gebhart/patrepeval huggingface dataset:
Inhibition of STAT3 activity with AG490 decreases the invasion of human pancreatic cancer cells in vitro (2006)

Signal transducer and activator of transcription 3 (STAT3) is a central cytoplasmic transcription factor. Abnormal activation of STAT3 plays a critical role in oncogenesis and has been found frequently in a wide variety of human tumors including pancreatic cancer. In this study, we elucidated the significance of the STAT3 signaling pathway on metastatic potentials of pancreatic cancer. We found that phosphorylated STAT3 (p-STAT3) protein levels were significantly higher in highly metastatic SW1990 cells compared to the poorly metastatic CaPan-2 cells, which expressed weak levels of this protein. Furthermore, a Janus kinase (JAK) specific inhibitor, AG490, significantly inhibited the expression of p-STAT3, and subsequently reduced invasion and adhesion potential of SW1990 cells compared to the cells treated with vehicle only. Finally, inhibition of the STAT3 signaling pathway by AG490 also led to a decrease in matrix metalloproteinase-2 and vascular endothelial growth factor expression at the protein and mRNA levels. These results demonstrate that activation of the STAT3 signaling pathway plays an important role in the progression of pancreatic cancer and that inhibition of this pathway may be useful for an anti-invasive therapeutic option in pancreatic cancer.
Body Composition and Hormonal Adaptations Associated with Forskolin Consumption in Overweight and Obese Men (2005)

Oral ingestion of forskolin (250 mg of 10% forskolin extract twice a day) for a 12-week period was shown to favorably alter body composition while concurrently increasing bone mass and serum free testosterone levels in overweight and obese men. The results indicate that forskolin is a possible therapeutic agent for the management and treatment of obesity.
The space complexity of approximating the frequency moments (1996)

The frequency moments of a sequence containing mi elements of type i, for 1 i n, are the numbers Fk = P n=1 m k . We consider the space complexity of randomized algorithms that approximate the numbers Fk, when the elements of the sequence are given one by one and cannot be stored. Surprisingly, it turns out that the numbers F0;F1 and F2 can be approximated in logarithmic space, whereas the approximation of Fk for k 6 requires n (1) space. Applications to data bases are mentioned as well.
Dynamics of the Lamellar−Cylindrical Transition in Weakly Segregated Diblock Copolymer Melts (1997)

We investigate the dynamics of the lamellar−cylindrical transition in weakly segregated diblock copolymer melts. We find the limit of stability of the lamellar phase with respect to the cylindrical phase and vice versa. We consider front propagation for stable phases invading metastable phases and compute the velocity and shape of such fronts close to coexistence.
Training staff to empower people with long-term conditions to undertake self care activities. (2010)

Self care can help people with long-term conditions take control of their lives. However, their interest and ability to engage with it may fluctuate over the course of an illness and many need support to undertake self care activities. A team of community matrons in NHS South of Tyne and Wear helped to develop and pilot an e-learning tool for staff, to remind them of the importance of self care and give advice on ways to support patients. The tool has since been rolled out to all staff groups.
Atypical PKCι contributes to poor prognosis through loss of apical-basal polarity and Cyclin E overexpression in ovarian cancer (2005)

We show that atypical PKCiota, which plays a critical role in the establishment and maintenance of epithelial cell polarity, is genomically amplified and overexpressed in serous epithelial ovarian cancers. Furthermore, PKCiota protein is markedly increased or mislocalized in all serous ovarian cancers. An increased PKCiota DNA copy number is associated with decreased progression-free survival in serous epithelial ovarian cancers. In a Drosophila in vivo epithelial tissue model, overexpression of persistently active atypical PKC results in defects in apical-basal polarity, increased Cyclin E protein expression, and increased proliferation. Similar to the Drosophila model, increased PKCiota proteins levels are associated with increased Cyclin E protein expression and proliferation in ovarian cancers. In nonserous ovarian cancers, increased PKCiota protein levels, particularly in the presence of Cyclin E, are associated with markedly decreased overall survival. These results implicate PKCiota as a potential oncogene in ovarian cancer regulating epithelial cell polarity and proliferation and suggest that PKCiota is a novel target for therapy.
Prognostic relevance of B7H1 and B7H3 protein expressions in metastatic clear cell renal cell carcinoma. (2010)

e15074 Background: The aim of the study was evaluate B7-H1 and B7-H3 glycoprotein expressions in tumor tissue of patients with clear cell renal cell carcinoma (CC-RCC). Methods: 78 patients affected by metastatic CC-RCC and undergoing interferon treatment between 1996 and 2005 were included in the study. The tumor tissue on the histopathologic slides was re-evaluated for clear cell origin by a pathologist who regarding primary diagnosis and patients' outcome. Finally, 45/78 patients were eligible. Nephrectomy specimens were immunostained using antibodies targeting B7-H1 and B7-H3 glycoproteins. The stained tumor tissue was scanned and digitized. The regions of positive staining were processed with the Image Scope software and expressed as a certain percentage rate of the predefined tumor-tissue. The percentage of glycoprotein-expression was associated with overall survival using the Kaplan-Meier method and the log rank test. Pathologic parameters of the SSIGN-score defined by the Mayo Clinic were compared with protein expression and survival. Results: There was no significant association between B7-H1 expression and survival or SSIGN-score. In contrast, B7-H3 expression was significantly associated with survival at a cutoff-level of 15% immunoreactivity. Furthermore we found that patients with a SSIGN-score 0-4 showed a 4% lower B7-H3 expression than those with a score 5-13. The multivariate model which included both, glycoproteins and SSIGN-score showed that patients with a SSIGN-score of 4-6, and 0-3, respectively had no survival advantage anymore after 50, 150 months of survival compared to a SSIGN-score of 7-9. Conclusions: In our study the B7-H1 glycoprotein could not be demonstrated as a prognostic factor. In contrast the B7-H3 glycoprotein could be proven as prognostic factor whose amount of expression correlates with survival and malignity (SSIGN-Score) of the CC-RCC. On the other hand according to our results, the SSIGN-Score seems to be a prognostic marker, which loses influence as it comes to advanced survival. In future B7-H3 could be used as an important prognostic factor for adjuvant and targeted therapy methods. No significant financial relationships to disclose.
Imaging vascular mechanics using ultrasound: Phantom and in vivo results (2010)

We introduce a new method for simultaneous imaging of tissue motion and flow with subsample accuracy in both axial and lateral directions. The method utilizes a phase-coupled 2D speckle tracking approach, which employs the true 2D complex cross correlation to find subpixel displacements in both axial and lateral directions. We have also modified the imaging sequence on a Sonix RP scanner to allow high frame rate 2D data collection in a limited field of view covering the region of interest (M2D-mode). Together with the robust 2D speckle tracking method, M2D imaging allows for capturing the full dynamics of the flow and wall/tissue motion, even when the flow is primarily in the lateral direction (with respect to the imaging beam). The fine vector displacement estimates in both axial and lateral directions are shown to allow for smooth and contiguous strain and shear strain calculations with minimal filtering. The quality of the displacement and strain fields is demonstrated by experimental results from a flow phantom (ATS Model 524) and in vivo images of the carotid artery in a healthy volunteer. The results clearly demonstrate the feasibility of simultaneous imaging of the vector flow field and the wall/tissue motion and the corresponding strains at high spatial and temporal sampling. This may provide an essential tool in modeling the fluid-solid interactions between the blood and blood vessel, a key challenge in vascular biomechanics.
Early-life seizures in rats increase susceptibility to seizure-induced brain injury in adulthood (1999)

We concluded that early-life seizures, without causing overt cellular injury, predispose the brain to the damaging effect of seizures later in life.
Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer (2010)

clinicaltrials.gov Identifier: NCT00302744.
Vaccination and type 1 diabetes mellitus (1999)

Papers p 1169 

The massive reduction of invasive disease due to Haemophilus influenzae type b has been an outstanding example of the value of immunisation. However, as has been the case with several vaccines, memory of the devastation caused by the disease rapidly fades and is replaced by concerns about the safety of the vaccine. These are often unfounded, but untold damage can result.1

Coincident with the increase in the number of vaccines given to children there has been a significant rise in the incidence of a number of poorly understood conditions, such as asthma, autism, and diabetes mellitus, has been noted in children in many countries.2 Of course this temporal association does not prove a causal link, and the increase in incidence often predates the introduction of most vaccines. However, the temporal associations have raised questions, and such concerns should not be dismissed out of hand.

Classen and Classen have suggested that immunisation after the age of …
Basic FGF Increases Communication between Cells of the Developing Neocortex (1998)

We have found that basic fibroblast growth factor (bFGF), applied to cortical progenitor cells in vitro, produces an increase in the expression of the gap junction protein connexin (Cx) 43 and in the mRNA encoding Cx 43. This effect was evident in both proliferating and nonproliferating cells. The elevated levels of mRNA suggest that bFGF is likely to exert its effect by upregulating the rate of transcription of the Cx 43 gene. We have further shown that the increase in Cx 43 expression is mediated through the receptor tyrosine kinase pathway and is associated with enhanced intercellular dye-coupling mediated by gap junctions. These results suggest that gap junction channels provide a direct conduit for mitogens released in response to bFGF to effectively regulate proliferation during corticogenesis.
Alterations of Vascular Reactivity in Atherosclerosis (1987)

We have previously found that vascular relaxation to acetylcholine and thrombin is markedly impaired in vessels from monkeys with diet-induced atherosclerosis. In the present study, we found that both normal and atherosclerotic vessels relaxed completely to the calcium ionophore A23187, which stimulates release of the endothelium-derived relaxing factor by nonreceptor-mediated mechanisms. Atherosclerotic vessels, however, were less sensitive to this agent. The finding that responses to the calcium ionophore were impaired in atherosclerosis suggests that abnormal endothelium-dependent relaxation in atherosclerotic vessels is not related entirely to alterations of thrombin and muscarinic receptors but may also be due to abnormal endothelium-derived relaxing factor production or transfer from the endothelium to the underlying vascular smooth muscle. Neither normal nor atherosclerotic iliac arteries constricted in response to acetylcholine when studied in the nonpreconstricted state. Constriction to acetylcholine in these vessels was not unmasked by removal of the endothelium. Thus, the smooth muscle of iliac vessels from monkeys contains few functioning muscarinic receptors. Impaired relaxation of atherosclerotic vessels to acetylcholine is not due to enhanced muscarinicmediated constriction or to production of an endothelium-derived constricting factor. In vivo studies were performed to determine if a-adrenergic coronary vascular constriction is enhanced in the presence of atherosclerosis. In anesthetized monkeys, myocardial oxygen consumption was increased by two mechanisms, aortic occlusion and phenylephrine infusion. During both aortic occlusion and phenylephrine infusion, decreases in coronary vascular resistance were similar in control and atherosclerotic monkeys. If a-adrenergic coronary constriction was enhanced in atherosclerotic coronary arteries, the decrease in coronary vascular resistance would have been blunted in atherosclerotic monkeys. These data suggest that coronary atherosclerosis is not associated with alterations of aadrenergic constriction. Thus, atherosclerosis impairs endothelial modulation of vascular smooth muscle reactivity in response to both receptor-mediated and nonreceptor-mediated agents. In vivo studies of a-adrenergic mediated coronary constriction did not demonstrate augmented responses in atherosclerotic animals. These in vivo and in vitro studies indicate that dietary-induced atherosclerosis in primates alters vascular responses in a heterogeneous manner. (Circulation Research 1987;61(suppl II):
Differential Effects of Commercial-Grade and Purified Poloxamer 188 on Renal Function (2014)

Poloxamer 188 (P188) is a non-ionic amphiphilic copolymer with hemorheologic, antithrombotic, anti-inflammatory, and cytoprotective properties. It potentially has clinical utility in diverse diseases, such as acute myocardial infarction, acute limb ischemia, shock, acute stroke, heart failure, and sickle cell crisis. P188 is available as an excipient-grade product, manufactured to National Formulary specifications, which we refer to as P188-NF. During synthesis of P188-NF, polymerization of its polyoxyethylene and polyoxypropylene components generates undesirable low molecular weight (LMW) substances, such as truncated polymers and glycols. In early clinical studies, P188-NF yielded unexpected renal dysfunction. Here, we explore the nature of the renal dysfunction associated with P188-NF and use a purified (more homogenous) form of P188-NF (P188-P) to show that removal of LMW substances is associated with substantially less renal dysfunction. In both a remnant-kidney animal model and in clinical studies, P188-P demonstrates a substantially improved renal safety profile.
DNA Fiber Fluorescence In Situ Hybridization Analysis of Immunoglobulin Class Switching in B-Cell Neoplasia: Aberrant CH Gene Rearrangements in Follicle Center-Cell Lymphoma (1998)

Abstract Immunoglobulin class switching usually involves deletion of part of the immunoglobulin CH region. By DNA fiber fluorescence in situ hybridization (FISH) with a barcode of probes covering the DH, JH, and CH genes, the configuration of the entire CH region can be visualized on single DNA molecules. Using this technique, we have studied class switching in three types of B-cell neoplasia, mantle-cell lymphoma (MCL), follicular lymphoma (FL) and hairy cell leukemia (HCL), representing B cells in, respectively, pregerminal center, germinal center, and postgerminal center stages of development. In MCL and FL, simultaneous detection of the t(11;14) and t(14;18) breakpoint with probes for the BCL-1 and BCL-2 loci, respectively, allowed differentiation between productive and nonproductive alleles. In none of 10 MCL cases was class switching detected. In 21 HCL, all nonimmunoglobulin M (IgM) cases had class-switch deletion consistent with the expressed isotype on at least one allele. In FL, however, a peculiar pattern of CH rearrangement was observed. In IgM expressing FL, the translocated alleles had switched in 11 of 13 cases, and the nontranslocated allele showed complex rearrangements downstream from the Cμ-Cδ genes in 9 of 13 cases. These downstream rearrangements may reflect tumor-specific deregulation of the class-switch machinery. All seven immunoglobulin G (IgG) expressing FL showed class switching on both alleles. Fiber FISH analysis also showed several polymorphisms. The most frequent one, present on 38% of all analyzed alleles, consisted of an extra Cγ gene or pseudogene in the 3′ cluster. © 1998 by The American Society of Hematology.
SELF-REGULATION OF GROWTH IN THREE DIMENSIONS (1973)

Multi-cell spheroids were grown in soft agar. When each spheroid was cultured in a large volume of medium, frequently renewed, all spheroids eventually reached a dormant phase at a diameter of approximately 3-4 mm and a population of approximately 10(6) cells. In the dormant spheroid, newly generated cells at the periphery balanced those lost by necrosis in the center. We propose that this dormant phase is due to a gradual reduction in the ratio of surface area to volume: a size is achieved beyond which there is insufficient surface area for the spheroid to eliminate catabolites and absorb nutrients. Thus, in the face of unlimited space and of new medium, three-dimensional cell populations become self-regulating. This phenomenon contrasts with standard tissue culture in which cell populations, living on a flat plane in two dimensions, will not stop growing in the face of unlimited space and new medium because the ratio of surface area to volume remains constant. These experiments provide a mechanism for our observations in vivo: before vascularization, solid tumors live by simple diffusion as three-dimensional spheroids or ellipsoids. They become dormant at a diameter of only a few millimeters; once vascularized, they are released from this dormant phase and begin exponential growth. Thus, tumor dormancy resulting from absence of angiogenesis in vivo, may operate by the same mechanism responsible for dormancy of spheroids in vitro.
Transgenic mice expressing IFN-gamma in the retina develop inflammation of the eye and photoreceptor loss. (1994)

IFN-gamma alters the antigenic properties of intraocular tissue and induces intraocular inflammation in mice. The results suggest a key position of IFN-gamma in the development of pathologic conditions related to intraocular inflammation and provide a useful animal model for the further study of inflammatory disorders, including autoimmune diseases.
Hepcidin and iron regulation, 10 years later (2011)

Under evolutionary pressure to counter the toxicity of iron and to maintain adequate iron supply for hemoglobin synthesis and essential metabolic functions, humans and other vertebrates have effective mechanisms to conserve iron and to regulate its concentration, storage, and distribution in tissues. The iron-regulatory hormone hepcidin, first described 10 years ago, and its receptor and iron channel ferroportin control the dietary absorption, storage, and tissue distribution of iron. Hepcidin causes ferroportin internalization and degradation, thereby decreasing iron transfer into blood plasma from the duodenum, from macrophages involved in recycling senescent erythrocytes, and from iron-storing hepatocytes. Hepcidin is feedback regulated by iron concentrations in plasma and the liver and by erythropoietic demand for iron. Genetic malfunctions affecting the hepcidin-ferroportin axis are a main cause of iron overload disorders but can also cause iron-restricted anemias. Modulation of hepcidin and ferroportin expression during infection and inflammation couples iron metabolism to host defense and decreases iron availability to invading pathogens. This response also restricts the iron supply to erythropoietic precursors and may cause or contribute to the anemia associated with infections and inflammatory disorders.
Semisynthesis of cytotoxic proteins using a modified protein splicing element (1998)

Two cytotoxic proteins, bovine pancreatic ribonuclease A (RNase A), and a restriction endonuclease from Haemophilus parainfluenzae (HpaI), were produced using a novel semisynthetic approach that utilizes a protein splicing element, an intein, to generate a reactive thioester at the C-terminus of a recombinant protein. Nucleophilic attack on this thioester by the N-terminal cysteine of a synthetic peptide ultimately leads to the ligation of the two reactants through a native peptide bond. This strategy was used to produce RNase A and HpaI by isolating inactive truncated forms of these proteins, the first 109 and 223 amino acids of RNase A and HpaI, respectively, as fusion proteins consisting of the target protein, an intein, and a chitin binding domain. Thiol-induced cleavage of the precursor led to the liberation of the target protein with a C-terminal thioester-tag. Addition of synthetic peptides representing the amino acids missing from the truncated forms led to the generation of full-length products that displayed catalytic activity indicative of the wild-type enzymes. The turnover numbers and Km for ligated and renatured RNase A were 8.2 s(-1) and 1.5 mM, in good agreement with reported values of 8.3 s(-1) and 1.2 mM (Hodges & Merrifield, 1975). Ligated HpaI had a specific activity of 0.5-1.5 x 10(6) U/mg, which compared favorably with the expected value of 1-2 x 10(6) U/mg (J. Benner, unpubl. obs.). Besides assisting in the production of cytotoxic proteins, this technique could allow the easy insertion of unnatural amino acids into a protein sequence.
Screening for the Preferred Substrate Sequence of Transglutaminase Using a Phage-displayed Peptide Library (2006)

Mammalian transglutaminase (TGase) catalyzes covalent cross-linking of peptide-bound lysine residues or incorporation of primary amines to limited glutamine residues in substrate proteins. Using an unbiased M13 phage display random peptide library, we developed a screening system to elucidate primary structures surrounding reactive glutamine residue(s) that are preferred by TGase. Screening was performed by selecting phage clones expressing peptides that incorporated biotin-labeled primary amine by the catalytic reactions of TGase 2 and activated Factor XIII (Factor XIIIa). We identified several amino acid sequences that were preferred as glutamine donor substrates, most of which have a marked tendency for individual TGases: TGase 2, QxPphiD(P), QxPphi, and QxxphiDP; Factor XIIIa, QxxphixWP (where x and phi represent a non-conserved and a hydrophobic amino acid, respectively). We further confirmed that the sequences were favored for transamidation using modified glutathione S-transferase (GST) for recombinant peptide-GST fusion proteins. Most of the fusion proteins exhibited a considerable increase in incorporation of primary amines over that of modified GST alone. Furthermore, we identified the amino acid sequences that demonstrated higher specificity and inhibitory activity in the cross-linking reactions by TGase 2 and Factor XIIIa.
On the action of ribosome-inactivating proteins: are plant ribosomes species-specific? (1982)

Correspondence| January 15 1982 On the action of ribosome-inactivating proteins: are plant ribosomes species-specific? F Stirpe F Stirpe Search for other works by this author on: This Site PubMed Google Scholar Biochem J (1982) 202 (1): 279–280. https://doi.org/10.1042/bj2020279 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Facebook Twitter LinkedIn MailTo Cite Icon Cite Get Permissions Citation F Stirpe; On the action of ribosome-inactivating proteins: are plant ribosomes species-specific?. Biochem J 15 January 1982; 202 (1): 279–280. doi: https://doi.org/10.1042/bj2020279 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsBiochemical Journal Search Advanced Search This content is only available as a PDF. © 1982 London: The Biochemical Society1982 Article PDF first page preview Close Modal You do not currently have access to this content.