gebhart/patrepeval huggingface dataset:
Pulsed Field Ablation Using a Lattice Electrode for Focal Energy Delivery (2020)

PFA using a lattice-tip ablation catheter for focal ablation produced durable atrial lesions and showed lower vulnerability to esophageal or phrenic nerve damage compared with RFA.
Antibody against poly(ethylene glycol) adversely affects PEG‐asparaginase therapy in acute lymphoblastic leukemia patients (2007)

The presence of anti-PEG was very closely associated with rapid clearance of PEG-ASNase. Further comprehensive studies are warranted to fully elucidate the effect of anti-PEG on PEG-conjugated agents. Screening and monitoring for anti-PEG may allow identification of patients for whom a modified dosing strategy or use of a non-PEGylated drug would be appropriate.
Molecular recognition of angiogenesis inhibitors fumagillin and ovalicin by methionine aminopeptidase 2 (1998)

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer and other human diseases. Fumagillin and ovalicin compose a class of structurally related natural products that potently inhibit angiogenesis by blocking endothelial cell proliferation. A synthetic analog of fumagillin, TNP-470, is currently undergoing clinical trials for treatment of a variety of cancers. A common target for fumagillin and ovalicin recently was identified as the type 2 methionine aminopeptidase (MetAP2). These natural products bind MetAP2 covalently, inhibiting its enzymatic activity. The specificity of this binding is underscored by the lack of inhibition of the closely related type 1 enzyme, MetAP1. The molecular basis of the high affinity and specificity of these inhibitors for MetAP2 has remained undiscovered. To determine the structural elements of these inhibitors and MetAP2 that are involved in this interaction, we synthesized fumagillin analogs in which each of the potentially reactive epoxide groups was removed either individually or in combination. We found that the ring epoxide in fumagillin is involved in the covalent modification of MetAP2, whereas the side chain epoxide group is dispensable. By using a fumagillin analog tagged with fluorescein, His-231 in MetAP2 was identified as the residue that is covalently modified by fumagillin. Site-directed mutagenesis of His-231 demonstrated its importance for the catalytic activity of MetAP2 and confirmed that the same residue is covalently modified by fumagillin. These results, in agreement with a recent structural study, suggest that fumagillin and ovalicin inhibit MetAP2 by irreversible blockage of the active site.
Controlled/“Living” Radical Polymerization of Styrene and Methyl Methacrylate Catalyzed by Iron Complexes (1997)

Controlled/“living” radical polymerization of styrene and methyl methacrylate has been achieved by atom transfer radical polymerization (ATRP) catalyzed by iron halide complexes under both homogeneous and heterogeneous conditions. A variety of coordinating ligands have been used including 4,4‘-bis(5-nonyl)-2,2‘-bipyridine, trialkylamines, triphenylphosphine, trialkylphosphines, and trialkylphosphites. The polymer number-average molecular weight (Mn) increases linearly with monomer conversion and matches the predicted molecular weight. The polymerization rate and molecular weight distribution (Mw/Mn = 1.1−1.5) are affected by the structure of the coordinating ligands and the monomers employed.
Lymph node‐induced immune tolerance in chronic lymphocytic leukaemia: a role for caveolin‐1 (2012)

Emerging evidence indicates that the tumour microenvironment (TME) regulates the behaviour of chronic lymphocytic leukaemia (CLL). However, the precise mechanism and molecules involved in this process remain unknown. Gene expression profiles of CLL cells from lymph node (LN), bone marrow (BM) and peripheral blood (PB) indicate overexpression of a tolerogenic signature in CLL cells in lymph nodes (LN-CLL). Based on their role in B cell biology, the progression of CLL, or immune regulation, a few genes of this 83-gene signature were selected for further analyses. We observed a significant correlation between the clinical outcomes and the expression of CAV1 (P = 0·041), FGFR1 isoform 8 (P = 0·032), PTPN6 (P = 0·031) and ZWINT (P < 0·001). CAV1, a molecule involved in the regulation of tumour progression in other cancers, was seven-fold higher in LN-CLL cells compared to BM- and PB-CLL cells. Knockdown of CAV1 expression in CLL cells resulted in significantly decreased migration (P = 0·016) and proliferation (P = 0·04). When CAV1 was knocked down in B and T cell lines, we observed an inability to form immune synapses. Furthermore, CAV1 knockdown in CLL cells impaired their ability to form immune synapses with autologous T lymphocytes and allogeneic, healthy T cells. Subsequent analyses of microarray data showed differential expression of cytoskeletal genes, specifically those involved in actin polymerization. Therefore, we report a novel role for CAV1 in tumour-induced immunosuppression during the progression of CLL.
Adeno-associated Virus Gene Therapy With Cholesterol 24-Hydroxylase Reduces the Amyloid Pathology Before or After the Onset of Amyloid Plaques in Mouse Models of Alzheimer's Disease (2009)

The development of Alzheimer's disease (AD) is closely connected with cholesterol metabolism. Cholesterol increases the production and deposition of amyloid-beta (Abeta) peptides that result in the formation of amyloid plaques, a hallmark of the pathology. In the brain, cholesterol is synthesized in situ but cannot be degraded nor cross the blood-brain barrier. The major exportable form of brain cholesterol is 24S-hydroxycholesterol, an oxysterol generated by the neuronal cholesterol 24-hydroxylase encoded by the CYP46A1 gene. We report that the injection of adeno-associated vector (AAV) encoding CYP46A1 in the cortex and hippocampus of APP23 mice before the onset of amyloid deposits markedly reduces Abeta peptides, amyloid deposits and trimeric oligomers at 12 months of age. The Morris water maze (MWM) procedure also demonstrated improvement of spatial memory at 6 months, before the onset of amyloid deposits. AAV5-wtCYP46A1 vector injection in the cortex and hippocampus of amyloid precursor protein/presenilin 1 (APP/PS) mice after the onset of amyloid deposits also reduced markedly the number of amyloid plaques in the hippocampus, and to a less extent in the cortex, 3 months after the injection. Our data demonstrate that neuronal overexpression of CYP46A1 before or after the onset of amyloid plaques significantly reduces Abeta pathology in mouse models of AD.
Mechanism of lipid‐body formation in prokaryotes: how bacteria fatten up (2004)

Neutral lipid accumulation is frequently observed in some Gram-negative prokaryotes like Acinetobacter sp. and most actinomycetes, including the pathogenic Mycobacterium tuberculosis and antibiotic producing streptomycetes. We examined the formation of wax ester- and triacylglycerol (TAG)-bodies in Acinetobacter calcoaceticus and Rhodococcus opacus using microscopic, immunological and biophysical methods. A general model for prokaryotic lipid-body formation is proposed, clearly differing from the current models for the formation of lipid inclusions in eukaryotes and of poly(hydroxyalkanoic acid) (PHA) inclusions in prokaryotes. Formation of lipid-bodies starts with the docking of wax ester synthase/acyl-CoA:diacylglycerol acyltransferase (WS/DGAT) to the cytoplasm membrane. Both, analyses of in vivo and in vitro lipid-body synthesis, demonstrated the formation of small lipid droplets (SLDs), which remain bound to the membrane-associated enzyme. SLDs conglomerated subsequently to membrane-bound lipid-prebodies which are then released into the cytoplasm. The formation of matured lipid-bodies in the cytoplasm occurred by means of coalescence of SLDs inside the lipid prebodies, which are surrounded by a half-unit membrane of phospholipids.
WLS inhibits melanoma cell proliferation through the β‐catenin signalling pathway and induces spontaneous metastasis (2012)

Elevated levels of nuclear β-catenin are associated with higher rates of survival in patients with melanoma, raising questions as to how ß-catenin is regulated in this context. In the present study, we investigated the formal possibility that the secretion of WNT ligands that stabilize ß-catenin may be regulated in melanoma and thus contributes to differences in ß-catenin levels. We find that WLS, a conserved transmembrane protein necessary for WNT secretion, is decreased in both melanoma cell lines and in patient tumours relative to skin and to benign nevi. Unexpectedly, reducing endogenous WLS with shRNAs in human melanoma cell lines promotes spontaneous lung metastasis in xenografts in mice and promotes cell proliferation in vitro. Conversely, overexpression of WLS inhibits cell proliferation in vitro. Activating β-catenin downstream of WNT secretion blocks the increased cell migration and proliferation observed in the presence of WLS shRNAs, while inhibiting WNT signalling rescues the growth defects induced by excess WLS. These data suggest that WLS functions as a negative regulator of melanoma proliferation and spontaneous metastasis by activating WNT/β-catenin signalling.
Facile synthesis of nanoporous carbons with controlled particle sizes by direct carbonization of monodispersed ZIF-8 crystals (2013)

Nanoporous carbon particles with different particle sizes are synthesized by simple carbonization of monodispersed zeolitic imidazolate framework-8 (ZIF-8) crystals. Quartz crystal microbalance (QCM) study proves that the use of small-sized nanoporous carbon can lead to both a large adsorption uptake and a faster sensor response for toxic toluene molecules.
Fetal gender and aneuploidy detection using fetal cells in maternal blood: analysis of NIFTY I data (2002)

The sensitivity of aneuploidy detection using fetal cell analysis from maternal blood is comparable to single marker prenatal serum screening, but technological advances are needed before fetal cell analysis has clinical application as part of a multiple marker method for non-invasive prenatal screening. The limitations of the present study, i.e. multiple processing protocols, are being addressed in the ongoing study.
A blood-oxygenation-dependent increase in blood viscosity due to a static magnetic field (2004)

As the magnetic field of widely used MR scanners is one of the strongest magnetic fields to which people are exposed, the biological influence of the static magnetic field of MR scanners is of great concern. One magnetic interaction in biological subjects is the magnetic torque on the magnetic moment induced by biomagnetic substances. The red blood cell is a major biomagnetic substance, and the blood flow may be influenced by the magnetic field. However, the underlying mechanisms have been poorly understood. To examine the mechanisms of the magnetic influence on blood viscosity, we measured the time for blood to fall through a glass capillary inside and outside a 1.5 T MR scanner. Our in vitro results showed that the blood viscosity significantly increased in a 1.5 T MR scanner, and also clarified the mechanism of the interaction between red blood cells and the external magnetic field. Notably, the blood viscosity increased depending on blood oxygenation and the shear rate of the blood flow. Thus, our findings suggest that even a 1.5 T magnetic field may modulate blood flow.
Growth stimulative effect of parathyroid hormone, calcitonin and N6,O2'-dibutyryl adenosine 3';5'-cyclic monophosphoric acid on chick embryonic cartilage cultivated in a chemically defined medium. (1980)

PTH (0.5 unit/ml) and CT (0.5 unit/ml) strongly stimulated the in vitro growth of the chick embryo femur in terms of elongation and dry weight increase as well as an increase in the protein, hexosamine, hydroxyproline, DNA and RNA content of the femur. A synergistic effect was observed when PTH and CT were simultaneously added to the medium, suggesting that the mechanism of the growth stimulating effect of one of these hormones might be different from that of the other. The exposure of PTH to the femur caused an increase in cyclic AMP content. The direct addition of dibutyryl cyclic AMP (1 mM) to the medium mimicked the effect of PTH on the cartilage. PTH, therefore, seems to stimulate the growth of cartilage via the increase in cyclic AMP content of the femur. CT had no effect on the cyclic AMP content of the femur.
Linear accelerator output variations and their consequences for megavoltage imaging (1998)

An experimental study of radiation output intensity fluctuations of a Philips SL25 linear accelerator is presented. Measurements are obtained using an electronic portal imaging device, and the consequences of the measured fluctuations for various different applications of megavoltage imaging including portal imaging, transit dosimetry and megavoltage computed tomography (MVCT) are discussed with examples. Fluctuations in output of +/- 0.7% (1 SD) are seen on every radiation pulse after photon noise and uncertainties caused by the detection system have been accounted for. Large fluctuations are also seen during the initial beam stabilization period (15%), during normal accelerator operation after the beam has been on for more than 1 min (4.5%) and during are therapy as a repeatable function of gantry angle (9%). Such output intensity fluctuations are shown to produce image artifacts in portal imaging devices with scanned detector readout and can also produce systematic errors in detector calibration that would lead to uncertainty in transit dose calculations. The propagation of these intensity fluctuations through MVCT image reconstruction is shown to produce ring artifacts in the reconstructed image. Sample portal and MVCT images are presented. All observed fluctuations in accelerator output are well within the manufacturer's specifications and do not affect the total dose delivered during normal treatment. Finally, megavoltage imaging is shown to be a powerful tool for accelerator quality assurance and treatment verification.
Three‐dimensional structure of the complex of 4‐guanidino‐Neu5Ac2en and influenza virus neuraminidase (1995)

Abstract The three‐dimensional X‐ray structure of a complex of the potent neuraminidase inhibitor 4‐guanidino‐Neu5Ac2en and influenza virus neuraminidase (Subtype N9) has been obtained utilizing diffraction data to 1.8 Å resolution. The interactions of the inhibitor, solvent water molecules, and the active site residues have been accurately determined. Six water molecules bound in the native structure have been displaced by the inhibitor, and the active site residues show no significant conformational changes on binding. Sialic acid, the natural substrate, binds in a half‐chair conformation that is isosteric to the inhibitor. The conformation of the inhibitor in the active site of the X‐ray structure concurs with that obtained by theoretical calculations and validates the structure‐based design of the inhibitor. Comparison of known high‐resolution structures of neuraminidase subtypes N2, N9, and B shows good structural conservation of the active site protein atoms, but the location of the water molecules in the respective active sites is less conserved. In particular, the environment of the 4‐guanidino group of the inhibitor is strongly conserved and is the basis for the antiviral action of the inhibitor across all presently known influenza strains. Differences in the solvent structure in the active site may be related to variation in the affinities of inhibitors to different subtypes of neuraminidase.
Targeted Microbubbles for Imaging Tumor Angiogenesis: Assessment of Whole-Body Biodistribution with Dynamic Micro-PET in Mice (2008)

Dynamic micro-PET allows assessment of in vivo biodistribution of VEGFR2-targeted MBs.
Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis (2008)

Angiogenesis-mediated progression of micrometastasis to lethal macrometastasis is the major cause of death in cancer patients. Here, using mouse models of pulmonary metastasis, we identify bone marrow (BM)-derived endothelial progenitor cells (EPCs) as critical regulators of this angiogenic switch. We show that tumors induce expression of the transcription factor Id1 in the EPCs and that suppression of Id1 after metastatic colonization blocked EPC mobilization, caused angiogenesis inhibition, impaired pulmonary macrometastases, and increased survival of tumor-bearing animals. These findings establish the role of EPCs in metastatic progression in preclinical models and suggest that selective targeting of EPCs may merit investigation as a therapy for cancer patients with lung metastases.
Angiotensin II-forming pathways in normal and failing human hearts. (1990)

Reduced preload and afterload to the heart are important effects of angiotensin converting enzyme (ACE) inhibitors in the treatment of congestive heart failure. However, since angiotensin II (Ang II) directly increases the strength of myocardial contraction, suppression of Ang II formation by ACE inhibitors could potentially reduce the beneficial effects of Ang II on the failing heart. To study how ACE inhibition suppresses cardiac Ang II formation in man, we characterized ACE-dependent and ACE-independent Ang II-forming pathways in eight normal and 24 failing human hearts obtained at cardiac transplantation. Ang II-forming activity in left ventricular (LV) membrane preparations was assessed by measuring the conversion of [125I]angiotensin I (Ang I) to [125I]Ang II. LV [125I]Ang II-forming activity in normal hearts (35.5 +/- 2.7 fmol/min/mg, n = 8) was not different from that in hearts from patients with ischemic cardiomyopathy (25.5 +/- 2.9 fmol/min/mg, n = 9) and was 48% lower (p less than 0.001) in hearts from patients with idiopathic cardiomyopathy (18.5 +/- 1.9 fmol/min/mg, n = 15).(ABSTRACT TRUNCATED AT 250 WORDS)
Iodine-131-labeled MAb F(ab')2 fragments are more efficient and less toxic than intact anti-CEA antibodies in radioimmunotherapy of large human colon carcinoma grafted in nude mice. (1990)

During one week, beginning 18 days after transplantation, nude mice bearing human colon carcinoma ranging from 115 to 943 mm3 (mean 335 mm3) were treated by repeated intravenous injections of either iodine-131-(131I) labeled intact antibodies or 131I-labeled corresponding F(ab')2 fragments of a pool of four monoclonal antibodies (MAbs) directed against distinct epitopes of carcinoembryonic antigen (CEA). Complete tumor remission was observed in 8 of 10 mice after therapy with F(ab')2 and 6 of the animals survived 10 mo in good health. In contrast, after treatment with intact MAbs, tumors relapsed in 7 of 8 mice after remission periods of 1 to 3.5 mo despite the fact that body weight loss and depression of peripheral white blood cells, symptoms of radiation toxicity, and the calculated radiation doses for liver, spleen, bone, and blood were increased or equal in these animals as compared to mice treated with F(ab')2.
Involvement of macrophage migration inhibitory factor in the evolution of rat adjuvant arthritis (1998)

These findings demonstrate an important role for MIF in the evolution of rat adjuvant arthritis.
Treatment of Wilsonʼs Disease with Triethylene Tetramine Hydrochloride (Trientine) (1990)

Penicillamine is the drug of choice for the treatment of Wilson's disease, whatever the stage of the illness. Toxic manifestations may preclude the use of this life-saving drug in some patients and discontinuation of penicillamine therapy usually leads to death. We report our experience with Trientine in seven patients, aged 13 to 33 years, with Wilson's disease who developed toxic manifestations with penicillamine that required discontinuation of therapy. These include two with nephrosis, one with neutropenia, two with thrombocytopenia, and one each with a SLE-like and a Henoch-Schonlein-like syndrome. The patients were treated for periods from 6 weeks to 16 years with a dose of 0.5 to 2 g/day. Trientine proved to be an effective alternative copper chelating agent in the treatment of Wilson's disease in patients with penicillamine-induced neutropenia, thrombocytopenia, SLE, and nephrosis. No serious untoward side effects were noted.
Clearance of red cells by monoclonal IgG3 anti-Din vivois affected by the VF polymorphism of FcγRIIIa (CD16) (2003)

Human red cells (RBC) coated with IgG anti-D are cleared from the circulation to the spleen by macrophages which express IgG receptors (Fcgamma R). Polymorphisms of Fcgamma RIIa and Fcgamma RIIIa affect IgG binding in vitro, and may alter the efficiency of clearance of immune complexes in vivo. In a RBC clearance study, 22 Rh D-negative subjects were given 100-400 micro g human monoclonal or polyclonal IgG anti-D i.m. followed 48 h later by 51Cr-labelled D+ RBC. The half lives of the infused D+ RBC were determined, together with the coating levels of anti-D on the D+ RBC. Fcgamma RIIA and FcgammaRIIIA genotyping was performed. Large ranges of phagocytosis and extracellular lysis of RBC in vitro, and of half lives of RBC in vivo, were observed. Clearance of RBC coated with monoclonal IgG3 anti-D (BRAD-3) was more rapid in five subjects homozygous for Fcgamma RIIIa-F/F158 than in three subjects expressing the Fcgamma RIIIa-V158 allele (P = 0.024). This effect was not observed, however, for those individuals given polyclonal anti-D. There was also no significant difference in the efficiency of RBC destruction in vitro or of RBC clearance in vivo between the subjects analysed for individual genotypes or alleles or combinations of alleles. In conclusion, the presence of the Fcgamma RIIIa-V158 allele compromised the efficiency of removal of RBC coated with IgG3 anti-D.
High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids (2012)

High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.
THE TREATY OF WAITANGI - ITS PRESERVATION (1994)

On the 6th February 1840, the Treaty of Waitangi was signed; New Zealand’s founding document. The Treaty remains a ‘living document’ and as such its preservation is of the utmost importance. Much has happened to the Treaty since 1840. It has been stored in basement cupboards; eaten by rodents and generally forgotten. In 1990 the Treaty was displayed for the first time in many years in its new permanent home, the National Archives Constitution Room.
CP-346086 (2003)

A microsomal triglyceride transfer protein (MTP) inhibitor, CP-346086, was identified that inhibited both human and rodent MTP activity [concentration giving half-maximal inhibition (IC50) 2.0 nM]. In Hep-G2 cells, CP-346086 inhibited apolipoprotein B (apoB) and triglyceride secretion (IC50 2.6 nM) without affecting apoA-I secretion or lipid synthesis. When administered orally to rats or mice, CP-346086 lowered plasma triglycerides [dose giving 30% triglyceride lowering (ED30) 1.3 mg/kg] 2 h after a single dose. Coadministration with Tyloxapol demonstrated that triglyceride lowering was due to inhibition of hepatic and intestinal triglyceride secretion. A 2 week treatment with CP-346086 lowered total, VLDL, and LDL cholesterol and triglycerides dose dependently with 23%, 33%, 75%, and 62% reductions at 10 mg/kg/day. In these animals, MTP inhibition resulted in increased liver and intestinal triglycerides when CP-346086 was administered with food. When dosed away from meals, however, only hepatic triglycerides were increased. When administered as a single oral dose to healthy human volunteers, CP-346086 reduced plasma triglycerides and VLDL cholesterol dose dependently with ED50s of 10 mg and 3 mg, and maximal inhibition (100 mg) of 66% and 87% when measured 4 h after treatment. After a 2 week treatment (30 mg/day), CP-346086 reduced total and LDL cholesterol and triglycerides by 47%, 72%, and 75%, relative to either individual baselines or placebo, with little change in HDL cholesterol. Together, these data support further evaluation of CP-346086 in hyperlipidemia.