gebhart/patrepeval huggingface dataset:
Aminoglycoside penetration, inactivation, and efficacy in cystic fibrosis sputum. (1985)

We studied sputum tobramycin concentrations after intravenous administration in 10 cystic fibrosis patients. Tobramycin concentrations were determined by a bioassay and a radioenzymatic assay (REA). The bacterial density of Pseudomonas aeruginosa in sputum was examined serially during therapy. Bioactivity of tobramycin in the sputum was low and increased little during treatment. In contrast, tobramycin content (as assayed by REA) showed a progressive accumulation of the drug to high concentrations: a mean of 82 micrograms/g sputum after 3 wk of therapy in 4 patients. Pseudomonas aeruginosa was eradicated from the sputum in 3 of 4 patients receiving antibiotic therapy for 3 wk. Eradication correlated with tobramycin sputum concentrations measured by REA, which were 20-fold greater than the apparent tobramycin inhibitory concentration. A bactericidal effect of aminoglycosides in the presence of sputum in vitro could only be reliably produced with concentrations 25-fold the MIC. We conclude that tobramycin penetrates cystic fibrosis (CF) sputum and accumulates over time. Although CF sputum antagonized the bioactivity of aminoglycosides, 3 wk of intravenous therapy combined with an antipseudomonal beta-lactam antibiotic may be effective in eradication of P. aeruginosa from sputum of certain CF patients.
Skin impedance from 1 Hz to 1 MHz (1988)

The impedance of skin coated with gel but otherwise unprepared was measured from 1 Hz to 1 MHz at ten sites on the thorax, leg, and forehead of ten subjects. For a 1-cm/sup 2/ area, the 1 Hz impedance varied from 10 k Omega to 1 M Omega , which suggests that the bipotential amplifier input impedance should be very high to avoid common-mode-to-differential-mode voltage conversion. The 1-MHz impedance was tightly clustered about 120 Omega . The 100-kHz impedance was about 220 Omega , which suggests that the variation in skin impedance can cause errors in two-electrode electrical impedance tomographs.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Liposomes from soya phospholipids as percutaneous drug carriers. 1st communication: qualitative in vivo investigations with antibody-loaded liposomes. (1990)

The penetration behaviour of liposome (prepared from NAT 106)-incorporated proteins was investigated in vivo by use of monoclonal antibodies (MOAB) as model substances on the skin of young pigs. Within 20 min of topical application, an even distribution of liposome-incorporated antibodies through all skin layers could be shown by means of an immunohistochemical stain.
Potent Neutralization of MERS-CoV by Human Neutralizing Monoclonal Antibodies to the Viral Spike Glycoprotein (2014)

The recently identified Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe and fatal acute respiratory illness in humans. However, no prophylactic and therapeutic agents specifically against MERS-CoV are currently available. Entry of MERS-CoV into target cells depends on binding of the receptor binding domain (RBD) of the viral envelope spike glycoprotein to the cellular receptor dipeptidyl peptidase 4 (DPP4). We report the isolation and characterization of two potent human RBD-specific neutralizing monoclonal antibodies (MERS-4 and MERS-27) derived from single-chain variable region fragments of a nonimmune human antibody library. MERS-4 and MERS-27 inhibited infection of both pseudotyped and live MERS-CoV with IC50 (half-maximal inhibitory concentration) at nanomolar concentrations. MERS-4 also showed inhibitory activity against syncytia formation mediated by interaction between MERS-CoV spike glycoprotein and DPP4. Combination of MERS-4 and MERS-27 demonstrated a synergistic effect in neutralization against pseudotyped MERS-CoV. Biochemical analysis indicated that MERS-4 and MERS-27 blocked RBD interaction with DPP4 on the cell surface. MERS-4, in particular, bound soluble RBD with an about 45-fold higher affinity than DPP4. Mutagenesis analysis suggested that MERS-4 and MERS-27 recognized distinct regions in RBD. These results suggest that MERS-4 and MERS-27 are RBD-specific potent inhibitors and could serve as promising candidates for prophylactic and therapeutic interventions against MERS-CoV infection.
Antimitotic Diterpenes from Erythropodium caribaeorum Test Pharmacophore Models for Microtubule Stabilization (2000)

[structure: see text] Six new antimitotic diterpenes, 2-7, have been isolated from the Caribbean octocoral Erythropodium caribaeorum. Structural variations encountered in this group of natural products test recently proposed pharmacophore models for microtubule stabilizing compounds.
Conformational changes and flexibility in T-cell receptor recognition of peptide–MHC complexes (2008)

A necessary feature of the immune system, TCR (T-cell receptor) cross-reactivity has been implicated in numerous autoimmune pathologies and is an underlying cause of transplant rejection. Early studies of the interactions of alphabeta TCRs (T-cell receptors) with their peptide-MHC ligands suggested that conformational plasticity in the TCR CDR (complementarity determining region) loops is a dominant contributor to T-cell cross-reactivity. Since these initial studies, the database of TCRs whose structures have been solved both bound and free is now large enough to permit general conclusions to be drawn about the extent of TCR plasticity and the types and locations of motion that occur. In the present paper, we review the conformational differences between free and bound TCRs, quantifying the structural changes that occur and discussing their possible roles in specificity and cross-reactivity. We show that, rather than undergoing major structural alterations or 'folding' upon binding, the majority of TCR CDR loops shift by relatively small amounts. The structural changes that do occur are dominated by hinge-bending motions, with loop remodelling usually occurring near loop apexes. As predicted from previous studies, the largest changes are in the hypervariable CDR3alpha and CDR3beta loops, although in some cases the germline-encoded CDR1alpha and CDR2alpha loops shift in magnitudes that approximate those of the CDR3 loops. Intriguingly, the smallest shifts are in the germline-encoded loops of the beta-chain, consistent with recent suggestions that the TCR beta domain may drive ligand recognition.
Lymphocyte Reactivity Contributes to Protection Conferred by Specific Antibody Passively Transferred to Herpes Simplex Virus-Infected Mice (1980)

Passively acquired immunity to herpes simplex virus (HSV) was studied in antithymocyte serum (ATS)-treated mice and athymic nude mice to determine whether immunocompetent lymphocytes contribute to the protection observed after transfer of HSV-specific antibody to infected animals. Mice were given three intraperitoneal injections of 0.1 ml of ATS at 24-h intervals. This treatment reduced concanavalin A and lipopolysaccharide stimulation of lymphocytes harvested from these animals by 90% when compared with the stimulation of lymphocytes harvested from untreated animals. It was found that intraperitoneal injection of 0.5 ml of specific antibody 8 h after corneal HSV type 1 infection or subcutaneous HSV type 2 infection did not protect ATS-treated animals from virus infection. Specific antibody passively transferred to ATS-treated animals 8 and 120 h postinfection also failed to protect lymphocyte-depleted animals from HSV. However, ATS-treated animals were protected from HSV infection by passively acquired antibody when lymphocytes harvested from these animals regained 80% of their ability to be stimulated with concanavalin A and lipopolysaccharide. It was also found that specific antibody conferred protection to nude mice infected with HSV only if they were first reconstituted with syngeneic thymus cells 48 h before infection. The results suggest that both antiviral antibody and thymus-derived lymphocytes contribute to the recovery of HSV-infected hosts after passive immunization.
Dependence of autocrine growth factor stimulation in platelet-derived growth factor-B-induced mouse brain tumor cells (2000)

In human gliomas, platelet-derived growth factor (PDGF) ligand and receptor mRNA are often co-expressed, which suggests the presence of an autocrine loop. To further investigate the significance of PDGF stimulation in brain tumors, we used a previously developed mouse tumor model, in which malignant brain tumors of neuroepithelial origin were induced by injecting a murine retrovirus containing the human PDGF B-chain gene into the brains of neonatal mice. In the present investigation, we have characterized a cell line established from such an experimentally induced tumor in an INK4a-/- mouse. Cultured tumor cells expressed nestin and NG2 chondroitin sulfate proteoglycan and are thus most likely derived from an oligodendrocyte precursor cell. Tumor cells produced PDGF-B protein and displayed constitutively activated PDGF alpha receptors. Autocrine receptor activation could be blocked with the specific PDGF receptor tyrosine kinase inhibitor CGP 57148B, which led to almost complete inhibition of cell proliferation, which was much less affected by a PDGF B-chain aptamer that inhibits binding of PDGF-B to PDGF receptors and is unlikely to be able to pass through the plasma membrane. Our results imply an important role for PDGF autocrine stimulation in both initiation and progression of a subtype of gliomas.
Gamma-Hydroxybutyrate (2002)

Gamma-hydroxybutyrate (GHB) has come a long way since early experiments in animals where it was found to induce a sleep-like state and from its use in general anaesthesia in human subjects. It has been found to be a naturally-occurring compound in the brain, a metabolite of GABA, the emerging ubiquitous inhibitory neurotransmitter. This has opened
Simulation of Endovascular Neurointervention Using Silicone Models: Imaging and Manipulation (2005)

Silicone models of cerebral aneurysm and stroke pathology were produced by copying the images of clinical cases to evaluate the simulation of endovascular procedures. Conventional silicone models, silicone suture models made from separate aneurysm sac and parent artery sutured together, and animal vascular models made from vessels obtained from pigs were made. The models were incorporated in the training system for simulation of endovascular procedures under digital subtraction angiography control using a portable angiography system. The conventional silicone models provided very close reproduction of the aneurysm and vessels, even the fine branches. However, greater resistance or impact was felt, especially when passing the device through curved vessels. Stroke models were insufficiently dilated by percutaneous transluminal angioplasty or stenting. The silicone suture model was useful to avoid damage to models of giant aneurysm or models with small orifices during the lost wax procedure, whereas the projection of domes was somewhat inaccurate. The animal vascular model could not provide accurate aneurysm shape and vessel diameter, although the feel during manipulation was much more realistic.
Upper Airway Stimulation for Obstructive Sleep Apnea: Past, Present, and Future (2015)

Obstructive sleep apnea (OSA) is an increasingly prevalent clinical problem with significant effects on both personal and public health. Continuous positive airway pressure (CPAP) has demonstrated excellent efficacy and low morbidity; long-term adherence rates approach 50%. Although traditional upper airway surgical procedures target the anatomic component of obstruction, upper airway stimulation tackles the twin goals of improving anatomic and neuromuscular pathology. After decades of trials demonstrating proof of concept of hypoglossal nerve stimulation in animal and human subjects, the results of a large multicenter, prospective trial were recently published. The trial demonstrated that hypoglossal nerve stimulation led to significant improvements in objective and subjective measurements of the severity of OSA. This novel approach is the first to combine sleep surgery techniques with a titratable medical device for the treatment of OSA. Further research is required to define optimal patient selection and device performance and to demonstrate long-term effectiveness.
Quantitative aspects of the interaction of bile acids with human serum albumin. (1982)

The interaction of human serum albumin with twelve bile acids (ba) has been studied by equilibrium dialysis technique using 3H- and 14C-labeled bile acids. The physiological bile acids studied were: cholic, chenodeoxycholic, deoxycholic, lithocholic, ursodeoxycholic, and 7-ketolithocholic acids, all in the free and conjugated (with glycine and taurine) forms. For each bile acid studied, the interaction was characterized by two classes of binding sites, the first consisting of 2--4 sites and the second of 8--30. K1 values (liter/mol) for the different bile acids were: cholic acid, 0.3 x 10(4); chenodeoxycholic acid, 5.5 x 10(4); deoxycholic acid, 4.0 x 10(4); ursodeoxycholic acid, 3.8 x 10(4); 7-ketolithocholic acid, 1.9 x 10(4); lithocholic acid, 20 x 10(4). The affinity constant of a bile acid for albumin decreases with an increase in the number of hydroxy groups and also with the replacement of 7-hydroxy by 7-keto groups. The affinity constant is similar for glycine and taurine conjugated bile acids, but is slightly higher for unconjugated than conjugated forms.
Predicting the Size of the Progeny Mapping Population Required to Positionally Clone a Gene (2007)

A key frustration during positional gene cloning (map-based cloning) is that the size of the progeny mapping population is difficult to predict, because the meiotic recombination frequency varies along chromosomes. We describe a detailed methodology to improve this prediction using rice (Oryza sativa L.) as a model system. We derived and/or validated, then fine-tuned, equations that estimate the mapping population size by comparing these theoretical estimates to 41 successful positional cloning attempts. We then used each validated equation to test whether neighborhood meiotic recombination frequencies extracted from a reference RFLP map can help researchers predict the mapping population size. We developed a meiotic recombination frequency map (MRFM) for approximately 1400 marker intervals in rice and anchored each published allele onto an interval on this map. We show that neighborhood recombination frequencies (R-map, >280-kb segments) extracted from the MRFM, in conjunction with the validated formulas, better predicted the mapping population size than the genome-wide average recombination frequency (R-avg), with improved results whether the recombination frequency was calculated as genes/cM or kb/cM. Our results offer a detailed road map for better predicting mapping population size in diverse eukaryotes, but useful predictions will require robust recombination frequency maps based on sampling more progeny.
Characterization of a cell surface glycoprotein IPO-3, expressed on activated human B and T lymphocytes. (1993)

We characterize the expression, biochemical structure, and function of a novel glycoprotein, IPO-3, up-regulated on activated human lymphocytes. IPO-3 is found on activated B cells, B cell lines, and hairy cell leukemias but is not expressed on T cell or nonlymphoid cell lines. IPO-3 is not B cell-specific as it is detected at low levels on CD45RO+ CD45RA- peripheral blood T cells and CD4+CD8+CD45RO+ CD45RA- thymocytes. The IPO-3 Ag is a single-chain heavily N-glycosylated phosphoglycoprotein approximately 75 to 95 kDa in size with a 42-kDa protein core. In vitro kinase assays revealed that IPO-3 has a protein kinase activity associated with it that is maintained even in Nonidet P-40 lysates. IPO-3 is up-regulated on resting B cells within 16 h after activation with different signals including anti-IgM, IL-4, or mAb to CD40, CD20, or Bgp95. It could also be induced on T cells via CD3-cross-linking, but the kinetics of IPO-3 induction was slower on T cells than on B cells. Cross-linking IPO-3 on B cells with mAb did not induce proliferation alone but did augment proliferation promoted by IL-4 and anti-CD40 and did trigger increases in [Ca2+]i in resting B cells. Binding of IPO-3 could not be inhibited by a variety of mAb to previously identified activation markers. Thus, the IPO-3 glycoprotein appears to be a novel marker of activated B and T lymphocytes, which may play a role in the regulation of lymphocyte activation.
Monoclonal Anti-Idiotype Antibodies Against the Murine B Cell Lymphoma 38C13: Characterization and Use as Probes for the Biology of the Tumor In Vivo and In Vitro (1985)

To establish a murine model for the monoclonal anti-idiotype immunotherapy of B cell lymphoma, a panel of rat and murine monoclonal anti-idiotype antibodies of several different isotypes was generated against the surface immunoglobulin of the murine B cell tumor 38C13 (38C). Xenogeneic antibodies were made from fusions of rat spleen cells immunized with the 38C idiotype. Syngeneic monoclonal anti-idiotypes were generated from mice immunized with the idiotype conjugated to the protein carrier KLH. Small differences were noted in the ability of the antibodies to cross-block one another, but all appeared to be directed against the same or closely spaced idiotopes on the immunoglobulin molecule. The antibodies selectively precipitated surface Ig from 38C tumor cells and not from normal mouse spleen cells. They were used to selectively stain 38C tumor cells in cell suspensions for FACS analysis or immunohistochemical staining of tissue sections from mice bearing the tumor. As the malignancy progressed, the number of tumor cells found in all tissues examined increased. Thus, the anti-Id antibodies provided a specific probe for tumor cell detection. The antibodies had no detectable effect on cell growth in vitro; however, they did cause the rapid transient loss of the expression of cell surface Ig. This modulation was concentration and time dependent but not 100% complete. Re-expression of the Id occurred by 24 h following removal of the anti-Id antibodies. When these antibodies were used in sensitive radioisotope and enzyme linked immunoassays, the tumor cells were found to secrete small amounts of idiotype in vitro and in vivo. The level of idiotype detected in vivo correlated with tumor growth and inversely with survival. This work is an attempt to develop further an animal model system in which to test the diagnostic and therapeutic effects of monoclonal anti-idiotype antibodies.
Effects of different anti‐tau antibodies on tau fibrillogenesis: RTA‐1 and RTA‐2 counteract tau aggregation (2005)

Tau is the major antigenic component of neurofibrillary pathology in tauopathy, including Alzheimer's disease. Although conversion of soluble tau to an insoluble polymerized fibrillar form is a key factor in the pathogenesis of tauopathy, the mechanism of the change is unclear and no inhibitors of fibril formation are available. Monoclonal antibodies against the 1st or 2nd repeat of the microtubule binding domain, but not the C-terminal 16 residues, completely inhibited tau aggregation into PHF. Furthermore, they did not inhibit tau-induced tubulin assembly. Thus, they are useful to investigate tau protein conversion and will be useful therapeutic lead materials.
Cationic Alkylaluminum-Complexed Zirconocene Hydrides as Participants in Olefin Polymerization Catalysis (2010)

The alkylaluminum-complexed zirconocene trihydride cation [(SBI)Zr(μ-H)(3)(Al(i)Bu(2))(2)](+), which is obtained by reaction of (SBI)ZrCl(2) with [Ph(3)C][B(C(6)F(5))(4)] and excess HAl(i)Bu(2) in toluene solution, catalyzes the formation of isotactic polypropene when exposed to propene at -30 °C. This cation remains the sole observable species in catalyst systems free of AlMe compounds. In the presence of AlMe(3), however, exposure to propene causes the trihydride cation to be completely converted, under concurrent consumption of all hydride species by propene hydroalumination, to the doubly Me-bridged cation [(SBI)Zr(μ-Me)(2)AlMe(2)](+). The latter then becomes the resting state for further propene polymerization, which produces, by chain transfer to Al, mainly AlMe(2)-capped isotactic polypropene.
Antihyperalgesic effect of aCannabis sativaextract in a rat model of neuropathic pain: mechanisms involved (2008)

This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1. The non-psychoactive compound, cannabidiol, is the only component present at a high level in the extract able to bind to this receptor: thus cannabidiol was the drug responsible for the antinociceptive behaviour observed. In addition, the results showed that after chronic oral treatment with cannabis extract the hepatic total content of cytochrome P450 was strongly inhibited as well as the intestinal P-glycoprotein activity. It is suggested that the inhibition of hepatic metabolism determined an increased bioavailability of cannabidiol resulting in a greater effect. However, in the light of the well known antioxidant and antiinflammatory properties of terpenes and flavonoids which could significantly contribute to the therapeutic effects, it cannot be excluded that the synergism observed might be achieved also in the absence of the cytochrome P450 inhibition.
Chromatic dispersion limitations in coherent lightwave transmission systems (1988)

Computer simulation is used to evaluate the chromatic dispersion limitations for both various coherent lightwave transmission systems and direct-detection on-off keying (OOK) systems. The results show that for a 2-dB dispersion penalty the maximum modulation rate ranges from 5 to 9 Gb/s for systems operating at 1.55 mu m with 15 ps/km-nm of chromatic dispersion and 100 km of fiber. The effect is less severe for OOK systems and most severe in coherent detection systems. Simulation results are in agreement with a available experimental data.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Automatic vehicle location systems: a tool for computer aided dispatch systems of the future (2003)

The evolution of the system design from the user perspective is presented, and the conditions that led to the need for vehicle location are examined. The operational expectation is compared with the attainable technical performance of such systems. The components of the system (location equipment, data transfer equipment, the display equipment, and the main processing unit), as they pertain to the Toronto pilot system, are reviewed. The various data-gathering methods are described, as are the original attempts to find a technology compatible with the local environment. The prospect of integrating the computer-aided dispatch system with the automatic vehicle location system to increase effectiveness of the dispatch center is discussed, with the need to maintain, in a dynamic manner, an updated mapping database. The error sources inherent in such systems are analyzed and ways to minimize them, where possible, are proposed.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>