gebhart/patrepeval huggingface dataset:
Toward MicroRNA–Based Therapeutics for Heart Disease (2008)

MicroRNAs act as negative regulators of gene expression by inhibiting the translation or promoting the degradation of target mRNAs. Because individual microRNAs often regulate the expression of multiple target genes with related functions, modulating the expression of a single microRNA can, in principle, influence an entire gene network and thereby modify complex disease phenotypes. Recent studies have identified signature expression patterns of microRNAs associated with pathological cardiac hypertrophy, heart failure, and myocardial infarction in humans and mouse models of heart disease. Gain- and loss-of-function studies in mice have revealed profound and unexpected functions for these microRNAs in numerous facets of cardiac biology, including the control of myocyte growth, contractility, fibrosis, and angiogenesis, providing glimpses of new regulatory mechanisms and potential therapeutic targets for heart disease. Especially intriguing is the discovery of a network of muscle-specific microRNAs embedded within myosin heavy chain genes, which control myosin expression and the response of the heart to stress and thyroid hormone signaling. Disease-inducing cardiac microRNAs can be persistently silenced in vivo through systemic delivery of antimiRs, allowing for the direct therapeutic modulation of disease mechanisms. Here, we summarize current knowledge of the roles of miRNAs in heart disease and consider the advantages and potential challenges of microRNA-based approaches compared to conventional drug-based therapies.
Decreased affinity of low density lipoprotein (LDL) particles for LDL receptors in patients with cholesteryl ester transfer protein deficiency (1995)

We have reported that the disorder of lipoprotein metabolism in hyperalphalipoproteinaemic patients with a deficiency of cholesteryl ester transfer protein (CETP) is characterized by the polydisperse low density lipoprotein (LDL) particles and the accumulation of cholesteryl ester (CE) in high density lipoprotein (HDL) particles, forming cholesterol-induced HDL (HDLc)-like particles. In the present study we have investigated the interaction of these abnormal LDL with LDL receptors of normal human fibroblasts. Since the ultracentrifugally separated LDL fraction (1.019 < d < 1.063 g mL-1) from the CETP-deficient patients contained HDLc-like particles, these particles were removed by anti-apolipoprotein (apo) A-I immunoaffinity column chromatography. The lipoproteins eluted in the unbound fraction of this column did not contain apo A-I, so this fraction was considered to be authentic LDL. The authentic LDL of the patients were deficient in CE and rich in triglycerides and apo B. The authentic LDL itself showed polydispersity, ranging in size from 23 nm to 30 nm. The affinity of these abnormal LDL particles for LDL receptors was analysed by a competitive assay in which cold LDL from the patients or control compete with 125I-labelled LDL for fibroblast LDL receptors. The concentration of LDL particles at which 50% of 125I-labelled normal LDL was replaced was two to three times higher for the patients than for the normal control. Therefore, the affinity of patient LDL was thought to be reduced compared to that of control LDL. These results demonstrate that CETP may play an important role in making LDL particles homogeneous and rich in CE.(ABSTRACT TRUNCATED AT 250 WORDS)
Sleep in the surgical intensive care unit: continuous polygraphic recording of sleep in nine patients receiving postoperative care. (1985)

Sleep was studied in nine patients for two to four days after major non-cardiac surgery by continuous polygraphic recording of electroencephalogram, electrooculogram, and electromyogram. Presumed optimal conditions for sleep were provided by a concerted effort by staff to offer constant pain relief and reduce environmental disturbance to a minimum. All patients were severely deprived of sleep compared with normal. The mean cumulative sleep time (stage 1 excluded) for the first two nights, daytime sleep included, was less than two hours a night. Stages 3 and 4 and rapid eye movement sleep were severely or completely suppressed. The sustained wakefulness could be attributed to pain and environmental disturbance to only minor degree. Sleep time as estimated by nursing staff was often grossly misjudged and consistently overestimated when compared with the parallel polygraphic recording. The grossly abnormal sleep pattern observed in these patients may suggest some fundamental disarrangement of the sleep-wake regulating mechanism.
Biodegradable polymers and composites in biomedical applications: from catgut to tissue engineering. Part 1 Available systems and their properties (2004)

Biodegradable polymers form a unique class of materials that created an entirely new concept when originally proposed as biomaterials. That is, for the first time, a material performing a structural application was designed to be completely resorbed and to become weaker over time. This concept was first applied successfully with catgut sutures and later, with more arguable results, on bone fixation plates and pins. Current research on new and improved biodegradable polymers is focused on more sophisticated biomedical applications to solve patients' problems with higher efficacy and the least possible pain. One example is tissue engineering, in which a biodegradable scaffold seeded with an appropriate cell type provides a substitute for damaged human tissue while the natural process of regeneration is completed. An overview is given of the degradation properties and mechanisms of biodegradable polymers, their processability and biocompatibility, focusing on the aspects most relevant to biomedical applications. The main families of biodegradable polymeric systems are described and the systems that are commercially available or that are currently being studied and proposed for specific medical applications are reviewed.
Systemic human minidystrophin gene transfer improves functions and life span of dystrophin and dystrophin/utrophin‐deficient mice (2008)

Duchenne muscular dystrophy (DMD) is the most common and lethal genetic muscle disease, caused by mutations in the dystrophin gene. No efficacious treatment is currently available. Here we report AAV vector systemic delivery and therapeutic benefits of the functional human minidystrophin gene in a severe and more reliable DMD mouse model, the dystrophin/utrophin double deficiency mouse (dys-/-:utrn-/-, dKO). These mice show many pathologic and phenotypic signs typical of DMD in humans including kyphosis and shorter life span, all of which are not seen in the mdx mice due to their utrophin upregulation that partially compensates the loss of dystrophin functions and leads to mild phenotypes. The therapeutic value of this new approach was demonstrated in both mdx and dKO murine models, in which we observed highly efficient minidystrophin gene expression, ameliorated muscle pathologies, improvement in growth and motility, inhibition of spine and limb deformation, and prolongation of life span.
Integrating meta-information management and reflection in middleware (2002)

The representation and management of meta-information is an important issue in reflective architectures. In the case of complex base-level systems, such as middleware platforms, this issue becomes even more crucial, given the large number of entities of different kinds that must be dealt with and especially, given the fact that such entities are normally distributed, which makes it difficult to maintain their consistency. The authors present an approach to represent and maintain middleware meta-information and show how it is integrated with their reflective architecture for middleware, which is based on the idea of multi-model reflection. The result is a principled way to control the use and evolution of meta-information in the platform, also offering a means to harness the power of reflection. The paper also outlines an implementation of the approach, as well as the major implications of its use.
Vitamin E as an Adjuvant in an Escherichia coli J5 Vaccine (1993)

Vitamin E was tested as an adjuvant in an Escherichia coli (O111:B4) J5 vaccine. Twenty cows were assigned to five groups of 4 cows. Cows in four groups were vaccinated with an E. coli J5 bacterin containing 5 ml of 10(9) boiled cells/ml. Vaccinations were at drying off, 30 d after drying off, and within 48 h after calving. Vaccine adjuvants differed among groups. The four treatment adjuvants were 5 ml of Freund's incomplete adjuvant, 5 ml of vitamin E, 2.5 ml of Freund's plus 2.5 ml of vitamin E, and 5 ml of PBS. Cows in the fifth group were unimmunized controls. A front mammary quarter of each cow was challenged by infusion of 10 micrograms of E. coli J5 lipopolysaccharide approximately 4 wk into lactation. Vitamin E alone enhanced serum IgM titers but had no effect on milk IgM or serum and milk IgG titers. The mixture of Freund's plus vitamin E resulted in peak IgG titers in serum and milk comparable with that of Freund's alone. Persistency of IgG titers in cows immunized with the Freund's plus vitamin E mixture was greater than the persistency of titers for cows immunized with the vaccine containing Freund's alone as the adjuvant. The mixture of Freund's plus vitamin E had a synergistic effect in reducing severity of systemic clinical signs.
Taxol Facilitates Axon Regeneration in the Mature CNS (2011)

Mature retinal ganglion cells (RGCs) cannot normally regenerate axons into the injured optic nerve but can do so after lens injury. Astrocyte-derived ciliary neurotrophic factor and leukemia inhibitory factor have been identified as essential key factors mediating this effect. However, the outcome of this regeneration is still limited by inhibitors associated with the CNS myelin and the glial scar. The current study demonstrates that Taxol markedly enhanced neurite extension of mature RGCs and PC12 cells by stabilization of microtubules and desensitized axons toward myelin and chondroitin sulfate proteoglycan (CSPG) inhibition in vitro without reducing RhoA activation. In vivo, the local application of Taxol at the injury site of the optic nerve of rats enabled axons to regenerate beyond the lesion site but did not affect the intrinsic regenerative state of RGCs. Furthermore, Taxol treatment markedly increased lens injury-mediated axon regeneration in vivo, delayed glial scar formation, suppressed CSPG expression, and transiently reduced the infiltration of macrophages at the injury site. Thus, microtubule-stabilizing compounds such as Taxol might be promising candidates as adjuvant drugs in the treatment of CNS injuries particularly when combined with interventions stimulating the intrinsic regenerative state of neurons.
Plasticity within the Antigen-Combining Site May Manifest as Molecular Mimicry in the Humoral Immune Response (2004)

Structural and physiological facets of carbohydrate-peptide mimicry were addressed by analyzing the Ab response to alpha-d-mannopyranoside. mAbs against alpha-d-mannopyranoside were generated and screened with the carbohydrate-mimicking 12 mer (DVFYPYPYASGS) peptide. Three mAbs, 2D10, 1H11, and 1H7, which were subjected to detailed analysis, exhibit diverse V gene usage, indicating their independent germline origins. Although the mAb 1H7 was specific in binding only to the immunizing Ag, the Abs 2D10 and 1H11 recognize the 12 mer peptide as well as the immunogen, alpha-d-mannopyranoside. The Abs that recognize mimicry appear to bind to a common epitope on the peptide and do not share the mode of peptide binding with Con A. Binding kinetics and thermodynamics of Ag recognition suggest that the Ab that does not recognize peptide-carbohydrate mimicry probably has a predesigned mannopyranoside-complementing site. In contrast, the mimicry-recognizing Abs adopt the Ag-combining site only on exposure to the sugar, exploiting the conformational flexibility in the CDRs. Although the mAb 1H7 showed unique specificity toward mannopyranoside, the mimicry-recognizing Abs 2D10 and 1H11 exhibited degenerate specificities with regard to other sugar moieties. It is proposed that the degeneracy of specificity arising from the plasticity at the Ag-combining site in a subset of the Ab clones may be responsible for exhibiting molecular mimicry in the context of Ab response.
Idiotype switching of CD4‐specific monoclonal antibodies can prolong the therapeutic effectiveness in spite of host anti‐mouse IgG antibodies (1987)

Immunotherapy using murine monoclonal antibodies (mAb) is limited by the host anti-mouse IgG response. Previous investigations demonstrated that a large proportion of the anti-mouse response was specific for idiotypic determinants of the mAb. This study demonstrates the feasibility of idiotype switching of therapeutic mAb to evade this anti-idiotype response. In this way prolongation of the therapeutic effectiveness of mAb treatment can be achieved. Using different CD4-specific mAb consecutively in rhesus monkeys it was possible to obtain therapeutic effectiveness in spite of host anti-mouse IgG antibodies, provided that no anti-idiotypic antibodies were present. Anti-constant part antibodies may even enhance therapeutic effectiveness.
Transient T cell depletion causes regression of melanoma metastases (2008)

NCT00299689 (ClinicalTrials.gov Identifier).
Studies of an immunomodulator, swainsonine. I. Enhancement of immune response by swainsonine in vitro. (1985)

Swainsonine isolated from Metarhizium sp., was found to enhance the activities of the mouse immune system in vitro. Concanavalin A stimulated lymphocyte proliferation and proliferative response in mixed lymphocytes culture, which were suppressed by immunosuppressive factor obtained from serum of sarcoma 180 tumor bearing mouse, were restored to normal levels by the addition of swainsonine. Furthermore, the concanavalin A induced incorporation of [3H]thymidine into mouse spleen cells was remarkably increased by treatment with swainsonine over a wide dose range, From studies using fluorescence activated cell sorting, swainsonine was shown to enhance the expression of concanavalin A receptors of spleen cells.
Three views of virtual reality: virtual environments in the US military (1993)

A virtual environment is a generic, relatively low-cost real-time interactive simulation. It is shown that the US military has been a primary supporter of real-time simulation for more than 60 years, ever since the development of the Link Flight Instrument Trainer in the late 1930s. The development of flight simulation systems and head-mounted displays are reviewed. The use of virtual environments for team training, battlefield review and tactics development is discussed. Several research projects involving virtual environments and military applications are described.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
The efficiency of cell targeting by recombinant retroviruses depends on the nature of the receptor and the composition of the artificial cell-virus linker (1992)

Using streptavidin-bound antibodies specific for both viral and cell membrane epitopes, we have reported previously that human cells may be infected by murine ecotropic retroviruses through an interaction with major histocompatibility complex class I and class II antigens, and thus have demonstrated that cell targeting by recombinant retroviruses is feasible. We report here that (i) growth factor or hormone receptors, such as those for epidermal growth factor (EGF) and insulin, can also mediate infection of human cells; (ii) a biotinylated cytokine or hormone can substitute for the anti-cell antibody in bispecific antibody complexes, thus extending the versatility of the method; (iii) although yields are low in our assay, infection efficiency clearly appears to depend upon the biochemical composition of molecular bridges because bi-functional antibody complexes are more efficient than cytokine-antibody complexes in the case of the EGF receptor. Finally, our study indicates that different cell membrane molecules are not equally efficient in allowing infection of human cells because targeting of the transferrin, high density lipoprotein and galactose receptors, as well as that of various membrane glycoconjugates, by murine ecotropic retroviruses did not lead to the establishment of a proviral state.
Comparison of genetically engineered herpes simplex viruses for the treatment of brain tumors in a scid mouse model of human malignant glioma. (1995)

Genetically engineered viruses and viral genes inserted into retroviral vectors are increasingly being considered for experimental therapy of brain tumors. A primary target of these viruses and vectors is human gliomas, the most frequently occurring primary human brain tumor. To investigate the potential of genetically engineered herpes simplex viruses (HSVs) in the therapy of these tumors, we compared the attributes of two viruses, a recombinant from which the gamma 1(34.5) gene had been deleted (R3616) and a recombinant in which the gamma 1(34.5) gene had been interrupted by a stop codon (R4009). Previous studies have shown that these recombinants were completely devoid of the ability to multiply in the central nervous system of rodents. To pursue these studies, we developed a scid mouse glioma model. Tumor cell response (survival) for 10(3), 10(4), and 10(5) implanted MT539MG glioma cells was 38, 23, and 15 days, respectively. The results were as follows: (i) both R3616 and R4009 replicate and cause cytolysis in diverse glioma cell lines of murine and human origin in vitro, and (ii) Winn-type assays 10(5) MT539MG cells coinoculated with R3616 or R4009 as compared to saline significantly prolonged survival in a dose-dependent fashion. Mice that received only tumor cells or the wild-type parent strain of the recombinants, HSV-1(F), died within 15 days. Survival was greatest with R4009. These experiments define both a model for screening oncolytic viruses and a genetically engineered virus of significant potential use as an oncolytic agent.
Production of Monoclonal Antibodies Toward Bovine Interferons-α Suitable for Immunopurification (1989)

Five murine hybridoma clones, producing monoclonal antibodies (MAbs) to bovine interferon-alpha (BoIFN-alpha) were established. One of these, F12, secreted MAbs giving high titers, in ELISA tests, neutralizing both BoIFN-alpha, -alpha C, and BoIFN-alpha D activities, belonging to the mouse IgG1 class, and having a binding affinity constant of 10(8) M-1. F12 MAbs were used for immunoaffinity purification of BoIFN-alpha, and recombinant BoIFN-alpha C from Escherichia coli extracts was purified to homogeneity in SDS-PAGE analysis and to a specific activity of 2 X 10(8) U/mg with 90% recovery of activity.
Comparison of Magnesium Sulfate and Sodium Sulfate for Removal of Water from Pesticide Extracts of Foods (2002)

Water-miscible solvents, such as acetone and acetonitrile, effectively extract both polar and nonpolar pesticide residues from nonfatty foods. The addition of sodium chloride to the resulting acetonitrile-water or acetone-water extract (salting out) results in the separation of the water from the organic solvent. However, the organic solvent layer (pesticide extract) still contains some residual water, which can adversely affect separation procedures that follow, such as solid-phase extraction and/or gas chromatography. Drying agents, such as sodium sulfate or magnesium sulfate, are used to remove the water from the organic extracts. In the present study, we used nuclear magnetic resonance spectroscopy to study the composition of the phases resulting from salting out and to compare the effectiveness of sodium sulfate and magnesium sulfate as drying agents. The study showed that considerable amounts of water remained in the organic phase after phase separation. Sodium sulfate was a relatively ineffective drying agent, removing little or no residual water from the organic solvent. Magnesium sulfate proved to be a much more effective drying agent.
Human hematopoietic survival and growth factor (1986)

A variety of biologic activities on human hematopoietic stem cells were detected in 12-O-tetradecanoylphorbol-13-acetate-stimulated leukocyte-conditioned medium (TPA-LCM). Partial purification of TPA-LCM demonstrated the presence of human-active granulocyte-macrophage colony-stimulating factor (GM-CSF; Mr 50-70Kd), macrophage-CSF (M-CSF; Mr greater than 100Kd) and possibly a third protein (Mr 24-26Kd) supporting survival and growth of hematopoietic stem cells in vitro. Activities investigated included GM-colony and erythroid burst-potentiation, burst-promoting activity (BPA) and delta granulocyte and delta burst-promoting activities (delta GPA and delta BPA).
Synthesis of isoesteres of p-amidinophenylpyruvic acid. Inhibitors of trypsin, thrombin, and pancreatic kallikrein (1975)

A series of amino acids, amidino acids, and amidino esters was synthesized and the compounds were evaluated for their inhibitory activity against bovine trypsin, bovine thrombin, and porcine pancreatic kallikrein and as anticoagulants. Among these compounds, ethyl 4-amidino-2-iodophenoxyacetate was found to be the most effective inhibitor of the enzymes in question, with a potency (Ki = 3.16 x 10-6 M vs. trypsin; Ki = 4.8 x 10-5 M vs. thrombin) similar to that of p-amidinophenylpyruvic acid (Ki = 6.0 x 10-6 M vs. trypsin; Ki = 2.0 x 10-5 M vs. thrombin). Ethyl 4-amidino-2-iodophenoxyacetate was also found to be the most effective in blocking the clotting activity of plasma, as indicated by significant prolongation of the partial thromboplastin time. This paper reports the synthetic methods, the enzyme inhibitory activity, and the structure-activity relationships observed.
The HLA-E gene encodes two differentially regulated transcripts and a cell surface protein (1992)

An HLA-E-specific oligonucleotide probe was used to study the expression of HLA-E. This probe detects two HLA-E transcripts, 1.8 and 2.7 kb in size, which are present in varying ratios in all tissues and cell lines investigated. We demonstrate that alternative poly(A) site usage accounts for the differential regulation of the two HLA-E mRNA species. Sequence analysis of three cDNA clones, representing the two transcripts of HLA-E, and of an HLA-E gene encoded by cosmid cd3.14, revealed identity of gene and cDNA in the 3' untranslated region. S1 nuclease protection assays confirmed that the two HLA-E transcripts are not alternative splicing products. Introduction of cd3.14, together with human beta 2 m into the murine myeloma cell line P3X63-Ag8.653, resulted in a cell surface expression of an HLA-class I heavy chain detectable by indirect immunofluorescence whereas transfection into the human beta 2m expressing mouse L cell line, J27 was negative with regard to cell surface expression. Cell surface labeling of transfectants and immunoprecipitation with a monomorphic HLA class I-specific antibody or an antibody against human beta 2m confirmed the presence of an HLA-E H chain on the cell surface. These results indicate that the HLA-E gene codes for a class I H chain that can be expressed on the cell surface.
Magnetic properties of nanostructured CoPt and FePt thin films (2000)

Polycrystalline MgO underlayer films lead to different preferred orientations of L1/sub 0/ CoPt and FePt films after the annealing process, depending on the thickness of the L1/sub 0/ films. L1/sub 0/ films with a thickness greater than 20 nm revealed mostly L1/sub 0/ [100] fiber texture and consequently in-plane anisotropy as determined by magnetic hysteresis. Strong perpendicular anisotropy due to the L1/sub 0/ [001] fiber texture was obtained for thicknesses below 10 nm. The /spl delta/M curve showed strong intergranular exchange coupling. The angular variation of coercivity showed the possibility of both domain wall motion and a rotational mechanism of magnetization reversal.