gebhart/patrepeval huggingface dataset:
Efficacy and Safety of Topical Lysostaphin Treatment of Persistent Nasal Carriage of Staphylococcus aureus (1971)

The efficacy of lysostaphin nasal spray and Neosporin ointment (Burroughs Wellcome & Co.) in altering nasal carriage of Staphylococcus aureus was studied with persistent carriers in an institution for mentally retarded children and adults. Treatment for 5 days with either agent significantly reduced carriage rates. This effect persisted through the 5th day after therapy with lysostaphin but not with Neosporin. By the 11th day after therapy, carriage rates in the treatment and control groups were not significantly different. Except for a single immediate wheal and flair skin test reaction, no other evidence of adverse reactions to topical lysostaphin was detected. No consistent changes in hemagglutination-inhibition titers to lysostaphin were observed after therapy. Lysostaphin appears to be slightly more effective than conventional topical antimicrobial therapy in reducing nasal carriage of staphylococci in this rigorously defined population of persistent carriers.
Insulin-resistant MDA-MB231 human breast cancer cells contain a tyrosine kinase inhibiting activity. (1993)

In most human breast cancer cell lines, insulin, via its own receptor, stimulates cell growth. However, in MDA-MB231 breast cancer cells, insulin at concentration as high as 100 nM has no effect on cell growth, although insulin receptors (IRs) are overexpressed in these cells (29.1 ng IR/10(6) cells), and IR binding characteristics are similar to other breast cancer cell lines. IR tyrosine kinase activity is markedly reduced both in intact MDA-MB231 cells and in isolated IRs purified on a wheat germ agglutinin affinity column. MDA-MB231 cells contain a factor that inhibits both basal and insulin-stimulated IR tyrosine kinase activity in a concentration-dependent manner. This inhibitory activity copurifies with the IR on insulin-Sepharose affinity chromatography and is also effective against the tyrosine kinase activity of the IR-related insulin-like growth factor-I receptor and the oncoprotein v-abl but is ineffective against c-src tyrosine kinase activity. It is possible, therefore, that this tyrosine kinase inhibitor plays a role in regulating the mitogenic potential of the IR in some human breast cancers.
Remapping the Insulin Gene/IDDM2 Locus in Type 1 Diabetes (2004)

Type 1 diabetes susceptibility at the IDDM2 locus was previously mapped to a variable number tandem repeat (VNTR) 5' of the insulin gene (INS). However, the observation of associated markers outside a 4.1-kb interval, previously considered to define the limits of IDDM2 association, raised the possibility that the VNTR association might result from linkage disequilibrium (LD) with an unknown polymorphism. We therefore identified a total of 177 polymorphisms and obtained genotypes for 75 of these in up to 434 pedigrees. We found that, whereas disease susceptibility did map to within the 4.1-kb region, there were two equally likely candidates for the causal variant, -23HphI and +1140A/C, in addition to the VNTR. Further analyses in 2,960 pedigrees did not support the difference in association between VNTR lineages that had previously enabled the exclusion of these two polymorphisms. Therefore, we were unable to rule out -23HphI and +1140A/C having an etiological effect. Our mapping results using robust regression methods show how precisely a variant for a common disease can be mapped, even within a region of strong LD, and specifically that IDDM2 maps to one or more of three common variants in a approximately 2-kb region of chromosome 11p15.
Stem cell factor stimulates neurogenesis in vitro and in vivo (2002)

Cerebral ischemia stimulates neurogenesis in proliferative zones of the rodent forebrain. To identify the signaling factors involved, cerebral cortical cultures prepared from embryonic mouse brains were deprived of oxygen. Hypoxia increased bromodeoxyuridine (BrdU) incorporation into cells that expressed proliferation markers and immature neuronal markers and that lacked evidence of DNA damage or caspase-3 activation. Hypoxia-conditioned medium and stem cell factor (SCF), which was present in hypoxia-conditioned medium at increased levels, also stimulated BrdU incorporation into normoxic cultures. The SCF receptor, c-kit, was expressed in neuronal cultures and in neuroproliferative zones of the adult rat brain, and in vivo administration of SCF increased BrdU labeling of immature neurons in these regions. Cerebral hypoxia and ischemia may stimulate neurogenesis through trophic factors, including SCF.
Sequence specificity of aminoglycoside-induced stop codon readthrough: Potential implications for treatment of Duchenne muscular dystrophy (2000)

As a result of their ability to induce translational readthrough of stop codons, the aminoglycoside antibiotics are currently being tested for efficacy in the treatment of Duchenne muscular dystrophy patients carrying a nonsense mutation in the dystrophin gene. We have undertaken a systematic analysis of aminoglycoside-induced readthrough of each stop codon in human tissue culture cells using a dual luciferase reporter system. Significant differences in the efficiency of aminoglycoside-induced readthrough were observed, with UGA showing greater translational readthrough than UAG or UAA. Additionally, the nucleotide in the position immediately downstream from the stop codon had a significant impact on the efficiency of aminoglycoside-induced readthrough in the order C > U > A > or = G. Our studies show that the efficiency of stop codon readthrough in the presence of aminoglycosides is inversely proportional to the efficiency of translational termination in the absence of these compounds. Using the same assay, we analyzed a 33-base pair fragment of the mouse dystrophin gene containing the mdx premature stop codon mutation UAA (A), which is also the most efficient translational terminator. The additional flanking sequences from the dystrophin gene do not significantly change the relatively low-level aminoglycoside-induced stop codon readthrough of this stop codon. The implications of these results for drug efficacy in the treatment of individual patients with Duchenne muscular dystrophy or other genetic diseases caused by nonsense mutations are discussed.
PinX1 suppresses bladder urothelial carcinoma cell proliferation via the inhibition of telomerase activity and p16/cyclin D1 pathway (2013)

These findings suggest that down-regulation of PinX1 play an important role in the tumorigenesis and development of UCB and that the expression of PinX1 as detected by IHC is an independent molecular marker in patients with UCB.
Four-wave mixing in semi-insulating InP and GaAs using the photorefractive effect (1984)

The photorefractive effect has been observed for the first time in semi-insulating InPe:Fe and GaAsCr. These materials are sensitive and versatile recording media for high bit rate parallel optical processing in the 0.8–1.8-μm spectral region using injection lasers of milliwatt power levels.
Diffusion-Weighted MRI "Claw Sign" Improves Differentiation of Infectious from Degenerative Modic Type 1 Signal Changes of the Spine (2014)

In patients with type 1 signal changes of the vertebral disk space, a claw sign is highly suggestive of degeneration and its absence strongly suggests diskitis/osteomyelitis.
Remyelination of the spinal cord following intravenous delivery of bone marrow cells (2002)

Bone marrow contains a population of pluripotent cells that can differentiate into a variety of cell lineages, including neural cells. When injected directly into the demyelinated spinal cord they can elicit remyelination. Recent work has shown that following systemic delivery of bone marrow cells functional improvement occurs in contusive spinal cord injury and stroke models in rat. We report here that secondary to intravenous introduction of an acutely isolated bone marrow cell fraction (mononuclear fraction) from adult rat femoral bones separated on a density gradient, ultrastructurally defined remyelination occurs throughout a focal demyelinated spinal cord lesion. The anatomical pattern of remyelination was characteristic of both oligodendrocyte and Schwann cell myelination; conduction velocity improved in the remyelinated axons. When the injected bone marrow cells were transfected to express LacZ, beta-galactosidase reaction product was observed in some myelin-forming cells in the spinal cord. Intravenous injection of other myelin-forming cells (Schwann cells and olfactory ensheathing cells) or the residual cell fraction of the gradient did not result in remyelination, suggesting that remyelination was specific to the delivery of the mononuclear fraction. While the precise mechanism of the repair, myelination by the bone marrow cells or facilitation of an endogenous repair process, cannot be fully determined, the results demonstrate an unprecedented level of myelin repair by systemic delivery of the mononuclear cells.
Micromotor-enabled active drug delivery for in vivo treatment of stomach infection (2017)

Advances in bioinspired design principles and nanomaterials have led to tremendous progress in autonomously moving synthetic nano/micromotors with diverse functionalities in different environments. However, a significant gap remains in moving nano/micromotors from test tubes to living organisms for treating diseases with high efficacy. Here we present the first, to our knowledge, in vivo therapeutic micromotors application for active drug delivery to treat gastric bacterial infection in a mouse model using clarithromycin as a model antibiotic and Helicobacter pylori infection as a model disease. The propulsion of drug-loaded magnesium micromotors in gastric media enables effective antibiotic delivery, leading to significant bacteria burden reduction in the mouse stomach compared with passive drug carriers, with no apparent toxicity. Moreover, while the drug-loaded micromotors reach similar therapeutic efficacy as the positive control of free drug plus proton pump inhibitor, the micromotors can function without proton pump inhibitors because of their built-in proton depletion function associated with their locomotion.Nano- and micromotors have been demonstrated in vitro for a range of applications. Here the authors demonstrate the in-vivo therapeutic use of micromotors to treat H. pylori infection.
Escape mechanisms of melanoma from immune system by soluble melanoma antigen. (1988)

We demonstrate in the B16 melanoma (C57BL/6 derived) system that the soluble form of tumor Ag preferentially suppresses immune responses 1) by inhibiting CTL activity in the effector phase and 2) by induction of specific Ts that block CTL generation in the induction phase. Soluble melanoma antigen Ag injected i.p. into the tumor-bearing host can effectively augment melanoma growth in vivo. Two T cell types with the L3T4+ or double-negative/I-J+ phenotype are involved in the suppression of anti-melanoma CTL responses and can easily be generated in the in vitro primary 12 h-culture. Anti-melanoma Ts recognizes the GM3(NeuAc) structure and distinguishes GM3 molecular species. This is because liposomes constructed with GM3(NeuAc) but not with GM3(NeuGc) gangliosides alone can effectively induce the melanoma-specific Ts. It is thus likely that tumor cells can escape from the immunologic surveillance system by stimulating the repertoire of Ts for self-Ag, GM3, which has existed even in the unprimed conditions in order to maintain self-tolerance. These would appear to be the major escape mechanisms.
Lipid profile and incidence of atrial fibrillation: A prospective cohort study in China (2018)

TC and LDL-C levels were inversely associated with incident AF, whereas no significant association of AF with HDL-C or TG levels was observed.
Synthesis of neoglycoconjugates using oligosaccharide transferring activity of ceramide glycanase (1991)

Ceramide glycanase (CGase) isolated from the leech Macrobdella decora was found to transfer the oligosaccharide en bloc from various glycosphingolipids to suitable acceptors. For example, CGase transferred the intact II3NeuAcGgOse4 from GM1 to 4-phenyl-1-butanol, 1,8-octanediol and various 1-alkanols having a chain length of six or more carbons. Among various 1-alkanols, 1-octanol was found to be the best acceptor. In an incubation mixture of 50 microliters containing 30 nmol of GM1, 50 micrograms of sodium cholate, 20 microliters of 1-octanol, and 0.1 unit of CGase, the ratio between hydrolysis and transglycosylation was approximately 3:1. Negative fast atom bombardment-mass spectral analysis of the enzymatically synthesized octyl-II3NeuAcGgOse4 showed a mass ion at m/z 1109.7 for the parent ion, consistent with its expected mass. NMR analysis of the enzymatically synthesized octyl-II3NeuAcGgOse4 showed that the Glc residue is linked to the octanol through a beta-linkage. Vicinal coupling constants of the ring protons of the sugar residues indicate that their pyranose ring geometries are not affected by the transferase activity. CGase also transferred the oligosaccharide from GM1 to CF3CO-NH(CH2)5CH2OH, (CH3)3CO-CO-NH(CH2)5CH2OH, (HOCH2)3C-NHCO-(CH2)4-COOMe, CH2 = CH-(CH2)7CH2OH and 1,2:3,4-di-O-isopropylidene-D-galactopyranose. The oligosaccharide transferring reaction carried out by CGase should become useful for the synthesis of neoglycoconjugates to study the biological functions expressed by glycan chains in glycosphingolipids.
News from the Field (2011)

CHOICE received notification of the approval of its Commercial Interior LEED application
Acquired Resistance of Non–Small Cell Lung Cancer Cells to MET Kinase Inhibition Is Mediated by a Switch to Epidermal Growth Factor Receptor Dependency (2010)

Cancer cells harboring MET amplification display striking sensitivity to selective small molecule inhibitors of MET kinase, prompting their clinical evaluation. Similar to the experience with traditional therapeutics, most patients responding to treatment with such molecular targeted therapeutics ultimately relapse with drug-resistant disease. In this study we modeled acquired resistance to experimental MET kinase inhibitor PF2341066 in MET-amplified non-small cell lung carcinoma (NSCLC) cell lines to identify drug resistance mechanisms that may arise in clinic. We found that activation of the epidermal growth factor receptor (EGFR) pathway emerges as a resistance mechanism in MET-amplified cells after prolonged exposure to PF2341066. Whereas combined inhibition of MET and EGFR kinases in MET-dependent NSCLC cells did not enhance their initial sensitivity to PF2341066, this combination dramatically suppressed the eventual emergence of drug-resistant clones after prolonged drug exposure. Conversely, activation of the EGFR pathway increased the yield of PF2341066-resistant clones, confirming the significance of this pathway in conferring resistance. Our findings support an intimate relationship between the EGFR and MET signaling pathways in NSCLC, and they suggest that combination treatment with MET and EGFR kinase inhibitors may be beneficial in MET-amplified NSCLC by reducing selection for drug resistant clones.
Integrative control of rectoanal reflex in guinea pigs through lumbar colonic nerves (2002)

The aim of the present study was to analyze the neuromodulation of rectoanal reflex activity by lumbar sympathetic nerves in guinea pigs. The mechanical activities of the rectum were recorded with a balloon connected to a pressure transducer, and those of the internal anal sphincter (IAS) were recorded with a custom-made strain gauge force transducer. Gradual and sustained rectal distension evoked the rectoanal reflex, causing cholinergic contractions of the rectum and synchronous nitrergic relaxations of the IAS. Section of the lumbar colonic nerves enhanced both rectal contractions and IAS relaxations. Section of the 13th thoracic cord abolished both rectal contractions and IAS relaxations, but section of the lumbar colonic nerves restored them. Lumbar sympathectomy and pithing sacral cords greatly diminished these rectal contractions and IAS relaxations, but the intrinsic reflex component remained. NG-nitro-L-arginine methyl ester enhanced the intrinsic reflex-mediated contraction of the rectum and abolished reflex-mediated relaxation of the IAS and converted into cholinergic contractions. The present results indicate that the extrinsic lumbar inhibitory outflow causes marked inhibition of the rectoanal reflex via the lumbar colonic nerves.
Eicosapentaenoic Acid Inhibits Oxidation of ApoB-containing Lipoprotein Particles of Different Size In Vitro When Administered Alone or in Combination With Atorvastatin Active Metabolite Compared With Other Triglyceride-lowering Agents (2016)

Eicosapentaenoic acid (EPA) is a triglyceride-lowering agent that reduces circulating levels of the apolipoprotein B (apoB)-containing lipoprotein particles small dense low-density lipoprotein (sdLDL), very-low-density lipoprotein (VLDL), and oxidized low-density lipoprotein (LDL). These benefits may result from the direct antioxidant effects of EPA. To investigate this potential mechanism, these particles were isolated from human plasma, preincubated with EPA in the absence or presence of atorvastatin (active) metabolite, and subjected to copper-initiated oxidation. Lipid oxidation was measured as a function of thiobarbituric acid reactive substances formation. EPA inhibited sdLDL (IC50 ∼2.0 μM) and LDL oxidation (IC50 ∼2.5 μM) in a dose-dependent manner. Greater antioxidant potency was observed for EPA in VLDL. EPA inhibition was enhanced when combined with atorvastatin metabolite at low equimolar concentrations. Other triglyceride-lowering agents (fenofibrate, niacin, and gemfibrozil) and vitamin E did not significantly affect sdLDL, LDL, or VLDL oxidation compared with vehicle-treated controls. Docosahexaenoic acid was also found to inhibit oxidation in these particles but over a shorter time period than EPA. These data support recent clinical findings and suggest that EPA has direct antioxidant benefits in various apoB-containing subfractions that are more pronounced than those of other triglyceride-lowering agents and docosahexaenoic acid.
The origin of the epicardium and the embryonic myocardial circulation in the mouse (1981)

The origin of the epicardium and the formation of the early blood vessels of the heart prior to the opening of the coronary arteries from the aorta have been studied in the 9-13.5 day post coitum (dpc) mouse embryo heart. The epicardium begins to appear by 9 dpc. The majority of the epicardial cells derive from the somatopleural investment of the septum transversum, from where they migrate, associated to form vesicles, to the dorsal aspect of the ventricles and atria. The epicardial cells then migrate over the lateral surfaces and the AV sulcus to the ventral aspect of the heart. In the subepicardial space around the sulci, the proliferating epithelial tissue is found, also in vesicular form, for a time. The ventrally migrating primordial epicardial tissue ensheaths lastly the truncus arteriosus, while the sinus venosus is coated with epicardium ab initio, where (and also in the SA sulcus) the epicardial cells derive in part from the cuboidal cells of the pleuroperitoneal canal and in part from the somatopleural cells. The early blood vessel formation follows in space and time the development of the epicardium. The first blood vessels appear by dpc by the invagination of the endocardium into the early sinus muscle, and at the same time in the ventricular chamber by the encasing of the endocardium, as the trabeculae become consolidated into the myocardial walls. By this process sinusoids are formed, some of which penetrate through the myocardium and which, by rapid proliferation, form an interconnected subepicardial plexus. These capillaries proliferate ventrally in the wide subepicardial space, reaching the septating truncus, in which the aorta and pulmonary artery are developing. The definitive coronary artery openings appear by 13 dpc, allowing the high pressure blood from the aorta to flow into a preexisting vascular bed.
Intrarenal cells, not bone marrow–derived cells, are the major source for regeneration in postischemic kidney (2005)

Ischemic injury to the kidney produces acute tubular necrosis and apoptosis followed by tubular regeneration and recovery of renal function. Although mitotic cells are present in the tubules of postischemic kidneys, the origins of the proliferating cells are not known. Bone marrow cells (BMCs) can differentiate across lineages to repair injured organs, including the kidney. However, the relative contribution of intrarenal cells and extrarenal cells to kidney regeneration is not clear. We produced transgenic mice that expressed enhanced GFP (EGFP) specifically and permanently in mature renal tubular epithelial cells. Following ischemia/reperfusion injury (IRI), EGFP-positive cells showed incorporation of BrdU and expression of vimentin, which provides direct evidence that the cells composing regenerating tubules are derived from renal tubular epithelial cells. In BMC-transplanted mice, 89% of proliferating epithelial cells originated from host cells, and 11% originated from donor BMCs. Twenty-eight days after IRI, the kidneys contained 8% donor-derived cells, of which 8.4% were epithelial cells, 10.6% were glomerular cells, and 81% were interstitial cells. No renal functional improvement was observed in mice that were transplanted with exogenous BMCs. These results show that intrarenal cells are the main source of renal repair, and a single injection of BMCs does not make a significant contribution to renal functional or structural recovery.
Mitogen-activated protein kinases and ribosomal S6 protein kinases are involved in signaling pathways shared by interleukin-11, interleukin-6, leukemia inhibitory factor, and oncostatin M in mouse 3T3-L1 cells. (1994)

The mechanisms of signaling pathways shared by interleukin (IL)-11, IL-6, leukemia inhibitory factor (LIF), and oncostatin M (ONC) remain elusive. We report here that treatment of 3T3-L1 cells with IL-11, IL-6, LIF, and ONC induces overlapping but distinct patterns of tyrosine phosphorylation and activates indistinguishable primary response genes. We further demonstrate for the first time that IL-11, IL-6, LIF, and ONC can trigger the activation of mitogen-activated protein kinases and the 85-92-kDa ribosomal S6 protein kinase (pp90rsk). In addition, our data also show that preincubation of cells with a tyrosine kinase inhibitor herbimycin A, but not with a serine/threonine kinase inhibitor H7, blocks activation of mitogen-activated protein kinases and pp90rsk. Interestingly, H7, but not herbimycin A, inhibits pp90rsk activity in the in vitro kinase assays. These results suggest that pp90rsk is one of the potential candidates for the H7-sensitive protein kinase(s), which is critical for the activation of primary response genes by these cytokines.
Interacting with the SOA-Based Internet of Things: Discovery, Query, Selection, and On-Demand Provisioning of Web Services (2010)

The increasing usage of smart embedded devices in business blurs the line between the virtual and real worlds. This creates new opportunities to build applications that better integrate real-time state of the physical world, and hence, provides enterprise services that are highly dynamic, more diverse, and efficient. Service-Oriented Architecture (SOA) approaches traditionally used to couple functionality of heavyweight corporate IT systems, are becoming applicable to embedded real-world devices, i.e., objects of the physical world that feature embedded processing and communication. In such infrastructures, composed of large numbers of networked, resource-limited devices, the discovery of services and on-demand provisioning of missing functionality is a significant challenge. We propose a process and a suitable system architecture that enables developers and business process designers to dynamically query, select, and use running instances of real-world services (i.e., services running on physical devices) or even deploy new ones on-demand, all in the context of composite, real-world business applications.