gebhart/patrepeval huggingface dataset:
The Synergy Between Stem Cell Factor (SCF) and Granulocyte Colony-stimulating Factor (G-CSF): Molecular Basis and Clinical Relevance (2002)

Stem cell factor (SCF), an essential growth factor in normal hematopoiesis, exerts potent effects when combined with cytokines. In particular, its synergy with granulocyte colony-stimulating factor (G-CSF) results in important biologic responses. These include enhancement of ex vivo long-term expansion of human primitive hematopoietic cells and increased mobilization of peripheral blood progenitor cells (PBPC) for transplantation. Despite the clinical importance of the interaction between SCF and G-CSF, the absence of a model system in which it could be studied at the cellular level had impaired the ability to understand the basis of their co-operation. To overcome this impediment, a system was recently generated which recapitulates the biologic synergy between SCF and G-CSF. MO7e-G cells have allowed the identification of key events in the synergistic actions of these cytokines on proliferation and gene expression. Among the biochemical and molecular events mediated by these cytokines are the down-regulation of p27kip1 and the independent phosphorylation of STAT3 on tyrosine and serine residues. Recent work has provided increasing evidence for the clinical importance of the combination of SCF and G-CSF. The elucidation of the intracellular events triggered by their receptors is now shedding light on key mediators of their synergistic effects. The identification of these pathways is of considerable importance for understanding fundamental aspects of hematopoiesis, and as potential targets for therapeutic intervention.
Interleukin-13 Induces Tissue Fibrosis by Selectively Stimulating and Activating Transforming Growth Factor β1 (2001)

Interleukin (IL)-13 is a key mediator of tissue fibrosis caused by T helper cell type 2 inflammation. We hypothesized that the fibrogenic effects of IL-13 are mediated by transforming growth factor (TGF)-beta. To test this hypothesis we compared the regulation of TGF-beta in lungs from wild-type mice and CC10-IL-13 mice in which IL-13 overexpression causes pulmonary fibrosis. IL-13 selectively stimulated TGF-beta(1) production in transgenic animals and macrophages were the major site of TGF-beta(1) production and deposition in these tissues. IL-13 also activated TGF-beta(1) in vivo. This activation was associated with decreased levels of mRNA encoding latent TGF-beta-binding protein-1 and increased mRNA encoding urinary plasminogen activator, matrix metalloproteinase (MMP)-9, and CD44. TGF-beta(1) activation was abrogated by the plasmin/serine protease antagonist aprotinin. It was also decreased in progeny of crosses of CC10-IL-13 mice and MMP-9 null mice but was not altered in crosses with CD44 null animals. IL-13-induced fibrosis was also significantly ameliorated by treatment with the TGF-beta antagonist soluble TGFbetaR-Fc (sTGFbetaR-Fc). These studies demonstrate that IL-13 is a potent stimulator and activator of TGF-beta(1) in vivo. They also demonstrate that this activation is mediated by a plasmin/serine protease- and MMP-9-dependent and CD44-independent mechanism(s) and that the fibrogenic effects of IL-13 are mediated, in great extent, by this TGF-beta pathway.
Poly(ethylene glycol) Star Polymer Hydrogels (1998)

Poly(ethylene glycol) (PEG) star polymer hydrogels were prepared by γ-irradiation of aqueous solutions of star PEG polymers. The swelling behavior of these gels in deionized water at 37 °C indicated that the gels prepared from PEG star polymers with a small number of long arms swelled to a greater extent than those prepared from PEG star polymers with a large number of short arms. PEG star polymers and branched PEG polymers were modified to incorporate acrylate groups on the ends of the polymer arms. These acrylated star or branched polymers were copolymerized with poly(ethylene glycol) diacrylate in the presence of UV light. The ensuing materials swelled to a greater extent than hydrogels prepared without acrylated star or branched PEG polymers. Number-average molecular weights were calculated using several rubber elasticity-based theories.
Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer (2006)

Cytokine receptors, which exist in membrane-bound and soluble forms, bind their ligands with comparable affinity. Although most soluble receptors are antagonists and compete with their membrane-associated counterparts for the ligands, certain soluble receptors are agonists. In these cases, complexes of ligand and soluble receptor bind on target cells to second receptor subunits and initiate intracellular signaling. The soluble receptors of the interleukin (IL)-6 family of cytokines (sIL-6R, sIL-11R, soluble ciliary neurotrophic factor receptor) are agonists capable of transmitting signals through interaction with the universal signal-transducing receptor for all IL-6 family cytokines, gp130. In vivo, the IL-6/sIL-6R complex stimulates several types of cells, which are unresponsive to IL-6 alone, as they do not express the membrane IL-6R. We have named this process trans-signaling. The generation of soluble cytokine receptors occurs via two distinct mechanisms-limited proteolysis and translation-from differentially spliced mRNA. We have demonstrated that a soluble form of the IL-6 family signaling receptor subunit gp130, which is generated by differential splicing, is the natural inhibitor of IL-6 trans-signaling responses. We have shown that in many chronic inflammatory diseases, including chronic inflammatory bowel disease, peritonitis, rheumatoid arthritis, asthma, as well as colon cancer, IL-6 trans-signaling is critically involved in the maintenance of a disease state, by promoting transition from acute to chronic inflammation. Moreover, in all these models, the course of the disease can be disrupted by specifically interfering with IL-6 trans-signaling using the soluble gp130 protein. The pathophysiological mechanisms by which the IL-6/sIL-6R complex regulates the inflammatory state are discussed.
Corneal dystrophies and keratoconus (1996)

This year's reports have given us a better understanding of several dystrophies as well as improvements in diagnosis and treatment. Eight corneal dystrophies have now been mapped to specific chromosomes and of these lattice, granular, Avellino, and Reis Bückler's dystrophies map to the same region of chromosome 5q, raising the question whether they are the result of mutations in separate genes or of mutations within alleles of a single gene. Phototherapeutic keratoplasty appears to offer an advantage in the initial treatment of several dystrophies whose symptoms arise from superficial corneal change. Some success has been reported in reducing the degree of hyperopic shift that accompanies deeper ablations. Further support for the genetic basis of keratoconus comes from a study in monozygotic twins and from improvements in quantitative videokeratographic indices, which have also improved our ability to distinguish keratoconus from other topographic abnormalities of the cornea. A new hypothesis for the mechanism of keratoconus proposes that an increased expression of interleukin-1 receptors, acting through a paracrine pathway, may disturb keratocyte activity and turnover, leading to a loss of stromal mass.
Temperature dependence of early and late currents in human cardiac wild-type and long Q-T ΔKPQ Na+ channels (1998)

Na+ current (INa) through wild-type human heart Na+ channels (hH1) is important for normal cardiac excitability and conduction, and it participates in the control of repolarization and refractoriness. INa kinetics depend strongly on temperature, but INa for hH1 has been studied previously only at room temperature. We characterized early INa (the peak and initial decay) and late INa of the wild-type hH1 channel and a mutant channel (DeltaKPQ) associated with congenital long Q-T syndrome. Channels were stably transfected in HEK-293 cells and studied at 23 and 33 degreesC using whole cell patch clamp. Activation and inactivation kinetics for early INa were twofold faster at higher temperature for both channels and shifted activation and steady-state inactivation in the positive direction, especially for DeltaKPQ. For early INa (<24 ms), DeltaKPQ decayed faster than the wild type for voltages negative to -20 mV but slower for more positive voltages, suggesting a reduced voltage dependence of fast inactivation. Late INa at 240 ms was significantly greater for DeltaKPQ than for the wild type at both temperatures. The majority of late INa for DeltaKPQ was not persistent; rather, it decayed slowly, and this late component exhibited slower recovery from inactivation compared with peak INa. Additional kinetic changes for early and peak INa for DeltaKPQ compared with the wild type at both temperatures were 1) reduced voltage dependence of steady-state inactivation with no difference in midpoint, 2) positive shift for activation kinetics, and 3) more rapid recovery from inactivation. This study represents the first description of human Na+ channel kinetics near physiological temperature and also demonstrates complex gating changes in the DeltaKPQ that are present at 33 degreesC and that may underlie the electrophysiological and clinical phenotype of congenital long Q-T Na+ channel syndromes.
Polymeryl Exchange between ansa-Zirconocene Catalysts for Norbornene−Ethene Copolymerization and Aluminum or Zinc Alkyls (2005)

Addition of aluminum or zinc alkyls (AlR3 or ZnR2, R = Me or Et) lowers the molar masses of norbornene−ethene (N/E) copolymers obtained with the catalyst systems Me2C(Ind)(Cp)ZrCl2/MAO or rac-C2H4(2-tBuMe2SiO-Ind)2ZrCl2/MAO to different degrees. These chain-shortening effects and changes in relative end-group abundance indicate the degree to which E/N copolymers growing at a Zr catalyst center are transferred to Al or Zn centers by alkyl−polymeryl exchange. Increased molar masses of copolymers obtained in the presence of added Al(iBu)3 indicate that this reagent suppresses polymer chain exchange between Zr catalyst centers and methylaluminum species contained in the MAO activator. These observations are interpreted in terms of reversible adduct formation between Al or Zn alkyls and cationic zirconocene alkyl species.
Purification and partial characterization of Cob(I)alamin adenosyltransferase from Pseudomonas denitrificans (1991)

Cob(I)alamin adenosyltransferase (EC 2.5.1.17) was purified to homogeneity from extracts of a Pseudomonas denitrificans recombinant strain and sequenced at its N terminus. It is a homodimer (each unit with an Mr of 28,000) encoded by cobO. The enzyme adenosylated all of the corrinoids isolated from this microorganism but did not adenosylate cobyrinic acid.
The cellular fate of mutant rhodopsin: quality control, degradation and aggresome formation (2002)

Mutations in the photopigment rhodopsin are the major cause of autosomal dominant retinitis pigmentosa. The majority of mutations in rhodopsin lead to misfolding of the protein. Through the detailed examination of P23H and K296E mutant opsin processing in COS-7 cells, we have shown that the mutant protein does not accumulate in the Golgi, as previously thought, instead it forms aggregates that have many of the characteristic features of an aggresome. The aggregates form close to the centrosome and lead to the dispersal of the Golgi apparatus. Furthermore, these aggregates are ubiquitinated, recruit cellular chaperones and disrupt the intermediate filament network. Mutant opsin expression can disrupt the processing of normal opsin, as co-transfection revealed that the wild-type protein is recruited to mutant opsin aggregates. The degradation of mutant opsin is dependent on the proteasome machinery. Unlike the situation with DeltaF508-CFTR, proteasome inhibition does not lead to a marked increase in aggresome formation but increases the retention of the protein within the ER, suggesting that the proteasome is required for the efficient retrotranslocation of the mutant protein. Inhibition of N-linked glycosylation with tunicamycin leads to the selective retention of the mutant protein within the ER and increases the steady state level of mutant opsin. Glycosylation, however, has no influence on the biogenesis and targeting of wild-type opsin in cultured cells. This demonstrates that N-linked glycosylation is required for ER-associated degradation of the mutant protein but is not essential for the quality control of opsin folding. The addition of 9-cis-retinal to the media increased the amount of P23H, but not K296E, that was soluble and reached the plasma membrane. These data show that rhodopsin autosomal dominant retinitis pigmentosa is similar to many other neurodegenerative diseases in which the formation of intracellular protein aggregates is central to disease pathogenesis, and they suggest a mechanism for disease dominance.
Treatment of intracranial human glioblastoma by direct intratumoral administration of 131I‐labelled anti‐tenascin monoclonal antibody BC‐2 (1992)

Ten patients with bulky brain glioblastoma, recurring after surgery, radiotherapy or chemotherapy, underwent direct intralesional radioimmunotherapy (RIT) using a monoclonal antibody (MAb), BC-2, raised against tenascin and labelled with 131I. Tenascin, the BC-2-recognized glycoprotein, is an antigen expressed by the stroma of malignant gliomas but not by normal cerebral tissue. Preliminary studies in animals have demonstrated the ability of anti-tenascin radiolabelled MAbs to detect and reduce tumours. A mean MAb dose of 1.93 mg (corresponding to 551.3 MBq of 131I) was injected directly into the tumour by means of a stereotaxic technique. Both systemic and local toxicity were negligible. After 24 hr, average tumour BC-2 uptake was 4.9% per gram and its effective half-life in neoplastic tissue was 66.5 hr: a mean radiation dose to target tissue of 36.48 cGy per MBq of injected 131I was delivered. Normal brain tissue and the major organs were spared. Most patients underwent multiple injections, reaching a cumulative tumour radiation ranging from 7,000 to 41,000 cGy. RIT failed to achieve any result in 4 of the 10 patients; in 3, the disease was stabilized; in the remaining 3, CT scan or NMR revealed 2 partial remission (greater than 50% reduction in tumour volume; PR) and I complete remission (CR). One patient with PR relapsed after II months; the other 2 patients were still maintaining their responses at the time of writing, 17 (CR) and 12 (PR) months after injection.
Low blood concentration of hydroxychloroquine is a marker for and predictor of disease exacerbations in patients with systemic lupus erythematosus (2006)

Low whole-blood HCQ concentrations are associated with SLE disease activity and are a strong predictor of disease exacerbation. Regular drug assaying and individual tailoring of treatment might help to improve the efficacy of HCQ treatment in patients with SLE.
Synthesis of nanogel–protein conjugates (2013)

The covalent conjugation of bovine serum albumin (BSA) to disulfide cross-linked polymeric nanogels is reported. Polymeric nanogel precursors were synthesized via a reversible addition-fragmentation chain transfer (RAFT) random copolymerization of poly(ethylene glycol) methyl ether methacrylate (PEGMA) and pyridyl disulfide methacrylate (PDSMA). Reaction of the p(PEGMA-<i>co</i>-PDSMA) with dithiothreitol resulted in the formation of nanogels. PDSMA serves as both a crosslinking agent and a reactive handle for the surface modification of the nanogels. Lipophilic dye, DiI, was sequestered within the nanogels by performing the crosslinking reaction in the presence of the hydrophobic molecule. Thiol-enriched BSA was conjugated to nanogels loaded with DiI via a disulfide reaction between the BSA and the surface exposed nanogel pyridyl disulfides. Conjugation was confirmed by fast protein liquid chromatography, dynamic light scattering, and agarose and polyacrylamide gel electrophoresis. We expect that this methodology is generally applicable to the preparation of nanogel-protein therapeutics.
Topical Ocular Drug Delivery to Inner Ear Disease and Sinusitis (2006)

Oral steroids are the main therapy for sensorineural deafness. We present the rare case of a patient whose hearing loss associated with inflammation of the inner ear and chronic sinusitis were improved with topical steroid therapy. A 68-year-old male presented with scleritis in the left eye, inflammation of the inner ear and chronic sinusitis. He received oral prednisolone 10 mg/d. However, the oral prednisolone was discontinued due to severe side effects. Topical administration of 0.1% betamethasone sodium phosphate improved the scleritis and incidentally also relieved his symptoms of recurrent otitis and sinusitis after several days. Audiometry revealed recovered acoustic sensation in the right ear, from 50 dB to 20 dB, and in the left ear from 70 to 35 dB with 1,000 Hz. Topical ocular drug delivery of steroids may be effective for inner ear disease and sinusitis in patients with systemic side effects to oral steroids.
Arterial gene transfer of acidic fibroblast growth factor for therapeutic angiogenesis in vivo: critical role of secretion signal in use of naked DNA (1997)

The paracrine effects of a secreted gene product may obviate the need for adjunctive vectors in strategies of arterial gene therapy.
Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer (2008)

The SFRP2 gene is a high-frequent target of epigenetic inactivation in human breast cancer. Its methylation leads to abrogation of SFRP2 expression, conferring a growth advantage to epithelial mammary cells. This altogether supports a tumor suppressive function of SFRP2. Although clinical patient outcome was not associated with SFRP2 methylation, the high frequency of this epimutation and its putative specificity to neoplastic cells may qualify SFRP2 promoter methylation as a potential candidate screening marker helping to improve early breast cancer detection.
Identification of major slowly growing pathogenic mycobacteria and Mycobacterium gordonae by high-performance liquid chromatography of their mycolic acids (1988)

A rapid, reverse-phase high-performance liquid chromatography method was used to detect rho-bromophenacyl mycolic acid ester patterns for strains of four major pathogenic Mycobacterium species and for the most commonly encountered saprophytic species, Mycobacterium gordonae. Mycobacteria in low numbers (2.5 X 10(6) CFU) were detected and identified to the species level. Standard chromatographic patterns characteristic of each species were established. Simple pattern recognition enabled rapid identification of M. tuberculosis, M. kansasii, M. avium, M. intracellulare, and M. gordonae.
Overexpression of Pim-1 in bladder cancer (2010)

Our results in this study suggest that Pim-1 may play a role in bladder cancer initiation and progression. Since Pim-1 is also involved in bladder cancer cell survival and drug resistance, Pim-1 is a potential candidate for targeted therapy in bladder cancer.
Growth inhibition of human tumor cell lines by antisense oligonucleotides designed to inhibit p120 expression. (1993)

The human nucleolar antigen p120 was detected with an anti-p120 monoclonal antibody (MAbp120) in most human malignant tumors (Freeman et al., Cancer Research, 48, 1244-1251, 1988). Stable transfection of the sense p120 cDNA caused malignant transformation of NIH/3T3 cells in vitro, and the antisense p120 constructs markedly delayed the growth of these transformed cells (Perlaky et al., Cancer Research, 52, 428-436, 1992). Several p120 antisense phosphorothioate oligonucleotides designed to hybridize with different regions of the p120 sequence were screened on human tumor cell lines in vitro. Marked growth inhibition of HeLa, LOX and HRCC cell lines was found, particularly with antisense p120 oligonucleotide ISIS 3466 in combination with N-[1-(2,3-dioleyloxy)propyl]-N,N,N-trimethylammonium chloride (DOTMA); oligonucleotide ISIS 3466 is complementary to a non-translated region at the 3' end of the molecule. Preliminary in vivo studies on human LOX ascites tumor in nude mice showed marked inhibitory effects on tumor growth by the antisense oligonucleotide ISIS 3466 in the presence of DOTMA when treated on alternate days.
Nuclear Membrane Dynamics and Reassembly in Living Cells: Targeting of an Inner Nuclear Membrane Protein in Interphase and Mitosis (1997)

The mechanisms of localization and retention of membrane proteins in the inner nuclear membrane and the fate of this membrane system during mitosis were studied in living cells using the inner nuclear membrane protein, lamin B receptor, fused to green fluorescent protein (LBR-GFP). Photobleaching techniques revealed the majority of LBR-GFP to be completely immobilized in the nuclear envelope (NE) of interphase cells, suggesting a tight binding to heterochromatin and/or lamins. A subpopulation of LBR-GFP within ER membranes, by contrast, was entirely mobile and diffused rapidly and freely (D = 0. 41 +/- 0.1 microm2/s). High resolution confocal time-lapse imaging in mitotic cells revealed LBR-GFP redistributing into the interconnected ER membrane system in prometaphase, exhibiting the same high mobility and diffusion constant as observed in interphase ER membranes. LBR-GFP rapidly diffused across the cell within the membrane network defined by the ER, suggesting the integrity of the ER was maintained in mitosis, with little or no fragmentation and vesiculation. At the end of mitosis, nuclear membrane reformation coincided with immobilization of LBR-GFP in ER elements at contact sites with chromatin. LBR-GFP-containing ER membranes then wrapped around chromatin over the course of 2-3 min, quickly and efficiently compartmentalizing nuclear material. Expansion of the NE followed over the course of 30-80 min. Thus, selective changes in lateral mobility of LBR-GFP within the ER/NE membrane system form the basis for its localization to the inner nuclear membrane during interphase. Such changes, rather than vesiculation mechanisms, also underlie the redistribution of this molecule during NE disassembly and reformation in mitosis.
Smooth Muscle Cell Proliferation Is Proportional to the Degree of Balloon Injury in a Rat Model of Angioplasty (1995)

Neointimal proliferation produced by balloon injury is related to balloon inflation pressure, supporting the concept of an SMC proliferative response proportional to the degree of injury. The increase in SMC proliferation is associated with a proportional increase in the early expression of the c-fos nuclear proto-oncogene.