gebhart/patrepeval huggingface dataset:
Nitric oxide‐mediated cGMP synthesis in oligodendrocytes in the developing rat brain (1997)

We investigated the nature of cGMP-synthesizing cells in the developing rat forebrain using cGMP-immunocytochemistry in combination with in vitro incubation of brain slices. When brain slices of immature rats, aged between 1 and 4 weeks, were incubated with sodium nitroprusside (SNP), a nitric oxide (NO) donor compound, in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX), small round cells with a few processes in and around the corpus callosum were visualized with the cGMP-antibody. The morphology and the distribution of the cGMP-positive cells were consistent with the criteria for oligodendrocytes. Furthermore, the cGMP-positive cells expressed 2′3′-cyclic nucleotide 3′-phosphodiesterase (CNPase) and gelsolin, which are marker proteins for oligodendrocytes. Therefore, we concluded that the cGMP-positive cells were oligodendrocytes. A subpopulation of the oligodendrocyte was found to be cGMP-immunoreactive also when slices were incubated in the absence of SNP. Furthermore, incubation of the slice in the presence of L-NAME, an inhibitor of NO synthase, but in the absence of SNP abolished cGMP immunostaining. In addition, some populations of neurons and astrocytes in restricted brain areas produced cGMP in response to the incubation with SNP as previously reported, whereas both ameboid and ramified microglial cells did not respond to the treatment. Atrial natriuretic peptide, a stimulator of particulate guanylyl cyclase, enhanced cGMP synthesis in astrocytes in some brain regions but not in oligodendrocytes. These findings indicate that oligodendrocytes in the immature rat brain express soluble guanylyl cyclase. No cGMP-positive oligodendrocytes were found in the mature rat brain, suggesting that cGMP may mediate signals related to myelinogenesis in the rat brain. GLIA 19:286–297, 1997. © 1997 Wiley-Liss, Inc.
Clinical studies on the sites of production and clearance of circulating adrenomedullin in human subjects. (1994)

Adrenomedullin is a novel hypotensive peptide, newly discovered in pheochromocytoma. Because immunoreactive adrenomedullin is present in human plasma, adrenomedullin may play a role in regulating blood pressure. A recent report showed that human adrenomedullin mRNA is expressed not only in pheochromocytoma but also in the normal adrenal medulla, kidney, lung, and ventricle. However, whether or not these organs actually release adrenomedullin into the circulation remains unknown. To investigate the sites of production and degradation of adrenomedullin in human subjects, we obtained blood samples from various sites and measured immunoreactive adrenomedullin concentrations. In study 1, blood samples were obtained from the infrarenal inferior vena cava, suprarenal inferior vena cava, superior vena cava, right atrium, right ventricle, pulmonary artery, pulmonary capillary, left ventricle, and aorta during cardiac catheterization in 15 patients with ischemic heart disease (67 +/- 10 years). In study 2, blood samples were taken from the infrarenal inferior vena cava, suprarenal inferior vena cava, right and left renal veins, and left adrenal vein in 5 hypertensive patients (42 +/- 14 years) suspected of having renovascular hypertension. In study 3, peripheral venous blood samples were obtained in 2 patients (males, 45 and 36 years old) with pheochromocytoma at rest and during hypertensive attacks. Plasma adrenomedullin concentrations were measured by a newly developed radioimmunoassay. In study 1, there were no significant differences in plasma adrenomedullin concentrations in various sites of the right-side circulation. There was no step-up of plasma adrenomedullin levels in the coronary sinus. However, the plasma concentration of adrenomedullin in aorta was slightly but significantly lower than in pulmonary artery.(ABSTRACT TRUNCATED AT 250 WORDS)
Effect of ozone and Tooth MousseTM on the efficacy of peroxide bleaching (2008)

The results of this study suggest that Tooth Mousse may be applied concurrently with the bleach, and not reduce bleaching effectiveness.
An array of binding sites for hepatocyte nuclear factor 4 of high and low affinities modulates the liver-specific enhancer for the human α1-microglobulin/bikunin precursor (1998)

Alpha1-Microglobulin and bikunin are two plasma glycoproteins encoded by a gene for alpha1-microglobulin/bikunin precursor (AMBP). The strict liver-specific transcription of the AMBP gene is controlled by an elaborate and remote enhancer made of six clustered boxes numbered 1 to 6 (core enhancer) that are binding sites for the hepatocyte-enriched nuclear factors HNF-1, HNF-4, HNF-3, HNF-1, HNF-3 and HNF-4 respectively. Three further boxes, 7 to 9, have now been found in the enhancer area in a position 5' of box 2, 5' of box 1 and 3' of box 6, respectively. Electrophoretic mobility-shift assays with nuclear extracts from the HepG2 hepatoma cell line demonstrated that boxes 7 and 8 are both functional HNF-4-binding sites of high and low affinity respectively, whereas no binding capacity of box 9 was detected by this method. Transfection of HepG2 and Chinese hamster ovary cells with chloramphenicol acetyltransferase constructs harbouring the core or extended AMBP enhancer with wild-type or mutated boxes and co-transfection with expression plasmids for a wild-type or defective HNF-4 identified box 7 as an essential element for the basal activity of this enhancer. The response of boxes 7 and 8 varies with the level of HNF-4 in cells. Box 9 exhibits a repressor activity that can be detected when box 8 is ablated. In vivo this corresponds to conditions of low box 8 occupancy when the intracellular level of HNF-4 is limited. These results reinforce the view that the AMBP enhancer is a quite elaborate and unusual example of a modular enhancer whose activity is fine-tuned by the level of cognate nuclear factors in the cell.
IL-21 Induces Differentiation of Human Naive and Memory B Cells into Antibody-Secreting Plasma Cells (2005)

IL-21 is a type I cytokine that influences the function of T cells, NK cells, and B cells. In this study, we report that IL-21 plays a major role in stimulating the differentiation of human B cells. When human B cells were stimulated through the BCR, IL-21 induced minimal proliferation, IgD down-modulation, and small numbers of plasma cells. In contrast, after CD40 engagement, IL-21 induced extensive proliferation, class switch recombination (CSR), and plasma cell differentiation. Upon cross-linking both BCR and CD40, IL-21 induced the largest numbers of plasma cells. IL-21 drove both postswitch memory cells as well as poorly responsive naive cord blood B cells to differentiate into plasma cells. The effect of IL-21 was more potent than the combination of IL-2 and IL-10, especially when responsiveness of cord blood B cells was examined. IL-21 costimulation potently induced the expression of both B lymphocyte-induced maturation protein-1 (BLIMP-1) and activation-induced cytidine deaminase as well as the production of large amounts of IgG from B cells. Despite the induction of activation-induced cytidine deaminase and CSR, IL-21 did not induce somatic hypermutation. Finally, IL-2 enhanced the effects of IL-21, whereas IL-4 inhibited IL-21-induced plasma cell differentiation. Taken together, our data show that IL-21 plays a central role in CSR and plasma cell differentiation during T cell-dependent B cell responses.
Impedance Phlebography (1972)

Impedance phlebography is a noninvasive method for monitoring the changes in venous blood volume which normally occur with deep breathing. Since these respiratory venous volume changes are diminished by venous thrombosis, impedance phlebography provides an indirect method for the diagnosis of this condition. Over 3,000 impedance examinations have now been carried out on 710 subjects in many different clinical settings. As later confirmed by venography, impedance phlebograms have been used to detect venous thrombosis in asymptomatic patients, and to rule out this diagnosis in patients whose signs and symptoms suggested venous thrombosis. The incidence of abnormal impedance phlebograms has conformed to predictions in various patient groups, ranging from 0% in normal volunteers (0 of 50 limbs) to 91% in patients with pulmonary emboli documented by lung scan and pulmonary angiogram (20 of 22 patients).
Development of an In Vitro Tracking System with Poly (vinyl alcohol) Hydrogel for Catheter Motion (2010)

Vascular diseases, such as ischemic heart disease, infarction, aneurysms, stroke and stenosis are a leading cause of serious long-term disability and their mortality rate is as high as that of cancers in many countries. Recently, neurovascular intervention using catheters is a minimally-invasive endovascular technique used to treat vascular disease of the brain, and a navigation system for catheters has been developed to facilitate surgical planning and to provide intra-operative assistance. Since the mechanical properties of a catheter play an important role in reaching the targeted disease, tracking of catheter movement during endovascular treatment may be useful to increase confirmation of the rate of successful operation. In this study, we developed an in vitro tracking system for catheter motion using poly (vinyl alcohol) hydrogel (PVA-H) to mimic an arterial wall. The employed models were made of PVA-H, which is sufficiently transparent to permit observation of catheter movement in the artery. This system is expected to contribute to validation of computer-based navigation systems for surgical assistance.
Supercritical Carbon Dioxide (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder (2012)

The N-methyl-d-aspartate (NMDA) receptor antagonist ketamine has rapid antidepressant effects in treatment-resistant major depressive disorder (MDD). In rats, ketamine selectively increased electroencephalogram (EEG) slow wave activity (SWA) during non-rapid eye movement (REM) sleep and altered central brain-derived neurotrophic factor (BDNF) expression. Taken together, these findings suggest that higher SWA and BDNF levels may respectively represent electrophysiological and molecular correlates of mood improvement following ketamine treatment. This study investigated the acute effects of a single ketamine infusion on depressive symptoms, EEG SWA, individual slow wave parameters (surrogate markers of central synaptic plasticity) and plasma BDNF (a peripheral marker of plasticity) in 30 patients with treatment-resistant MDD. Montgomery-Åsberg Depression Rating Scale scores rapidly decreased following ketamine. Compared to baseline, BDNF levels and early sleep SWA (during the first non-REM episode) increased after ketamine. The occurrence of high amplitude waves increased during early sleep, accompanied by an increase in slow wave slope, consistent with increased synaptic strength. Changes in BDNF levels were proportional to changes in EEG parameters. Intriguingly, this link was present only in patients who responded to ketamine treatment, suggesting that enhanced synaptic plasticity - as reflected by increased SWA, individual slow wave parameters and plasma BDNF - is part of the physiological mechanism underlying the rapid antidepressant effects of NMDA antagonists. Further studies are required to confirm the link found here between behavioural and synaptic changes, as well as to test the reliability of these central and peripheral biomarkers of rapid antidepressant response.
A new technique to efficiently entrap leuprolide acetate into microcapsules of polylactic acid or copoly(lactic/glycolic) acid. (1988)

The aim of this work was to develop injectable microcapsules containing leuprolide acetate, that would deliver that drug at a zero-order rate over a period of about one month. A large amount of leuprolide acetate, a hydrophilic drug, was entrapped into polylactic aicd (PLA) and copoly-(lactic/glycolic) acid (PLGA) microcapsules prepared by an in-water dring method using a (w/o)/w emulsion. The basic techniques were designed to increase the viwcosities of the inner water phase and w/o emulsion. Under the conditions used, it was possible for the drug to be completely entrapped by the microcapsules in the range of 10 to 20% on the basis of the polymer. However, the release profiles of the drug in vitro were inadequate for controlled release for one month.
Glycerol addition and conservation of fresh and cryopreserved ram spermatozoa (2002)

Fresh extended ram semen has a short fertile lifespan whereas acceptable fertility with cryopreserved semen is achieved only by laparoscopy, which limits widespread artificial insemination in sheep. Although glycerol is considered essential for freezing spermatozoa, it is often included in extenders for short-term storage at above-freezing temperatures. To test the hypothesis that glycerol reduces the function of fresh sperm, ram semen was divided into two aliquots and diluted with commercial extenders that were identical, except that one contained 7% glycerol (n = 6). In a second experiment, ram semen was prepared for cryopreservation by a one-step dilution with a 7% glycerol extender or gradually, with a two-step protocol, to test the hypothesis that the method and time of glycerol addition affects sperm quality after freezing and thawing (n = 7). For both experiments, semen was diluted in a synthetic oviductal fluid (SOF-m) and sperm quality was assessed by computer-assisted motility, viability and chlortetracycline fluorescence (CTC) patterns (an indicator of capacitation status). The presence of glycerol did not affect the quality of fresh sperm (P &gt; 0.27). For cryopreserved sperm, the method of glycerol addition also did not affect thawed sperm. However, a decrease in sperm motility and viability, and different distribution of CTC patterns occurred due to the duration of time in extender and in SOF-m (P ≤ 0.0002). Cryo-capacitation was also observed. In conclusion, the presence of glycerol in the extender did not reduce ram sperm quality during conservation of the semen at 5°C or when it was used to completely and rapidly dilute the semen before cooling for cryopreservation. Key words: Sheep, Triladyl, Biladyl, chlortetracycline, artificial insemination, spermatozoa.
Thymidine labeling index and Ki-67 growth fraction in lesions of the breast. (1989)

Thymidine labeling index (TLI) and Ki-67 growth fraction (KGF) are two indicators of proliferative activity in breast cancer. The authors examined the relationship between TLI and KGF in 36 breast lesions (28 invasive ductal carcinomas and 8 benign lesions). TLI and KGF values were determined in separately labeled tissue sections as well as in frozen tissue sections labeled with both Ki-67 and tritiated thymidine. In separately labeled sections of carcinoma mean TLI was 6.8 while mean KGF was 16.0. For double-labeled sections of carcinoma mean TLI and KGF values were 6.1 and 16.4, respectively. Strong correlation between TLI and KGF of malignant tumors was found by both methods: r = 0.90 (P less than 0.001) for separately labeled sections, and r = 0.96 (P less than 0.001) for double-labeled sections. In double-labeled sections of benign lesions strong correlation between TLI and KGF also was observed (r = 0.94, P less than 0.001); however, in separately labeled benign breast tissue there was no significant correlation between TLI and KGF (r = 0.38). This may have been the result of variable sampling of small proliferative foci in separate sections of benign breast tissue. The strong correlation between TLI and KGF in breast carcinoma suggests that KGF may have prognostic implications similar to those of the TLI.
The Fc Portion of Antibody to Yellow Fever Virus NS1 Is a Determinant of Protection against YF Encephalitis in Mice (1993)

The mechanism by which antibodies to the flavivirus nonvirion protein NS1 protect mice against encephalitis is unknown but their binding to cell surface NS1 raises the possibility of involvement of an Fc piece-directed immune function. To investigate this, we prepared the F(ab')2 moiety of a protective IgG2a monoclonal antibody (Mab) against yellow fever virus (YF) NS1 and isolated IgG2a- and IgG2b-secreting isotype switch variants from a hybridoma that secretes a nonprotective IgG1 anti-YF NS1 Mab. Each Mab, complexed to NS1, bound to macrophage Fc receptor (FcR) but only the IgG2a and IgG2b Mabs sensitized YF-infected cells to complement-mediated cytolysis. Passively transferred IgG2a Mabs, but not F(ab')2, IgG1, or IgG2b Mabs, interfered with replication of YF in mouse brain. IgG2a Mabs protected mice against YF encephalitis but passive transfer of a mixture of variant IgG2a and parent IgG1 Mabs, or of unrelated IgG2a and IgG1 Mabs directed at the same NS1 epitope, resulted in markedly reduced protection, findings that may bear on flavivirus vaccine design. IgG2a Mab interfered with CNS YF replication in, and protected, C3-depleted mice, but not mice treated with high-dose cyclophosphamide to eliminate antibody-dependent killer cell activity. Taken together, these results indicate that epitope specificity alone may be inadequate to account for protection by anti-NS1 antibody and are consistent with involvement of an FcR-dependent protective mechanism that is governed by antibody isotype.
Alpha-melanocyte-stimulating hormone reduces endotoxin-induced liver inflammation. (1996)

Alpha-Melanocyte-stimulating hormone (MSH) is a potent anti-inflammatory agent in many models of inflammation, suggesting that it inhibits a critical step common to different forms of inflammation. We showed previously that alpha-MSH inhibits nitric oxide (NO) production in cultured macro-phages. To determine how alpha-MSH acts in vivo, we induced acute hepatic inflammation by administering endotoxin (LPS) to mice pretreated with Corynebacterium parvum, alpha-MSH prevented liver inflammation even when given 30 min after LPS administration. To determine the mechanisms of action of alpha-MSH, we tested its influence on NO, infiltrating inflammatory cells, cytokines, and chemokines. Alpha-MSH inhibited systemic NO production, hepatic neutrophil infiltration, and increased hepatic mRNA abundance for TNF alpha, and the neutrophil and monocyte chemokines (KC/IL-8 and MCP-1). We conclude that alpha-MSH prevents LPS-induced hepatic inflammation by inhibiting production of chemoattractant chemokines which then modulate infiltration of inflammatory cells. Thus, alpha-MSH has an effect very early in the inflammatory cascade.
Targeted Therapy with Eculizumab for Inherited CD59 Deficiency (2014)

Patients with CD59 deficiency have progressive neurologic dysfunction and episodes of hemolytic anemia. Eculizumab, a complement inhibitor, was administered to reverse hemolytic anemia in a patient. After the anemia improved, neurologic improvement was also noted.
Liver Dihydropyrimidine Dehydrogenase Activity in Human, Cynomolgus Monkey, Rhesus Monkey, Dog, Rat and Mouse (1998)

Interspecies differences in dihydropyrimidine dehydrogenase (DPD), the initial and rate-limiting enzyme in pyrimidine degradation, were assessed in cytosol from livers isolated from human, monkey, dog, rat, and mouse. Hepatic DPD activity was measured by an HPLC assay with on-line radioactivity detection, using 14C-5-fluorouracil as a substrate. Activity was highly variable within each species and significant interspecies differences in liver DPD activity were observed. The order of activity was mouse > rat > human > dog > or = cynomolgus monkey > rhesus monkey. These data suggest that careful selection must be made when choosing in vivo models of human DPD for the preclinical development of novel fluoropyrimidine anticancer agents and DPD inhibitors.
Catalytic Consumption of Nitric Oxide by Prostaglandin H Synthase-1 Regulates Platelet Function (2000)

Nitric oxide (( small middle dot)NO) plays a central role in vascular homeostasis via regulation of smooth muscle relaxation and platelet aggregation. Although mechanisms for ( small middle dot)NO formation are well known, removal pathways are less well characterized, particularly in cells that respond to ( small middle dot)NO through activation of soluble guanylate cyclase. Herein, we report that ( small middle dot)NO is catalytically consumed by prostaglandin H synthase-1 (PGHS-1) through acting as a reducing peroxidase substrate. With purified ovine PGHS-1, ( small middle dot)NO consumption requires peroxide (LOOH or H(2)O(2)), with a K(m)( (app)) for 15(S)hydroperoxyeicosatetraenoic acid (HPETE) of 3. 27 +/- 0.35 microm. During this, 2 mol ( small middle dot)NO are consumed per mol HPETE, and loss of HPETE hydroperoxy group occurs with retention of the conjugated diene spectrum. Hydroperoxide-stimulated ( small middle dot)NO consumption requires heme incorporation, is not inhibited by indomethacin, and is further stimulated by the reducing peroxidase substrate, phenol. PGHS-1-dependent ( small middle dot)NO consumption also occurs during arachidonate, thrombin, or activation of platelets (1-2 microm.min(-1) for typical plasma platelet concentrations) and prevents ( small middle dot)NO stimulation of platelet soluble guanylate cyclase. Platelet sensitivity to ( small middle dot)NO as an inhibitor of aggregation is greater using a platelet-activating stimulus () that does not cause ( small middle dot)NO consumption, indicating that this mechanism overcomes the anti-aggregatory effects of ( small middle dot)NO. Catalytic consumption of ( small middle dot)NO during eicosanoid synthesis thus represents both a novel proaggregatory function for PGHS-1 and a regulated mechanism for vascular ( small middle dot)NO removal.
Recognition of core and flanking amino acids of MHC class II-bound peptides by the T cell receptor (2002)

CD4 T cells recognize peptides bound to major histocompatibility complex (MHC) class II molecules. Most MHC class II molecules have four binding pockets occupied by amino acids 1, 4, 6, and 9 of the minimal peptide epitope, while the residues at positions 2, 3, 5, 7, and 8 are available to interact with the T cell receptor (TCR). In addition MHC class II bound peptides have flanking residues situated outside of this peptide core. Here we demonstrate that the flanking residues of the conalbumin peptide bound to I-A(k) have no effect on recognition by the D10 TCR. To study the role of peptide flanks for recognition by a second TCR, we determined the MHC and TCR contacting amino acids of the I-A(b) bound Ealpha peptide. The Ealpha peptide is shown to bind I-A(b) using four alanines as anchor residues. TCR recognition of Ealpha peptides with altered flanking residues again suggested that, in general, no specific interactions occurred with the peptide flanks. However, using an HLA-DM-mediated technique to measure peptide binding to MHC class II molecules, we found that the peptide flanking residues contribute substantially to MHC binding.
Role of adipose triglyceride lipase (PNPLA2) in protection from hepatic inflammation in mouse models of steatohepatitis and endotoxemia (2013)

These findings unravel a novel protective role of ATGL against hepatic inflammation which could have important implications for metabolic and inflammatory liver diseases.