gebhart/patrepeval huggingface dataset:
DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine. (1999)

Epidemiology studies have indicated that certain dietary components, including well-cooked meat, are risk determinants for colon cancer. Cooked meat can contain significant quantities of heterocyclic aromatic amines (HCAs), which have been established as carcinogens in laboratory animals. 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is usually the most mass-abundant HCA, with concentrations up to 480 ppb. We used accelerator mass spectrometry to establish whether DNA and protein adducts can be detected in humans exposed to a quantity of PhIP comparable with levels of exposure that occur in the diet. Five human volunteers were administered a dietary-relevant dose of [14C]PhIP (70-84 microg) 48-72 h before surgery for removal of colon tumors. Blood samples were collected at various time points, and albumin, hemoglobin, and WBC DNA were extracted for analysis by accelerator mass spectrometry. Tissue samples were collected during surgery and used to assess either tissue available doses of [14C]PhIP or adduct levels. The results of this study show: (a) PhIP is activated to a form that will bind to albumin, hemoglobin, and WBC DNA in peripheral blood. WBC DNA adducts were unstable and declined substantially over 24 h; (b) PhIP is bioavailable to the colon, with levels in normal tissue in the range 42-122 pg PhIP/g tissue; and (c) PhIP binds to both protein and DNA in the colon. DNA adduct levels in the normal tissue were 35-135 adducts/10(12) nucleotides, which was significantly lower than tumor tissue. The results of this study demonstrate that PhIP is bioavailable to the human colon following defined dietary-relevant doses and forms DNA and protein adducts.
Identification and Molecular Characterization of m3 Muscarinic Receptor Dimers (1999)

Several studies suggest, but do not prove directly, that muscarinic receptors may be able to form dimeric or oligomeric arrays. To address this issue in a more direct fashion, we designed a series of biochemical experiments using a modified version of the rat m3 muscarinic receptor (referred to as m3') as a model system. When membrane lysates prepared from m3' receptor-expressing COS-7 cells were subjected to Western blot analysis under non-reducing conditions, several immunoreactive species were observed corresponding in size to putative receptor monomers, dimers, and oligomers. However, under reducing conditions, the monomeric receptor species represented the only detectable immunoreactive protein, consistent with the presence of disulfide-linked m3 receptor complexes. Similar results were obtained when native m3 muscarinic receptors present in rat brain membranes were analyzed. Control experiments carried out in the presence of high concentrations of the SH group alkylating agent, N-ethylmaleimide, suggested that disulfide bond formation did not occur artifactually during the preparation of cell lysates. The formation of m3' receptor dimers/multimers was confirmed in coimmunoprecipitation studies using differentially epitope-tagged m3' receptor constructs. In addition, these studies showed that m3' receptors were also able to form non-covalently associated receptor dimers and that m3' receptor dimer formation was receptor subtype-specific. Immunological studies also demonstrated that m3' receptor dimers/multimers were abundantly expressed on the cell surface. Site-directed mutagenesis studies indicated that two conserved extracellular Cys residues (Cys-140 and Cys-220) play key roles in the formation of disulfide-linked m3' receptor dimers. These results provide the first direct evidence for the existence of muscarinic receptor dimers and highlight the specificity and molecular diversity of G protein-coupled receptor dimerization/oligomerization.
The function of the Periaxin gene during nerve repair in a model of CMT4F* (2002)

Mutations in the Periaxin (PRX) gene are known to cause autosomal recessive demyelinating Charcot-Marie-Tooth (CMT4F) and Dejerine-Sottas disease. The pathogenesis of these diseases is not fully understood. However, progress is being made by studying both the periaxin-null mouse, a mouse model of the disease, and the protein-protein interactions of periaxin. L-periaxin is a constituent of the dystroglycan-dystrophin-related protein-2 complex linking the Schwann cell cytoskeleton to the extracellular matrix. Although periaxin-null mice myelinate normally, they develop a demyelinating peripheral neuropathy later in life. This suggests that periaxin is required for the stable maintenance of a normal myelin sheath. We carried out sciatic nerve crushes in 6-week-old periaxin-null mice, and, 6 weeks later, found that although the number of myelinated axons had returned to normal, the axon diameters remained smaller than in the contralateral uncrushed nerve. Not only do periaxin-null mice have more hyper-myelinated axons than their wild-type counterparts but they also recapitulate this hypermyelination during regeneration. Therefore, periaxin-null mice can undergo peripheral nerve remyelination, but the regulation of peripheral myelin thickness is disrupted.
Towards automatic cell identification in DIC microscopy (1998)

A general method is proposed for constructing templates of cells in differential interference contrast (DIC) microscopy. This takes account of the optics which generate DIC images, and is applicable to both transparent and semi-transparent cells of simple and complex shapes. Then, a template matching methodology is presented, which uses fast Fourier transforms to fit templates of a range of sizes and orientations to images. For illustration, this is used to automatically identify and measure individual Candida yeast cells in clusters.
Effect of acute and chronic ascorbic acid on flow‐mediated dilatation with sedentary and physically active human ageing (2004)

Peripheral conduit artery flow-mediated dilatation decreases with ageing in humans. The underlying mechanisms and efficacy of preventive strategies are unknown. Brachial artery flow-mediated dilatation was determined at baseline and after ascorbic acid (vitamin C) intravenous infusion and chronic supplementation (500 mg day(-1) for 30 days) in three groups of healthy men: young sedentary (n= 11; 25 +/- 1 years, mean +/-s.e.m.), older sedentary (n= 9; 64 +/- 2), and older endurance-exercise trained (n= 9; 64 +/- 2). At baseline, flow-mediated dilatation (normalized for the hyperaemic stimulus) was approximately 45% lower in the older (0.015 +/- 0.001) versus young (0.028 +/- 0.004) sedentary men (P < 0.01), but was preserved in older exercising men (0.028 +/- 0.004). Ascorbic acid infusion increased plasma concentrations > 15-fold in all groups and restored flow-mediated dilatation in the sedentary older men (to 0.023 +/- 0.002; P > 0.1 versus other groups), with no effects in the other two groups. Oral ascorbic acid supplementation did not affect flow-mediated dilatation in any group. Brachial artery endothelium-independent dilatation (sublingual nitroglycerin) did not differ among the groups at baseline nor change with ascorbic acid administration. These results provide the first evidence for an important role of oxidative stress in both the impairment in peripheral conduit artery flow-mediated dilatation with sedentary human ageing and the preservation of flow-mediated dilatation with physically active ageing.
Intraoperative blood pressure and cerebral perfusion: strategies to clarify hemodynamic goals (2014)

Blood pressure can vary considerably during anesthesia. If blood pressure falls outside the limits of cerebrovascular autoregulation, children can become at risk of cerebral ischemic or hyperemic injury. However, the blood pressure limits of autoregulation are unclear in infants and children, and these limits can shift after brain injury. This article will review autoregulation, considerations for the hemodynamic management of children with brain injuries, and research on autoregulation monitoring techniques.
Prevalence of sexual dysfunction in women: Results of a survey study of 329 women in an outpatient gynecological clinic (1993)

Few studies have investigated the prevalence of sexual dysfunction in nonclinical samples. In the present study, a standardized sexual function questionnaire was administered to 329 healthy women, aged 18-73 years, all of whom were enrolled in a Women's Wellness Center. About two-thirds of the sample were married or living with a partner, and most women were employed outside of the home. A broad range of sexual behavior frequencies were observed, with 48.5% reporting at least weekly intercourse, compared to 28.4% who were not sexually active at the time of study. Among the most common sexual problems reported were anxiety or inhibition during sexual activity (38.1%), lack of sexual pleasure (16.3%), and difficulty in achieving orgasm (15.4%). Other common problems were lack of lubrication (13.6%) and painful intercourse (11.3%), each of which was significantly more prevalent in the postmenopausal group. Despite these difficulties, 68.6% of the sample rated their overall sexual relationship as satisfactory. Age and relationship status were significant predictors of sexual satisfaction, with older women and singles reporting a higher incidence of sexual problems. Educational level, religious affiliation, and employment status were not predictive of sexual dysfunction in the present study.
Olefin epoxidation by manganese (IV) porphyrins: evidence for two reaction pathways (1987)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTOlefin epoxidation by manganese (IV) porphyrins: evidence for two reaction pathwaysJohn T. Groves and Michael K. SternCite this: J. Am. Chem. Soc. 1987, 109, 12, 3812–3814Publication Date (Print):June 1, 1987Publication History Published online1 May 2002Published inissue 1 June 1987https://pubs.acs.org/doi/10.1021/ja00246a067https://doi.org/10.1021/ja00246a067research-articleACS PublicationsRequest reuse permissionsArticle Views1026Altmetric-Citations154LEARN 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
Estrogen receptor degradation: a CUE for endocrine resistance? (2011)

Despite the undoubted success of adjuvant endocrine therapies that target the estrogen receptor pathway, not all women with estrogen receptor-positive breast cancer respond to these therapies, and many who initially respond will subsequently relapse. Deregulation of various aspects of estrogen receptor signaling has been highlighted as a mechanism of resistance and as a basis for alternative therapeutic approaches. However, a recent publication refocuses attention on the estrogen receptor itself by showing that the ubiquitin-binding CUE domain-containing protein 2 is a regulator of estrogen receptor protein degradation and a marker of endocrine resistance in breast cancer.
Repercussões da Anemia Ferropriva na gestação (2010)

Este estudo e resultado de uma pesquisa bibliografica que objetivou revisar informacoes disponiveis na literatura acerca do papel do ferro durante a gestacao, enfatizando os agravos a saude da gestante e do bebe decorrentes de sua deficiencia. A anemia por carencia de ferro representa a deficiencia nutricional de maior prevalencia em todo o mundo, e e considerada um grave problema de saude publica. As gestantes e as criancas menores de dois anos sao os grupos biologicos mais vulneraveis, em funcao do aumento das necessidades desse mineral nessas fases da vida. As causas da anemia ferropriva estao relacionadas ao desequilibrio entre a absorcao e as necessidades orgânicas desse mineral, que podem ser decorrentes de varios outros fatores. Dentre os sinais clinicos mais frequentes estao palidez, fadiga, cansaco, deficiencia psicomotora, irritabilidade, entre outros. A anemia ferropriva durante a gestacao pode causar efeitos prejudiciais tanto para a mae como para o recem-nascido.
A Detector for a Chronic Implantable Atrial Tachyarrhythmia Monitor (2008)

Continuous long-term monitoring of atrial fibrillation (AF) and tachycardia (AT) is an unmet clinical need, which could be met with a chronically-implanted monitor. Improved therapeutic decisions based on accurate monitoring of parameters, such as daily AF/AT burden (hours/ day) may lead to improvements in clinical outcomes such as reduction in hospitalizations, symptoms, and strokes. This paper describes an AF/AT detector that detects AF as well as AT with an irregular ventricular response, and a supplementary AT detector for AT with more regular ventricular response. Seven databases with significant durations of AF, AT, and sinus rhythm were used to evaluate the performance of the detectors. All patient records with AF (N = 124) were detected by the AF/AT detector to have AF/AT burden with a mean, median, and 75 percentile of absolute error in burden detection of 8.8, 0, and 4 min, respectively. In patients having AF burden (= or > 10 min), the AF/AT detector was found to have burden accuracy within 20% of true burden in 96% of patients. The specificity was 94%, defined as follows: in patient records without AF/AT (N = 174), the percentage with AF/AT burden = or < 10 min in the 24-h recordings. The AF/AT detector underestimatesAT burden, thus degrading performance, in patients with significant amounts of AT with more regular ventricular response. The supplementary AT detector reduces the underestimation of AT while overestimating burden in patients without a significant amount of AT. The detectors described here could be implemented in an implantable monitor for accurate long-term AF/AT monitoring.
Targeted Quantum Dot Conjugates for siRNA Delivery (2007)

Treatment of human diseases such as cancer generally involves the sequential use of diagnostic tools and therapeutic modalities. Multifunctional platforms combining therapeutic and diagnostic imaging functions in a single vehicle promise to change this paradigm. in particular, nanoparticle-based multifunctional platforms offer the potential to improve the pharmacokinetics of drug formulations, while providing attachment sites for diagnostic imaging and disease targeting features. We have applied these principles to the delivery of small interfering RNA (siRNA) therapeutics, where systemic delivery is hampered by rapid excretion and nontargeted tissue distribution. Using a PEGlyated quantum dot (QD) core as a scaffold, siRNA and tumor-homing peptides (F3) were conjugated to functional groups on the particle's surface. We found that the homing peptide was required for targeted internalization by tumor cells, and that siRNA cargo could be coattached without affecting the function of the peptide. Using an EGFP model system, the role of conjugation chemistry was investigated, with siRNA attached to the particle by disulfide cross-linkers showing greater silencing efficiency than when attached by a nonreducible thioether linkage. Since each particle contains a limited number of attachment sites, we further explored the tradeoff between number of F3 peptides and the number of siRNA per particle, leading to an optimized formulation. Delivery of these F3/siRNA-QDs to EGFP-transfected HeLa cells and release from their endosomal entrapment led to significant knockdown of EGFP signal. By designing the siRNA sequence against a therapeutic target (e.g., oncogene) instead of EGFP, this technology may be ultimately adapted to simultaneously treat and image metastatic cancer.
Cytokine-Mediated Regulation of Human B Cell Differentiation into Ig-Secreting Cells: Predominant Role of IL-21 Produced by CXCR5+ T Follicular Helper Cells (2007)

Differentiation of B cells into Ig-secreting cells (ISC) is critical for the generation of protective humoral immune responses. Because of the important role played by secreted Ig in host protection against infection, it is necessary to identify molecules that control B cell differentiation. Recently, IL-21 was reported to generate ISC from activated human B cells. In this study, we examined the effects of IL-21 on the differentiation of all human mature B cell subsets--neonatal, transitional, naive, germinal center, IgM-memory, and isotype-switched memory cells--into ISC and compared its efficacy to that of IL-10, a well-known mediator of human B cell differentiation. IL-21 rapidly induced the generation of ISC and the secretion of vast quantities IgM, IgG and IgA from all of these B cell subsets. Its effect exceeded that of IL-10 by up to 100-fold, highlighting the potency of IL-21 as a B cell differentiation factor. Strikingly, IL-4 suppressed the stimulatory effects of IL-21 on naive B cells by reducing the expression of B-lymphocyte induced maturation protein-1 (Blimp-1). In contrast, memory B cells were resistant to the inhibitory effects of IL-4. Finally, the ability of human tonsillar CD4+CXCR5+CCR7- T follicular helper (TFH) cells, known to be a rich source of IL-21, to induce the differentiation of autologous B cells into ISC was mediated by the production of IL-21. These findings suggest that IL-21 produced by TFH cells during the primary as well as the subsequent responses to T cell-dependent Ag makes a major contribution to eliciting and maintaining long-lived humoral immunity.
Flexible Or Fixed: A Comparative Review Of Linear And Cyclic Cancer-Targeting Peptides (2012)

Peptides can serve as versatile cancer-targeting ligands and have been used for clinically relevant applications such as cancer imaging and therapy. A current and long-standing focus within peptide research is the creation of structurally constrained peptides generated through cyclization. Cyclization is envisioned to enhance the selective binding, uptake, potency and stability of linear precursors. This review compares closely related linear and cyclic peptides in these respects. Peptide cyclization generally improves the selective binding and stability of linear precursors; however, not all cyclization strategies and constrained geometries enhance these properties to the same extent. In some instances, linear analogues actually have better cancer-targeting properties compared with their cyclic counterparts. Although cyclization does not necessarily improve the cancer-targeting properties of linear analogues, cyclic peptides may obtain properties that allow them to be used for additional applications. This review aims to convey the advantages and limitations of cyclic cancer-targeting peptides.
EFFECT OF HEMORRHAGIC SHOCK ON ENDOTOXIN-INDUCING TNF PRODUCTION AND INTRA-TISSUE LIPOPOLYSACCHARIDE-BINDING PROTEIN mRNA EXPRESSION AND THEIR RELATIONSHIP (1997)

In order to further elucidate effect of hemorrhagic shock on endotoxin-inducing cytokine production, the present study was designed to investigate the production of tumor necrosis factor alpha (TNF alpha) induced by low-dose (1 microgram/kg) of lipopolysaccharide (LPS) and its cellular sources after hemorrhagic shock (HS) in rats. With combination of expression of lipopolysaccharide-binding protein (LBP) mRNA in the liver, lungs, and kidneys, we further analyzed a possible mechanism for increasing sensitivity to LPS by shock. We found in vivo that plasma TNF alpha levels in the HS + LPS group were 20-fold higher than those in the HS group (p < .01) and 2.7-fold higher than those in the LPS group (p < .05). It was shown in vitro that the capacity of the peripheral white blood cells to produce TNF alpha in response to LPS stimulation was significantly decreased by 126% (p < .01) and 57% (p < .05) compared with the pre-shock levels and sham group, respectively, at the end of resuscitation following shock, and still markedly inhibited 3 h after resuscitation, while the capacity of hepatic Kupffer's cells to produce TNF alpha was significantly increased by 110% compared with the sham group (p < .01) after shock and resuscitation. Results from RT-PCR showed that expression of LBP mRNA in the liver, lungs, and kidneys was increased after shock and resuscitation. It is suggested that hemorrhagic shock could significantly strengthen endotoxin to induce TNF alpha production, which might be due to up-regulation of LBP expression in tissues after shock, and the tissue macrophage population may be the main source for cytokine production in shock.
Self-assembly hollow nanosphere for enzyme encapsulation (2010)

This paper studies a kind of self-assembled hollow nanosphere for L-asparaginase encapsulation, and it was found that the hollow spheres not only enable a high loading of enzyme, but also show semi-permeability which could prevent the enzyme from leaving while allowing substrates and products to pass through to maintain the enzyme activity, and the encapsulated L-asparaginase showed significantly higher stability.
Improved generation of C57BL/6J mouse embryonic stem cells in a defined serum‐free media (2004)

C57BL/6 is a well-characterized mouse strain that is used extensively for immunological and neurological research. The establishment of C57BL/6 ES cell lines has facilitated the study of gene-altered mice in a pure genetic background-however, relatively few such lines exist. Using a defined media supplement, knockout serum replacement (KSR) with knockout DMEM (KSR-KDMEM), we find that we can readily establish ES cell lines from blastocysts of C57BL/6J mice. Six lines were established, all of which were karyotypically normal and could be maintained in the undifferentiated state on mouse embryonic fibroblast (MEF) feeders. One line was further tested and found to be karyotypically stable and germline competent, both prior to manipulation and after gene targeting. For this cell line, efficiencies of cell cloning and chimera generation were greater when maintained in KSR-KDMEM. Our work suggests that the use of defined serum-free media may facilitate the generation of ES cells from inbred mouse strains.