gebhart/patrepeval huggingface dataset:
Pathophysiology of venous thromboembolism. (1991)

Venous thromboembolism is complex with a multifactorial etiology. The Virchow triad (changes in blood flow, changes in vessel wall, and changes in the properties of blood) gives the main factors involved in venous thromboembolism. Venous stasis during immobilization in general anesthesia, stroke with hemiparesis, and heart failure plays a central role. The thromboembolic process can be initiated by a disturbance in the normal "hemostatic balance," with an increased thrombogenic potential, due to release of thromboplastin and collagen exposure during vessel wall injury by stasis and hypoxia, decreased fibrinolysis during surgery, malignancy, among others. Many substances modify these processes, including heparan sulfate, AT III, protein C, t-PA inhibitor, and alpha 2-antiplasmin.
Generation of a Mammalian Cell Line Deficient in Glucose-regulated Protein Stress Induction through Targeted Ribozyme Driven by a Stress-inducible Promoter (1995)

GRP94 is an endoplasmic reticulum (ER) localized glycoprotein with Ca2+ binding and protein chaperoning properties. Using a ribozyme driven by a stress-inducible promoter and targeted against grp94 mRNA, we have generated a cell line deficient in its ability to induce GRP94. The effect of the ribozyme is mediated by the cleavage of the grp94 message just downstream of the initiation codon, and not by an antisense effect, as determined by the level of intact grp94 mRNA. Unexpectedly, this cell line's ability to induce GRP78 is also impaired. Transient overexpression of recombinant human lysosomal hydrolase alpha-L-iduronidase in the ribozyme expressing cells indicates that the secretion ratio of this enzyme is reduced by about 6-fold. Additionally, the ribozyme expressing cells showed increased sensitivity to Ca2+ depletion from ER caused by either A23187 or thapsigargin, an ER-Ca(2+)-ATPase inhibitor, but not to tunicamycin. These combined results show that the induction of GRP94 may play important roles in ER to nuclear signaling, protein sorting and secretion, and specific protection against Ca2+ depletion stress.
DEMINERALIZED PERFORATED BONE IMPLANTS IN CRANIOFACIAL SURGERY (1992)

Between July 1990 and September 1991, demineralized perforated allogeneic bone implants (Pacific Coast Tissue Bank, Los Angeles, CA) were placed in 72 patients. Because many patients received more than one implant, a total of 248 implants were used in 80 procedures. The technology of processing demineralized bone implants is described in detail. All patients were operated on by one surgeon (K.E.S.) at the Humana Craniofacial Institute in Dallas, Texas. Forty-one patients had craniofacial deformities, 16 had secondary deformities following cleft lip and palate repair, 8 had bony defects following removal of tumors, and 10 had various skeletal deformities following trauma. Of the 72 patients, 6 had two surgical procedures during which additional implants were inserted. Implants placed in the cranial vault and the maxillary complex, including alveolar grafts, were inlay grafts, whereas implants placed in the orbital, nasal, paranasal, temporal, and malar areas were onlay grafts used for contouring, augmentation, or both. Complications were limited to delayed wound healing in 6 patients. According to our observations, demineralized perforated bone implants represent an encouraging alternative to autogenous bone grafting. Further clinical and experimental studies are necessary to obtain more information about this material.
IFN‐α enhances CD40 ligand‐mediated activation of immature monocyte‐derived dendritic cells (2002)

Type I IFN are immune modulatory cytokines that are secreted during early stages of infection. Type I IFN bridge the innate and the adaptive immune system in humans and mice. We compared the capacity of type I and II IFN to induce the functional maturation of monocyte-derived dendritic cells (MoDC). Extending our earlier observation that type I IFN promote DC maturation, we report that these cytokines also enhance DC differentiation by augmenting CD40 ligand (CD40L)-induced cytokine secretion by MoDC. Type I IFN alone were poor inducers of MoDC maturation as compared with other stimuli. They up-regulated the expression of HLA-DR, CD80, CD86, partially CCR7 but not CD83, partially reduced antigen-uptake function, increased the levels of IL-12p35 mRNA, and prolonged surface expression of peptide-MHC class I complexes for presentation to cytotoxic T lymphocytes, but did not induce migration towards CCL21 chemokine. However, type I IFN were potent co-factors for CD40L-mediated function. Here, they enhanced CD40L-mediated IL-6, IL-10 and IL-12p70 secretion. Furthermore, when combined with IL-1beta and/or IL-4, IFN-alpha2a type I IFN increased CD40L-mediated IL-12p70 production by 2- to 3-fold, and biased the IL-12 p40/p70 ratio towards the IFN-gamma inducing p70 heterodimer, this correlating with higher levels of IFN-gamma secretion by allogeneic T cell subsets and NK cells. Our results suggest that the rapid expression of CD40L, IFN and IL-1beta at sites of infection and inflammation can act in concert on immature DC, thereby linking innate and adaptive immune responses. In this way, type I IFN play a dual role as DC maturation factors and enhancers of CD40L-mediated DC activation.
Biocompatibility of ferric calcium phosphorous oxide ceramics. (1992)

The objective of this investigation was to ascertain the biocompatability of a ferric calcium phosphorous oxide ceramic (FECAP). The FECAP ceramic was fabricated from stock powders combined in a ratio of 46:40:14 by weight of Fe2O3:CaO:P2O5. The composite oxides were mixed for homogeneity, pressed into a 20g block, and calcined in a crucible at 1100 degrees C for 12 hours. The calcined ceramic was then ground in a ball mill before separation into particle sizes of 38-45 microns and 63-75 microns, by an automatic siever and shaker. Calcined powders of each particle size were mixed with polyvinyl alcohol binder (0.025g PVA/1.0g of FECAP), and pressed into 0.5g pellets in a 5/16" (internal diameter) die at a 1820 kilogram load using a Carver hydraulic press. FECAP pellets were then sintered at 1100 degrees C for 12 hours. For this investigation, sixty albino (Sprague-Dawley) rats weighing 125-425 g each, were distributed into four groups: non-operated controls, sham-operated controls, and two groups subcutaneously implanted with ceramics 38-45 microns and 63-75 microns FECAP ceramics, respectively. Three rats from each group were sacrificed at three, five, seven, and twenty-one days post-surgery. Morphologic examination of the implant and implant site as well as hematocrit data indicate that this ferric-calcium-phosphorous oxide ceramic is biocompatible. Data obtained todate suggest that sintered FECAP should have a wide variety of dental and medical applications, especially where iron deficiency is a concern.
Inducible production of nitric oxide in osteoblast-like cells and in fetal mouse bone explants is associated with suppression of osteoclastic bone resorption. (1994)

Nitric oxide (NO) has been suggested to be involved in the regulation of osteoclast activity. Since osteoblasts, through the release of various factors, are the main regulators of osteoclastic resorption, first we have investigated whether osteoblast-like cells and fetal mouse long bone explants are able to produce NO. Second, we have assessed the effect of NO on osteoclastic resorption in whole bone cultures. In this study we show that primary rat osteoblast-like cells as well as the clonal rat osteoblast-like cell line UMR-106, stimulated with IFN-gamma together with TNF-alpha and LPS, produce NO, measured as nitrite production. IL-1 alpha enhanced while TGF-beta 2 inhibited TNF-alpha + IFN-gamma + LPS-stimulated NO production in UMR-106 cells dose dependently. Both the cytokines, however, had no effect when given alone. The competitive inhibitor of NO production, NG-monomethyl-arginine (L-NMMA), and cycloheximide abolished the increase in nitrite production induced by TNF-alpha + IFN-gamma + LPS, while hydrocortisone had no effect, as previously reported for chondrocytes. Calciotropic hormones had either no effect [1,25(OH)2D3] or had a small inhibitory effect (parathyroid hormone) on stimulated NO production. Furthermore, we found that in cultured fetal mouse long bone explants the combination of TNF-alpha + IFN-gamma + LPS as well as the NO donor sodium nitroprusside could inhibit osteoclastic resorption, measured as 45Ca release. The inhibition of resorption was prevented by concurrent administration of L-NMMA. Histological evaluation revealed that the TNF-alpha + IFN-gamma + LPS-induced inhibition of 45Ca release was associated with a decrease in the number of tartrate-resistant acid phosphatase-positive osteoclasts. We propose that the NO production by osteogenic cells (osteoblasts and chondrocytes) may represent an important regulatory mechanism of osteoclastic activity especially under pathological conditions characterized by release of bone-resorbing inflammatory cytokines.
Recognizing and managing toxicities of molecular targeted therapies for colorectal cancer. (2006)

Traditional therapeutic concepts and treatment regimens for colorectal cancer are currently changing with the demonstration of the efficacy of biologic agents in this disease setting. The addition of the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab (Avastin) to conventional chemotherapy in the first- and second-line settings has shown a survival benefit; this outcome has helped to rapidly change the standard of care. Other targeted agents, such as anti-epidermal growth factor receptor (EGFR) antibodies, have shown proof of efficacy in colorectal cancer as well. The molecular targeted therapies are associated with toxicity profiles that are distinctly different from those seen with conventional chemotherapy. A notable difference is the absence of high risk for myelosuppression, diarrhea, or alopecia, which are common side effects of cytotoxic chemotherapy. This article will explore the toxicities associated with targeted therapies in detail in an attempt to provide assistance to the practicing oncologist in detecting and managing these side effects in their patients. In particular, the article will focus on the side effects associated with the three currently approved targeted drugs: the anti- VEGF monoclonal antibody bevacizumab and the anti-EGFR monoclonal antibodies cetuximab (Erbitux) and panitumumab (Vectibix).
Prelude to the Crisis (1999)

Four features of pre-crisis Indonesia stand out. These centre around the absence of any "early warning" indicators of impending collapse,2 and they set the stage for our subsequent analysis.
Pathogenesis of Shigella Diarrhea: Evidence for a Developmentally Regulated Glycolipid Receptor for Shigella Toxin Involved in the Fluid Secretory Response of Rabbit Small Intestine (1988)

Shigella toxin reproduces the major manifestations of shigellosis in ligated intestinal loops from adult rabbits and binds to a microvillus membrane (MVM) glycolipid receptor, globotriaosylceramide (Gb3). Because neonatal human shigellosis is uncommon, we used the animal model for obtaining MVMs from rabbits of different ages to determine the presence of toxin receptors and Gb3 and to measure the fluid secretory response to toxin in ligated ileal loops. A single class of MVM receptors for 125I-labeled shigella toxin, first detected at 20 d of age, reached adult levels by 24 d (n = 1.7-23.8 X 10(10)/micrograms of protein; K = 1.1-3.8 X 10(9) M-1). Binding was specific for toxin subunit B. A toxin binding MVM glycolipid, identified as Gb3, was detected in animals greater than or equal to 16 d of age by high-performance thin-layer chromatography and autoradiography. Fluid secretion in response to shigella toxin in ligated small bowel loops occurred in temporal relation to the appearance of Gb3, a result thus indicating the involvement of Gb3 in mediating the toxin effects.
Amino acid sequence of the human fibronectin receptor. (1987)

The amino acid sequence deduced from cDNA of the human placental fibronectin receptor is reported. The receptor is composed of two subunits: an alpha subunit of 1,008 amino acids which is processed into two polypeptides disulfide bonded to one another, and a beta subunit of 778 amino acids. Each subunit has near its COOH terminus a hydrophobic segment. This and other sequence features suggest a structure for the receptor in which the hydrophobic segments serve as transmembrane domains anchoring each subunit to the membrane and dividing each into a large ectodomain and a short cytoplasmic domain. The alpha subunit ectodomain has five sequence elements homologous to consensus Ca2+-binding sites of several calcium-binding proteins, and the beta subunit contains a fourfold repeat strikingly rich in cysteine. The alpha subunit sequence is 46% homologous to the alpha subunit of the vitronectin receptor. The beta subunit is 44% homologous to the human platelet adhesion receptor subunit IIIa and 47% homologous to a leukocyte adhesion receptor beta subunit. The high degree of homology (85%) of the beta subunit with one of the polypeptides of a chicken adhesion receptor complex referred to as integrin complex strongly suggests that the latter polypeptide is the chicken homologue of the fibronectin receptor beta subunit. These receptor subunit homologies define a superfamily of adhesion receptors. The availability of the entire protein sequence for the fibronectin receptor will facilitate studies on the functions of these receptors.
Late-Stage Cancer Patients Remain Highly Responsive to Immune Activation by the Selective TLR8 Agonist Motolimod (VTX-2337) (2015)

Late-stage cancer patients are highly sensitive to TLR8 activation by motolimod. Tumor burden, advanced age, and prior treatment history with cytotoxic agents did not moderate or modify the response predicted by nonclinical studies and confirmed in healthy volunteers. Clin Cancer Res; 21(24); 5445-52. ©2015 AACR.
Mania-like behavior induced by disruption of CLOCK (2007)

Circadian rhythms and the genes that make up the molecular clock have long been implicated in bipolar disorder. Genetic evidence in bipolar patients suggests that the central transcriptional activator of molecular rhythms, CLOCK, may be particularly important. However, the exact role of this gene in the development of this disorder remains unclear. Here we show that mice carrying a mutation in the Clock gene display an overall behavioral profile that is strikingly similar to human mania, including hyperactivity, decreased sleep, lowered depression-like behavior, lower anxiety, and an increase in the reward value for cocaine, sucrose, and medial forebrain bundle stimulation. Chronic administration of the mood stabilizer lithium returns many of these behavioral responses to wild-type levels. In addition, the Clock mutant mice have an increase in dopaminergic activity in the ventral tegmental area, and their behavioral abnormalities are rescued by expressing a functional CLOCK protein via viral-mediated gene transfer specifically in the ventral tegmental area. These findings establish the Clock mutant mice as a previously unrecognized model of human mania and reveal an important role for CLOCK in the dopaminergic system in regulating behavior and mood.
New Features in World System Teletext (1984)

World System Teletext is now firmly established as a practical working service in several countries. Operating experience over the past seven years has shown the soundness of the basic concepts, with the ruggedness of the transmissions and economy of the decoders being of vital importance.
Surface modification of silicon and polydimethylsiloxane surfaces with vapor-phase-deposited ultrathin fluorosilane films for biomedical nanodevices (2006)

Ultrathin coatings of fluorosilane films for silicon and polydimethylsiloxane (PDMS) nanochannels are desirable to control the hydrophobicity of the surface and reduce or prevent undesired protein adsorption or cell interactions critical for the performance of most biomedical micro/nanodevices. Surface modifications using vapor-phase deposition become increasingly important for some biomedical nanodevices and have advantages over liquid-phase deposition since the vapor phase can permeate more efficiently into silicon nanochannels. In this study, vapor-phase deposition was used to deposit ultrathin films of four fluorosilanes on silicon and PDMS and identify deposition conditions for an optimal process. The films were characterized by means of a contact angle analyzer for hydrophobicity, an ellipsometer for film thickness, and an atomic force microscope for surface roughness of these films. Results of this study and relevant mechanisms are the subject of this article.
Complete sequence and structure of the gene for human adenosine deaminase (1986)

The nucleotide sequence of the human adenosine deaminase gene was determined. The gene was isolated in a series of overlapping lambda phage clones containing human germ line DNA. A total of 36,741 base pairs were sequenced, including 32,040 base pairs from the transcription initiation site to the polyadenylation site, 3935 base pairs of 5'-flanking DNA, and 766 base pairs of 3'-flanking DNA. The gene contains 12 exons separated by 11 introns. The exons range in size from 62 to 325 base pairs while the introns are 76-15 166 base pairs in size. The area sequenced contains 23 copies of Alu repetitive DNA and a single copy of an "O" family repeat. All but one of these repeat sequences are located in the first three introns or the 5'-flanking region. The apparent promoter region of the gene lacks the "TATA" and "CAAT" sequences often found in eucaryotic promoters and is extremely G/C rich. Contained within this region are areas homologous to other G/C-rich promoters, including six decanucleotide sequences that are highly homologous to sequences identified as functional binding sites for transcription factor Sp1.
High performance detection of biomolecules using a high magnetic field electrospray ionization source/Fourier transform ion cyclotron resonance mass spectrometer (1995)

An improved, high-performance version of the concentric vacuum chamber design is shown for forming ions at high pressure in a strong magnetic field and detecting them in an adjacent Fourier transform ion cyclotron resonance mass spectrometry (FTICR) trapped ion cell. Improvements in system design, including primarily the addition of a mechanical shutter to halt the flow of neutrals to the trapped ion cell during FTICR detection, allow a more than 100-fold improvement in pressure drop between the source and analyzer chamber to be realized. Within a 20 cm distance, ions formed in an electrospray ion source at atmosphere are transported across five concentric tube conductance limits to a trapped ion cell at a shuttered pressure below 2×10−9 Torr. High resolution detection of electrosprayed proteins is demonstrated and, for example, mass resolutions of 1×105 for the +14 charge state of horse heart myoglobin (at m/z 1211) and 2×105 for +5 charge state of bovine insulin (at m/z 1147) are obtained. The original advantages of the concentric tube vacuum chamber are retained. Forming the ions within the magnetic field permits a 40-fold enhancement in sensitivity to be obtained. Narrow kinetic energy distributions are achieved because magnetic field confinement eliminates the need for complex electric focusing assemblies that exhibit mass discrimination and broaden the kinetic energy distribution. Finally, the shutter is demonstrated to serve effectively as an alternative to pulsed valve assemblies for the transient introduction of a collision gas to the trapped ion cell.
Decoding Products of Diversity Pathways from Stock Solutions Derived from Single Polymeric Macrobeads (2001)

Binary encoding with chloroaromatic diazoketone tags allows for efficient decoding from either beads (1) or stock solutions (2), which were derived from a “one-bead, one-stock-solution” chemical technology platform. This process is demonstrated in the partial decoding of a library of 4,320 dihydropyrancarboxamides. Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2002/2001/z17257_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Androgen Receptor as a Therapeutic Target for Androgen Independent Prostate Cancer (2006)

Prostate cancer is the leading cause of nonskin malignancy and the second leading cause of cancer death in men. Androgen deprivation therapy is the first-line of systemic therapy against advanced prostate cancer. All advanced prostate cancers eventually grow despite castrate levels of testosterone. We review the evidence that androgen independent prostate cancer continues to require androgen receptor activity for growth, the mechanisms of androgen receptor activation in the castrate setting, and possible points of intervention for novel therapies targeting the androgen receptor and prostate cancer.
Effect of a Fish Oil–Containing Beverage on Changes in Plasma Lipid Fatty Acids in Patients With Malabsorption (2010)

Some patients with severe malabsorption can absorb oral ω-3 fatty acid supplements and incorporate these fatty acids into serum phospholipids and triglycerides. However, side effects are very common, and no anti-inflammatory effect was found, presumably related to the modest level of fatty acid change.
Recent advances in understanding the cell death pathways activated by anticancer therapy (2005)

Over the past two decades, the role of apoptosis in the cytotoxicity of anticancer drugs has become clear. Apoptosis may occur via a death receptor-dependent (extrinsic) or independent (intrinsic or mitochondrial) pathway. Mitochondria play a central role in cell death in response to DNA damage, and mediate the interaction(s) of various cytoplasmic organelles, including the endoplasmic reticulum, Golgi apparatus, and lysosomes. The mitochondrial pathway of cell death is mediated by Bcl-2 family proteins, a group of antiapoptotic and proapoptotic proteins that regulate the passage of small molecules, such as cytochrome c, Smac/Diablo, and apoptosis-inducing factor, which activates caspase cascades, through the mitochondrial transition pore. In addition, apoptosis can induce autophagic cell death via crosstalk between the two pathways upon treatment with anticancer drugs. The current review focused on recent advances surrounding the mechanism(s) of cell death induced by anticancer agents and discussed potential molecular targets for enhancing the chemotherapeutic effect(s) of anticancer agents.