gebhart/patrepeval huggingface dataset:
Priming with recombinant influenza virus followed by administration of recombinant vaccinia virus induces CD8+ T-cell-mediated protective immunity against malaria. (1993)

Live vectors expressing foreign antigens have been used to induce immunity against several pathogens. However, for the virulent rodent malaria parasite Plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or Salmonella, expressing the circumsporozoite protein of this parasite, failed to induce protection. We generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of P. yoelii known to be recognized by CD8+ T cells and demonstrated that this vector induced class I major histocompatibility complex-restricted cytotoxic T cells against this foreign epitope. Immunization of mice with this recombinant influenza virus, followed by a recombinant vaccinia virus expressing the entire circumsporozoite protein, induced protective immunity against sporozoite-induced malaria. The sequence of immunization appears to be crucial, since a primer injection with recombinant vaccinia virus, followed by a booster injection with recombinant influenza virus, failed to induce protection. The protection induced by immunization with these recombinant viruses is mostly mediated by CD8+ T cells, as treatment of mice with anti-CD8 monoclonal antibody abolishes the anti-malarial immunity. The use of different live vectors for primer and booster injections has a synergistic effect on the immune response and might represent an effective general strategy for eliciting protective immune responses to key antigens of microbial pathogens.
High Levels of CXCL10 Are Produced by Intestinal Epithelial Cells in AIDS Patients with Active Cryptosporidiosis but Not after Reconstitution of Immunity (2006)

Chemokines play key roles in attracting immune cells to sites of infections. However, few data on chemokine expression in the gut during human infections are available. We examined expression of chemokines in intestinal tissues of AIDS patients during active Cryptosporidium infection and during resolution of such an infection. The chemokines and cytokines in cell lysates from jejunal biopsy tissues were assayed by a 22-multiplex bead immunoassay. CXCL10 (IP-10) and its receptor, CXCR3, in sections were studied by immunohistochemistry. In biopsies from AIDS patients with active cryptosporidiosis, four chemokines (CXCL10, CCL11 [eotaxin], CCL5 [RANTES], and CCL2 [monocyte chemoattractant protein 1]) and three cytokines (interleukin-1alpha [IL-1alpha], IL-10, and granulocyte colony-stimulating factor) were detected. The level of CXCL10 was significantly increased in AIDS patients with cryptosporidiosis compared to the level in AIDS patients without cryptosporidiosis or in normal volunteers (median in AIDS patients with cryptosporidiosis, 508 pg/mg protein, compared to 111 pg/mg and 72 pg/mg protein in AIDS patients without cryptosporidiosis and in normal volunteers, respectively [P < 0.05 and P < 0.005, respectively, as determined by a Mann-Whitney test]). The level of CXCL10 correlated with the parasite burden (as measured by the number of Cryptosporidium oocysts in the stools) and also with the IL-1alpha concentration (Pearson correlation values, 0.961 [P < 0.01] and 0.737 [P < 0.05]). As determined by immunohistochemistry, CXCL10 localized to epithelial cells at the site of infection. Following effective antiparasite and antiretroviral therapy, Cryptosporidium infections resolved, and the levels of CXCL10 decreased to normal levels. We hypothesized that CXCL10 plays an important role in the resolution of cryptosporidiosis by attracting immune effector cells to the site of infection. By contrast, in AIDS patients lacking effector cells, CXCL10 may contribute to the immunopathogenesis by recruiting inflammatory cells.
Patterned Surfaces Combining Polymer Brushes and Conducting Polymer via Colloidal Template Electropolymerization (2011)

A dual patterned conducting polymer array combined with polymer brushes has been fabricated using a facile and novel approach. The method involved a Langmuir-Blodgett-like deposition of latex microsphere particles, electropolymerization, and polymer brush synthesis into the inside cavities of the highly ordered macroporous polymer network. Detailed facts of importance to specialist readers are published as ”Supporting Information”. Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Reduction of LDL cholesterol by a monoclonal antibody to PCSK9 in rodents and nonhuman primates (2012)

Aim: PCSK9 regulates serum LDL cholesterol (LDL-C) by binding hepatic LDL receptor (LDLR) and targeting it to the lysosome for degradation. Fully human monoclonal antibodies were generated against PCSK9 to block its interaction with LDLR and decrease serum LDL-C. Materials & methods: A high affinity human monoclonal antibody, REGN727/SAR236553 (REGN727), was isolated using VelocImmune® technology and evaluated for effects in relevant animal models. Results: After 8 weeks on a high carbohydrate diet, humanized Pcsk9hum/hum mice had elevated serum PCSK9 and LDL-C levels. REGN727 effectively reduced LDL-C back to prediet levels. Administration of REGN727 to hyperlipidemic Pcsk9hum/humLdlr -/+ mice led to significantly reduced LDL‑C and increased hepatic LDLR levels. Furthermore, administration of a single intravenous dose of REGN727 to normal cynomolgus monkeys reduced serum LDL-C levels by up to 75% for >;20 days. Conclusion: Based on these preclinical findings, REGN727 may provide an effective treatment for hypercholesterolemia. Further clinical investigations are ongoing.
ClinVar: public archive of relationships among sequence variation and human phenotype (2013)

ClinVar (http://www.ncbi.nlm.nih.gov/clinvar/) provides a freely available archive of reports of relationships among medically important variants and phenotypes. ClinVar accessions submissions reporting human variation, interpretations of the relationship of that variation to human health and the evidence supporting each interpretation. The database is tightly coupled with dbSNP and dbVar, which maintain information about the location of variation on human assemblies. ClinVar is also based on the phenotypic descriptions maintained in MedGen (http://www.ncbi.nlm.nih.gov/medgen). Each ClinVar record represents the submitter, the variation and the phenotype, i.e. the unit that is assigned an accession of the format SCV000000000.0. The submitter can update the submission at any time, in which case a new version is assigned. To facilitate evaluation of the medical importance of each variant, ClinVar aggregates submissions with the same variation/phenotype combination, adds value from other NCBI databases, assigns a distinct accession of the format RCV000000000.0 and reports if there are conflicting clinical interpretations. Data in ClinVar are available in multiple formats, including html, download as XML, VCF or tab-delimited subsets. Data from ClinVar are provided as annotation tracks on genomic RefSeqs and are used in tools such as Variation Reporter (http://www.ncbi.nlm.nih.gov/variation/tools/reporter), which reports what is known about variation based on user-supplied locations.
Biosynthesis and in vivo localization of the decapentaplegic-Vg-related protein, DVR-6 (bone morphogenetic protein-6). (1993)

DVR-6 (BMP-6 or Vgr-1) is a member of the TGF-beta superfamily of polypeptide signaling molecules. In situ hybridization studies have previously shown that DVR-6 RNA is expressed in a variety of cell types in the mouse embryo, but no information has been available on protein localization and biosynthesis. We have produced a polyclonal antibody to the proregion of DVR-6 and used it to localize the protein in whole mount and sectioned embryonic, newborn, and adult mouse tissues. DVR-6 protein is expressed in the mouse nervous system beginning at 9.5 days postcoitum (d.p.c.) and continues through adulthood. A variety of epithelial tissues also produce DVR-6 protein, including the suprabasal layer of the skin, bronchiolar epithelium, and the cornea. Additionally, a stably transfected cell line, BMGE+H/D6c4, is used to study the biosynthesis of DVR-6 protein and evidence is presented for translational regulation of DVR-6 expression.
Chromosomal position of rearranging gene segments influences allelic exclusion in transgenic mice. (1992)

Formation of a complete immunoglobulin heavy-chain transcription unit involves the ordered rearrangement of variable (V), diversity (D), and joining (J) region gene segments. In antibody-producing cells, this process is regulated such that only one of two antibody genes is expressed. Experiments with transgenic mice suggest that this mechanism, known as allelic exclusion, is mediated through the membrane-bound form of the immunoglobulin heavy chain. However, in all transgenic lines produced to date exclusion of the endogenous genes by the transgene is incomplete. To characterize the molecular basis for this escape from regulation, we have examined the rearrangements of endogenous immunoglobulin heavy-chain genes. We find that a transgene that encodes the membrane-bound form of human IgM efficiently inhibits rearrangements of endogenous gene segments located at the 5' end of the heavy-chain locus. However, recombining elements found at the 3' end of the locus escape and continue to undergo recombination. A transgene that encodes the secreted form of the same immunoglobulin protein has no effect on recombination, regardless of position of the recombining segment in the chromosome. These results have important implications for our understanding of the control of allelic exclusion.
Cyclic Hydroxamic Acids Derived from Indole (1956)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCyclic Hydroxamic Acids Derived from IndoleWilliam B. Wright Jr. and Kenneth H. CollinsCite this: J. Am. Chem. Soc. 1956, 78, 1, 221–224Publication Date (Print):January 1, 1956Publication History Published online1 May 2002Published inissue 1 January 1956https://doi.org/10.1021/ja01582a061Request reuse permissionsArticle Views534Altmetric-Citations36LEARN 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 InReddit PDF (443 KB) Get e-Alertsclose Get e-Alerts
Silica Coated Paper Substrate for Paper-Spray Analysis of Therapeutic Drugs in Dried Blood Spots (2011)

Paper spray is a newly developed ambient ionization method that has been applied for direct qualitative and quantitative analysis of biological samples. The properties of the paper substrate and spray solution have a significant impact on the release of chemical compounds from complex sample matrices, the diffusion of the analytes through the substrate, and the formation of ions for mass spectrometry analysis. In this study, a commercially available silica-coated paper was explored in an attempt to improve the analysis of therapeutic drugs in dried blood spots (DBS). The dichloromethane/isopropanol solvent has been identified as an optimal spray solvent for the analysis. The comparison was made with paper spray using chromatography paper as substrate with methanol/water as solvent for the analysis of verapamil, citalopram, amitriptyline, lidocaine, and sunitinib in dried blood spots. It has been demonstrated that the efficiency of recovery of the analytes was notably improved with the silica coated paper and the limit of quantitation (LOQ) for the drug analysis was 0.1 ng mL(-1) using a commercial triple quadrupole mass spectrometer. The use of silica paper substrate also resulted in a sensitivity improvement of 5-50-fold in comparison with chromatography papers, including the Whatman ET31 paper used for blood cards. Analysis using a hand-held miniature mass spectrometer Mini 11 gave LOQs of 10-20 ng mL(-1) for the tested drugs, which is sufficient to cover the therapeutic ranges of these drugs.
Regulation of a Sesquiterpene Cyclase in Cellulase-Treated Tobacco Cell Suspension Cultures (1990)

The regulation of an elicitor-inducible sesquiterpene cyclase in tobacco (Nicotiana tabacum) cell suspension cultures was investigated. Sesquiterpene cyclase activity was absent from control cell cultures but induced to a maximum within 15 hours of cellulase addition to the cell cultures. The induction of the cyclase activity was correlated with an absolute amount of the cyclase protein as measured in immunoblots. Both the in vivo synthesis rate, measured as the incorporation of [(35)S]methionine by cell cultures into immunoprecipitable cyclase protein, and the cyclase mRNA translational activity, measured as the incorporation of [(35)S]methionine into immunoprecipitable cyclase protein synthesized by in vitro translation of isolated RNA, were maximal at that time when the increase in cyclase enzyme activity was maximal. Using thiouridine to selectively label and isolate de novo synthesized mRNA, the in vitro translation products encoded by the newly synthesized RNA from elicitor-treated, but not control, cell cultures contained immunoprecipitable cyclase protein. These results suggest that the induction of the sesquiterpene cyclase in elicitor-treated cell cultures is primarily regulated by transcriptional control of the cyclase gene.
Pharmacokinetics of RheothRx Injection in Healthy Male Volunteers (1997)

The objectives of this study were to evaluate the safety and tolerability of RheothRx (poloxamer 188) injection administered as an intravenous (i.v.) infusion to healthy male volunteers and to determine the pharmacokinetic profile of poloxamer 188. Thirty-six healthy male volunteers were enrolled in a randomized, double-blind, placebo-controlled, dose-escalation trial for RheothRx injection. The volunteers were randomized to three treatment groups (12 per treatment group, with eight receiving active therapy and four receiving placebo). In each treatment group, volunteers received RheothRx injection or placebo as an i.v. infusion on two occasions at least 3 weeks apart to make a total of six doses being studied (10, 30, and 45 mg/kg/h for 72 h, 60 mg/kg/h for 43.3 to 72 h, 60 and 90 mg/kg/h for 24 h). Serial plasma samples were collected during and up to 36 h after the end of the infusions; urine was collected over intervals from the start of the infusion until 36 h after the infusions were terminated. Plasma and urine samples were assayed for poloxamer 188 by gel-permeation chromatography. Pharmacokinetic parameter values were calculated by noncompartmental and compartmental methods. Poloxamer 188 was eliminated primarily by renal excretion. Estimates of clearance, elimination rate constant, and apparent volume of distribution at steady state values were independent of infusion rate. Poloxamer 188 displayed no apparent infusion rate dependence in its pharmacokinetics.
Evidence for a Role of Basic Fibroblast Growth Factor in Rat Embryonic Growth and Differentiation* (1988)

The possibility that basic fibroblast growth factor (FGF) plays a role in the regulation of mammalian embryogenesis was investigated. When transplanted under the renal capsule of syngeneic juvenile hosts, 10-day-old rat embryos grow rapidly, and tissue differentiation occurs in an essentially normal manner. Infusion of antiserum to bovine FGF into the renal artery of kidneys bearing such transplants significantly retarded their growth, and differentiation of all tissues of endodermal and some of those of mesodermal origin was completely suppressed; differentiation of other tissues of mesodermal origin was partially inhibited. Infusion of nonimmune serum had no such effects. Infusion of recombinant bovine FGF into the renal artery stimulated growth of embryo transplants on the infused kidney, but not of those under the renal capsule of the contralateral kidney, and it did not affect growth of the infused kidney itself. These results suggest that FGF may be important for growth and differentiation of endodermal and some mesodermal tissues of mammalian embryos.
IP-10/CXCL10 and MIG/CXCL9 as novel markers for the diagnosis of lymphoma-associated hemophagocytic syndrome (2013)

Lymphoma-associated hemophagocytic syndrome (LAHS) is a serious disorder, and its early diagnosis and treatment with appropriate chemotherapy are very important. However, reliable markers for early diagnosis of LAHS have not been identified. We screened serum cytokines using a newly introduced assay system, cytometric bead array (CBA), and identified interferon-inducible protein 10 (IP-10)/CXCL10 and monokine induced by interferon gamma (MIG)/CXCL9 as useful markers. Serum concentrations of IP-10 and MIG at the time of LAHS diagnosis were greater than 500 and 5,000 pg/ml, respectively. The sensitivity and specificity for LAHS diagnosis were 100 and 95 %, respectively, when we set the above values as the cut-off levels. Serum levels of these two chemokines were already elevated at the time of admission and significantly decreased after successful treatment, indicating their usefulness for both the diagnosis and therapeutic outcomes for LAHS. IP-10 and MIG were also useful in distinguishing severe from moderate/mild LAHS, and B-cell-type LAHS from T-cell/natural killer cell-type LAHS. Furthermore, IP-10 and MIG were of use to distinguish LAHS from sepsis in patients with hematologic malignancies. Rapid measurement of IP-10 and MIG by CBA appeared to be important for early diagnosis and treatment of LAHS.
Plasma Melatonin Levels and Nocturnal Transitions between Sleep and Wakefulness (1982)

During night (11 p.m.-7a.m.) blood was sampled in darkness via an indwelling intravenous catheter simultaneously with polygraphic sleep registration in 7 normal men. The nocturnal melatonin secretion patterns exhibited secretory episodes. Spontaneous waking episodes were shown to be significantly correlated to the occurrence of melatonin peaks (chi c2 = 9.0, p less than 0.005 Melatonin nadirs were significantly associated with rapid eye movement periods (chi c2 = 12.8, P less than 0.005) but not with other sheep stages evaluated by standard criteria. It is hypothesized that melatonin secreted in connection with arousals during night may in turn act to restore sleep in humans.
Application of data compression to a large bibliographic data base (1981)

Background: Several criteria are described in the literature to diagnose a submucous cleft palate. Commonly the differences in the extent of the submucous cleft will not be as overt as in open clefts. Nevertheless, complete submucous cleft palate may cause imperfect palato-pharyngeal closure so that the affected person needs to undergo speech training and surgical treatment. Patients: We investigated 30 patients who underwent palatal repair to correct this disorder. They were evaluated according to the Koch's documentation system. Results: In all patients an additional malformation of the inner nose was found: The vomer was not fused with the palatal shelves. There were with different degrees of severity of this malformation and they were not necessarily correlated with the extent of the palatal cleft. Conclusion: In our opinion, this malformation of the vomer should be seen as a typical symptom of classical submucous cleft palate. Discussion is needed on how the vomerine malformation should be incorporated into the surgical procedure. Since we know from septal surgery that a basal septal perforation will lead to disturbances of nasal breathing. Copyright 2001 European Association for Cranio-Maxillofacial Surgery.
A new pulsatile total artificial heart using a single centrifugal pump. (1992)

A new pulsatile total artificial heart (TAH) system, combining a single centrifugal pump (CFP) with two three-way valves, was developed. One port of each three-way valve was connected to the inlet and outlet of a CFP, respectively. The other two ports of each valve ware connected to the right and left atrium, pulmonary artery, and aorta. The CFP can perfuse the pulmonary and systemic circulation alternately with pulsatile flow. A prototype system composed of a Sarns' CFP and solenoid valves was connected to a mock circulatory system resulting in 1) a pulsatile TAH that could be produced with a single CFP, 2) 5 L/min of pulsatile output with a normal flow wave form that can be obtained alternately on the right and left side by switching the solenoid valves, and 3) flow balance between the left and the right that could be controlled easily by the length of switching duration. This new system could be miniaturized and is feasible for a totally implantable TAH.
Epidemiology of clinically diagnosed Alzheimer's disease (1986)

This report reviews the current status of descriptive and analytic epidemiology of clinically diagnosed Alzheimer's disease (AD). Since AD can be diagnosed with certainty only at autopsy, currently available epidemiological data are based on a presumed clinical diagnosis. Current data indicate that AD represents a major health problem, at least in the developed countries. The prevalence ratio for AD ranges between 1.9 and 5.8 cases per 100 population aged 65 and over. Moreover, its prevalence is likely to increase in the next twenty years as a consequence of current demographic trends. The prevalence ratio for AD increases steeply with age and is higher in females. Incidence rates show a similar pattern, suggesting that AD should not be subdivided in a presenile and a senile form based on age of onset alone. Annual incidence rates of 2.4 cases per 100,000 population between ages 40 and 60, and 127 cases per 100,000 population after age 60 have been reported. Several case-control studies show that the occurrence of either dementia or Down's syndrome in other family members, advanced age of the mother at subject's birth, and head injury are possible risk factors.