gebhart/patrepeval huggingface dataset:
Human relaxins in normal, benign and neoplastic breast tissue (1994)

Immunoreactive relaxin is present in human breast cyst fluid and postpartum milk without concurrent detectable serum levels, suggesting that the breast is a site of relaxin synthesis. Monoclonal and polyclonal antibodies to human relaxin H2 have been used to immunolocalize relaxins in normal, benign and neoplastic breast tissues with the avidin-biotin immunostaining technique. In view of the similarities in amino acid sequence between H1 and H2 relaxins, these antibodies to H2 relaxin are likely to detect either or both relaxins present in tissue sections. Staining patterns with these antibodies were identical and showed positive diffuse cytoplasmic staining in normal, lobular and ductal epithelium and in myoepithelial cells in breast tissues from normal prepubertal, cyclic, gestational, lactational and postmenopausal females. Relaxin staining was also present in epithelial and myoepithelial cells of ducts and lobules in benign breast disease as well as in metaplastic epithelium of apocrine microcysts. All breast carcinomas (infiltrating ductal, tubular, medullary, intraductal and infiltrating lobular carcinomas) had strong uniform cytoplasmic staining within the neoplastic epithelial cells. All staining was abolished in normal and neoplastic tissues when the polyclonal antibody was preabsorbed with relaxin. It was necessary to distinguish between the possibilities of relaxins being sequestered by breast tissue and local synthesis. Therefore, the expression of the H1, H2 or both human relaxin genes in normal and neoplastic breast tissues was studied by the isolation of RNA, synthesis of first strand cDNA and amplification by PCR using primer sets which amplified either both H1 and H2, or specifically only H1 or H2 relaxin. The coamplification of both relaxin genes was verified by Southern analysis, diagnostic restriction enzyme digestion and sequencing. The primer set for H1 relaxin detected H1 gene expression in 1 out of 8 normal and 9 out of 12 neoplastic breast RNA samples. The H2 relaxin gene was found to be expressed in 3 out of 8 of the normal samples but in all 12 of the neoplastic samples, suggesting that this gene is expressed at higher copy number in the neoplastic tissues. This is the first demonstration of the cellular immunolocalization of relaxin and relaxin gene expression in normal and neoplastic breast. This should allow further exploration of relaxin's role(s) in normal breast physiology and in its tumorigenesis.
Aprepitant for Erlotinib-Induced Pruritus (2010)

changes in the major coronary arteries or aorta.Microthrombi were noted in the lumen of many small myocardial arteries (Fig. 1A), and there was evidence of an early evolving anterior myocardial infarction.The marrow was hypercellular with clustered hyperlobulated megakaryocytes (Fig. 1B).A peripheral-blood smear was positive for at least one mutated V617F JAK2 allele.Patients with essential thrombocythemia may present with signs of coronary ischemia. 4Recent diagnostic criteria for this disorder have lowered the platelet threshold from 600,000 to 450,000 per cubic millimeter. 5Our patient's fulminant presentation with coronary occlusion, myocardial infarction, and multiple myocardial microthrombi was almost certainly an initial presentation of occult essential thrombocythemia.Screening for the JAK2 mutation is likely to be of value in selected patients with otherwise unexplained coronary ischemic events and mild thrombocytosis and may be useful in patients with other undiagnosed arterial or venous thrombotic disorders.
Dexmedetomidine for sedation in pediatric patients who received more than 20 sessions of radiation therapy: two cases report (2016)

Dexmedetomidine is a highly selective α<sub>2</sub>-adrenoceptor agonist that demonstrates anxiolytic and analgesic properties without inducing respiratory compromise, which makes it a suitable agent for procedural sedation and imaging studies. In our current case reports, intravenous dexmedetomidine infusion was used to provide sedation to 2 pediatric patients over more than 20 sessions of radiation therapy. On both occasions, dexmedetomidine provided adequate sedation without respiratory depression. However, the required dosage increased with repeated radiation therapy sessions.
Use of a cloned double stranded cDNA coding for a major androgen dependent protein in rat seminal vesicle secretion: the effect of testosterone in gene expression (1981)

The abundant class of poly(A+)RNA [poly(A+)RNA11S] from rat seminal vesicle was used to synthesize ds-cDNA11S. The ds-cDNA11S was inserted and cloned into the Pst I site of pBR-322 using E. coli RR1 as host. Colony filter hybridization and restriction mapping was used to demonstrate that a 620 NTP long insert in a plasmid clone (pSV2) represents the almost full length structural gene coding for a precursor to the seminal vesicle secretion protein IV (SVS IV). The entire insert was sequenced and the coding region was matched with the known amino acid sequence. Most of the signal peptide sequence was derived from the DNA sequence. The insert in pSV2 was labelled and used to study the effect of testosterone on the accumulation of mRNA SVS IV. Administration of testosterone to castrated rats resulted in the induction of mRNA SVS IV from a few molecules per cell to levels of over 100,000 after 96 h of hormone treatment.
Cyclopolymerization of N,N-Dipropargylamines and N,N-Dipropargyl Ammonium Salts (2008)

The cyclopolymerization of polar, ionic N,N-dibutyl-N,N-dipropargylammonium bis(trifluoromethylsulfonyl)imide (M1), N,N-dimethyl-N,N-dipropargylammonium bis(trifluoromethylsulfonyl)imide (M2), N,N-dipropargylmorpholinium bis(trifluoromethylsulfonyl)imide (M3), and N-propyl-N,N-dipropargylamine (M4) using five different well-defined Schrock- and trifluoroacetate-modified Grubbs-type initiators was investigated. Ru-based initiators allowed for the polymerization of M1−M3 with average isolated polymer yields around 25−40%, however, poly-M2 and poly-M3 thus prepared consisted >95% of five-membered ring structures, i.e., (3,4-(1H-2,5-dihydropyrrolylene)vinylene)s units. In contrast, the use of the Schrock type initiator Mo(N-2,6-iPr2C6H3)(CHMe2Ph)(OC(CH3)(CF3)2)2 allowed for quantitative polymer yields, whereas, poly-M2 prepared by the action of this initiator was based on both five- and six-membered, i.e., (3,5-(1,2,5,6-tetrahydropyridinylene)methylidene) cyclic units. Polymers were synthesized with molecular weights Mn < 21 800 g/mol and polydispersity indices in the range of 1.04 < PDI < 1.37 and 1.01 < PDI < 1.08 with Ru- and Mo-based initiators, respectively. They were additionally investigated for their thermal stability and ionic conductivity. Finally, the solvatochromic behavior of the polymers prepared was studied. Particularly, solutions of poly-M1 prepared by the action of Ru-based initiators displayed a high sensitivity toward traces of water in N,N-dimethylformamide.
Structure and Solution Dynamics of [(Ph3P)2Pd(Ph)(FHF)] (2000)

The bifluoride complex trans-[(Ph3P)2Pd(Ph)(FHF)] (1) was studied by single-crystal X-ray diffraction, IR, and variable-temperature 1H, 19F, and 31P NMR spectroscopy. Like other transition-metal bifluorides, 1 exhibits fluxional behavior (NMR) in solution at room temperature. When exchange processes are frozen (−60 °C), the solution structure of 1 is consistent with the solid-state X-ray data. Although all structural and spectroscopic data point to MF···HF rather than M···FHF character for 1, 19F NMR magnetization transfer experiments demonstrated a minor contribution of HF dissociation to the exchange. The main process that governs F/F exchange in 1 is intramolecular (ΔH⧧ = 33.7 ± 2.1 kJ mol-1; ΔS⧧ = −56.1 ± 9.6 J mol-1 K-1), likely occurring via pentacoordinate [(Ph3P)2Pd(Ph)(η2-FHF)], in which both fluorines are coordinated to Pd. DFT calculations for two model Pd bifluoride complexes [(R3P)2Pd(Me)(FHF)] (R = H, Me) indicated virtually unrestricted rotation around the Pd−FHF bond.
Clearance of the original hepatitis B virus YMDD-motif mutants with emergence of distinct lamivudine-resistant mutants during prolonged lamivudine therapy (2000)

Tyrosine-methionine-aspartate-aspartate (YMDD)-motif mutants may emerge and elicit immune clearance during prolonged lamivudine treatment. The aim of this study was to investigate the virological events following development of the original mutants. Twenty-three patients who developed YMDD-motif mutants during the Asian lamivudine trial were included. Serial serum samples from these patients were subjected to sequence analysis to identify new mutants. Site-directed mutagenesis experiments were performed to investigate whether the new mutations were responsible for lamivudine resistance. Of the 23 patients included, 13 harbored either one or a mixture of the two common YMDD-motif mutants (methionine 552-to-isoleucine [M552I] and leucine 528-to-methionine/methionine 552-to-valine [L528M/M552V]) throughout the course, whereas in the remaining 10 patients, distinct mutants became dominant over the original mutants to cause continuing chronic hepatitis. Of them, 3 developed an alanine 529-to-threonine (A529T) mutant, 6 developed a leucine 528-to-methionine/methionine 552-to-isoleucine (L528M/M552I) mutant, and 1 developed these two mutants sequentially. Site-directed mutagenesis experiments confirmed that the aforementioned mutations were responsible for the resistance to lamivudine in vitro. The nucleotide substitution in the A529T mutant concomitantly generated a stop codon at the surface gene, leading to impaired secretion of HBsAg. Strikingly, the replication of this mutant was lamivudine dependent. These results suggested that distinct lamivudine-resistant mutants could emerge and replace the original YMDD-motif mutants as the cause of continuing chronic hepatitis during prolonged lamivudine therapy.
A NAC Gene Regulating Senescence Improves Grain Protein, Zinc, and Iron Content in Wheat (2006)

Enhancing the nutritional value of food crops is a means of improving human nutrition and health. We report here the positional cloning of Gpc-B1, a wheat quantitative trait locus associated with increased grain protein, zinc, and iron content. The ancestral wild wheat allele encodes a NAC transcription factor (NAM-B1) that accelerates senescence and increases nutrient remobilization from leaves to developing grains, whereas modern wheat varieties carry a nonfunctional NAM-B1 allele. Reduction in RNA levels of the multiple NAM homologs by RNA interference delayed senescence by more than 3 weeks and reduced wheat grain protein, zinc, and iron content by more than 30%.
Hypotonicity induces membrane protrusions and actin remodeling via activation of small GTPases Rac and Cdc42 in Rat-1 fibroblasts (2003)

An important consequence of cell swelling is the reorganization of the F-actin cytoskeleton in different cell types. We demonstrate in this study by means of rhodamine-phalloidin labeling and fluorescence microscopy that a drastic reorganization of F-actin occurs in swollen Rat-1 fibroblasts: stress fibers disappear and F-actin patches are formed in peripheral extensions at the cell border. Moreover, we demonstrate that activation of both Rac and Cdc42, members of the family of small Rho GTPases, forms the link between the hypotonic stimulation and F-actin reorganization. Indeed, inhibition of the small GTPases RhoA, Rac, and Cdc42 (by Clostridium difficile toxin B) prevents the hypotonicity-induced reorganization of the actin cytoskeleton, whereas inhibition of RhoA alone (by C. limosum C3 exoenzyme) does not preclude this rearrangement. Second, a direct activation and translocation toward the actin patches underneath the plasma membrane is observed for endogenous Rac and Cdc42 (but not for RhoA) during cell swelling. Finally, transfection of Rat-1 fibroblasts with constitutively active RhoA, dominant negative Rac, or dominant negative Cdc42 abolishes the swelling-induced actin reorganization. Interestingly, application of cRGD, a competitor peptide for fibronectin-integrin association, induces identical membrane protrusions and changes in the F-actin cytoskeleton that are also inhibited by C. difficile toxin B and dominant negative Rac or Cdc42. Moreover, cRGD also induces a redistribution of endogenous Rac and Cdc42 to the newly formed submembranous F-actin patches. We therefore conclude that hypotonicity and cRGD remodel the F-actin cytoskeleton in Rat-1 fibroblasts in a Rac/Cdc42-dependent way.
Metal Ions Differentially Influence the Aggregation and Deposition of Alzheimer's β-Amyloid on a Solid Template (2007)

The abnormal deposition and aggregation of beta-amyloid (Abeta) on brain tissues are considered to be one of the characteristic neuropathological features of Alzheimer's disease (AD). Environmental conditions such as metal ions, pH, and cell membranes are associated with Abeta deposition and plaque formation. According to the amyloid cascade hypothesis of AD, the deposition of Abeta42 oligomers as diffuse plaques in vivo is an important earliest event, leading to the formation of fibrillar amyloid plaques by the further accumulation of soluble Abeta under certain environmental conditions. In order to characterize the effect of metal ions on amyloid deposition and plaque growth on a solid surface, we prepared a synthetic template by immobilizing Abeta oligomers onto a N-hydroxysuccinimide ester-activated solid surface. According to our study using ex situ atomic force microscopy (AFM), Fourier transform infrared spectroscopy (FT-IR), and thioflavin T (ThT) fluorescence spectroscopy, Cu2+ and Zn2+ ions accelerated both Abeta40 and Abeta42 deposition but resulted only in the formation of "amorphous" aggregates. In contrast, Fe3+ induced the deposition of "fibrillar" amyloid plaques at neutral pH. Under mildly acidic environments, the formation of fibrillar amyloid plaques was not induced by any metal ion tested in this work. Using secondary ion mass spectroscopy (SIMS) analysis, we found that binding Cu ions to Abeta deposits on a solid template occurred by the possible reduction of Cu ions during the interaction of Abeta with Cu2+. Our results may provide insights into the role of metal ions on the formation of fibrillar or amorphous amyloid plaques in AD.
Novel point mutations leading to type 1 antithrombin deficiency and thrombosis (1991)

Direct sequencing of antithrombin III (AT) gene fragments specifically amplified by the polymerase chain reaction was utilized to identify the molecular basis of type 1 AT deficiency in two unrelated kindreds, both with thrombotic disease. Two novel point mutations were identified, deletion of a T from the second position of codon 81 in one propositus and insertion of a G in codon 424 in the second kindred. The AT 81(-T) frameshift mutation leads to a premature stop signal in codon 89, while the AT 424(+G) allele has a premature stop only one codon short of the normal gene. The latter mutation changes the eight carboxy terminal residues of AT, including 429Cys, and increases the proportion of polar amino acids in this region. We suggest that altered folding of the mutant protein may explain the AT deficiency.
Immunoglobulins, Complement and Foreign Antigens in Human Tumor Cells (1976)

Fluorescein-labeled antibodies (FA) to human immunoglobulins, complement, fetal proteins and other antigens were used to search for these immunologic reactants in malignant and benign neoplasia as well as in control tissues. The FA reacted with five or more target antigens in 42 of 59 (70%) malignant tumors and 21 of 23 (40%) benign tumors. The remaining neoplasia and normal tissues showed positive staining with fewer than five specific antibodies. IgM, IgA, B1C, fetal proteins and HSV were the antigens found most frequently. This indicates that neoplasia exhibits immunologic activity more frequently than normal tissue.
Improved Chemical Synthesis of UDP-Galactofuranose (2001)

[reaction: see text] A reliable and efficient synthetic route to UDP-alpha-D-galactofuranose (UDP-Galf) has been developed. Reaction of UMP-N-methylimidazolide with Galf 1-phosphate proceeds rapidly to provide UDP-Galf with excellent reproducibility and in a yield approximately twice as high as those reported previously.
Investigation of Arsenic-Stressed Yeast (Saccharomyces cerevisiae) as a Bioassay in Homeopathic Basic Research (2011)

This study investigated the response of arsenic-stressed yeast (Saccharomyces cerevisiae) towards homeopathically potentized Arsenicum album, a duckweed nosode, and gibberellic acid. The three test substances were applied in five potency levels (17x, 18x, 24x, 28x, 30x) and compared to controls (unsuccussed and succussed water) with respect to influencing specific growth parameters. Five independent experiments were evaluated for each test substance. Additionally, five water control experiments were analyzed to investigate the stability of the experimental setup (systematic negative control experiments). All experiments were randomized and blinded. Yeast grew in microplates over a period of 38 h in either potentized substances or water controls with 250 mg/l arsenic(V) added over the entire cultivation period. Yeast's growth kinetics (slope, Et50, and yield) were measured photometrically. The test system exhibited a low coefficient of variation (slope 1.2%, Et50 0.3%, yield 2.7%). Succussed water did not induce any significant differences compared to unsuccussed water. Data from the control and treatment groups were both pooled to increase statistical power. In this study with yeast, no significant effects were found for any outcome parameter or any homeopathic treatment. Since in parallel experiments arsenic-stressed duckweed showed highly significant effects after application of potentized Arsenicum album and duckweed nosode preparations from the same batch as used in the present study, some specific properties of this experimental setup with yeast must be responsible for the lacking response.
INTERLEUKIN-1β AND INTERFERON-γ REGULATE INTERLEUKIN-6 PRODUCTION IN CULTURED HUMAN INTESTINAL EPITHELIAL CELLS (1997)

Recent studies suggest that interleukin-6 (IL-6) is produced in the intestinal mucosa during sepsis and endotoxemia and that the enterocyte may be a source of IL-6 in these conditions. The regulation of IL-6 production in the enterocyte is not fully understood. We tested the hypothesis that IL-6 production in the enterocyte is regulated by proinflammatory cytokines. This was done by treating cultured Caco-2 cells, a transformed human intestinal epithelial cell line, with different concentrations of tumor necrosis factor-alpha (TNF-alpha), IL-1 beta, IL-6 or interferon-gamma (IFN-gamma). IL-6 production by the Caco-2 cells was determined by ELISA. The expression of IL-6 mRNA was determined by reverse-transcriptase polymerase chain reaction. IL-6 was not produced in unstimulated Caco-2 cells. Treatment of the Caco-2 cells with IL-1 beta resulted in a dose- and time-dependent stimulation of IL-6 production with a maximal effect noted at an IL-1 beta concentration of .5 ng/mL at 24 h. IFN-gamma alone did not stimulate IL-6 production but potentiated the effect of IL-1 beta in a synergistic fashion. Treatment of the Caco-2 cells with IL-1 beta induced expression of IL-6 mRNA with a response noticed after 30 min. TNF-alpha and IL-6 did not influence the production of IL-6 in the Caco-2 cells. The results suggest that enterocyte IL-6 production is stimulated by IL-1 beta and that this effect is potentiated by IFN-gamma. The regulation of IL-6 production in the enterocyte may be specific for IL-1 beta, since neither TNF nor IL-6 stimulated IL-6 production.
Translation initiation: a critical signalling node in cancer (2009)

Mammalian target of rapamycin (mTOR) is a master regulator of translation initiation that controls the recruitment of ribosomes to mRNA templates in response to intracellular and extracellular cues. Evidence suggests that mTOR and its direct downstream targets, S6K and eIF4E/4E-BP, play significant roles in oncogenesis, and that inhibiting this pathway holds promise as an anti-proliferative approach. Recent genome-wide analyses of mutations in human cancers indicate that transformed cells activate a handful of processes and signalling pathways that are major contributors to their phenotype. Here we review the current literature implicating mTOR and translation initiation downstream of many of these various signalling pathways and processes usurped in human cancers. This review highlights the widespread activation of mTOR/eIF4E following acquisition of oncogenic lesions and its implication in promoting the transformation phenotype and indicates that targeting the control of translation initiation makes logical sense as a broad-acting therapeutic approach.
Animal cell technology : products of today, prospects for tomorrow (1994)

Chairman's statement Making and selecting recombinant cell lines cell line characterisation complex media formulations Protein and / or serum free cultures Ammonia/ Glutamine and other inhibitors Apoptosis and cell biology Perfusion cultures and segregation methods Fixed and Fluidized beds Porus microcarriers hollow fibre bioreactors Novel bioreactors Bioreactor comparisons Novel measurements and assays Physical factors in bioreactors bioreactor operation strategies Kinetics and modelling Downstream processing Products from animal cells in culture Post translational modifications Cells in culture for toxicology studies Product safety and consistency testing.
Temporal modulation of TGF-beta 1 and beta-actin gene expression in pig skin and muscular fibrosis after ionizing radiation. (1993)

Although radiation-induced fibrosis has long been characterized by excess fibroblast proliferation and extracellular matrix deposition, the origin of cell activation in these complications of radiotherapy or radiation accidents is still controversial. The present work was designed to test the hypothesis that the abnormal production of TGF-beta 1 in irradiated tissues results in continuous signals for tissue repair and long-term cell activation. We examined gene expression of this growth factor in a well-characterized pig model of radiation-induced fibrosis, using Northern-blot and slot-blot hybridizations and indirect immunofluorescence. We found that the TGF-beta 1 mRNA level was increased 19-fold in the irradiated skin during the early erythematous phase, which started 3 weeks after irradiation. During the later phases of fibrosis, from 6 to 12 months after irradiation, the TGF-beta 1 gene was highly expressed in the repaired skin and the underlying muscular fibrotic tissue, with 10- and 8-fold maximal increases, respectively. In addition, we found that the beta-actin mRNA level was increased in the fibrotic tissue. Immunostaining for TGF-beta 1 revealed the presence of the protein in endothelial cells of capillaries, in myofibroblasts, and in the collagenous matrix of the fibrotic tissue. These results suggest that TGF-beta 1 may be one of the key cytokines involved in the cascade of events that leads to radiation-induced fibrosis, at both early and late stages.