gebhart/patrepeval huggingface dataset:
Renal Nerves Promote Sodium Excretion in Angiotensin-Induced Hypertension (1998)

To determine whether the sympathetic nervous system contributes to the hypertension induced by pathophysiological increments in plasma angiotensin II (Ang II) concentration, we determined the neurally induced changes in renal excretory function during chronic intravenous infusion of Ang II. Studies were carried out in five conscious chronically instrumented dogs subjected to unilateral renal denervation and surgical division of the urinary bladder into hemibladders to allow separate 24-hour urine collection from the denervated and innervated kidneys. After control measurements, Ang II was infused for 5 days at a rate of 4.8 pmol/kg per minute (5 ng/kg per minute); this was followed by a 5-day recovery period. Twenty-four-hour control values for mean arterial pressure (MAP) and for the ratio of denervated to innervated kidneys (DEN/INN) for urinary sodium, potassium, and creatinine excretion were 93+/-5 mm Hg, 1.17+/-0.09, 1.10+/-0.10, and 1.00+/-0.02, respectively. As expected, Ang II infusion caused sodium retention for several days before sodium balance was achieved at an elevated MAP (day 5=124+/-4 mm Hg). Moreover, by day 2 of Ang II-induced hypertension, there were significant reductions in the DEN/INN for sodium and potassium, which persisted for the 5 days of Ang II infusion; on day 5, the DEN/INN values for sodium and potassium were 0.71+/-0.10 and 0.91+/-0.12, respectively. In contrast, the DEN/INN for creatinine was unchanged from control levels during Ang II infusion, and measurements of renal hemodynamics indicated comparable reductions in glomerular filtration rate (approximately 13%) and renal plasma flow (approximately 25%) during Ang II infusion. This indicates that the renal nerves promoted sodium and potassium excretion during Ang II-induced hypertension by inhibiting tubular reabsorption of these electrolytes. Thus, this study provides no support for the hypothesis that increased renal sympathetic nerve activity impairs sodium excretion and contributes to Ang II-induced hypertension.
Dynamic Gd-DTPA-enhanced MR imaging of the kidney: experimental results. (1989)

To determine the normal appearance of dynamic enhanced renal magnetic resonance (MR) images, 25 rabbits were injected with Gd-DTPA and 32 consecutive gradient-recalled images were acquired. Several rabbits were also imaged in dehydrated (five animals) and overhydrated (seven animals) states. A reproducible renal enhancement pattern is observed that can be divided into three phases. During the first phase, a peripheral dark band appears, probably representing arrival of Gd-DTPA within the arterioles and vasa recta. The second phase begins as a second dark band migrating centripetally toward the medulla; this likely represents the concentration of Gd-DTPA in the descending limb of the loop of Henle. The third phase is characterized by a gradual darkening in the papilla, probably caused by concentration of Gd-DTPA within the collecting ducts. Hydration status influences the duration of these phases. These observations can be explained by the anatomy and physiologic characteristics of the nephron, as well as the MR characteristics of Gd-DTPA at different concentrations.
An Extracellular Protease ofStreptococcus gordoniiHydrolyzes Type IV Collagen and Collagen Analogues (1999)

Streptococcus gordonii is a frequent cause of infective bacterial endocarditis, but its mechanisms of virulence are not well defined. In this study, streptococcal proteases were recovered from spent chemically defined medium (CDM) and fractionated by ammonium sulfate precipitation and by ion-exchange and gel filtration column chromatography. Three proteases were distinguished by their different solubilities in ammonium sulfate and their specificities for synthetic peptides. One of the enzymes cleaved collagen analogs Gly-Pro 4-methoxy-beta-naphthylamide, 2-furanacryloyl-Leu-Gly-Pro-Ala (FALGPA), and p-phenylazobenzyloxycarbonyl-Pro-Leu-Gly-Pro-Arg (pZ-peptide) and was released from the streptococci while complexed to peptidoglycan fragments. Treatment of this protease with mutanolysin reduced its 180- to 200-kDa mass to 98 kDa without loss of enzymatic activity. The purified protease cleaved bovine gelatin, human placental type IV collagen, and the Aalpha chain of fibrinogen but not albumin, fibronectin, laminin, or myosin. Enzyme activity was inhibited by phenylmethylsulfonyl fluoride, indicating that it is a serine-type protease. Maximum production of the 98-kDa protease occurred during growth of S. gordonii CH1 in CDM containing 0.075% total amino acids at pH 7.0 with minimal aeration. Higher initial concentrations of amino acids prevented the release of the protease without reducing cell-associated enzyme levels, and the addition of an amino acid mixture to an actively secreting culture stopped further enzyme release. The purified protease was stored frozen at -20 degreesC for several months or heated at 50 degreesC for 10 min without loss of activity. These data indicate that S. gordonii produces an extracellular gelatinase/type IV collagenase during growth in medium containing minimal concentrations of free amino acids. Thus, the extracellular enzyme is a potential virulence factor in the amino acid-stringent, thrombotic, valvular lesions of bacterial endocarditis.
Splicing of Messenger RNA Precursors (1986)

The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size ...Read More
Four-wave mixing wavelength conversion efficiency in semiconductor traveling-wave amplifiers measured to 65 nm of wavelength shift (1994)

The efficiency of broadband optical wavelength conversion by four-wave mixing in semiconductor traveling-wave amplifiers is measured for wavelength shifts up to 65 nm using a tandem amplifier geometry. A quantity we call the relative conversion efficiency function, which determines the strength of the four-wave mixing nonlinearity, was extracted from the data. Using this quantity, gain requirements for lossless four-wave mixing wavelength conversion are calculated and discussed. Signal to background noise ratio is also measured and discussed in this study.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Mucosal Immunity to Herpes Simplex Virus Type 2 Infection in the Mouse Vagina Is Impaired by In Vivo Depletion of T Lymphocytes (1998)

Intravaginal (IVAG) inoculation of wild-type herpes simplex virus type 2 (HSV-2) in mice causes epithelial infection followed by lethal neurological illness, while IVAG inoculation of attenuated HSV-2 causes epithelial infection followed by development of protective immunity against subsequent IVAG challenge with wild-type virus. The role of T cells in this immunity was studied by in vivo depletion of these cells with monoclonal antibodies. Three groups of mice were used for each experiment: nonimmune/challenged mice, immune/challenged mice, and immune depleted mice [immune mice depleted of a T-cell subset(s) shortly before challenge with HSV-2]. Mice were assessed for epithelial infection 24 h after challenge, virus protein in the vaginal lumen 3 days after challenge, and neurological illness 8 to 14 days after challenge. Monoclonal antibodies to CD4, CD8, or Thy-1 markedly reduced T cells in blood, spleen, and vagina, but major histocompatibility complex class II antigens were still partially upregulated in the vaginal epithelium after virus challenge, indicating that virus-specific memory T-cell function was not entirely eliminated from the vagina. Nevertheless, immune mice depleted of CD4+ and CD8+ T cells, Thy-1+ T cells, or CD8+ T cells alone had greater viral infection in the vaginal epithelium than nondepleted immune mice, indicating that T cells contribute to immunity against vaginal HSV-2 infection. All immune depleted mice retained substantial immunity to epithelial infection and were immune to neurological illness, suggesting that other immune mechanisms such as virus-specific antibody may also contribute to immunity.
Improvement in pump function with endocardial biventricular pacing increases with activation time at the left ventricular pacing site in failing canine hearts (2011)

Recently, attention has been focused on comparing left ventricular (LV) endocardial (ENDO) with epicardial (EPI) pacing for cardiac resynchronization therapy. However, the effects of ENDO and EPI lead placement at multiple sites have not been studied in failing hearts. We hypothesized that differences in the improvement of ventricular function due to ENDO vs. EPI pacing in dyssynchronous (DYSS) heart failure may depend on the position of the LV lead in relation to the original activation pattern. In six nonfailing and six failing dogs, electrical DYSS was created by atrioventricular sequential pacing of the right ventricular apex. ENDO was compared with EPI biventricular pacing at five LV sites. In failing hearts, increases in the maximum rate of LV pressure change (dP/dt; r = 0.64), ejection fraction (r = 0.49), and minimum dP/dt (r = 0.51), relative to DYSS, were positively correlated (P < 0.01) with activation time at the LV pacing site during ENDO but not EPI pacing. ENDO pacing at sites with longer activation delays led to greater improvements in hemodynamic parameters and was associated with an overall reduction in electrical DYSS compared with EPI pacing (P < 0.05). These findings were qualitatively similar for nonfailing hearts. Improvement in hemodynamic function increased with activation time at the LV pacing site during ENDO but not EPI pacing. At the anterolateral wall, end-systolic transmural function was greater with local ENDO compared with EPI pacing. ENDO pacing and intrinsic activation delay may have important implications for management of DYSS heart failure.
Etoposide bioavailability after oral administration of the prodrug etoposide phosphate in cancer patients during a phase I study. (1996)

Similarly to E, the main toxicity of the prodrug EP is dose-dependent leukoneutropenia, which is dose-limiting at the oral MTD of 150 mg/m2/d for 5 days. The recommended oral dose of EP is 125 mg/m2/d for 5 days every 3 weeks in poor-risk patients. Compared with literature data, oral EP has a 19% higher F value compared with oral E either at low or high doses. This higher F in E from oral prodrug EP appears to be a pharmacologic advantage that could be of potential pharmacodynamic importance for this drug.
Age-dependent biomechanical properties of the skin (2013)

The skin fulfills one of its most important functions, that is protection from mechanical injuries, due to the mechanism of reversible deformation of the structure. Human skin is a complex living material but in biomechanical tests it reveals its homogeneous nature. Biomechanical skin parameters change with time. Results of thickness measurements, where the skin was subjected to pressure, revealed that the Young's modulus increased linearly with age. The process of ageing is the reason why the skin becomes thinner, stiffer, less tense and less flexible. Skin tension measured during in vivo uniaxial load and the elasticity modulus are higher in children than in elderly adults. Furthermore, mean ultimate skin deformation before bursting is 75% for newborns and 60% for the elderly. Several types of the main lines were distinguished on the skin. The static lines, described by Langer, correspond to the lines of maximum tension, the Kraissl's lines correspond to the movements of the skin during muscle work, whereas the Borges lines are the relaxed skin tension lines. Biomechanical tests of the human skin help to quantify the effectiveness of dermatological products, detect skin diseases, schedule and plan surgical and dermatological interventions and treatments.
Depolarization of multiply scattered waves by spherical diffusers: Influence of the size parameter (1994)

We study numerically, using the Mie theory, light transmission through a multiply scattering medium composed of a collection of uncorrelated, optically inactive spherical particles. The characteristic length over which a plane-wave field is depolarized depends on whether it is initially linearly or circularly polarized and on the size of the particles. In a medium containing particles small compared to the wavelength (Rayleigh regime), the characteristic length of depolarization for incident linearly polarized light is found to exceed that for incident circularly polarized light, while the opposite is true in a medium composed of particles large compared to the wavelength (Mie regime). A comparison of numerical results with the data from measurements on suspensions of polystyrene latex spheres in water is made. Agreement between these simulations and experiment is good for the range of sizes considered in this paper. We also discuss the relevance of the helicity-flip model to the analysis of these data.
Interleukin 4 receptor expression and growth inhibition of gastric carcinoma cells by interleukin 4. (1992)

The expression of the interleukin 4 (IL-4) receptor (IL-4R) and effects of human recombinant IL-4 on human gastric carcinoma cell lines were studied. We demonstrated that IL-4 inhibited the growth of gastric carcinoma cells in a dose dependent manner (0.1-100 units/ml) in a [3H]thymidine incorporation proliferation assay. The gastric carcinoma cells varied in sensitivity to treatment with low dose IL-4. Treatment of cells with IL-4 altered the morphology of the cells to a "flattened" morphological shape resembling differentiation. The IL-4-mediated growth inhibition was significantly abrogated by neutralization of IL-4 with specific anti-IL-4 antibody. IL-4R expression on the cell surface was determined by assessing biotin-labeled IL-4 binding to cells using flow cytometry. IL-4R expression ranged from 5 to 85% of total cell population in the gastric carcinoma cell lines assessed. There was a positive correlation between the sensitivity to IL-4-mediated growth inhibition and IL-4R expression. By Northern blot analysis, we demonstrated that mRNA of IL-4R was expressed in the gastric carcinoma cells. Using in situ hybridization, we confirmed that IL-4R mRNA was expressed in the gastric carcinoma cell at the single cell level. By using a sensitive polymerase chain reaction technique, we demonstrated that gastric carcinoma cells expressed IL-4 mRNA, suggesting a possible autocrine loop. These studies indicate that IL-4 can significantly modulate gastric carcinoma cells that possess IL-4R. IL-4R on gastric carcinoma cells may be a potential therapeutic target site for IL-4-directed therapy.
Review (1998)

AP2 (APETALA2) and EREBPs (ethylene-responsive element binding proteins) are the prototypic members of a family of transcription factors unique to plants, whose distinguishing characteristic is that they contain the so-called AP2 DNA-binding domain. AP2/ REBP genes form a large multigene family, and they play a variety of roles throughout the plant life cycle: from being key regulators of several developmental processes, like floral organ identity determination or control of leaf epidermal cell identity, to forming part of the mechanisms used by plants to respond to various types of biotic and environmental stress. The molecular and biochemical characteristics of the AP2/EREBP transcription factors and their diverse functions are reviewed here, and this multigene family is analyzed within the context of the Arabidopsis thaliana genome sequence project.
A placebo-controlled trial of the immune modulator, lentinan, in HIV-positive patients: a phase I/II trial. (1998)

Lentinan is a beta 1-->3 glucan isolated from Lentinus edodes (Shiitake mushroom) which has immune modulating properties. We have conducted two phase I/II placebo-controlled trials on a total of 98 patients. In one study at the San Francisco General Hospital (SFGH), ten patients each were administered 2, 5, or 10 mg of lentinan or placebo i.v. once a week for eight weeks. In the second study at the Community Research Initiative in New York (CRI), two groups of 20 patients each were administered 1 or 5 mg of lentinan i.v. twice a week for 12 weeks, and ten patients were administered placebo (vehicle containing mannitol plus dextran 40) i.v. twice a week. Entry criteria were an HIV positive test, CD4 levels of 200-500 cells, age 18-60 years, and without current opportunistic infections. This study confirms, in Caucasian subjects also, the good tolerability of lentinan observed in Japanese cancer patients. Side effects were mainly mild, especially when infusion was carried out over a 30-minute period. In the SFGH study, where administration was over a ten minute period, there were nine side effects severe enough to be reported to the FDA (one case each of anaphylactoid reaction, back pain, leg pain, depression, rigor, fever, chills, granulocytopenia and elevated liver enzymes) and there were four patients who discontinued therapy because of side effects. In the CRI study, where infusion was over a 30-minute period, there were no side effects reportable to the FDA and there were four dropouts due to side effects or personal preference. Most side effects resolved promptly after the discontinuation of medication, and all of them were relieved within 24 hours. Patients in the study have shown a trend toward increases in CD4 cells and in some patients neutrophil activity. Because of the small numbers, these values do not have statistical significance. Inasmuch as no side effects such as anemia, leukopenia, pancreatitis or neuropathy were seen, and in view of the positive effects of lentinan on certain surrogate markers (recognizing that these were small studies), we recommended a long-term clinical trial of lentinan in combination with didanosine (ddI) or zidovudine in HIV positive patients. Most patients in these trials did not have measurable p24 levels. In the CRI trials of ten patients with elevated p24 levels, eight on lentinan and two on placebo had decreased p24 levels. Of these decreases, those with lentinan and one with placebo were marked. These results were provocative and needed confirmation. Subsequent to this study, a trial of lentinan in combination with didanosine (ddI) showed a mean increase of 142 CD4 cells/mm3 over a twelve month period, in contrast to a decrease in CD4 cells in patients on ddI alone (Gordon et al. 1995).
Dextran Sodium Sulfate (DSS) Induces Colitis in Mice by Forming Nano-Lipocomplexes with Medium-Chain-Length Fatty Acids in the Colon (2012)

Inflammatory bowel diseases (IBDs), primarily ulcerative colitis and Crohn's disease, are inflammatory disorders caused by multiple factors. Research on IBD has often used the dextran sodium sulfate (DSS)-induced colitis mouse model. DSS induces in vivo but not in vitro intestinal inflammation. In addition, no DSS-associated molecule (free glucose, sodium sulfate solution, free dextran) induces in vitro or in vivo intestinal inflammation. We find that DSS but not dextran associated molecules established linkages with medium-chain-length fatty acids (MCFAs), such as dodecanoate, that are present in the colonic lumen. DSS complexed to MCFAs forms nanometer-sized vesicles ~200 nm in diameter that can fuse with colonocyte membranes. The arrival of nanometer-sized DSS/MCFA vesicles in the cytoplasm may activate intestinal inflammatory signaling pathways. We also show that the inflammatory activity of DSS is mediated by the dextran moieties. The deleterious effect of DSS is localized principally in the distal colon, therefore it will be important to chemically modify DSS to develop materials beneficial to the colon without affecting colon-targeting specificity.
Dual Requirement for Rho and Protein Kinase C in Direct Activation of Phospholipase D1 Through G Protein-coupled Receptor Signaling (2000)

G protein-coupled and tyrosine kinase receptor activation of phospholipase D1 (PLD1) play key roles in agonist-stimulated cellular responses such as regulated exocytosis, actin stress fiber formation, and alterations in cell morphology and motility. Protein Kinase C, ADP-ribosylation factor (ARF), and Rho family members activate PLD1 in vitro; however, the actions of the stimulators on PLD1 in vivo have been proposed to take place through indirect pathways. We have used the yeast split-hybrid system to generate PLD1 alleles that fail to bind to or to be activated by RhoA but that retain wild-type responses to ARF and PKC. These alleles then were employed in combination with alleles unresponsive to PKC or to both stimulators to examine the activation of PLD1 by G protein-coupled receptors. Our results demonstrate that direct stimulation of PLD1 in vivo by RhoA (and by PKC) is critical for significant PLD1 activation but that PLD1 subcellular localization and regulated phosphorylation occur independently of these stimulatory pathways.
Bovine Chymosin: A Computational Study of Recognition and Binding of Bovine κ-Casein (2010)

Bovine chymosin is an aspartic protease that selectively cleaves the milk protein kappa-casein. The enzyme is widely used to promote milk clotting in cheese manufacturing. We have developed models of residues 97-112 of bovine kappa-casein complexed with bovine chymosin, using ligand docking, conformational search algorithms, and molecular dynamics simulations. In agreement with limited experimental evidence, the model suggests that the substrate binds in an extended conformation with charged residues on either side of the scissile bond playing an important role in stabilizing the binding pose. Lys111 and Lys112 are observed to bind to the N-terminal domain of chymosin displacing a conserved water molecule. A cluster of histidine and proline residues (His98-Pro99-His100-Pro101-His102) in kappa-casein binds to the C-terminal domain of the protein, where a neighboring conserved arginine residue (Arg97) is found to be important for stabilizing the binding pose. The catalytic site (including the catalytic water molecule) is stable in the starting conformation of the previously proposed general acid/base catalytic mechanism for 18 ns of molecular dynamics simulations.
Multi-Photon Polymerization of Waveguide Structures Within Three-Dimensional Photonic Crystals (2002)

Photonic crystals with line and point defects are desirable for application as photonic bandgap waveguides and optical cavities, respectively. Here such defects have been introduced into photonic crystals using a laser scanning confocal microscope. High-resolution 3D patterns are created inside the colloidal crystals (see Figure) via multi-photon polymerization.
HIV-1 Fusion Inhibitor Peptides Enfuvirtide and T-1249 Interact with Erythrocyte and Lymphocyte Membranes (2010)

Enfuvirtide and T-1249 are two HIV-1 fusion inhibitor peptides that bind to gp41 and prevent its fusogenic conformation, inhibiting viral entry into host cells. Previous studies established the relative preferences of these peptides for membrane model systems of defined lipid compositions. We aimed to understand the interaction of these peptides with the membranes of erythrocytes and peripheral blood mononuclear cells. The peptide behavior toward cell membranes was followed by di-8-ANEPPS fluorescence, a lipophilic probe sensitive to the changes in membrane dipole potential. We observed a fusion inhibitor concentration-dependent decrease on the membrane dipole potential. Quantitative analysis showed that T-1249 has an approximately eight-fold higher affinity towards cells, when compared with enfuvirtide. We also compared the binding towards di-8-ANEPPS labeled lipid vesicles that model cell membranes and obtained concordant results. We demonstrated the distinct enfuvirtide and T-1249 membranotropism for circulating blood cells, which can be translated to a feasible in vivo scenario. The enhanced interaction of T-1249 with cell membranes correlates with its higher efficacy, as it can increase and accelerate the drug binding to gp41 in its pre-fusion state.