gebhart/patrepeval huggingface dataset:
Comparison of nested PCR with immunofluorescent-antibody assay for detection of Ehrlichia canis infection in dogs treated with doxycycline (1997)

A partial 16S rRNA gene was amplified in Ehrlichia canis-infected cells by nested PCR. The assay was specific and did not amplify the closely related Ehrlichia chaffeensis, Ehrlichia muris, Neorickettsia helminthoeca, and SF agent 16S rRNA genes. The assay was as sensitive as Southern hybridization, detecting as little as 0.2 pg of E. canis DNA. By this method, all blood samples from four dogs experimentally infected with E. canis were positive as early as day 4 postinoculation, which was before or at the time of seroconversion. One hundred five blood samples from dogs from Arizona and Texas (areas of E. canis endemicity) and 30 blood samples from dogs from Ohio (area of E. canis nonendemicity) were examined by nested PCR and immunofluorescent-antibody (IFA) test. Approximately 84% of dogs from Arizona and Texas had been treated with doxycycline before submission of blood specimens. Among Arizona and Texas specimens, 46 samples were PCR positive (44%) and 80 were IFA positive (76%). Forty-three of 80 IFA-positive samples (54%) were PCR positive, and 22 of 25 IFA-negative samples (88%) were negative in the nested PCR. None of the Ohio specimens were IFA positive, but 5 specimens were PCR positive (17%). Our results indicate that the nested PCR is highly sensitive and specific for detection of E. canis and may be more useful in assessing the clearance of the organisms after antibiotic therapy than IFA, especially in areas in which E. canis is endemic.
The health of our children continues to improve--but... (a litany of change--Part III). (1996)

The National Center for Health Statistics supplies extensive and detailed survey results that support the general underlying perspective of an improving trend in the health status of children in the United States. Included in the survey were 47,000 households with more than 17,000 children, less than eighteen years of age. Nevertheless, there were several negative trends in children's health and safety in the 1980s. The negative trends included (1) failure to maintain the level of women getting prenatal care set in the 1970s; (2) the infant mortality rate in 1990 of 9.2 per 1000 of live births is higher than that in twenty-three industrialized countries; (3) injuries have emerged as the major cause of childhood mortality, morbidity, and disability; (4) disparities along racial and income-related lines continue at a serious level. The author also discusses the dental needs of children and the use of dental services.
Molecular Cloning, Expression, and Enzymatic Characterization of Rabbit Hydroxysteroid Sulfotransferase AST-RB2 (ST2A8) (1998)

Cytosolic sulfotransferases, which consist of at least three gene families, play a major role in activation and detoxification of both endogenous and exogenous chemicals. We recently purified a rabbit sulfotransferase, AST-RB2, showing high activities to both hydroxysteroids and amines. To characterize this enzyme, a rabbit cDNA library was screened using anti-AST-RB2 antibodies. The isolated cDNA was judged to encode AST-RB2 (ST2A8) based on the amino acid sequences of peptide fragments obtained from purified AST-RB2. The cDNA showed high similarity to other mammalian hydroxysteroid sulfotransferases (ST2) at the amino acid level (58-68%), but low similarity to aryl sulfotransferases (ST1) (less than 37%). The protein expressed in Escherichia coli catalyzed sulfation of typical ST2 substrates. Therefore, ST2A8 was judged to belong to the ST2 family from both its primary structure and substrate specificity. The ST2A8 protein expressed in E. coli clearly differed from rat ST2A1 and ST2A2 on its localization (cytosol/insoluble fraction ratio). ST2A8 had no activity to lithocholate, but showed the highest catalysis on dehydroepiandrosterone and testosterone among the four forms (ST2A1, ST2A2, ST2A3, and ST2A8), indicating a clear difference between ST2A forms in substrate specificity to endogenous chemicals.
Deacetylase Activity Associates with Topoisomerase II and Is Necessary for Etoposide-induced Apoptosis (2001)

DNA topoisomerase II (topo II) is a ubiquitous nuclear enzyme that is involved in DNA replication, transcription, chromosome segregation, and apoptosis. Here we show by immunoprecipitation, pull down with glutathione S-transferase fusion proteins, and yeast two-hybrid analysis that both topo IIalpha and -beta physically interact with the histone deacetylase HDAC1. The in vitro DNA decatenation activity of recombinant topo IIalpha and -beta is inhibited by association with catalytically inactive, recombinant HDAC1. We provide evidence for the in vivo significance of the topo II-HDAC1 association, showing that inhibition of HDAC activity with trichostatin A suppresses apoptosis induced by the topo II poison etoposide, but not by the topoisomerase I inhibitor camptothecin. We suggest that chromatin remodeling by an HDAC-containing complex facilitates both topo II-catalyzed DNA rearrangement and etoposide-induced DNA damage in vivo.
Absence of enhanced systemic inflammatory response at 18 weeks of gestation in women with subsequent pre‐eclampsia (2002)

In contrast to findings from women with overt pre-eclampsia, the present study indicates that there are no indications of intensified systemic inflammatory response at 18 weeks of gestation in women who later develop pre-eclampsia.
Dipyridamole dilates large coronary arteries in conscious dogs. (1983)

The effects of 0.25 mg/kg dipyridamole on left ventricular (LV) pressures, LV dP/dt, heart rate, aortic pressures, left circumflex coronary blood flow, and left circumflex coronary arterial diameters and on calculations of late diastolic coronary resistance and large coronary cross-sectional area were studied in 15 conscious dogs. Injection of dipyridamole, a drug that has a mechanism of action dependent on myocardial adenosine production, caused sustained increases in mean coronary blood flow (244 +/- 28%), large coronary arterial cross-sectional area (28 +/- 3.2%), heart rate (32 +/- 3.6%), and LV dP/dt (23 +/- 3.0%) and reductions in late diastolic coronary resistance (73 +/- 2.4%) and mean arterial pressure (14 +/- 1.9%). Neither beta-adrenergic-receptor blockade alone nor in conjunction with constant heart rate affected the dilation of large coronary arteries to dipyridamole significantly. Ganglionic blockade with hexamethonium also had little effect on the response of large and small coronary vessels to dipyridamole. Surprisingly neither beta-adrenergic-receptor nor ganglionic blockade abolished the rise in LV dP/dt observed after dipyridamole. Aminophylline, however, effectively eliminated the dilation of large coronary arteries and resistance coronary vessels in response to dipyridamole. In summary, as long as dipyridamole does not induce severe sustained hypotension it exerts potent effects on both coronary arterial resistance and large coronary arteries in the conscious dog. The coronary dilation is independent of reflex adrenergic activation, but appears dependent on myocardial adenosine production.
Molecular Mechanism of EGFR-TKI Resistance (2009)

EGFR活性型変異を有する肺腺癌はEGFRチロシンキナーゼ阻害薬であるゲフィチニブやエルロチニブが著効する．しかし，EGFR活性型変異を有する肺腺癌の25∼30%はゲフィチニブに自然耐性を示す．また，奏効症例においてもその大半が1年程度で獲得耐性を生じ再燃するため，EGFR活性型変異を有する肺腺癌におけるゲフィチニブ耐性の克服は臨床的にも重要な検討課題である．EGFRのT790M second mutationやMET増幅が,獲得耐性のそれぞれ50%および20%に関与することが知られているが，残りの30%の症例の耐性機序および自然耐性の機序は不明である．著者らは，肝細胞増殖因子（HGF）による第三の耐性機序を明らかにした．癌細胞自身あるいは間質の線維芽細胞が産生するHGFは，その受容体であるMETをリン酸化し，EGFRやErbB3とは無関係にPI3K/Akt経路を活性化することにより，ゲフィチニブ耐性を誘導した．HGF-MET阻害薬はHGFによるEGFR-TKI耐性を克服することも見出した．以上より，HGF-MET経路はEGFR-TKIの治療効果をより高める上で，非常に重要な標的と考えられる．
Combined Serum Paraoxonase Knockout/Apolipoprotein E Knockout Mice Exhibit Increased Lipoprotein Oxidation and Atherosclerosis (2000)

Serum paraoxonase (PON1), present on high density lipoprotein, may inhibit low density lipoprotein (LDL) oxidation and protect against atherosclerosis. We generated combined PON1 knockout (KO)/apolipoprotein E (apoE) KO and apoE KO control mice to compare atherogenesis and lipoprotein oxidation. Early lesions were examined in 3-month-old mice fed a chow diet, and advanced lesions were examined in 6-month-old mice fed a high fat diet. In both cases, the PON1 KO/apoE KO mice exhibited significantly more atherosclerosis (50-71% increase) than controls. We examined LDL oxidation and clearance in vivo by injecting human LDL into the mice and following its turnover. LDL clearance was faster in the double KO mice as compared with controls. There was a greater rate of accumulation of oxidized phospholipid epitopes and a greater accumulation of LDL-immunoglobulin complexes in the double KO mice than in controls. Furthermore, the amounts of three bioactive oxidized phospholipids were elevated in the endogenous intermediate density lipoprotein/LDL of double KO mice as compared with the controls. Finally, the expression of heme oxygenase-1, peroxisome proliferator-activated receptor gamma, and oxidized LDL receptors were elevated in the livers of double KO mice as compared with the controls. These data demonstrate that PON1 deficiency promotes LDL oxidation and atherogenesis in apoE KO mice.
Buried Polar Residues in Coiled-Coil Interfaces, (2001)

Coiled coils, estimated to constitute 3-5% of the encoded residues in most genomes, are characterized by a heptad repeat, (abcdefg)(n), where the buried a and d positions form the interface between multiple alpha-helices. Although generally hydrophobic, a substantial fraction ( approximately 20%) of these a- and d-position residues are polar or charged. We constructed variants of the well-characterized coiled coil GCN4-p1 with a single polar residue (Asn, Gln, Ser, or Thr) at either an a or a d position. The stability and oligomeric specificity of each variant were measured, and crystal structures of coiled-coil trimers with threonine or serine at either an a or a d position were determined. The structures show how single polar residues in the interface affect not only local packing, but also overall coiled-coil geometry as seen by changes in the Crick supercoil parameters and core cavity volumes.
Cytotoxic Chemotherapy and CD4+ Effector T Cells: An Emerging Alliance for Durable Antitumor Effects (2012)

Standard cytotoxic chemotherapy can initially achieve high response rates, but relapses often occur in patients and represent a severe clinical problem. As increasing numbers of chemotherapeutic agents are found to have immunostimulatory effects, there is a growing interest to combine chemotherapy and immunotherapy for synergistic antitumor effects and improved clinical benefits. Findings from recent studies suggest that highly activated, polyfunctional CD4+ effector T cells have tremendous potential in strengthening and sustaining the overall host antitumor immunity in the postchemotherapy window. This review focuses on the latest progresses regarding the impact of chemotherapy on CD4+ T-cell phenotype and function and discusses the prospect of exploiting CD4+ T cells to control tumor progression and prevent relapse after chemotherapy.
Expression and Segregation of Genes Encoding CryIA Insecticidal Proteins in Cotton (1998)

Epistatic and environmental effects on foreign gene expression in cotton ( Gossypium hirsutum L.) could influence the breeding, stability and, in the case of pest resistance, efficacy and durability of the foreign gene. This study was undertaken to characterize the expression an segregation of two foreign cryIA genes in a range of insect‐resistant cotton lines derived in three backgrounds. The cryIA genes encoded insecticidal proteins from the bacterium Bacillus thuringiensis spp. kurstaki . The transformed cotton lines, MON 81 expressing the cryIA(b) gene and MON 249 expressing the cryIA(c) gene, were crossed to 14 cotton isolines with five different insect‐resistance traits. CryIA gene expression and variation were examined in terminal leaves of 2293 F 2 progeny and subsequently in 12 F 2:4 lines [ cryIA(b) only] in field experiments conducted at two locations in Texas. CryIA gene expression was variable and influenced by genetic and environmental factors. Site‐of‐gene‐insertion and cotton‐background effects were significa sources of variation for the cryIA gene. Significant epistatic and/or somadonal effects increased plant‐to‐plant variation and caused cryIA gene expression to behave as a quantitative trait. Environmental effects, between and within locations and over time, decreased parent‐offspring correlations of mean cryIA gene expression between individuals from the F 2 and F 2:4 generations. Gene dosage at the cryIA locus influenced insecticidal protein concentration in F 2 populations with the cryIA (b) gene insert—homozygotes produced 14% more CryIA(b) protein than hemizygotes. The CryIA phenotype segregated as a simple, dominant Mendelian trait. However, non‐Mendelian segregation occurred in some lines derived from MON 249. Expression of cryIA genes in cotton lines was influenced by one or more of the following: site of gene insertion, gene construct, background genotype, epistasis, somaclonal mutations, and the physical environment. These results indicate that appropriate evaluation and selection procedures should be used in a breeding program to develop new cotton lines with pest‐resistant traits conferred by foreign genes. Moreover, that a practical backcross breeding program could be used to develop cotton cultivars combining one or more pestresistant traits from foreign and native gene sources.
Temporally and spatially shaped fully-fiberized ytterbium-doped pulsed MOPA (2011)

We report a fully-fiberized, pulsed ytterbium-doped master oscillator power amplifier (MOPA) for materials processing applications providing both a temporal pulse and spatial beam shaping capability operating at a maximum average output power of 100 W. Adaptive temporal pulse shaping using an in-line electro-optic modulator was incorporated to reduce the impact of dynamic gain saturation and optical Kerr/Raman nonlinearities. The MOPA is capable of generating 2.5 mJ flattopped optical pulses with 20 kW peak power as well as other user-defined, shaped pulses. Spatial beam shaping is obtained using a pair of axicon (conical) lenses at the end of the beam delivery optic allowing ring shaped output beams to be generated from the otherwise collimated Gaussian output.
Wide spectrum single quantum well superluminescent diodes at 0.8 μm with bent optical waveguide (1993)

An AlGaAs quantum well superluminescent diodes (SLDs) with 68 nm spectral width at 5 mW output power have been developed. With 4 μm mesa stripe angled at 7° with respect to the output facet, the spectral ripple was less than 10% for uncoated devices.
Therapeutic Potential of 4-1BB (CD137) As a Regulator for Effector CD8 + T Cells (2001)

A fundamental problem of antitumor immunity is tumor-induced immunosuppression. Tumor cells often down-regulate expression of co-stimulatory molecules, tumor antigens, and major histocompatibility complex (MHC) molecules on tumor cells, secrete immunosuppressive substance such as transforming growth factor-beta (TGF-beta) or interleukin-4 (IL-4), and induce apoptosis of effector T cells to escape surveillance. A major goal of antitumor or antivirus immunotherapy is to generate long-lived protective T cells that enable killing of target cells. In this review, we discuss the importance of 4-1BB for development or survival of functionally active effector CD8(+) T cells against tumors, virus infection, and allogeneic immune responses and for potential therapeutic application.
Vaccinia virus-bacteriophage T7 expression vector for complementation analysis of late gene processes. (1999)

A vaccinia virus-bacteriophage T7 RNA polymerase hybrid transient expression vector has been developed for complementation analysis of late gene functions in vaccinia virus. The conditionally defective virus ts21 was modified to express the bacteriophage T7 RNA polymerase. The derived virus, vtsT7, was conditionally defective in viral late gene expression but produced high levels of a target protein under the control of a T7 promoter at non-permissive temperatures. The level of beta-galactosidase expression under the control of a T7 promoter was slightly lower in vtsT7 infections than those with the prototypical T7 RNA polymerase vector vTF7.3. However, the levels of expression for the human immunodeficiency virus envelope gene, a protein which undergoes post-translational modification, was slightly higher in vtsT7 infections, suggesting that some proteins may be expressed better in the absence of vaccinia virus late gene expression. Infections using vtsT7 at a low m.o.i. at 39 degrees C resulted in the accumulation of high molecular mass, non-linear replicative intermediates of vaccinia virus DNA replication and high levels of expression of a transfected gene proximal to a T7 promoter. The virus vtsT7 provides a means for the analysis of potential trans-acting factors participating in vaccinia virus late processes such as resolution of DNA replicative intermediates.
Anti-inflammatory and antiproliferative actions of PPAR-γ agonists on T lymphocytes derived from MS patients (2003)

Peroxisomal proliferator-activated receptors (PPARs) belong to a nuclear receptor superfamily of ligand-activated transcription factors. The PPAR-gamma isoform is expressed in human T lymphocytes, and oral administration of PPAR-gamma agonists ameliorates the clinical course and histopathological features in experimental autoimmune encephalomyelitis, an animal model for multiple sclerosis, suggesting a potential role for PPAR-gamma agonists in the treatment of autoimmune diseases. To assess a potential therapeutic role of PPAR-gamma agonists in multiple sclerosis, we compared the immunomodulatory effects of the thiazolidinedione (TZD) drugs pioglitazone (PIO) and ciglitazone and the non-TZD PPAR-gamma agonist GW347845 on human T leukemia cells (Jurkat cells) and phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) derived from 21 multiple sclerosis patients and 12 healthy donors. PIO, ciglitazone, and GW347845 suppressed PHA-induced T cell proliferation by 40-50% and secretion of interferon-gamma and tumor necrosis factor alpha, by 30-50%. Inhibition of proliferation was increased to approximately 80% and that of proinflammatory cytokine secretion, to 80-90% when PBMCs were first preincubated with PPAR-gamma agonists and re-exposed at the time of PHA stimulation, indicating a sensitizing effect of PPAR-gamma agonists. Inhibition of proliferation was also observed in the tetanus toxoid-specific T cell line KHS.TT2, albeit to a lesser extent. The antiproliferative effects of PIO and GW347845 were accompanied by a decrease of cell viability. Electron microscopy and Western blot analysis revealed DNA condensation and down-regulation of bcl-2, suggesting the induction of apoptosis in activated T lymphocytes. In summary, the data support the potential use of PPAR-gamma agonists as immunomodulatory, therapeutic agents for autoimmune diseases.
Intravitreal sustained release corticosteroid-5-fluoruracil conjugate in the treatment of experimental proliferative vitreoretinopathy. (1996)

Both the intravitreal sustained-release dexamethasone-5-FU device and the triamcinolone-5-FU suspension effectively inhibit the progression of PVR in a rabbit model. Simultaneous delivery of 5-FU and corticosteroid may target different components of the wound-healing process in this disease.
Gastrointestinal Effects of Low-Digestible Carbohydrates (2009)

Low-digestible carbohydrates (LDCs) are carbohydrates that are incompletely or not absorbed in the small intestine but are at least partly fermented by bacteria in the large intestine. Fiber, resistant starch, and sugar alcohols are types of LDCs. Given potential health benefits (including a reduced caloric content, reduced or no effect on blood glucose levels, non-cariogenic effect) the prevalence of LDCs in processed foods is increasing. Many of the benefits of LDCs are related to the inability of human digestive enzymes to break down completely the carbohydrates into absorbable saccharides and the subsequent fermentation of unabsorbed carbohydrates in the colon. As a result, LDCs may affect laxation and cause gastrointestinal effects, including abdominal discomfort, flatus, and diarrhea, especially at higher or excessive intakes. Such responses, though transient, affect the perception of the well-being of consumers and their acceptance of food products containing LDCs. Current recommendations for fiber intake do not consider total LDC consumption nor recommend an upper limit for LDC intake based on potential gastrointestinal effects. Therefore, a review of published studies reporting gastrointestinal effects of LDCs was conducted. We included only studies published in refereed journals in English. Additionally, we excluded studies of subjects with incomplete or abnormal functioning gastrointestinal tracts or where antibiotics, stimulant laxatives, or other drugs affecting motility were included. Only in studies with a control period, either placebo treatment or no LDC treatment, were included. Studies must have included an acceptable measure of gastrointestinal effect. Sixty-eight studies and six review articles were evaluated. This review describes definitions, classifications, and mechanisms of LDCs, evaluates published human feeding studies of fifteen LDCs for associations between gastrointestinal effects and levels of LDC intake, and presents recommendations for LDC consumption and further research.