gebhart/patrepeval huggingface dataset:
Characterization of Norfloxacine Release from Tablet Coated with a New pH-Sensitive Polymer, P-4135F (1999)

A new pH-sensitive polymer, P-4135F, was evaluated as a colon delivery device for norfloxacine (NFLX) which is used for the therapy of patients with Vero toxin-producing Escherichia coli gastroenteritis. P-4135F has a dissolution threshold pH of 7.2 which is higher than the conventional pH-sensitive polymers, Eudragit S100 and L100. To compare the dissolution site of P-4135F coated tablets with other enteric polymer coatings, mini-tablets containing sodium fluorescein (FL) as a model drug were prepared by coating them with the three polymers. After oral administration of FL mini-tablets to rats, the first-appearance time, Ti, of FL into the systemic circulation was measured. The Tis were 0.7+/-0.2 h for Eudragit L100, 1.8+/-0.4 h for S100 and 2.0+/-0.3 h for P-4135F. Direct inspection of the dissolution process of the FL mini-tablets after oral administration to rats was performed by abdominal incision studies. All of the coated FL mini-tablets started to dissolve in the rat ileum. The dissolution sites were identified to be proximal to the ileocecal junction for P-4135F, at the middle part of the ileum for Eudragit S100 and at the proximal part of the ileum for Eudragit L100. NFLX tablets with different membrane thicknesses of P-4135F were prepared and were orally administered to beagle dogs. The colon delivery efficiency was evaluated by measuring the Ti of NFLX into the systemic circulation. The mean Tis were 1.33+/-0.33 h for 56.8+/-0.5 microm membranes, 3.75+/-0.25 h for 64.6+/-0.7 microm membranes, 4.00+/-1.00 h for 70.5+/-0.5 microm membranes and 3.00+/-1.00 h for 74.9+/-0.4 microm membranes. By comparing the Ti, 4.33+/-0.33 h, obtained after oral administration of NFLX in a pressure-controlled colon delivery capsule, and the colon arrival time, 3.5+/-0.3 h, determined by a sulfasalazine test in beagle dogs. P-4135F coated NFLX tablets appeared to dissolve and disintegrate before reaching the colon. Studies using rats and beagle dogs have suggested that P-4135F dissolves in the lower part of the small intestine, i.e., the ileum. These studies also suggest that this new polymer will be useful for the delivery of NFLX to the lower part of the small intestine.
Plasma YKL-40 (2008)

Plasma YKL-40 was identified as an obesity-independent marker of type 2 diabetes related to fasting plasma glucose and plasma IL-6 levels.
Bartonella bacilliformis stimulates endothelial cells in vitro and is angiogenic in vivo. (1990)

Bartonellosis, a biphasic disease caused by motile intracellular bacteria, produces in its tissue phase a characteristic dermal eruption (Verruga peruana) resulting from a pronounced endothelial cell proliferation. Bacteria are found in the interstitium and within the cytoplasm of endothelial cells (Rocha-Lima inclusion). The aim of this study was to determine if Bartonella bacilliformis produce a substance(s) that might be responsible for the vascular proliferation seen in the Verruga. This was assessed in an in vitro system using human endothelial cells and measuring proliferation as well as production of tissue type plasminogen activator after exposure to the endothelial cultures to B. bacilliformis extracts. Our results indicate that B. bacilliformis possess an activity that stimulates endothelial cell proliferation up to three times that of control. The factor(s) is specific for endothelial cells, heat sensitive, larger than 12 to 14 kd, not enhanced by heparin, has no affinity for heparin, and is precipitated by 45% ammonium sulfate. In addition, the B. bacilliformis extracts stimulate production of t-PA antigen in a concentration-dependent fashion. This activity is also heat sensitive and not lost after dialysis (12 to 14 kd). B. bacilliformis extracts, however, do not increase the production of plasminogen activator inhibitor. It was also determined that B. bacilliformis extracts stimulate the formation of new blood vessels in an in vivo model for angiogenesis. These results describe a bacterial factor(s) that stimulates two important steps in the development of new blood vessels in vitro, as well as the formation of new blood vessels in vivo. Determining the mechanism of action, combined with a complete characterization of this factor(s), may help in understanding the pathogenesis not only of the Verruga and angiogenesis in general but also the recently described Cat-Scratch-associated epithelioid hemangiomas in patients with AIDS and Kaposi sarcoma.
Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. Nutritional Prevention of Cancer Study Group. (1996)

Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made
Vitamin C Transport in Oxidized Form across the Rat Blood–Retinal Barrier (2004)

To elucidate the mechanisms of vitamin C transport across the blood-retinal barrier (BRB) in vivo and in vitro. METHODS. [(14)C]Dehydroascorbic acid (DHA) and [(14)C]ascorbic acid (AA) transport in the retina across the BRB were examined using in vivo integration plot analysis in rats, and the transport mechanism was characterized using a conditionally immortalized rat retinal capillary endothelial cell line (TR-iBRB2) as an in vitro model of the inner BRB.The apparent influx permeability clearance (K(in)) per gram of retina of [(14)C]DHA and [(14)C]AA was found to be 2.44 x 10(3) microL/(min x g retina) and 65.4 microL/(min x g retina), respectively. In the retina and brain, the K(in) of [(14)C]DHA was approximately 38 times greater than that of [(14)C]AA, whereas there was no major difference in the heart. The K(in) of [(14)C]DHA in the retina was eight times greater than that in the brain. HPLC analysis revealed that most of the vitamin C accumulated in AA form in the retina. These results suggest that vitamin C is mainly transported in DHA form across the BRB and accumulates in AA form in the rat retina. In an in vitro uptake study in TR-iBRB2 cells, the initial uptake rate of [(14)C]DHA was 37 times greater than that of [(14)C]AA, which is in agreement with the results of the in vivo study. [(14)C]DHA uptake by TR-iBRB2 cells took place in an Na(+)-independent and concentration-dependent manner with a K(m) of 93.4 microM. This process was inhibited by substrates and inhibitors of glucose transporters. [(14)C]DHA uptake was inhibited by D-glucose in a concentration-dependent manner with a 50% inhibition concentration of 5.56 mM. Quantitative real-time PCR and immunostaining analyses revealed that expression of GLUT1 and -3 was greater than that of the Na(+)-dependent L-ascorbic acid transporter (SVCT)-2 in TR-iBRB2 cells.Vitamin C is mainly transported across the BRB as DHA mediated through facilitative glucose transporters and accumulates as AA in the rat retina.
Propensity for a leucine zipper-like domain of human immunodeficiency virus type 1 gp41 to form oligomers correlates with a role in virus-induced fusion rather than assembly of the glycoprotein complex. (1994)

For a number of viruses, oligomerization is a critical component of envelope processing and surface expression. Previously, we reported that a synthetic peptide (DP-107) corresponding to the putative leucine zipper region (aa 553-590) of the transmembrane protein (gp41) of human immunodeficiency virus type 1 (HIV-1) exhibited alpha-helical secondary structure and self-associated as a coiled coil. In view of the tendency of this type of structure to mediate protein association, we speculated that this region of gp41 might play a role in HIV-1 envelope oligomerization. However, later it was shown that mutations which should disrupt the structural elements of this region of gp41 did not affect envelope processing, transport, or surface expression (assembly oligomerization). In this report we compare the effects of amino acid substitutions within this coiled-coil region on structure and function of both viral envelope proteins and the corresponding synthetic peptides. Our results establish a correlation between the destabilizing effects of amino acid substitutions on coiled-coil structure in the peptide model and phenotype of virus entry. These biological and physical biochemical studies do not support a role for the coiled-coil structure in mediating the assembly oligomerization of HIV-1 envelope but do imply that this region of gp41 plays a key role in the sequence of events associated with viral entry. We propose a functional role for the coiled-coil domain of HIV-1 gp41.
Myelin regeneration in demyelinating disorders: new developments in biology and clinical pathology (2007)

Central nervous system remyelination is mainly mediated by oligodendrocyte precursor cells, although subventricular zone-derived cells contribute to the repair of periventricular lesions. Oligodendrocyte precursor cells may differentiate into astrocytes and Schwann cells following injury and exhibit more stem cell-like features than previously recognized. A complex matrix of environmental factors, including cytokines, chemokines and growth factors, act upon oligodendrocyte precursor cells, causing their activation and eventual differentiation into remyelinating oligodendrocytes. Inflammatory cells contribute by providing components of the signalling matrix and by the phagocytic removal of myelin debris. Many factors within the signalling environment have redundant functions - a feature of regeneration with implications for developing remyelination therapies. Advances in remyelination biology have been accompanied by more detailed analyses of remyelination in multiple sclerosis and important translational developments, including the ability to identify myelin by positron emission tomography.
The ATP Binding Cassette Transporters Pdr5 and Snq2 of Saccharomyces cerevisiae Can Mediate Transport of Steroids in Vivo (1996)

Multiple or pleiotropic drug resistance in the yeast Saccharomyces cerevisiae can arise from overexpression of the Pdr5 and Snq2 ATP binding cassette multidrug transporters. Expression of Pdr5 and Snq2 is regulated by the two transcription factors Pdr1 and Pdr3, as multidrug-resistant pdr1 and pdr3 gain-of-function mutants overexpress both drug efflux pumps. One such pdr1 mutant allele was previously cloned in a genetic screen by its ability to suppress the squelching toxicity mediated by an estradiol-inducible chimeric VP16-human estrogen receptor (VEO) expressed in yeast (Gilbert, D. M. , Heery, D. M., Losson, R., Chambon, P., and Lemoine, Y. (1993) Mol. Cell. Biol. 13, 462-472). In this study, we demonstrate that relief of estradiol toxicity in yeast cells expressing VEO requires functional PDR5 and SNQ2 genes, since a Deltapdr5 Deltasnq2 double deletion leads to an increased estradiol toxicity. Furthermore, using URA3 as an estradiol-inducible reporter gene, we show that Pdr5 and Snq2, when overexpressed from high-copy plasmids, can reduce the intracellular concentration of estradiol. In contrast, a Deltapdr5 Deltasnq2 double deletion mutant accumulates almost 30-fold more intracellular estradiol than the isogenic wild type. Indirect immunofluorescence showed that a pdr1-3 mutant massively overexpresses Pdr5 at the plasma membrane, suggesting that estradiol efflux from the cells occurs across the plasma membrane. Our data demonstrate that Pdr5 and Snq2 can transport steroid substrates in vivo and suggest that steroids and/or related membrane lipids could represent physiological substrates for certain yeast ABC transporters, which are otherwise involved in the development of pleiotropic drug resistance.
Series elastic actuator development for a biomimetic walking robot (1999)

Series elastic actuators have linear springs intentionally placed in series between the motor and actuator output. The spring strain is measured to get an accurate estimate of force. A second order linear actuator model is broken into two fundamental cases: fixed load-high force (forward transfer function), and free load-zero force (impedance). This model is presented with dimensional analysis and extends previous linear models to include friction. Using the model and dimensionless groups, we examine nonlinear effects of motor saturation as it relates to large force bandwidth and nonlinear friction effects such as stiction. The model also helps to clarify how the springs help and hinder the operation of the actuator. The information gained from the model helps to create a design procedure for series elastic actuators. Particular emphasis is placed on choosing the spring constant for the elastic element.
Growing protein‐doped sinapic acid crystals for laser desorption: An alternative preparation method for difficult samples (1993)

Abstract This paper describes several protocols for growing large, protein‐doped 3,5‐dimethoxy‐4‐hydroxy‐ trans ‐cinnamic acid crystals. Examination of these crystals using laser desorption shows that the mass spectra obtained from the crystals can be useful for biochemical analysis. One particular crystal growing protocol allowed a non‐covalently bound heme group of horse muscle myoglobin to remain attached to the polypeptide following laser ablation and ionization. Crystals could be grown in solutions that contained involatile solvents that normally inhibit polypeptide ion production, such as glycerol. These crystals were protein doped and produced acceptable analytical mass spectra. The results suggest that some problems associated with the frequently used droplet‐drying method of sample preparation are caused by the changing concentration conditions present in drying solutions.
Intravenous Iron Supplementation in Distance Runners with Low or Suboptimal Ferritin (2013)

IV supplementation can effectively increase iron stores in iron-deficient runners within 6 wk and, if Hbmass is compromised, may enhance endurance capacity by facilitating erythropoiesis. Hbmass appears a more sensitive tool for measuring changes in whole body hemoglobin than hemoglobin concentration and may be useful in the diagnosis and follow-up for iron deficiency.
Optimization and validation of mitochondria-based functional assay as a useful tool to identify BH3-like molecules selectively targeting anti-apoptotic Bcl-2 proteins (2013)

This method based on MOMP is a useful screening tool for identifying BH3 mimetics with selective toxicity against breast cancer cell mitochondria protected by the three major Bcl-2 anti-apoptotic proteins.
Chinese medicinal herbs modulate mutagenesis, DNA binding and metabolism of benzo[a]pyrene (1992)

Abstract Oldenlandia diffusa (OD) and Scutellaria barbata (SB) have been used in traditional Chinese medicine for treating liver, lung and rectal tumours while Astragalus membranaceus (AM) and Ligustrum lucidum (LL) are often used as an adjunct in cancer therapy. In this study, we determined the effects of aqueous extracts of these four herbs on benzo[a]pyrene (BaP)‐induced mutagenesis using Salmonella typhimurium TA100 as the bacterial tester strain and rat liver 9000 × g supernatant as the metabolic activation system. The effects of these herbs on [ 3 H]BapP binding to calf thymus DNA and formation of BaP‐DNA adducts were assessed. Organosoluble and water‐soluble metabolites of BaP were extracted and analysed by high performance liquid chromatography (HPLC) and alumina column liquid chromatography. Mutagenesis assays revealed that all four herbs produced a significant concentration‐dependent inhibition of His + revertants induced by BaP. At a concentration of 1.5 mg/plate, SB and OD in combination exhibited an additive effect, whereas AM and LL in combination demonstrated an antagonistic effect. The trend of inhibition of these four herbs on BaP‐induced mutagenesis was: SB &gt; LL &gt; OD &gt; AM. LL, OD and SB significantly inhibited BaP binding to DNA. LL and SB significantly reduced BaP‐DNA adduct formation and SB significantly decreased formation of organosoluble metabolites of BaP. Our data suggest that these Chinese medicinal herbs possess cancer chemopreventive properties.
Serum neutrophil gelatinase-associated lipocalin (NGAL) as a marker of acute kidney injury in critically ill children with septic shock (2008)

Serum NGAL is a highly sensitive but nonspecific predictor of acute kidney injury in critically ill children with septic shock. Further validation of serum NGAL as a biomarker of acute kidney injury in this population is warranted.
High-power 1.3-μm InGaAsP-InP amplifiers with tapered gain regions (1996)

Tapered structures fabricated in InGaAsP-InP 1.3-μm quantum-well material have been evaluated as high-gain high-saturation-power amplifiers. The devices, which had a 1-mm-long ridge-waveguide input gain section followed by a 2-mm-long tapered section, demonstrated an unsaturated gain of 26 dB at 2.0 A and about 30 dB at 2.8 A. Saturated output power at 2.8 A was >750 mW. At 2.0-A drive current and /spl ap/10-mW input power, the relative intensity noise of the amplified signal was /spl les/-160 dB/Hz at frequencies /spl ges/2 GHz.
Survival and development of bovine blastocysts produced in vitro after assisted hatching, vitrification and in-straw direct rehydration (1997)

The purpose of this study was to establish an efficient combination of assisted hatching and cryopreservation procedures for producing bovine embryos in vitro. A total of 1312 day 7 blastocysts were subjected randomly to 14 different combinations of three factors: osmotic stress, assisted hatching and vitrification. Re-expansion, initiation and completion of the hatching process, as well as attachment to the culture dish, were analysed by SAS Genmod procedure. Incubation with sucrose was found to decrease survival rates; among the assisted hatching procedures used, zona fenestration resulted in higher survival rates compared with partial zona dissection and controls; and vitrification decreased survival and further development. The combined effect of sucrose incubation and vitrification decreased further development markedly, as did partial zona dissection followed by vitrification. Partial zona dissection performed in medium containing sucrose severely lowered embryo survival. Zona fenestration without sucrose incubation followed by vitrification did not compromise further embryo development: 86%, 84% and 79% of the blastocysts initiated, completed hatching and attached to the bottom, respectively. These data were not different from the controls (80%, 76% and 63%, respectively; P > 0.05). Cell count analysis revealed a decrease in the total number of cells as a result of the assisted hatching and vitrification compared with controls (135 versus 202, respectively; P < 0.0001). Although embryo transfer results (36% pregnancy rate and 30% calving rate) require further improvement, this combination of methods may prove useful in the commercial production of bovine embryos in vitro.
Nonmyeloablative allogeneic stem cell transplantation (NST) for lymphoid malignancies using pentostatin/low-dose total body irradiation (2004)

Between 9/01 and 8/03 13 patients with relapsed/refractory lymphoid malignancies have undergone NST. The median age at transplantation was 52 years (range 21–63). The median number of prior therapies was 5 (range 1–7). Diseases transplanted represented a broad variety of lymphoid malignancies including Hodgkin’s disease (n = 3) and non-Hodgkin’s lymphoma (n = 10). The conditioning regimen consisted of Pentostatin 4 mg/m2/day IV on days -21, -20, and -19, followed by low dose total body irradiation on day -1. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine/mycophenolate mofetil. Stem cell transplantation was from matched related (n = 5) or matched unrelated (n = 8) donors. All toxicities were minimal. At day +28 the median values for donor chimerism were 90% (range 55%–100%) for CD3+ cells and 95% (range 50%–100%) for WBC. At day +70 the respective median values were 95% (range 50%–100%) and 100% (range 80%–100%) respectively. Sustained engraftment has been observed in all cases to date and no patients have required donor leukocytes. Acute GVHD has been seen in 6/13 patients, and chronic GVHD in 6/8 evaluable patients. Treatment related mortality is 15% (one death from intracranial hemorrhage, one death from chronic GVHD). With a median follow-up for surviving patients of 11.2 months, the event-free survival and overall survival are presently projected at 73%. Of six patients who underwent autologous stem cell transplantation as their immediate prior therapy (excluding salvage therapy prior to NST), five have had remission durations which have exceeded their prior remission duration with autologous transplantation (P = 0.07 by logrank). An additional patient with Waldenstrom’s macroglobulinemia had evidence of minimal residual disease (persistent marrow disease and an elevated IgM) for six months post transplant, and with no further therapy at one year post transplant has a normal marrow and IgM levels. The use of Pentostatin/TBI as a preparative regimen for NST in patients with refractory/relapsed lymphoid malignancies is associated with minimal toxicity, sustained engraftment, and an acceptable treatment related mortality given the patient population. The observation that a number of patients have had remission inversions (compared with immediately prior high-dose chemotherapy/autologous stem cell transplantation) and the occurrence of a late remission in the absence of other therapy offers indirect evidence of a graft-versus-lymphoma effect.
Predominant Expression of Platelet-Activating Factor Receptor in the Rat Brain Microglia (1996)

Cellular localization of platelet-activating factor (PAF) receptor in the rat brain was determined by (1) in situ hybridization, (2) Northern blot analysis in primary cell cultures of neurons, microglia, astrocytes, and fibroblasts, and (3) Ca2+ imaging in hippocampal culture. In situ hybridization revealed that the PAF receptor mRNA is expressed intensely in microglia and moderately in neurons. Northern blot analysis revealed that PAF receptor mRNA is the most abundant in microglia. In primary hippocampal cultures, PAF elevated intracellular Ca2+ concentration in microglia and also in neurons, but to a lesser extent. These results suggest predominant presence of PAF receptor in microglia. Cultured microglia also expressed cPLA2 mRNA the most intensely. PAF-activated microglia released arachidonic acid in a Ca(2+)-dependent manner and without conversion to its derivatives. We propose that microglia as well as neurons contribute to PAF-related events in the CNS by releasing arachidonic acid.
Spectroscopy-Based Quantitative Fluorescence Resonance Energy Transfer Analysis (2006)

The combination of green fluorescent protein mutants and fluorescence resonance energy transfer (FRET) forms a powerful tool for ion channel studies. A key to successful application of green fluorescent protein-based FRET is to reliably separate the FRET signal from various non-FRET fluorescence emissions that coexist in any experimental system. This chapter introduces a FRET quantification method that is based on fluorescence spectroscopic microscopy. Application of this "spectra FRET" method to both the confocal imaging of Xenopus oocytes and the epifluorescence imaging of culture cells is described. The fluorescence intensity ratio measurement, a complementary non-FRET method for identifying the channel subunit stoichiometry, is also discussed.