gebhart/patrepeval huggingface dataset:
Decreased Hepatic Insulin-Like Growth Factor (IGF)-I and Increased IGF Binding Protein-1 and -2 Gene Expression in Experimental Uremia (1997)

The imbalance between normal insulin-like growth factor-I (IGF-I) and markedly increased IGF binding protein (IGFBP) plasma levels plays a pathogenic role for growth retardation and catabolism in children with chronic renal failure. To investigate the mechanism of these alterations, experiments were performed in an experimental model of uremia in rats (5/6 nephrectomy) and in pair-fed and ad libitum-fed sham-operated controls. Using a specific solution hybridization/RNase protection assay, we observed a marked reduction of hepatic IGF-I messenger RNA (mRNA) abundance at steady state in uremic animals (37 ± 5% of control) compared both with pair-fed (65 ± 10%) and ad libitum-fed controls (100± 11%) (P < 0.001). Reduced IGF-I gene expression was clearly organ-specific; it was most pronounced in liver (significant vs.. pair-fed controls) and lung and muscle tissue (significant vs.. ad libitum-fed controls); no change was observed in kidney and heart tissue. To determine a potential mechanism of reduced hepatic IGF-I gene expression in uremia, the hepatic GH receptor gene expression in the same experimental animals was analyzed by specific solution hybridization/RNase protection assay. Uremic animals had a 20–30% reduction of hepatic GH receptor mRNA abundance compared with controls. Hepatic GHBP expression in uremia was decreased in parallel. Despite the reduction of hepatic IGF-I mRNA abundance, plasma IGF-I levels in uremia were not different from ad libitum-fed controls. This discrepancy is explained by an increased concentration of IGFBPs in uremic plasma. By RIA, plasma IGFBP-1 levels in uremia were increased 4-fold; by Western immunoblot, plasma IGFBP-2 levels were increased 7-fold and plasma IGFBP-4 levels were increased 2-fold compared with both control groups. Intact IGFBP-3 (Mr,∼ 48 kDa) and low molecular IGFBP-3 fragments were not significantly different among the three groups. By Northern blot analysis, hepatic IGFBP-1 mRNA levels in uremia were 2-fold higher than in controls. IGFBP-2 mRNA abundance in liver tissue was increased 4-fold, whereas in kidney there was a significant reduction of IGFBP-2 mRNA (30% of control). IGFBP-4 mRNA was increased by 50% in kidney but not in liver. Plasma insulin and corticosterone levels were not different among the groups. Our study shows that hepatic IGF-I gene expression was specifically reduced in uremia, partially as the consequence of a reduced hepatic GH receptor gene expression. One of the mechanisms contributing to increased IGFBP levels in uremia is increased hepatic gene expression of IGFBP-1 and IGFBP-2. The imbalance between reduced hepatic IGF-I production and increased hepatic IGFBP-1 and -2 production is likely to play a pathogenic role for catabolism and growth failure in CRF.
Gene Transfer Optimization with Lipospermine-Coated DNA (1993)

Designed synthetic DNA carriers represent an attractive alternative to the widely used calcium phosphate gene transfer technique. In this context, we developed a class of nucleic acid binding lipids, the lipopolyamines, which spontaneously condense DNA on a cationic lipid layer. The resulting nucleolipidic particles transfect most animal cells efficiently. However, compaction depends on many experimental factors, some of which have been varied here to give optimal transfection efficiency. When plasmid condensation by the lipospermine is performed in the absence of competing polyions or serum proteins, or when the gene of interest is diluted into carrier DNA, transfection efficiency is increased by 2-3 orders of magnitude. With these improvements, chloramphenicol acetyl transferase activity resulting from transfection of as little as 25 ng could easily be detected by a nonradioactive ELISA test.
Management of migraine during pregnancy (2009)

Abstract In Pregnancy is a series of reviews focusing on the management of women with psychiatric and neurological conditions during pregnancy. In this article, Dr MacGregor discusses the effect of pregnancy on migraine and the treatment choices available to women during pregnancy and lactation. Copyright © 2009 Wiley Interface Ltd
Antisense human neuroglia related cell adhesion molecule hNr-CAM, reduces the tumorigenic properties of human glioblastoma cells. (2000)

On the basis of these results, we conclude that hNr-CAM is a valid target for potential gene therapy of glioblastoma tumors.
Lipstatin, an inhibitor of pancreatic lipase, produced by Streptomyces toxytricini. I. Producing organism, fermentation, isolation and biological activity. (1987)

Lipstatin, a new and very potent inhibitor of pancreatic lipase (the key enzyme of intestinal fat digestion) was isolated from Streptomyces toxytricini. Lipstatin contains a beta-lactone structure that probably accounts for the irreversible lipase inhibition. The IC50 of lipstatin for pancreatic lipase is 0.14 microM. In mice triolein absorption was dose-dependently inhibited by lipstatin, whereas oleic acid was absorbed normally. Other pancreatic enzymes, such as phospholipase A2 and trypsin, were not inhibited even at an inhibitor concentration of 200 microM.
Immunological mechanisms elicited at the tumour site by lymphocyte activation gene‐3 (LAG‐3) versus IL‐12: sharing a common Th1 anti‐tumour immune pathway (2004)

The experimentally induced TS/A murine mammary carcinoma is poorly immunogenic and mainly infiltrated by antigen-presenting cells (APCs), namely macrophages and immature dendritic cells (DCs). Human (h) and mouse (m) lymphocyte activation gene-3 (LAG-3 or CD233) is a physiological MHC class II ligand and powerful APC activator. A gene transfer approach has revealed its anti-tumour activity in this model: hLAG-3 was more effective than mLAG-3. To obtain a clearer picture of the immunoregulatory mechanisms associated with the rejection dynamics of h- and m-LAG-3 transfectants, immunohistochemistry and confocal microscopy analyses of TS/A-hLAG-3, TS/A-mLAG-3, and control TS/A-pc tumours were performed. The immune events elicited by mLAG-3 and m-interleukin (IL)-12 were also compared, since their rejection kinetics were quite similar, and LAG-3 enables IL-12 production by macrophages and DCs. Both the TS/A-h- and, to a lesser extent, the m-LAG-3 rejection areas were characterized by an impressive recruitment of APCs, granulocytes, NK cells, CD4+ T lymphocytes and CD8+ IFNgamma-expressing cells. In both cases, infiltration by APCs was accompanied by strong CD80 and CD86 expression and macrophage nitric oxide (NO) synthase up-regulation. Distinct expression of IL-12 and CXCL9 was also found, especially in the draining lymph nodes. T lymphocytes and CD86-expressing APCs were significantly prevalent in both the TS/A-h- and the m-LAG-3 compared with the TS/A-mIL-12 rejection area. Production of IFNgamma, TNFalpha and IL1beta, and chemokines, namely CXCL5, CXCL9, CXCL10, CXCL11, CCL5, and CCL2, by infiltrating leukocytes and signs of defective neovascularization were detected in tumours expressing h-LAG-3-, m-LAG-3-, and m-IL-12. However, IFNgamma, CCL2, and CCL5 production prevailed in the TS/A-hLAG-3 rejection area. Taken together, these results indicate that LAG-3 expression by engineered tumour cells efficiently promotes intra-tumoural recruitment, activation, and Th1 commitment of APCs, and leads to a wide intra-tumoural influx of non-specific and specific reactive cells, and the release of immunoregulatory and cytotoxic mediators. Many of LAG-3's anti-tumour activities are shared with IL-12.
ChemInform Abstract: Synthesis of 5′‐C‐ and 2′‐O‐(Bromoalkyl)‐Substituted Ribonucleoside Phosphoramidites for the Post‐Synthetic Functionalization of Oligonucleotides on Solid Support. (2000)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Vaccination with DNA Encoding the Immunodominant LACK Parasite Antigen Confers Protective Immunity to Mice Infected with Leishmania major (1997)

To determine whether DNA immunization could elicit protective immunity to Leishmania major in susceptible BALB/c mice, cDNA for the cloned Leishmania antigen LACK was inserted into a euykaryotic expression vector downstream to the cytomegalovirus promoter. Susceptible BALB/c mice were then vaccinated subcutaneously with LACK DNA and challenged with L. major promastigotes. We compared the protective efficacy of LACK DNA vaccination with that of recombinant LACK protein in the presence or absence of recombinant interleukin (rIL)-12 protein. Protection induced by LACK DNA was similar to that achieved by LACK protein and rIL-12, but superior to LACK protein without rIL-12. The immunity conferred by LACK DNA was durable insofar as mice challenged 5 wk after vaccination were still protected, and the infection was controlled for at least 20 wk after challenge. In addition, the ability of mice to control infection at sites distant to the site of vaccination suggests that systemic protection was achieved by LACK DNA vaccination. The control of disease progression and parasitic burden in mice vaccinated with LACK DNA was associated with enhancement of antigen-specific interferon-gamma (IFN-gamma) production. Moreover, both the enhancement of IFN-gamma production and the protective immune response induced by LACK DNA vaccination was IL-12 dependent. Unexpectedly, depletion of CD8(+) T cells at the time of vaccination or infection also abolished the protective response induced by LACK DNA vaccination, suggesting a role for CD8(+) T cells in DNA vaccine induced protection to L. major. Thus, DNA immunization may offer an attractive alternative vaccination strategy against intracellular pathogens, as compared with conventional vaccination with antigens combined with adjuvants.
Ubiquitin-Mediated Stress Response in the Spinal Cord After Transient Ischemia (2008)

These results indicate that the vulnerability of motor neuron of the spinal cord might be partially attributed to the different response in ubiquitin-mediated stress response after transient ischemia.
A Natural CCR2 Antagonist Relieves Tumor-associated Macrophage-mediated Immunosuppression to Produce a Therapeutic Effect for Liver Cancer (2017)

Hepatocellular carcinoma (HCC) is a common malignant tumor in the digestive tract with limited therapeutic choices. Although sorafenib, an orally administered multikinase inhibitor, has produced survival benefits for patients with advanced HCC, favorable clinical outcomes are limited due to individual differences and resistance. The application of immunotherapy, a promising approach for HCC is urgently needed. Macrophage infiltration, mediated by the CCL2/CCR2 axis, is a potential immunotherapeutic target. Here, we report that a natural product from Abies georgei, named 747 and related in structure to kaempferol, exhibits sensitivity and selectivity as a CCR2 antagonist. The specificity of 747 on CCR2 was demonstrated via calcium flux, the binding domain of CCR2 was identified in an extracellular loop by chimera binding assay, and in vivo antagonistic activity of 747 was confirmed through a thioglycollate-induced peritonitis model. In animals, 747 elevated the number of CD8+ T cells in tumors via blocking tumor-infiltrating macrophage-mediated immunosuppression and inhibited orthotopic and subcutaneous tumor growth in a CD8+ T cell-dependent manner. Further, 747 enhanced the therapeutic efficacy of low-dose sorafenib without obvious toxicity, through elevating the numbers of intra-tumoral CD8+ T cells and increasing death of tumor cells. Thus, we have discovered a natural CCR2 antagonist and have provided a new perspective on development of this antagonist for treatment of HCC. In mouse models of HCC, 747 enhanced the tumor immunosuppressive microenvironment and potentiated the therapeutic effect of sorafenib, indicating that the combination of an immunomodulator with a chemotherapeutic drug could be a new approach for treating HCC.
Toward Analysis of Proteins in Single Cells: A Quantitative Approach Employing Isobaric Tags with MALDI Mass Spectrometry Realized with a Microfluidic Platform (2016)

Protein identification and quantification in individual cells is essential to understand biological processes such as those involved in cell apoptosis, cancer, biomarker discovery, disease diagnostics, pathology, or therapy. Compared with present single cell genome analysis, probing the protein content of single cells has been hampered by the lack of a protein amplification technique. Here, we report the development of a quantitative mass spectrometric approach combined with microfluidic technology reaching the detection sensitivity of high abundant proteins in single cells. A microfluidic platform with a series of chambers and valves, ensuring a set of defined wells for absolute quantification of targeted proteins, was developed and combined with isotopic labeling strategies employing isobaric tags for relative and absolute quantitation (iTRAQ)-labels. To this aim, we adapted iTRAQ labeling to an on-chip protocol. Simultaneous protein digestion and labeling performed on the microfluidic platform rendered the labeling strategy compatible with all necessary manipulation steps on-chip, including the matrix delivery for MALDI-TOF analysis. We demonstrate this approach with the apoptosis related protein Bcl-2 and quantitatively assess the number of Bcl-2 molecules detected. We anticipate that this approach will eventually allow quantification of protein expression on the single cell level.
Zur Reaktion von Triafulvenen mit Isonitrilen. Eine einfache Synthese von diphenylsubstituierten funktionalisierten Cyclobuten-Derivaten und deren Folgeprodukten (1987)

Reaction of Triafulvenes with Isonitriles. A Simple Synthesis of Diphenyl-Substituted Functionalized Cyclobutene Derivatives and Related Products The reactions of triafulvenes 1a-e with a series of isonitriles 2a-e are investigated. From 1a-c in aprotonic media 2-methylenecyclobutene-1-one imines (3a-h) are formed in good yields, which are characterized by spectral data, hydrolysis to 2-methylenecyclobutene-1-ones 4 and independent synthesis of a selected hydrolysis product (4c). In protonic media the products 3, e.g. 3b,e, incorporate a solvent molecule to give N-alkyl pyrrols 7,8. Triafulvenes 1d and 1e give other types of products, whose structures are likely to be 12-15. A mechanism for the reaction of triafulvenes with isonitriles is presented, in which an allenic ketene intermediate plays a central role for the formation of all products obtained.
SUCCESSFUL 72-HOUR COLD STORAGE OF DOG KIDNEYS WITH UW SOLUTION (1988)

Effects of three cold-storage solutions on kidney function in dogs were examined with the isolated perfused (IPK) kidney model and the autotransplant model. EuroCollins' (EC) solution, phosphate-buffered sucrose solution, and a new solution developed at the University of Wisconsin (UW) were studied. Kidneys were cold-stored for 48 hr or 72 hr. With the IPK model, cold storage for 48 hr or 72 hr in each of the three solutions caused creatinine clearance to decrease by 80%-90%. More protein was excreted by kidneys stored for 48 hr in PBS solution than by kidneys stored in EC or UW solution; protein excretion after 72 hr of storage was similar for kidneys stored in EC or UW solution. Sodium reabsorption decreased after 48 hr or 72 hr of storage, but was higher in kidneys stored in UW solution (83% and 56%, respectively) than in EC solution (52% and 22%, respectively). With the autotransplant model, 40% of the kidneys were viable after 48-hr storage in PBS solution, but 80% viable when stored in EC solution and 100% were viable when stored in UW solution. All kidneys were viable when stored for 72 hr in UW solution; none were viable when stored for 72 hr in EC solution. These results suggest that UW solution effectively preserves kidneys for 72 hr. We previously reported successful 72-hr pancreas preservation. Recently UW solution was able to preserve canine livers for 30 hr. Thus, this single solution appears to be effective for preserving all intraabdominal organs and may simplify cold storage of organs for transplantation.
Combined space/time diversity technique for narrowband TDMA mobile radio systems (1989)

A new diversity technique is presented which employs antenna (space) diversity in conjunction with time staggering to allow the receiver to collect energy from several paths without phase or gain adjustments. The technique is particularly suited to narrowband TDMA where the receiver is likely to include an equaliser, and the resulting performance gains are characterised, taking the GSM system as an example.
Spatial control of neuronal cell attachment and differentiation on covalently patterned laminin oligopeptide substrates (1994)

The spatial control of neuronal cell attachment and differentiation via specific receptor mediated interactions, may provide an effective means for the in vitro reconstruction of neuronal cell architecture. In this study, receptor-specific oligopeptide sequences derived from the extracellular matrix (ECM) molecule laminin, a potent neural cell attachment and differentiation promoter were covalently bound on fluorinated ethylene propylene (FEP) films. The degree of receptor-specific cell attachment and the ability to spatially control neurite outgrowth by covalently patterning the oligopeptide sequences on the FEP film surface were assessed. FEP films were first chemically activated with a Radio Frequency Glow Discharge (RFGD) process that covalently replaces the surface fluorine atoms with reactive hydroxyl groups. Oligopeptides containing the YIGSR sequence from the B1 chain of laminin and the water soluble oligopeptide containing the IKVAV sequence (CSRARKQAASIKVAVSADR) from the A chain were covalently bound to the hydroxylated FEP films. Electron Spectroscopy for Chemical Analysis (ESCA) verified the covalent attachment of the oligopeptides to the material surface. The degree of receptor mediated NG108-15 cell attachment on immobilized CDPGYIGSR films was determined using competitive binding media. A 78% reduction in cell attachment was observed on films containing CDPGYIGSR in the cell plating medium. Only a 23% reduction in cell attachment was noted on films plated in medium containing a mock CDPGYIGSK sequence. FEP films immobilized with the IKVAV oligopeptide sequence were shown to mediate PC12 cell attachment and a competitive binding medium also significantly attenuated cell attachment on the immobilized films. The spatial patterning of these oligopeptide sequences to the FEP surface was shown to localize cell attachment and neurite extension on the patterned pathways. The surrounding unmodified FEP surface was inhibitory in serum containing medium and prevented cellular interactions outside the oligopeptide modifications. The spatial immobilization of laminin oligopeptides on FEP films provides a means to organize the attachment and differentiation of neuronal cells in a receptor-specific manner.
Reference Values for Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) and the Ratio of Insulin-Like Growth Factor-I to IGFBP-3 throughout Childhood and Adolescence (2005)

To facilitate the diagnosis of GH deficiency and monitor GH therapy, we constructed two reference models to allow comparison of serum IGF binding protein (IGFBP)-3 concentrations and IGF-I to IGFBP-3 ratios among children throughout childhood and adolescence. This report presents equations for determining the sd score of IGFBP-3 and IGF-I to IGFBP-3 measurements for individual patients. The data set contains serum values from 468 healthy children and adolescents (232 males, 236 females; ages 1.1-18.3 yr) whose height, weight, and body mass index were within +/- 3 sd of means. Puberty was classified according to breast development (B) and testicular volume into pre-, early, mid-, and late puberty. The values of IGFBP-3 and IGF-I to IGFBP-3 ratios were log transformed, and multiple linear regression analysis was used to identify models for converting serum concentrations into sd scores. The models include the variables of age, gender, and puberty and take into account the interactions among these variables. The best linear models explain 42% of the variation in serum IGFBP-3 concentrations and 50% of the variation in serum IGF-I to IGFBP-3 concentrations. The relationship between age and log(IGFBP-3) was positive for boys in pre-, early, and midpuberty. In late puberty, values were higher than earlier in puberty, and there was a negative relationship with age. For girls the relationship between age and log(IGFBP-3) also was positive in pre- and early puberty, with larger effect for girls older than 8 yr. Values for girls in midpuberty were relatively constant, and in late puberty values were higher than earlier in puberty, and there was a negative relationship with age. The relationship between age and log(IGF-I to IGFBP-3 ratio) was positive for boys in pre-, early, and early midpuberty (volume = 9-14 ml). In late midpuberty (volume = 15-19 ml), the relationship between age and IGF-I to IGFBP-3 ratio was negative. In late puberty, values were relatively constant and higher than earlier in puberty. For girls in prepuberty, the relationship with age was positive, with a larger effect in girls older than 8 yr. In early puberty, the girls' values were relatively constant. In early midpuberty (B = 3), log(IGF-I to IGFBP-3 ratio) values were higher for girls than boys of the same age. In late midpuberty (B = 4), the relationship with age was negative, and in late puberty values were relatively constant and higher than earlier in puberty.
Antibody-IL-2 fusion proteins: A novel strategy for immune potentiation (1997)

Advances in genetic engineering and expression systems have led to rapid progress in the development of immunoglobulins fused to other proteins. These ‘antibody fusion proteins’ have novel properties and include antibodies fused to the cytokine interleukin-2. In the present review we describe strat egies for construction of these antibody-interleukin-2 fusion proteins and discuss their in vitro and in vivo properties. Antibody-interleukin-2 fusion proteins retain both antibody associated functions such as antigen binding, complement activation and Fc gamma receptor binding as well as interleukin-2 associated functions such as the stimulation of proliferation of CTLL2 cells. In vivo, they produce strong potentiation of the host immune response against any associated antigen. In addition these novel molecules are able to target tumor cells and produce a specific and effective T cell response capable of eliminating the tumor. These properties suggest that antibody-interleukin-2 fusion proteins will be useful in the diagnosis and/or treatment of human cancer as well as in the potentiation of human immune response against any associated antigen.