT genomic clones to interphase nuclei. When the data obtained by FISH and by reverse transcriptase-PCR analyses are combined, 22 of 26 cell lines showed alterations of at least one allele of the FHIT gene. Our data indicate that the FHIT gene is disrupted in HNSCCs and hence, loss of FHIT function may be important in the development and/or progression of head and neck cancers.
Mammalian interspecies substitution of immune modulatory alleles by genome editing (2016)

We describe a fundamentally novel feat of animal genetic engineering: the precise and efficient substitution of an agronomic haplotype into a domesticated species. Zinc finger nuclease in-embryo editing of the RELA locus generated live born domestic pigs with the warthog RELA orthologue, associated with resilience to African Swine Fever. The ability to efficiently achieve interspecies allele introgression in one generation opens unprecedented opportunities for agriculture and basic research.
Electrostatic Control of Ions and Molecules in Nanofluidic Transistors (2005)

We report a nanofluidic transistor based on a metal-oxide-solution (MOSol) system that is similar to a metal-oxide-semiconductor field-effect transistor (MOSFET). Using a combination of fluorescence and electrical measurements, we demonstrate that gate voltage modulates the concentration of ions and molecules in the channel and controls the ionic conductance. Our results illustrate the efficacy of field-effect control in nanofluidics, which could have broad implications on integrated nanofluidic circuits for manipulation of ions and biomolecules in sub-femtoliter volumes.
O2‐03‐01: TOMM40, APOE and preclinical memory decline (2011)

TOMM40 encodes the translocase of the outer mitochondrial membrane pore subunit, and is in linkage disequilibrium with apolipoprotein E (APOE). APOEe4 is linked to long (L) poly-T variants within intron 6 of TOMM40 while APOEe3 can be associated with either with a short (S) or L variant (that is generally very long [VL], or more than 30 T residues). TOMM40 has been proposed to interact or even underlie the APOEe4 effect on risk and age of onset of Alzheimer's disease (AD) (Roses et al, 2009), and this has been supported by several small cohorts to date. We now compare the effects of TOMM40 and APOE genotype on preclinical longitudinal memory decline. Since 1994, we have been enrolling cognitively normal individuals in a prospective cognitive aging study and have shown memory declines preclinically in APOEe4 carriers beginning around ages 55-60 years. TOMM40 genotyping was completed in 639 members of this cohort. Poly-T lengths for each chromosome were converted to genotypes using the following standards: S (14-20 T residues) and L (>21 T residues, and including VL). We estimated the longitudinal effect of age on memory using statistical models that simultaneously modeled cross sectional and longitudinal effects of age on the auditory verbal learning test long term memory score (AVLT) by APOE, TOMM40, and the interaction between the two. Mean age (58.2 years), education (15.6 years), gender (69.6% women), and follow-up duration (6.1 years) did not differ between LL (n = 250), SL (n = 301), and SS (n = 88) participants. Controlling for TOMM40, APOE e4 significantly influenced memory decline velocity (p = .04) and acceleration (p = .008); controlling for APOEe4, TOMM40 LL genotype also significantly influenced memory decline velocity (p = .04) and acceleration (p = .04). There was no significant interaction between APOE and TOMM40 (p = .48). Visual inspection of the graphs suggested that TOMM40 LL may exert an early effect reflected in blunted test-retest improvement while APOEe4 may exert a more delayed “toxic” effect resulting in accelerated decline of previously attained memory skills. Both TOMM40 and APOE significantly influence age-related memory decline, and appear to do so independently of each other.
Effect of Recombinant Human Bone Morphogenetic Protein‐4 with Carriers in Rat Calvarial Defects (2003)

Surgical implantation of rhBMP-4/ACS may be used to support bone regeneration in the rat calvarial critical-sized defect, and rhBMP-4/beta-TCP may be able to regenerate bone in the rat calvarial critical-sized defect without complication. In addition, both ACS and beta-TCP may be considered as available carriers for rhBMP-4.
Systematic Analysis of Repeated Gene Delivery into Animal Lungs with a Recombinant Adenovirus Vector (1996)

Adenovirus-based vectors are promising candidates for genetic therapy of cystic fibrosis (CF). Because adenoviruses naturally infect airway cells, they grow to very high titers, and the transgenes carried by the adenoviruses are expressed at high levels. In addition, adenoviruses are relatively safe because the disease caused by the wild-type virus is self-limiting. One disadvantage of adenovirual vectors is that the transgene expression would be transient because adenoviruses do not integrate their DNA into the genome of the host cells. Adenoviral gene delivery into the lungs is also complicated by the anatomy of the airways and the defense mechanisms of the recipient. To assess the feasibility of adenovirus-mediated gene therapy for CF, a recombinant adenovirus carrying a lacZ gene was delivered into animal lungs to study the efficiency and cellular distribution of gene transfer, the duration of gene expression, the possible histopathology of the lungs after gene transfer, and the efficacy of repeated administrations of the viral agent. The results of these studies demonstrate that (i) efficient gene transfer into animal lungs can be achieved; (ii) a near-homogenous delivery of the vectors can be achieved by airway instillation, although the pattern of transduction varies among individual animals; (iii) pathological effects are generally mild in CD1 mice; (iv) gene expression is transient; (v) repetitive gene transfer is achievable, but becomes progressively less efficient, and (vi) immune responses are induced against both the viral and transgene products.