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1
Hoeppner, Astrid, Frank Thomas, Alma Rueppel, Reinhard Hensel, Wulf Blankenfeldt, Peter Bayer, and Annette Faust. "Structure of the corrinoid:coenzyme M methyltransferase MtaA fromMethanosarcina mazei." Acta Crystallographica Section D Biological Crystallography 68, no. 11 (October 18, 2012): 1549–57. http://dx.doi.org/10.1107/s090744491203853x.
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The zinc-containing corrinoid:coenzyme M methyltransferase MtaA is part of the methanol–coenzyme M–methyltransferase complex ofMethanosarcina mazei. The whole complex consists of three subunits: MtaA, MtaB and MtaC. The MtaB–MtaC complex catalyses the cleavage of methanol (bound to MtaB) and the transfer of the methyl group onto the cobalt of cob(I)alamin (bound to MtaC). The MtaA–MtaC complex catalyses methyl transfer from methyl-cob(III)alamin (bound to MtaC) to coenzyme M (bound to MtaA). The crystal structure of the MtaB–MtaC complex fromM. barkerihas previously been determined. Here, the crystal structures of MtaA fromM. mazeiin a substrate-free but Zn2+-bound state and in complex with Zn2+and coenzyme M (HS-CoM) are reported at resolutions of 1.8 and 2.1 Å, respectively. A search for homologous proteins revealed that MtaA exhibits 23% sequence identity to human uroporphyrinogen III decarboxylase, which has also the highest structural similarity (r.m.s.d. of 2.03 Å for 306 aligned amino acids). The main structural feature of MtaA is a TIM-barrel-like fold, which is also found in all other zinc enzymes that catalyse thiol-group alkylation. The active site of MtaA is situated at the narrow bottom of a funnel such that the thiolate group of HS-CoM points towards the Zn2+ion. The Zn2+ion in the active site of MtaA is coordinated tetrahedrallyviaHis240, Cys242 and Cys319. In the substrate-free form the fourth ligand is Glu263. Binding of HS-CoM leads to exchange of the O-ligand of Glu263 for the S-ligand of HS-CoM with inversion of the zinc geometry. The interface between MtaA and MtaC for transfer of the methyl group from MtaC-bound methylcobalamin is most likely to be formed by the core complex of MtaB–MtaC and the N-terminal segment (a long loop containing three α-helices and a β-hairpin) of MtaA, which is not part of the TIM-barrel core structure of MtaA.
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Vivan, Rodrigo Ricci, Juliane Maria Guerreiro-Tanomaru, Roberta Bosso-Martelo, Bernardo Cesar Costa, Marco Antonio Hungaro Duarte, and Mário Tanomaru-Filho. "Push-out Bond Strength of Root-end Filling Materials." Brazilian Dental Journal 27, no. 3 (June 2016): 332–35. http://dx.doi.org/10.1590/0103-6440201600340.
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Abstract The aim of this study was to evaluate the bond strength of root-end filling materials. Forty 2-mm-thick slices were obtained from human single-rooted teeth. After root canal preparation using a 1.5 mm diameter cylindrical drill, the dentinal walls were prepared by diamond ultrasonic tip (CVD T0F-2). The specimens were divided according the material (n=10): MTA Angelus (MTAA), MTA Sealer (MTAS, experimental), Sealer 26 (S26) and zinc oxide and eugenol cement (ZOE). The push-out test was performed in a mechanical test machine (EMIC DL 2000) at 1 mm/min speed. The failure type was evaluated by stereomicroscopy. The results were subjected to ANOVA and Tukey test, at 5% significance level. MTAA (19.18 MPa), MTAS (19.13 MPa) and S26 (15.91 MPa) showed higher bond strength (p<0.05). ZOE (9.50 MPa) showed the least bond strength values (p<0.05). Adhesive failure was prevalent in all groups, except for ZOE, which showed mixed failures. It was concluded that root-end filling materials MTA Angelus, MTA Sealer and Sealer 26 showed higher bond strength to dentinal walls than zinc oxide and eugenol cement after retrograde preparation.
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Shawar, S. M., R. G. Cook, J. R. Rodgers, and R. R. Rich. "Specialized functions of MHC class I molecules. I. An N-formyl peptide receptor is required for construction of the class I antigen Mta." Journal of Experimental Medicine 171, no. 3 (March 1, 1990): 897–912. http://dx.doi.org/10.1084/jem.171.3.897.
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Maternally transmitted factor (Mtf) is a mitochondrial gene that controls the antigenic polymorphism of the MHC class I maternally transmitted antigen (Mta). Synthetic peptides from the NH2 terminus of the mitochondrially encoded NADH dehydrogenase subunit 1 (ND1) mimic Mtf peptide activity in an allele-specific manner. We show that the minimal ND1-alpha peptide length recognized by Mtaa-specific polyclonal CTLs was between 8 and 12 amino acids, while some Mtaa-specific CTL clones recognized a six amino acid peptide. The N-formyl group at the NH2 terminus of ND1 was essential for Mta activity. Competition experiments using N-substituted ND1-alpha peptides showed that an N-formyl peptide receptor on the target cell, which differs from the chemotactic peptide receptor, was required for Mta expression. The specificity of this receptor can account for the distinct immune restriction of Mta in which Mtf peptides are uniquely restricted by Hmt. It is possible that the Hmt gene product is the N-formyl peptide receptor itself and that it represents a class I antigen presentation molecule specialized for binding, transport, and immune presentation of N-formyl-peptide antigens of mitochondrial and prokaryotic origin.
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Rudik, Irina S., Olesya N. Katasonova, Olga B. Mokhodoeva, Tatyana A. Maryutina, Boris Ya Spivakov, and Igor V. Ilyukhin. "SEPARATION OF P t (IV), P d (II) AND R h (III) FROM CHLORIDE SOLUTIONS BY MULTISTAGE SOLVENT EXTRACTION USING NITROGEN-CONTAINING EXTRACTANTS." Industrial laboratory. Diagnostics of materials 85, no. 4 (May 15, 2019): 5–10. http://dx.doi.org/10.26896/1028-6861-2019-85-4-5-10.
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The possibility of Pd (II), Pt (IV), and Rh (III) separation from chloride solutions by solvent extraction in rotating coiled columns (RCC) is demonstrated. The reagents most frequently used in extraction of platinum metals were selected as extractants: trioctylamine (TOA), methyltrialkylammonium chloride (MTAA), tributylphosphate (TBP), N, N, N',N'-tetra-re-octyldiglyTOlamide (TODGA). The completeness of extraction of the platinum group metals from individual and mixed hydrochloric acidic and chloride solutions was studied depending on the nature and concentration of the extractant, acidity of the test solutions and other factors. Optimal conditions for the quantitative extraction of metals from model hydrochloric acidic and chloride solutions and subsequent selective separation at the stripping stage are specified. A scheme of multistaged extraction separation of Pd (II), Pt (IV), and Rh (III) from chloride solutions using a 0.05 M solution of MTAA in toluene as a stationary phase in RCC is proposed. The scheme includes extraction of Pd (II) and Pt (IV) ions from a chloride solution (0, 1 M HCl + 30 g/liter NT) into the organic phase with simultaneous separation of Rh(III) remaining in the aqueous phase, and sequential stripping of Pd (II) and Pt (IV) from the organic phase with a 0.01 M solution of thiourea in 0.1 M HCl and a 1 M solution of thiourea in 0.5 M HCl, respectively. The scheme was tested in separation of the platinum group metals from the technological solution of a given composition. The degree of metal extraction with a 0.05 M MTAA solution in toluene and sequential stripping with thiourea solutions is 99.5% for Rh (III), 99.9% for Pd (II), and 97.4% for Pt (IV). The separated water fractions of rhodium and platinum after leaving the column did not contain impurities of other platinum metals whereas the water fraction of palladium contained 0.5% Pt.
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Dakyaga, Francis, Alphonce G. Kyessi, and Joel M. Msami. "Water Access Today and Tomorrow: Domestic Water Sustainability under Informal Water Supply Markets in Dar es Salaam, Tanzania." Journal of Sustainable Development 11, no. 6 (November 29, 2018): 120. http://dx.doi.org/10.5539/jsd.v11n6p120.
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The article examined domestic water access sustainability under informally driven water supply market, drawing on suppliers-consumers’ perspectives. Analysis was done on the capacities of the informal water suppliers for sustainable water provision, how the informal water markets operate, and clients’ perspectives of water access today and tomorrow. Four different data set were comparatively analyzed from interviews with the Municipal Water Engineer (MWE), Ward Health Officer (WHO), 3 Mtaa leaders from 3 informal settlements, interviews with 43 informal water sellers from three informal settlements, including a survey of (n = 292) clients in three informal settlements. It was realized that though informal water suppliers are sociocultural capable of providing flexible and gender-sensitive water supply services, households have unsustainable access to improved water due to the financial, hydro-technical, institutional and organizational in capacities of the informal water sellers coupled with the low financial abilities of low-income earning households to continuously purchase water for domestic activities. It was observed that informal settlements’ dwellers are less likely to meet their water supply needs in the near future if their income status together with the financial, hydro-technical, organizational and institutional capacities of the informal water sellers are not improved.
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Kobayashi, Kazufumi, Sadahisa Ogasawara, Aya Takahashi, Yuya Seko, Hidemi Unozawa, Rui Sato, Shunji Watanabe, et al. "Evolution of Survival Impact of Molecular Target Agents in Patients with Advanced Hepatocellular Carcinoma." Liver Cancer 11, no. 1 (December 6, 2021): 48–60. http://dx.doi.org/10.1159/000519868.
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Background and Aims: The prognosis of patients with advanced hepatocellular carcinoma (HCC) is expected to improve as multiple molecular target agents (MTAs) are now available. However, the impact of the availability of sequential MTAs has not been fully verified yet. Approach and Results: We retrospectively collected the data on the whole clinical course of 877 patients who received any MTAs as first-line systemic therapy for advanced HCC between June 2009 and March 2019. The study population was divided into 3 groups according to the date of first-line MTA administration (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). Then, we compared the number of MTAs used, overall survival (OS), and MTA treatment duration among the 3 groups. Analysis was also performed separately for advanced-stage and nonadvanced-stage HCC. The proportion of patients who received multiple MTAs was remarkably increased over time (1.1%, 10.2%, and 42.6% in periods 1, 2, and 3, respectively, p < 0.001). The median OS times were prolonged to 10.4, 11.3, and 15.2 months in periods 1, 2, and 3, respectively (p = 0.016). Similarly, the MTA treatment durations were extended (2.7, 3.2, and 6.6 months in periods 1, 2, and 3, respectively; p < 0.001). We confirmed that the correlation between OS and MTA treatment duration was strengthened (period 1: 0.395, period 2: 0.505, and period 3: 0.667). All these trends were pronounced in the patients with advanced-stage HCC but limited in the patients with nonadvanced-stage HCC. Conclusions: The availability of multiple MTAs had steadily improved the prognosis of patients with advanced HCC patients, particularly advanced-stage HCC patients.
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Baldissera, Renata, Ricardo Rosa, Manuela Santini, Angela Nascimento, Milton Kuga, Jefferson Pereira, Francisco Montagner, and Marcus Só. "CLSM assessment of tubule penetration and bacterial leakage evaluation of two resin-based sealer." Journal of Research in Dentistry 2, no. 5 (September 1, 2014): 388. http://dx.doi.org/10.19177/jrd.v2e52014388-397.
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AIM: The aims of this study were to assess the penetration of two endodontic sealers (salicylate and epoxy resin-based sealers) into dentinal tubules using CLSM; and to evaluate the bacterial leakage of roots filled with the same sealers associated with gutta-percha. MATERIAL AND METHODS: For sealer penetrability assessment, thirty bovine roots were instrumented and divided into three groups: AHP: EDTA + filling with AH Plus and gutta-percha (n=10), MTAF: EDTA + filling with MTA Fillapex and gutta-percha (n=10), control group: canals were not irrigated with EDTA and were filled with gutta-percha and AH Plus (n=5) or MTA Fillapex (n=5). Rhodamine B was added to the sealers in order to provide adequate fluorescence. The roots were transversely sectioned 3mm from the apex to enable CLSM analysis. Leakage was evaluated for turbidity of the broth in a split chamber model system for 30 days, using Enterococcus faecalis as a microbial marker. Thirty roots were instrumented and divided in four grupos: AHP: filling with AH Plus and gutta-percha (n=10); MTAF: filling with MTA Fillapex and gutta-percha (n=10); positive control: filling with gutta-percha without sealer (n = 5); negative control: sealing with cyanoacrylate to test the seal of the system (n = 5). RESULTS: The medians for dentinal tubule penetration were 6.8% (AHP) and 6.6% (MTAF) (P = 0.82). The average time for bacterial leakage was 8 days in both experimental groups (P = 0.79). CONCLUSION: MTA Fillapex and AH Plus presented similar behavior regarding dentinal tubule penetration and bacterial leakage.
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Kobayashi, Kazufumi, Sadahisa Ogasawara, Aya Takahashi, Yuya Seko, Satoshi Tsuchiya, Kenji Iwai, Rui Sato, et al. "Transition of molecular target agent therapy in advanced hepatocellular carcinoma: A multicenter, retrospective study." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 317. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.317.
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317 Background: There have been considerable advances in systemic chemotherapy for hepatocellular carcinoma (HCC) in recent times. Currently, four molecular target agents (MTA) are available for HCC treatment in Japan. Sequential therapy using multiple MTAs is being considered as the gold standard of treatment. However, the effectiveness of the treatment strategy transition for HCC remains unclear. The present study aimed to clarify the current practical use of MTAs and its effectiveness in HCC treatment. Methods: In this multicenter, retrospective study, we collected and analyzed the clinical data of 877 patients who underwent MTA therapy for HCC from June 2009 to March 2019 at several institutes in Japan. The patients were classified into 3 groups as per the period of initial MTA treatment beginning (period 1: 2009–2012, n = 267; period 2: 2013–2016, n = 352; period 3: 2017–2019, n = 258). These 3 periods were defined to have approximately same term. Period 3 means the era of multiple MTAs because of the approval of regorafenib in Japan in 2017. We assessed the patient characteristics, MTA use, and prognosis of the 3 groups. Results: The proportion of patients with advanced-stage HCC, defined according to the Barcelona Clinic Liver Cancer staging system, in each period was 70.1%, 66.5%, and 62.0% in period 1, 2, and 3, respectively. MTA use for intermediate stages increased with the passage of time ( p = 0.052). The proportion of multiple MTAs use was remarkably increased in the 3 groups (1.1%, 10.2%, and 42.6%, respectively, p < 0.0001). Child-Pugh score, proportion of macrovascular invasion, extrahepatic metastasis, and α-fetoprotein (AFP) ≥400 ng/mL showed no significant difference among the 3 groups. The median overall survival was 11.9 months for the entire cohort and 10.4, 11.3, and 15.2 months, for period 1, 2, and 3, respectively. It is noteworthy that the prognosis of patients with HCC improved over time ( p = 0.016). With respect to progression-free survival, the median value was 3.0 months for the entire cohort and 2.7, 2.8, and 4.7 months for period 1, 2, and 3, respectively ( p < 0.0001). The treatment duration was also prolonged with time (2.7, 3.2, and 6.6 months for period 1, 2, and 3, respectively; p < 0.0001). Multivariate analysis using Cox proportional hazard model showed that HCV infection, Child-Pugh score, performance status, α-fetoprotein ≥400 ng/mL, presence of macrovascular invasion, and period 3 for initial MTA introduction were independent prognostic factors. Conclusions: Sequential therapy with multiple MTAs has gained popularity with time and is considered to improve patient prognosis. The development of MTA therapy for HCC is expected to continue. Therefore, further studies are needed to help determine the appropriate drugs, the sequence of MTA use, and the precise transition time.
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Dubuissez, Marion, Ingrid Loison, Sonia Paget, Han Vorng, Saliha Ait-Yahia, Olivier Rohr, Anne Tsicopoulos, and Dominique Leprince. "Protein Kinase C-Mediated Phosphorylation of BCL11B at Serine 2 Negatively Regulates Its Interaction with NuRD Complexes during CD4+T-Cell Activation." Molecular and Cellular Biology 36, no. 13 (May 9, 2016): 1881–98. http://dx.doi.org/10.1128/mcb.00062-16.
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The transcription factor BCL11B/CTIP2 is a major regulatory protein implicated in various aspects of development, function and survival of T cells. Mitogen-activated protein kinase (MAPK)-mediated phosphorylation and SUMOylation modulate BCL11B transcriptional activity, switching it from a repressor in naive murine thymocytes to a transcriptional activator in activated thymocytes. Here, we show that BCL11B interacts via its conserved N-terminal MSRRKQ motif with endogenous MTA1 and MTA3 proteins to recruit various NuRD complexes. Furthermore, we demonstrate that protein kinase C (PKC)-mediated phosphorylation of BCL11B Ser2 does not significantly impact BCL11B SUMOylation but negatively regulates NuRD recruitment by dampening the interaction with MTA1 or MTA3 (MTA1/3) and RbAp46 proteins. We detected increased phosphorylation of BCL11B Ser2 uponin vivoactivation of transformed and primary human CD4+T cells. We show that following activation of CD4+T cells, BCL11B still binds toIL-2andId2promoters but activates their transcription by recruiting P300 instead of MTA1. Prolonged stimulation results in the direct transcriptional repression ofBCL11Bby KLF4. Our results unveil Ser2 phosphorylation as a new BCL11B posttranslational modification linking PKC signaling pathway to T-cell receptor (TCR) activation and define a simple model for the functional switch of BCL11B from a transcriptional repressor to an activator during TCR activation of human CD4+T cells.
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Godsey, Michael H., Natalya N. Baranova, Alexander A. Neyfakh, and Richard G. Brennan. "Crystal Structure of MtaN, a Global Multidrug Transporter Gene Activator." Journal of Biological Chemistry 276, no. 50 (October 1, 2001): 47178–84. http://dx.doi.org/10.1074/jbc.m105819200.
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MtaN (Multidrug Transporter Activation, N terminus) is a constitutive, transcriptionally active 109-residue truncation mutant, which contains only the N-terminal DNA-binding and dimerization domains of MerR family member Mta. The 2.75 Å resolution crystal structure of apo-MtaN reveals a winged helix-turn-helix protein with a protruding 8-turn helix (α5) that is involved in dimerization by the formation of an antiparallel coiled-coil. The hydrophobic core and helices α1 through α4 are structurally homologous to MerR family member BmrR bound to DNA, whereas one wing (Wing 1) is shifted. Differences between the orientation of α5 with respect to the core and the revolution of the antiparallel coiled-coil lead to significantly altered conformations of MtaN and BmrR dimers. These shifts result in a conformation of MtaN that appears to be incompatible with the transcription activation mechanism of BmrR and suggest that additional DNA-induced structural changes are necessary.
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Xu, Yongbin, Chun-Shan Quan, Xiaoling Jin, Xuanzhen Jin, Jing Zhao, Liming Jin, Jin-Sik Kim, Jianyun Guo, Shengdi Fan, and Nam-Chul Ha. "Crystallization and preliminary X-ray diffraction analysis of the interaction ofAeromonas hydrophilaMtaN-1 withS-adenosylhomocysteine." Acta Crystallographica Section F Structural Biology Communications 71, no. 4 (March 20, 2015): 393–96. http://dx.doi.org/10.1107/s2053230x15003647.
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Prokaryotic 5′-methylthioadenosine/S-adenosylhomocysteine nucleosidase (MtaN) is a multifunctional enzyme that can hydrolyzeS-adenosyl-L-homocysteine (SAH) andS-methyl-5′-thioadenosine (MTA) to giveS-ribosyl-L-homocysteine (SRH) andS-methyl-5′-thioribose (MTR), respectively. This reaction plays a key role in several metabolic pathways, including biological methylation, polyamine biosynthesis, methionine recycling and bacterial quorum sensing. Structurally, MtaN belongs to the MtnN subfamily of the purine nucleoside phosphorylase (PNP)/uridine phosphorylase (UDP) phosphorylase family.Aeromonas hydrophilahas two MtnN subfamily proteins: MtaN-1, a periplasmic protein with an N-terminal signal sequence, and MtaN-2, a cytosolic protein. In this study, MtaN-1 fromAeromonas hydrophilawas successfully expressed and purified using Ni–NTA affinity, Q anion-exchange and gel-filtration chromatography. Crystals of the protein in complex with the substrate SAH were obtained and diffracted to a resolution of 1.4 Å. The crystals belonged to the trigonal space groupP3121 orP3221, with unit-cell parametersa=b= 102.7,c= 118.8 Å. The asymmetric unit contained two molecules of MtaN-1 complexed with SAH.
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Cañadillas-Delgado, Laura, Óscar Fabelo, Jorge Pasán, Mariadel Déniz, Carla Martínez-Benito, Pau Díaz-Gallifa, Tomás Martín, and Catalina Ruiz-Pérez. "Three new europium(III) methanetriacetate metal-organic frameworks: the influence of synthesis on the product topology." Acta Crystallographica Section B Structural Science, Crystal Engineering and Materials 70, no. 1 (January 16, 2014): 19–27. http://dx.doi.org/10.1107/s2052520613034550.
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Three new metal-organic framework structures containing EuIIIand the little explored methanetriacetate (C7H7O63−, mta3−) ligand have been synthesized. Gel synthesis yields a two-dimensional framework with the formula [Eu(mta)(H2O)3]n·2nH2O, (I), while two polymorphs of the three-dimensional framework material [Eu(mta)(H2O)]n·nH2O, (II) and (III), are obtained through hydrothermal synthesis at either 423 or 443 K. Compounds (I) and (II) are isomorphous with previously reported GdIIIcompounds, but compound (III) constitutes a new phase. Compound (I) can be described in terms of dinuclear [Eu2(H2O)4]6+units bonded through mta3−ligands to form a two-dimensional framework with topology corresponding to a (6,3)-connected binodal (43)(466683)-kgdnet, where the dinuclear [Eu2(H2O)4]6+units are considered as a single node. Compounds (II) and (III) have distinct three-dimensional topologies, namely a (41263)(4966)-nianet for (II) and a (41065)(41164)-K2O2; 36641net for (III). The crystal density of (III) is greater than that of (II), consistent with the increase of temperature, and thereby autogeneous pressure, in the hydrothermal synthesis.
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Qi, Fengna, Honglei Sun, Li Zhang, and Jingwei Zheng. "Comparison of curative effect between different retrograde filling materials in young permanent molar root canal therapy." Cellular and Molecular Biology 67, no. 6 (February 27, 2022): 305–10. http://dx.doi.org/10.14715/cmb/2021.67.6.40.
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The first mandible and maxilla permanent molars are the first permanent teeth that grow next to the deciduous teeth and may decay due to carelessness. Their caries can spread to the pulpal tentacles and cause pulpal and periapical diseases. In the current study, we tried to compare the curative effect of different retrograde filling materials, i.e. white MTA, gray MTA, Portland cement, and IRM, in young permanent molar root canal therapy. Because IL-1β stimulates bone degradation by osteoclasts, IL-1β gene expression was also measured for further evaluation. For this purpose, 400 students (240 boys and 160 girls) aged 8 to 11 years referred to the Pediatric Dental Center for first permanent molar root canal therapy were selected during two years. After recording the demographic characteristics of each patient, the first permanent molar teeth were examined by a general dentist with Abslang and decayed teeth were considered to have both discolorations in their grooves and apparent opacity. The patients, who need root canal therapy, were divided into four groups. The first group was treated with gray MTA. The second group was treated with white MTA. The third group received Portland cement for root canal therapy. The fourth group was treated with IRM. Also, IL-1β gene expression was evaluated by the real-time PCR technique. Relative changes in gene expression in PBMC cells were performed using One Way ANOVA. SPSS 18 software was used to determine the correlation of gene expression in PBMCs. The results showed that there was no significant difference between the groups in terms of age (p = 0.12) and gender (p = 0.24). Also, the need for endodontic treatment in the mandible (n = 278) was higher than the maxilla (n = 85) and both jaws (n = 37). But there was no significant difference between the groups in terms of the need for endodontic treatment (p = 0.32). The results of Pearson correlation coefficients between studied groups in terms of IL-1β gene expression showed that gray MTA and white MTA were not statistically different, but MTAs were generally different from Portland cement and IRM, with higher IL-1β gene expression. In general, the results showed that the teeth in the vicinity of gray MTA and white MTA showed a more appropriate response than Portland cement and IRM, so the use of MTA and its preference over other materials is recommended. In the case of Portland cement, more studies are needed to reach a conclusion comparing this material with MTA.
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Sloan, Shelby, Fiona Brown, Mackenzie Long, JoBeth Helmig-Mason, Stacey Beck, Ji Hyun Chung, Walter Hanel, et al. "PRMT5 Inhibition Modulates E2F1 and P53 to Restore Cell Cycle Regulation and Drive DNA Damage Response in Ibrutinib-Resistant Mantle Cell Lymphoma." Blood 138, Supplement 1 (November 5, 2021): 787. http://dx.doi.org/10.1182/blood-2021-153992.
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Abstract Introduction: Ibrutinib is widely used for relapsed/refractory mantle cell lymphoma (MCL), however nearly 1/3 of patients have primary resistance and the remaining patients will inevitably acquire resistance with poor overall survival. There is an urgent need for novel therapies targeting pro-survival signaling pathways triggered by ibrutinib resistance. Pharmacologic inhibition of Protein Arginine Methyltransferase 5 (PRMT5) represents a novel therapeutic approach to overcome ibrutinib resistant MCL (IR-MCL). PRMT5 has many essential functions in normal and malignant B cells, however in the context of IR-MCL the mechanisms of PRMT5 inhibitor mediated cell death have not been described. Genomic co-deletions of MTAP/CDKN2A are commonly detected in IR-MCL cells. MTAP deletion and subsequent accumulation of the metabolite MTA, sensitizes cells to further inhibition of PRMT5. Although the published literature defines this therapeutic rationale for targeting PRMT5 in cancers with co-deletion of MTAP/CDKN2A, the literature lacks studies specifically targeting PRMT5 in IR-MCL. Methods: Here we report the primary mechanism of PRMT5 inhibitor mediated cell death in the context of IR-MCL, utilizing a combination of Whole Exome Sequencing (WES), RNA-seq, protein expression, and cell cycle analysis (PI-DNA staining with flow cytometry) in 8 MCL cell lines and 3 patient derived xenografts (PDXs) of IR-MCL. Pharmacologic inhibition of PRMT5 was performed with two selective compounds: PRT-382 and C220 (Prelude Therapeutics). Inducible CRISPR/CAS9-gRNA was used to selectively knock out MTAP and CDKN2A. Results: Comparing MCL cell lines with primary ibrutinib resistance, we found an inverse correlation between PRT-382 ic50 and ibrutinib ic50 (Spearman: r = -0.94, p = 0.017). In MCL cell lines, low expression of MTAP also correlated with lower global Symmetric Di-Methyl Arginine (SDMA) and enhanced sensitivity to C220 respectively (Pearson: r = 0.84, p = 0.01; r = 0.87, p = 0.01). Genomic deletion of MTAP in a cell line with primary ibrutinib resistance (Jeko MTAP-WT) enhanced sensitivity to PRMT5i, whereas MTAP knock-in (KI) in CCMCL, an MTAP-null cell line, decreased sensitivity to PRMT5i. The treatment of Jeko-MTAP-KI and CCMCL-MTAP-KO with MTA, further confirmed that genomic deletion of MTAP confers enhanced vulnerability to PRMT5i in MCL cell lines. In a PDX generated in our lab from an MCL patient with acquired IR, treatment with PRT-382 decreased tumor infiltration of multiple organs and ki-67 compared to ibrutinib or control (H&E and IHC staining). To mechanistically address the nature of the anti-tumor activity of PRMT5i in IR-MCL, we treated PDX mice with PRT-382 or vehicle control for 2 weeks to obtain ex-vivo samples for NGS methods. Splenic MCL tumor cells (Hu-CD19+) where subjected to transcriptomic profiling by RNA-seq (n=3 per Tx group). RNA-seq revealed 1014 down and 1124 up differentially expressed genes (DEGs) (q < 0.01, |log2FC| > 0.05). Gene Set Enrichment Analysis (GSEA) identified activation of the p53 pathway (NES = 1.73), with repression of E2F targets, G2M checkpoints, Epithelial to Mesenchymal Transition (EMT), and PRMT5 targets among the top gene sets modulated with PRMT5i (NES = -2.51, -2.26, -2.06, -1.79). Comparing genomic alterations across MCL cell lines and 3 PDXs of IR-MCL, co-deletion of MTAP/CDKN2A and/or a functional/WT copy of TP53 defines a therapeutic vulnerability to PRMT5i in 9 out of 11 cases (82%). In MCL, PRMT5i resulted in p53-dependent G1/S cell cycle arrest and p53-dependent DNA damage induced apoptosis by transcriptional activation of the p53 target genes (CDKN1A, BBC3, BAX, PHLDA3, andSESN1). Western blot analysis confirmed E2F target gene repression (TK1, CCNA2, CHK1, CDK1) and accumulation of DNA damage response proteins (cleaved PARP, cleaved CASP3, p-H2AX) that are further enhanced with combination of doxorubicin. Conclusion: Pharmacologic inhibition of PRMT5 with the clinical-grade, novel small molecule inhibitor (PRT543, Prelude Therapeutics) merits further investigation in ongoing clinical trials (NCT03886831, clinicaltrials.gov), specifically for the treatment of IR-MCL with deletion of MTAP and prior to the genomic mutation of TP53. We are currently exploring novel combinations to maximize the therapeutic potential of PRMT5 inhibition in this disease. Disclosures Byrd: Vincerx Pharmaceuticals: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Novartis, Trillium, Astellas, AstraZeneca, Pharmacyclics, Syndax: Consultancy, Honoraria; Newave: Membership on an entity's Board of Directors or advisory committees. Vaddi: Prelude Therapeutics: Current Employment, Current equity holder in publicly-traded company. Scherle: Prelude Therapeutics: Current Employment, Current equity holder in publicly-traded company. Baiocchi: Prelude Therapeutics: Consultancy; viracta: Consultancy, Current holder of stock options in a privately-held company; Codiak Biosciences: Research Funding; Atara Biotherapeutics: Consultancy.
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Yamamura, Toshihiro, Kaoru Tamura, Daisuke Kobayashi, Motoki Inaji, Yuka Toyama, Shoko Hara, Yoji Tanaka, Tadashi Nariai, Kenji Ishii, and Taketoshi Maehara. "NI-1 METHYLTHIOADENOSINE PHOSPHOLYLASE STATUS CORRELATES WITH PROGNOSIS AND METHIONINE UPTAKE IN IDH MUTANT ASTROCYTOMA." Neuro-Oncology Advances 4, Supplement_3 (December 1, 2022): iii16. http://dx.doi.org/10.1093/noajnl/vdac167.060.
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Abstract Purpose Methylthioadenosine phosphorylase (MTAP) immunohistochemistry staining has been proposed as a surrogate of Cyclin-dependent kinase inhibitor 2A homozygous deletion (CDKN2A HD) in various type of tumors. This study was designed to determine whether MTAP status correlates with clinical outcome and uptake of 11C-methionine in astrocytoma with IDH mutations. Methods We conducted a MTAP immunohistochemistry staining of 30 IDH-mutant astrocytoma patients who underwent 11C-methionine positron emission tomography scans prior to surgical resection from 2000 to 2020. The tumor-to-normal ratio (T/N) of 11C-methionine uptake was calculated by dividing the mean standardized uptake value (SUV) for the tumor by the mean SUV of the normal brain. Results Eight of the thirty astrocytomas harboring IDH mutations exhibited loss of cytoplasmic MTAP expression, which is accompanied with a poor prognosis. The median progression free survival (PFS) in IDH-mutant astrocytoma patients with loss of MTAP was 1.88 years, significantly shorter than that of those with MTAP retention (6.80 years, p=0.003). The median Overall survival (OS) in IDH-mutant astrocytoma patients with loss of MTAP was 5.23 years, again significantly shorter than that of those with MTAP retention (p=0.0191). Multivariate analysis revealed MTAP status to be an independent prognostic marker for PFS in IDH-mutant astrocytoma patients. The median T/N ratio in tumors with loss of cytoplasmic MTAP expression was 2.12 (IQR 1.92-2.50), i.e., significantly higher than that of tumors with MTAP retention (1.65, IQR 1.23-1.94, p=0.0116, U test). Conclusion Our study showed MTAP status to correlate with clinical outcome and T/N ratio of astrocytoma patients with IDH mutations.
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Parekh, Samir, Jose M. Polo, Rita Shaknovich, Przemyslaw Juszczynski, Paola Lev, Stella M. Ranuncolo, Yingnan Yin, et al. "BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms." Blood 110, no. 6 (September 15, 2007): 2067–74. http://dx.doi.org/10.1182/blood-2007-01-069575.
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AbstractThe BCL6 transcriptional repressor is the most commonly involved oncogene in diffuse large B-cell lymphomas (DLBCLs). Constitutive expression of BCL6 mediates lymphomagenesis through aberrant proliferation, survival, and differentiation blockade. Binding of BCL6 to the SMRT/N-CoR corepressors mediates the BCL6 survival effect in DLBCL. Although the basis for differentiation blockade is unknown in DLBCL, recent data suggest that BCL6 binding to the MTA3 corepressor might be involved. We report that BCL6 and MTA3 are coexpressed in normal germinal center B cells and DLBCL. Depletion of MTA3 in DLBCL cells induced a differentiation-related BCL6 target gene (PRDM1), but not target genes involved in survival. Accordingly, MTA3 and PRDM1 expression are mutually exclusive in germinal center B cells. We performed chromatin immunoprecipitation (ChIP)–on-chip mapping of the PRDM1 locus, identifying a novel BCL6 binding site on intron 3 of the PRDM1 gene, and show that BCL6 recruits MTA3 to this site. In DLBCL cells, MTA3 depletion induced plasmacytic differentiation but did not decrease viability of DLBCL cells. However, MTA3 depletion synergized with a specific BCL6 inhibitor that blocks SMRT/N-CoR binding to decrease DLBCL viability. Taken together, these results show that BCL6 regulates distinct transcriptional programs through the SMRT/N-CoR and MTA3 corepressors, respectively, and provides a basis for combinatorial therapeutic targeting of BCL6.
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Stillman, I. E., M. Brezis, S. N. Heyman, F. H. Epstein, K. Spokes, and S. Rosen. "Effects of salt depletion on the kidney: changes in medullary oxygenation and thick ascending limb size." Journal of the American Society of Nephrology 4, no. 8 (February 1994): 1538–45. http://dx.doi.org/10.1681/asn.v481538.
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Previous studies have shown that salt depletion enhances the susceptibility of the kidney to nephrotoxins (amphotericin, cyclosporine, and contrast). To study the renal response to salt depletion, Sprague-Dawley rats were fed a sodium-deficient diet (N = 12) with pair-fed controls (N = 13) for 4 wk. In addition, rats from each group underwent 24-h water deprivation studies (N = 9; four salt deprived, five normal). Plastic 1-micron horizontal sections of mid-inner stripe were examined, and cross-sectional areas of the medullary thick ascending limb (mTAL) were analyzed. The mTAL of the salt-deprived rats were smaller (P = 0.04) and showed greater variance in size (P = 0.02) than control (618 +/- 106 versus 693 +/- 50 microns2). However, mean glomerular and collecting duct cross-sectional areas were unaffected by salt intake. Cross-sectional areas of long- and short-loop mTAL were significantly different, regardless of group (518 +/- 78 versus 732 +/- 92 microns2). Maximal urinary concentrating ability was found to correlate with mTAL cross-sectional area (r = 0.85; P = 0.004) and with long-loop mTAL size (r = 0.77; P = 0.016). However, it did not significantly correlate with short loop mTAL size (r = 0.53; P = 0.14).(ABSTRACT TRUNCATED AT 250 WORDS)
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Basse, Clémence, Claire Morel, Céline Callens, Gaëlle Pierron, Vincent Servois, Anne Vincent-Salomon, Aude Jobard, et al. "Exploitation of Precision Medicine Trials Data: Examples of Long Responders From the SHIVA01 Trial." JCO Precision Oncology, no. 2 (November 2018): 1–11. http://dx.doi.org/10.1200/po.18.00048.
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Purpose Precision medicine trials constitute a precious source of molecular data with prospective clinical annotations allowing the exploration of patients’ subpopulations according to specific clinical or biological questions. Using the SHIVA01—the first randomized trial comparing molecularly targeted therapy on the basis of tumor molecular profiling versus conventional chemotherapy in metastatic cancer patients who failed standard of care therapy—annotated database, we report cases of patients treated in the trial with targeted therapy who experienced an objective response or prolonged disease stabilization in light of patients’ molecular alterations. Patients and Methods We selected all patients included in SHIVA01 treated with a molecularly targeted agent (MTA) who experienced an objective response or disease stabilization that lasted longer than 6 months according to Response Evaluation Criteria in Solid Tumors version 1.1. Results Among the 170 patients who received MTAs in the SHIVA01 trial, 15 patients (9%) experienced an objective response (n = 3) or disease stabilization that lasted longer than 6 months (n = 12). The most frequent histologic subtypes were breast cancer (27%) and cervical cancer (20%). Six patients, including three patients with breast cancer, were treated with abiraterone on the basis of androgen receptor protein overexpression. Five patients were treated with everolimus on the basis of a PTEN heterozygous deletion with loss of protein expression, PIK3CA mutation, or both alterations. The remaining four patients were treated with tamoxifen, erlotinib, imatinib, and vemurafenib on the basis of progesterone receptor expression, EGFR amplification, KIT mutation, and BRAF mutation, respectively. TP53 mutations were absent in responder patients. Conclusion Analysis of patients who experienced objective responses or disease stabilization that lasted longer than 6 months allowed the identification of potential biomarkers of sensitivity and resistance to MTAs.
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Tulsani, SG, N. Chikkanarasaiah, and S. Bethur. "An in Vivo Comparison of Antimicrobial Efficacy of Sodium Hypochlorite and Biopure MTAD™ against Enterococcus Faecalis in Primary Teeth: A qPCR Study." Journal of Clinical Pediatric Dentistry 39, no. 1 (September 1, 2014): 30–34. http://dx.doi.org/10.17796/jcpd.39.1.c4q2155r16817219.
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Objectives: Biopure MTAD™, a new root canal irrigant has shown promising results against the most common resistant microorganism, E. faecalis, in permanent teeth. However, there is lack of studies comparing its antimicrobial effectiveness with NaOCl in primary teeth. The purpose of this study was to compare the in vivo antimicrobial efficacy of NaOCl 2.5% and Biopure MTAD™ against E. faecalis in primary teeth. Study design: Forty non vital single rooted primary maxillary anterior teeth of children aged 4-8 years, were irrigated either with NaOCl 2.5% (n=15), Biopure MTAD™ (n=15) and 0.9% Saline (n=10, control group). Paper point samples were collected at baseline (S1) and after chemomechanical preparation (S2) during the pulpectomy procedure. The presence of E. faecalis in S1 & S2 was evaluated using Real time Polymerase Chain Reaction. Results: Statistical significant difference was found in the antimicrobial efficacy of NaOCl 2.5 % and BioPure MTAD™ when compared to saline (p>0.05). However, no statistical significant difference was found between the efficacies of both the irrigants. Conclusions: NaOCl 2.5% and BioPure MTAD™, both irrigants are equally efficient against E. faecalis in necrotic primary anterior teeth. MTAD is a promising irrigant, however clinical studies are required to establish it as ideal root canal irrigant in clinical practice.
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Alrahman, Mewan Salahalddin A., Bestoon Muhammed Faraj, and Kawa F. Dizaye. "Assessment of Nitrofurantoin as an Experimental Intracanal Medicament in Endodontics." BioMed Research International 2020 (February 18, 2020): 1–13. http://dx.doi.org/10.1155/2020/2128473.
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Background and Objectives. Multiple antibacterial agents have been mixed and used as an intracanal medicament-like modified triple antibiotic paste (MTAP) to eliminate Enterococcus faecalis (EF), which has been most frequently identified in the cases of failed root canal treatment and periapical lesions. This study is aimed at using a single antibacterial agent, nitrofurantoin (Nit), as an experimental intracanal medicament paste against different clinical isolates of EF bacteria and at comparing its antimicrobial efficacy with MTAP. Materials and Methods. Three strains of EF (S1, S2, and S3) were clinically isolated. A total of 198 straight single-rooted human teeth were collected and divided randomly into three main groups: group N (Nit) (n=90), group M (MTAP) (n=90), and group W (distilled water) (n=18). The main groups were subdivided into three subgroups according to the strain of EF: in groups N and M, subgroups S1, S2, and S3 (n=30), while in group W, subgroups S1, S2, and S3 (n=6). Then, each subgroup of N and M was divided into five groups (n=6) according to the concentrations of Nit or MTAP (6.25, 12.5, 25, 50, and 100 mg/mL). The colony-forming unit (CFU) of EF from the canal lumen and dentinal chips was measured. Results. Nit could eradicate S1, S2, and S3 completely with concentrations of 6.25, 12.5, and 25 mg/mL, respectively, while MTAP showed complete eradication of the three strains only at 25 mg/mL. In all the groups, it was found that the CFU counts of EF in the dentinal chips were higher than those in the root canal lumen. Conclusion. At the concentration of 25 mg/mL, the Nit paste is effective in eradicating EF completely when it is used as an intracanal medicament.
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Sasaki, Shoh, Maiko Takeda, Takanori Hirose, Tomomi Fujii, Hiroe Itami, Tomoko Uchiyama, Kohei Morita, et al. "Correlation of MTAP Immunohistochemistry With CDKN2A Status Assessed by Fluorescence In Situ Hybridization and Clinicopathological Features in CNS WHO Grade 2 and 3 Meningiomas: A Single Center Cohort Study." Journal of Neuropathology & Experimental Neurology 81, no. 2 (December 13, 2021): 117–26. http://dx.doi.org/10.1093/jnen/nlab127.
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Abstract CDKN2A homozygous deletion has occasionally been reported in atypical and anaplastic meningiomas and is considered as one of the genetic alterations commonly involved in their recurrence and malignant progression. Methylthioadenosine phosphorylase (MTAP) immunohistochemistry is a promising surrogate marker for CDKN2A homozygous deletion in different cancers but has not been examined in meningiomas. We performed CDKN2A FISH and MTAP immunohistochemistry on specimens from 30 patients with CNS WHO grade 2 (n = 27) and 3 (n = 3) meningiomas, including specimens from primary and recurrent tumors and then determined whether MTAP immunohistochemistry correlated with CDKN2A homozygous deletion and clinicopathological features. CDKN2A homozygous deletion was detected in 12% (3/26) of CNS WHO grade 2 and 67% (2/3) of CNS WHO grade 3 meningiomas; 3 cases exhibited temporal and/or spatial heterogeneity. MTAP loss was in excellent concordance with CDKN2A homozygous deletion (sensitivity; 100%, specificity; 100%). MTAP loss/CDKN2A homozygous deletion correlated with cellular proliferation (mitotic rate; p = 0.001, Ki-67 labeling index; p = 0.03) and poor prognosis (overall survival; p = 0.01, progression free survival; p < 0.001). Thus, MTAP immunostaining can be a surrogate marker for CDKN2A homozygous deletion in meningiomas, and MTAP loss/CDKN2A homozygous deletion may be an important prognostic factor for meningiomas.
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Dagogo-Jack, Ibiayi, Russell Madison, Douglas A. Mata, Alexa Betzig Schrock, Tyler Janovitz, Brennan Decker, Richard S. P. Huang, et al. "Comprehensive molecular profiling of pleural mesothelioma according to histologic subtype." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 8555. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.8555.
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8555 Background: Malignant pleural mesothelioma (MPM) is an aggressive malignancy with limited therapeutic options. Immunotherapy has emerged as an effective therapeutic strategy, particularly in the non-epithelioid MPM subgroup. An improved understanding of the molecular profile of MPM may inform targeted therapeutic approaches and provide insights into factors underlying differential sensitivity to therapies. Methods: We performed comprehensive genomic profiling of MPMs from 980 patients, with histologic subtyping on a subset (n = 340; n = 235 epithelioid, n = 48 sarcomatoid, n = 57 biphasic). Analyses included quantifying tumor mutational burden (TMB), assessing microsatellite instability (MSI), and evaluating PD-L1 expression (Dako 22C3). Results: Median TMB of MPM was 1.74 (0.87-2.61) mutations per megabase (mut/mb). Median TMB was comparable for non-epithelioid (biphasic, sarcomatoid) vs epithelioid MPM (1.25 mut/mb vs 1.25 mut/mb, p = 0.43). In the overall cohort, inactivating alterations in the following genes were most prevalent: CDKN2A (49%), BAP1 (44%), CDKN2B (42%), MTAP (35%), and NF2 (33%). MTAP loss co-occurred with CDKN2A and CDKN2B loss in > 99% and 94% of cases, respectively. MTAP loss was observed in 28% of epithelioid vs 46% of non-epithelioid MPMs (p = 0.03). BAP1 alterations were detected in 51% of epithelioid vs 36% of non-epithelioid MPMs (p = 0.81). PD-L1 expression was assessed in 308 MPMs, among which 153 (49%) had PD-L1 ≥1%, including 35 (11%) with PD-L1 ≥50%. Among 164 specimens that underwent histologic subtyping and PD-L1 evaluation, PD-L1 was expressed in 46 (71%) non-epithelioid MPMs compared to 49 (51%) epithelioid MPMs (p = 0.03). Given the high prevalence of alterations involving the two genes, we evaluated impact of BAP1 and MTAP status on PD-L1 and TMB. TMB (1.74 mut/mb vs 1.74 mut/mb) and PD-L1 expression (50% vs 54%) were comparable in BAP1-altered vs wildtype specimens. Although TMB was comparable in MTAP-deficient and MTAP-intact tumors (1.25 mut/mb vs 1.74 mut/mb), more tumors with MTAP loss expressed PD-L1 (68% vs 44%, p = 0.0004). Conclusions: Compared to epithelioid MPM, non-epithelioid tumors demonstrate comparable TMB, higher PD-L1 expression, and enrichment for MTAP loss. As MTAP is frequently altered in MPM, further study is indicated to explore the relationship between MTAP status and MPM biology, including sensitivity to therapeutics such as immunotherapy and synthetic lethal approaches.
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Dewi, Feryariska, Dini Asrianti, and Anggraini Margono. "MICROLEAKAGE EVALUATION OF MODIFIED MINERAL TRIOXIDE AGGREGATE EFFECT TOWARD MARGINAL ADAPTATION ON CERVICAL DENTIN PERFORATION." International Journal of Applied Pharmaceutics 9 (January 1, 2018): 10. http://dx.doi.org/10.22159/ijap.2017.v9s2.03.
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Objective: To analyze the marginal adaptation of conventional MTA (ProRoot®MTA) and modified MTA (MTA Flow™) on perforated dentin.Methods: Forty specimens of human’s premolar teeth with lateral perforations were sealed by conventional MTA (n=20) and modified MTA (n=20). After 24 hours, the specimens were immersed in Indian ink for 24 hours, then embedded in resin and sectioned longitudinally in mesial-distal direction. The score of microleakage was determined using stereo microscope (SteREO Discovery. V12, Carl Zeiss) with 20x magnification. Statistical analysis was done by Chi Square (p<0,05).Results: Less microleakage score (0,5-1mm) was detected in modified MTA (25%) compared to conventional MTA (45%), although not statistically significant.Conclusion: Microleakage were detected in both conventional and modified MTA as material for cervical dentin perforation treatment, although modified-MTA group showed less microleakage score.
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Kikeri, D., S. Azar, A. Sun, M. L. Zeidel, and S. C. Hebert. "Na(+)-H+ antiporter and Na(+)-(HCO3-)n symporter regulate intracellular pH in mouse medullary thick limbs of Henle." American Journal of Physiology-Renal Physiology 258, no. 3 (March 1, 1990): F445—F456. http://dx.doi.org/10.1152/ajprenal.1990.258.3.f445.
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To determine mechanisms of intracellular pH (pHi) regulation in mouse medullary thick limbs (MTAL), pHi was measured in MTAL suspensions and in the isolated perfused MTAL by use of 2',7'-bis(carboxyethyl)-5(6)carboxyfluorescein (BCECF). A method to obtain MTAL suspensions from the mouse outer medulla is reported. Characterization of suspensions with microscopy, anti-Tamm-Horsfall antibody labeling, measurement of O2 consumption, and adenosine 3',5'-cyclic monophosphate responses to antidiuretic hormone indicated that these suspensions were highly purified for viable MTAL tubules. The resting pHi was 7.41 +/- 0.02 (means +/- SE) in N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid-buffered media and 7.23 +/- 0.02 in CO2- HCO3(-)-buffered media, both at extracellular pH 7.4. MTAL tubules exhibited rapid pHi recovery from intracellular acidification. Recovery of pHi was dependent on luminal Na+ (apparent Km = 13.2 +/- 3.2 mM) and was inhibited by amiloride (apparent Ki = 10.6 microM), consistent with the activity of an apical Na(+)-H+ antiporter. Antiporter activity was enhanced by acidification and was diminished at the resting pHi. Recovery from intracellular alkalinization (rapid withdrawal of CO2- HCO3-) was sensitive to the stilbene anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, Cl(-)-insensitive, and Na(+)-sensitive, consistent with the activity of a Na(+)-(HCO3-)n symporter. Both transporters were significantly involved in steady-state pHi regulation in the presence of CO2- HCO3-. In contrast, the Na(+)-H+ antiporter played the dominant role in steady-state pHi regulation in the absence of CO2- HCO3-.
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Ito, O., Y. Kondo, N. Takahashi, K. Omata, and K. Abe. "Role of calcium in insulin-stimulated NaC1 transport in medullary thick ascending limb." American Journal of Physiology-Renal Physiology 269, no. 2 (August 1, 1995): F236—F241. http://dx.doi.org/10.1152/ajprenal.1995.269.2.f236.
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It has been reported that insulin stimulates directly NaCl transport in the rabbit medullary thick ascending limb (MTAL) [O. Ito, Y. Kondo, N. Takahashi, K. Kudo, Y. Imai, K. Omata, and K. Abe. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F265-F270, 1994]. In the present investigation, we evaluated the role of Ca2+ in insulin-stimulated NaCl transport in rabbit MTAL by in vitro microperfusion methods. In control experiments, insulin increases transepithelial voltage (Vte) and net lumen-to-bath Cl-flux (JCl). The effects of insulin on Vte and JCl in a Ca2+ -free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' -tetraacetic acid did not differ from those in a Ca2+ -containing control solution. Direct measurements of cytosolic free Ca2+ ([Ca2+]i) with fura 2 fluorescence showed that insulin caused no detectable change in [Ca2+]i in MTAL cells. Chelation of intracellular Ca2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid inhibited the actions of insulin in Vte and JCl without affecting basal values. We examined further whether calmodulin is also involved in insulin-stimulated NaCl transport in MTAL using two dissimilar inhibitors of calmodulin, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7). TFP and W-7 inhibited the action of insulin in a dose-dependent manner, with maximal inhibition of both agents of > 90%. The half-maximal inhibition by TFP and W-7 was approximately 50 and 100 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Balto, Hanan, Fouad Salama, Sultan Al-Mofareh, and Faisal Al-Yahya. "Evaluation of Different Irrigating Solutions on Smear Layer Removal of Primary Root Dentin." Journal of Contemporary Dental Practice 16, no. 3 (2015): 187–91. http://dx.doi.org/10.5005/jp-journals-10024-1659.
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ABSTRACT Aim To evaluate the efficacy of ethanolic extract of Salvadora persica (S. persica) and BioPure MTAD (a mixture of a tetracycline isomer, an acid, and a detergent) in removing the intracanal smear layer of primary teeth. Materials and methods The root canal of 40 extracted human primary anterior teeth were cleaned, shaped and grouped into experimental (n = 30) and control (n = 10). The root canals of the positive (n = 5) and the negative control (n = 5) were irrigated for 3 minutes with 5 ml of 17% ethylenediaminetetraacetic acid (EDTA) or saline respectively. The canals in the experimental groups were irrigated for 3 minutes with 5 ml of 1 mg/ml ethanolic extract of S. persica (n = 15) or BioPure MTAD (n = 15) and then flushed with 2 ml of saline. The presence or absence of smear layer at the coronal and middle portion of each canal were examined under a scanning electron microscope (SEM). Results A significant d ifference (p = 0 .004) i n s mear l ayer removal between S. persica and MTAD at the middle third of the canal was observed. MTAD solution was as effective as 17% EDTA in removing the smear layer. Conclusion MTAD was significantly more effective in smear layer removal than S. persica solution at the middle third of the canal wall. Clinical significance Both tested irrigant solutions have the ability to remove the intracanal smear from primary root dentin following cleaning and shaping of the root canal and could be an alternative to EDTA. How to cite this article Balto H, Salama F, Al-Mofareh S, Al-Yahya F. Evaluation of Different Irrigating Solutions on Smear Layer Removal of Primary Root Dentin. J Contemp Dent Pract 2015;16(3):187-191.
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Adjei, Alex A., Charles Erlichman, Jeff A. Sloan, Joel M. Reid, Henry C. Pitot, Richard M. Goldberg, Prema Peethambaram, et al. "Phase I and Pharmacologic Study of Sequences of Gemcitabine and the Multitargeted Antifolate Agent in Patients With Advanced Solid Tumors." Journal of Clinical Oncology 18, no. 8 (April 8, 2000): 1748–57. http://dx.doi.org/10.1200/jco.2000.18.8.1748.
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PURPOSE: Multitargeted antifolate (MTA) is an investigational agent that, like gemcitabine, exhibits broad activity in solid tumors. A phase I trial of MTA and gemcitabine was undertaken, based on the demonstration of preclinical cytotoxic synergy. PATIENTS AND METHODS: Thirty-five patients (group I) received 164 courses (median, four; range, one to 14 courses) of treatment of gemcitabine at doses of 1,000 and 1,250 mg/m2 on days 1 and 8 and MTA at doses of 200, 300, 400, 500, and 600 mg/m2, given 90 minutes after gemcitabine on day 1. Courses were repeated every 3 weeks. Because the day 8 dose of gemcitabine was reduced or omitted in 57% of courses due to neutropenia, 21 patients (group II) were treated on an alternate schedule, with MTA administered on day 8 rather than day 1. This group received 85 treatment courses (median, four; range, one to 10 courses). RESULTS: The most common and dose-limiting toxicity was neutropenia. Other toxicities included nausea, fatigue, rash, and elevated hepatic transaminases. The maximum-tolerated dose was gemcitabine/MTA 1,000/500 mg/m2 for group I and 1,250/500 mg/m2 for group II. Thirteen objective responses were documented (colorectal cancer, n = 3; non–small-cell lung cancer, n = 3; cholangiocarcinoma, n = 2; ovarian carcinoma, n = 2; mesothelioma, n = 1; breast cancer, n = 1; and adenocarcinoma of unknown primary site, n = 1). Gemcitabine had no effect on the disposition of MTA. CONCLUSION: The gemcitabine/MTA combination is broadly active and warrants further evaluation. The sequence of gemcitabine administered on days 1 and 8 with MTA administered on day 8 is better tolerated and is recommended for further study at doses of gemcitabine/MTA 1,250/500 mg/m2.
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Lai, Xuelei, Montserrat Soler-Lopez, Wangsa T. Ismaya, Harry J. Wichers, and Bauke W. Dijkstra. "Crystal structure of recombinant tyrosinase-binding protein MtaL at 1.35 Å resolution." Acta Crystallographica Section F Structural Biology Communications 72, no. 3 (February 19, 2016): 244–50. http://dx.doi.org/10.1107/s2053230x16002107.
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Mushroom tyrosinase-associated lectin-like protein (MtaL) binds to matureAgaricus bisporustyrosinasein vivo, but the exact physiological function of MtaL is unknown. In this study, the crystal structure of recombinant MtaL is reported at 1.35 Å resolution. Comparison of its structure with that of the truncated and cleaved MtaL present in the complex with tyrosinase directly isolated from mushroom shows that the general β-trefoil fold is conserved. However, differences are detected in the loop regions, particularly in the β2–β3 loop, which is intact and not cleaved in the recombinant MtaL. Furthermore, the N-terminal tail is rotated inwards, covering the tyrosinase-binding interface. Thus, MtaL must undergo conformational changes in order to bind mature mushroom tyrosinase. Very interestingly, the β-trefoil fold has been identified to be essential for carbohydrate interaction in other lectin-like proteins. Comparison of the structures of MtaL and a ricin-B-like lectin with a bound disaccharide shows that MtaL may have a similar carbohydrate-binding site that might be involved in glycoreceptor activity.
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Phuphanich, S., M. Chamberlain, T. Mikkelsen, X. Ye, S. A. Grossman, T. Batchelor, G. Lesser, J. D. Fisher, and S. Desideri. "A phase I study of SDX-102 for the treatment of patients with MTAP-deficient recurrent malignant gliomas." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 2063. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.2063.
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2063 Background: De novo purine biosynthesis entails two metabolic pathways of which one pathway is frequently impaired in cancer due to gene deletion of the rate limiting enzyme, methythioadenosine phosphorylase (MTAP). In MTAP-deficient cancers, SDX-102 inhibits purine biosynthesis by blocking the remaining synthetic pathway. This study was to determine the maximum tolerated dose (MTD), toxicity and pharmacokinetic activity of SDX-102 in the treatment of recurrent MTAP-deficient malignant gliomas. Methods: Eligible patients had recurrent supratentorial MTAP-deficient malignant gliomas treated previously with surgery, radiation and = 2 regimens of chemotherapy. Dose escalation was conducted separately for patients taking enzyme inducing anti-seizure drugs (EIASD+) and for those not (EIASD-). The starting dose in both groups was 80 mg/m2/day continuous infusion for 5 days every 3 weeks, cycle length was 3 weeks. Dose escalation was in a stepwise fashion in cohorts of three patients, up to a maximum dose of 125 mg/m2/day. Results: 118 patients were screened of which 39 (33%) had MTAP-deficient tumors. 21 patients (14 males/7 females) were enrolled between 9/17/04 and 3/17/06. Median age was 50 years (23–76); median KPS was 90 (60–100); 16 patients (76%) had GBM. Two dose levels of SDX-102 were tested in the EIASD+ group: 80 mg/m2/day (n=4) and 100 mg/m2/day (n=3), 3/3 dose limiting toxicity (DLT) were noted with grade 3 mucositis at 100 mg/m2/day , so in the EIASD+ group the MTD was 80 mg/m2/day. Three dose levels were tested in the EIASD- group: 80 mg/m2/day (n=4), 100 mg/m2/day (n=7), 1/3 patients had DLT (Grade 4 mucositis) at 100 mg/m2/day and the cohort was expanded for additional 3 patients without DLT noted; and 125 mg/m2/day (n=3) amongst whom no DLT was observed. No MTD was determined in the EIASD- group because the MTAP assay became unavailable through the sponsor. There were a range of 1–14 cycles administered in this patient population. Conclusions: SDX-102 infusion is safe and feasible in patients with recurrent MTAP-deficient malignant gliomas. The MTD in EIASD+ patients is 80 mg/m2/day. The EIASD-group MTD has not been determined however the highest dose tested is 125 mg/m2/day. No significant financial relationships to disclose.
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Montrose-Rafizadeh, C., and W. B. Guggino. "Role of intracellular calcium in volume regulation by rabbit medullary thick ascending limb cells." American Journal of Physiology-Renal Physiology 260, no. 3 (March 1, 1991): F402—F409. http://dx.doi.org/10.1152/ajprenal.1991.260.3.f402.
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Previous studies demonstrated that Ca2(+)-activated K+ channels in luminal membrane of rabbit medullary thick ascending limb cells (MTAL) are activated on exposure of the cells to hyposmotic solutions [J. Taniguchi and W. B. Guggino. Am. J. Physiol. 257 (Renal Fluid Electrolyte Physiol. 26): F347-F352, 1989]. In this study, we investigated the mechanism of activation of Ca2(+)-activated K+ channels in MTAL cells exposed to hyposmotic solutions. MTAL cells swell in hyposmotic medium and regulate volume back toward the starting volume. This regulatory volume decrease (RVD) is inhibited at high medium K+ concentrations or by presence of quinine or Ba2+ in extracellular medium, suggesting involvement of K+ channels. Measurements of intracellular Ca2+ concentrations with fura-2 show that intracellular Ca2+ rises in hyposmotic solutions and that this rise does not occur in absence of extracellular Ca2+. Nifedipine and verapamil also inhibit rise in intracellular Ca2+. Decreasing intracellular Ca2+ by removal of external Ca2+ in presence of EDTA or by chelation of intracellular Ca2+ with 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) inhibits RVD. We conclude that hypotonic solutions activate K+ efflux probably via K+ channels and Ca2+ influx via a nifedipine- and verapamil-sensitive pathway. Lowering intracellular Ca2+ removes the ability of MTAL cells to regulate volume in hyposmotic solutions.
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Talukder, Amjad H., Anupama Gururaj, Sandip K. Mishra, Ratna K. Vadlamudi, and Rakesh Kumar. "Metastasis-Associated Protein 1 Interacts with NRIF3, an Estrogen-Inducible Nuclear Receptor Coregulator." Molecular and Cellular Biology 24, no. 15 (August 1, 2004): 6581–91. http://dx.doi.org/10.1128/mcb.24.15.6581-6591.2004.
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ABSTRACT The transcriptional activity of estrogen receptor alpha (ER-α) is modified by regulatory action and interactions of coactivators and corepressors. Recent studies have shown that the metastasis-associated protein 1 (MTA1) represses estrogen receptor element (ERE)-driven transcription in breast cancer cells. With a yeast two-hybrid screen to clone MTA1-interacting proteins, we identified a known nuclear receptor coregulator (NRIF3) as an MTA1-binding protein. NRIF3 interacted with MTA1 both in vitro and in vivo. NRIF3 bound to the C-terminal region of MTA1, while MTA1 bound to the N-terminal region of NRIF3, containing one nuclear receptor interaction LXXLL motif. We showed that NRIF3 is an ER coactivator, hyperstimulated ER transactivation functions, and associated with the endogenous ER and its target gene promoter. MTA1 repressed NRIF3-mediated stimulation of ERE-driven transcription and interfered with NRIF3's association with the ER target gene chromatin. In addition, NRIF3 deregulation enhanced the responsiveness of breast cancer cells to estrogen-induced stimulation of growth and anchorage independence. Furthermore, we found that NRIF3 is an estrogen-inducible gene and activated ER associated with the ER response element in the NRIF3 gene promoter. These findings suggest that NRIF3, an MTA1-interacting protein, is an estrogen-inducible gene and that regulatory interactions between MTA1 and NRIF3 might be important in modulating the sensitivity of breast cancer cells to estrogen.
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Al-Janahi, Eiman, Georgios Ponirakis, Hanadi Al Hamad, Surjith Vattoth, Ahmed Elsotouhy, Ioannis N. Petropoulos, Adnan Khan, et al. "Corneal Nerve and Brain Imaging in Mild Cognitive Impairment and Dementia." Journal of Alzheimer's Disease 77, no. 4 (October 13, 2020): 1533–43. http://dx.doi.org/10.3233/jad-200678.
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Background: Visual rating of medial temporal lobe atrophy (MTA) is an accepted structural neuroimaging marker of Alzheimer’s disease. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic technique that detects neuronal loss in peripheral and central neurodegenerative disorders. Objective: To determine the diagnostic accuracy of CCM for mild cognitive impairment (MCI) and dementia compared to medial temporal lobe atrophy (MTA) rating on MRI. Methods: Subjects aged 60–85 with no cognitive impairment (NCI), MCI, and dementia based on the ICD-10 criteria were recruited. Subjects underwent cognitive screening, CCM, and MTA rating on MRI. Results: 182 subjects with NCI (n = 36), MCI (n = 80), and dementia (n = 66), including AD (n = 19, 28.8%), VaD (n = 13, 19.7%), and mixed AD (n = 34, 51.5%) were studied. CCM showed a progressive reduction in corneal nerve fiber density (CNFD, fibers/mm2) (32.0±7.5 versus 24.5±9.6 and 20.8±9.3, p < 0.0001), branch density (CNBD, branches/mm2) (90.9±46.5 versus 59.3±35.7 and 53.9±38.7, p < 0.0001), and fiber length (CNFL, mm/mm2) (22.9±6.1 versus 17.2±6.5 and 15.8±7.4, p < 0.0001) in subjects with MCI and dementia compared to NCI. The area under the ROC curve (95% CI) for the diagnostic accuracy of CNFD, CNBD, CNFL compared to MTA-right and MTA-left for MCI was 78% (67–90%), 82% (72–92%), 86% (77–95%) versus 53% (36–69%) and 40% (25–55%), respectively, and for dementia it was 85% (76–94%), 84% (75–93%), 85% (76–94%) versus 86% (76–96%) and 82% (72–92%), respectively. Conclusion: The diagnostic accuracy of CCM, a non-invasive ophthalmic biomarker of neurodegeneration, was high and comparable with MTA rating for dementia but was superior to MTA rating for MCI.
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Pereira, Inês Raquel, Catarina Carvalho, Siri Paulo, José Pedro Martinho, Ana Sofia Coelho, Anabela Baptista Paula, Carlos Miguel Marto, et al. "Apical Sealing Ability of Two Calcium Silicate-Based Sealers Using a Radioactive Isotope Method: An In Vitro Apexification Model." Materials 14, no. 21 (October 27, 2021): 6456. http://dx.doi.org/10.3390/ma14216456.
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The aim of this study was to evaluate and compare the sealing ability of two calcium silicate-based sealers (TotalFill BC RRM Fast Set Putty and White ProRoot MTA) when used as apical plugs in immature teeth through nuclear medicine. Single-rooted extracted teeth (n = 34) had their crowns and root tip sectioned to obtain 14 mm long root segments to simulate an in vitro apexification model. Were created two experimental groups, namely MTA (n = 12) and BC (n = 12), and two control groups, PG (positive group, n = 5) and NG (negative group, n = 5). On the 4th day after placing the respective apical plug, the apical portions of the teeth were submerged in a solution of sodium pertechnetate (99mTcNaO4) for 3 h. Statistical analysis showed a significant difference between the MTA group and the controls (p < 0.05). The BC group had a significant difference regarding the negative control (p < 0.001) but showed no statistical significance regarding the positive control (p = 0.168). There was a statistically significant difference (p = 0.009) between the BC group (7335.8 ± 2755.5) and the MTA group (4059.1 ± 1231.1), where the last showed less infiltration. Within the limitations of this study, White ProRoot MTA had a significantly better sealing ability than TotalFill BC RRM Fast Set Putty.
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Çırakoğlu, Serenad, Buket Baddal, and Aylin İslam. "The Effectiveness of Laser-Activated Irrigation on the Apical Microleakage Qualities of MTA Repair HP and NeoMTA Plus in Simulated Immature Teeth: A Comparative Study." Materials 13, no. 15 (July 23, 2020): 3287. http://dx.doi.org/10.3390/ma13153287.
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There are limited data regarding the potential effect of erbium, chromium: yttrium–scandium–gallium–garnet (Er,Cr:YSGG) laser-activated irrigation (LAI) on the microleakage qualities of calcium silicate-based cements. The objective of the present study was to assess the effect of LAI on the microleakage qualities of MTA Repair HP (MTA-HP) and NeoMTA Plus (Neo) used in root-end filling and to compare the antimicrobial effectiveness of MTA- HP. Two experimental sets were conducted: antimicrobial activity (agar diffusion test/at 24, 48 h) and microleakage (glucose leakage model/at 1st, 10th, 20th days). Antimicrobial activities of MTA-HP, Neo, Biodentine, ProRoot and MTA Angelus were evaluated, and inhibition zones were observed not only against a range of Gram-positive and Gram-negative bacteria but also against yeast at 48h. For microleakage evaluation, fifty teeth were prepared to simulate the clinical situation where the root-tips (apex) are open, and randomly divided into two experimental groups (n = 20/group) according to the cement type (MTA-HP and Neo), and two control (n = 5/group) groups. Each experimental group was further divided into two subgroups (n = 10/group) with respect to LAI: MTA-HP, L-HP, Neo, L-Neo. A statistical difference was only detected between Neo and L-HP groups on day 1. Subsequently, MTA-HP exhibited superior microleakage quality compared to Neo in the short-term. Er,Cr:YSGG laser-activated irrigation could be used as a reliable technique without creating adverse effects on the sealing abilities of MTA Repair HP and NeoMTA Plus.
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Marquezan, Flavia Kolling, Patricia Maria Poli Kopper, Angela Isabel dos Santos Dullius, Diego Machado Ardenghi, and Renata Grazziotin-Soares. "Effect of Blood Contamination on The Push-Out Bond Strength of Calcium Silicate Cements." Brazilian Dental Journal 29, no. 2 (March 2018): 189–94. http://dx.doi.org/10.1590/0103-6440201801766.
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Abstract This study investigated the effect of blood-contamination on the push-out bond strength of BiodentineTM (BD) and MTA Angelus® (MTA-A) to root dentin over time. Twenty-five teeth were sectioned horizontally to obtain 120 root slices. The lumens were filled with MTA-A or BD: 60 for each cement (30 uncontaminated and 30 blood contaminated). Push out bond strength to dentin was assessed at 24 h (n=10), 7 days (n=10) and 28 days (n=10). Failure modes were classified as: cohesive, adhesive or mixed failure. Two-way ANOVA was used to investigate the interaction between blood contamination vs. hydration period. Mann Whitney test compared different materials in each period, and it also compared the contaminated versus uncontaminated material for each period. Friedman, followed by Dunn`s test, compared periods of hydration for each material, regardless of blood contamination. Failure modes were reported descriptively. The interaction hydration period vs. blood contamination was highly significant for MTA-A (P=0.001) and it was not significant for BD (P=0.474). There were no differences between bond strength of uncontaminated and contaminated BD in any of the periods. Bond strength of uncontaminated MTA-A increased at each time of hydration; but it remained stable over time for blood-contaminated samples. BD had higher bond strength than MTA-A in all periods of hydration. Cohesive failure predominated. Only for MTA-A, the over time bond strength to dentin was affected by blood contamination.
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Whan, Alex, Nicole Robinson, Prakash Lakshmanan, Susanne Schmidt, and Karen Aitken. "A quantitative genetics approach to nitrogen use efficiency in sugarcane." Functional Plant Biology 37, no. 5 (2010): 448. http://dx.doi.org/10.1071/fp09260.
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The economic and environmental consequences of inefficient use of nitrogen (N) fertiliser in agricultural crops is of concern worldwide, so new crop varieties with improved nitrogen use efficiency (NUE) are sought. Here, we report the first study of mapping quantitative trait loci (QTL) for nitrogen physiology traits in sugarcane. QTL analysis was undertaken for each parent of a segregating bi-parental sugarcane mapping population. We grew 168 progeny under limiting (0.2 mM NH4NO3) and non-limiting (5.0 mM NH4NO3) N supplies in two glasshouse experiments. Significant marker-trait associations (MTA) were detected in each treatment for shoot dry weight, root dry weight, total shoot N, shoot internal NUE (iNUE; measured as units shoot dry weight per unit N), leaf protein content and glutamine synthetase (GS) activity. MTA for GS activity did not co-locate with other traits except leaf protein content, indicating that variation in GS activity is not linked to plant size or iNUE during early growth. Under high N, there were no significant MTA for iNUE among markers from the male parent, Q165, an Australian commercial cultivar, but six MTA were found for markers inherited from the female parent, IJ76–514, a Saccharum officinarum ancestral variety. The results indicate that variation for iNUE under high N may be lower in commercial varieties than unimproved genotypes. Further, four MTA were consistent with previous field-based research on sugar and biomass production. Our study provides initial evidence that QTL may be incorporated in sugarcane breeding programs targeting improved NUE.
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Gu, Rui-Min, Yuan Wei, John R. Falck, U. Murali Krishna, and Wen-Hui Wang. "Effects of protein tyrosine kinase and protein tyrosine phosphatase on apical K+ channels in the TAL." American Journal of Physiology-Cell Physiology 281, no. 4 (October 1, 2001): C1188—C1195. http://dx.doi.org/10.1152/ajpcell.2001.281.4.c1188.
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We have previously demonstrated that the protein level of c-Src, a nonreceptor type of protein tyrosine kinase (PTK), was higher in the renal medulla from rats on a K-deficient (KD) diet than that in rats on a high-K (HK) diet (Wang WH, Lerea KM, Chan M, and Giebisch G. Am J Physiol Renal Physiol 278: F165–F171, 2000). We have now used the patch-clamp technique to investigate the role of PTK in regulating the apical K channels in the medullary thick ascending limb (mTAL) of the rat kidney. Inhibition of PTK with herbimycin A increased NP o, a product of channel number ( N) and open probability ( P o), of the 70-pS K channel from 0.12 to 0.42 in the mTAL only from rats on a KD diet but had no significant effect in tubules from animals on a HK diet. In contrast, herbimycin A did not affect the activity of the 30-pS K channel in the mTAL from rats on a KD diet. Moreover, addition of N-methylsulfonyl-12,12-dibromododec-11-enamide, an agent that inhibits the cytochrome P-450-dependent production of 20-hydroxyeicosatetraenoic acid, further increased NP o of the 70-pS K channel in the presence of herbimycin A. Furthermore, Western blot detected the presence of PTP-1D, a membrane-associated protein tyrosine phosphatase (PTP), in the renal outer medulla. Inhibition of PTP with phenylarsine oxide (PAO) decreased NP o of the 70-pS K channel in the mTAL from rats on a HK diet. However, PAO did not inhibit the activity of the 30-pS K channel in the mTAL. The effect of PAO on the 70-pS K channel was due to indirectly stimulating PTK because pretreatment of the mTAL with herbimycin A abolished the inhibitory effect of PAO. Finally, addition of exogenous c-Src reversibly blocked the activity of the 70-pS K channel in inside-out patches. We conclude that PTK and PTP have no effect on the low-conductance K channels in the mTAL and that PTK-induced tyrosine phosphorylation inhibits, whereas PTP-induced tyrosine dephosphorylation stimulates, the apical 70-pS K channel in the mTAL.
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Downard, Alison J., Alan M. Bond, Lyall R. Hanton, and Graham A. Heath. "A Comparison of Solution, Microcrystalline Solid, and Thin Film Phase Voltammetry of [Co(mtas)2](X)n (mtas = bis(2-(dimethylarsino)phenyl)methylarsine; X = BF4-, n = 3; X = ClO4-, n = 2, 3; X = BPh4-, n = 2)." Inorganic Chemistry 34, no. 25 (December 1995): 6387–95. http://dx.doi.org/10.1021/ic00129a025.
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Kikeri, D., A. Sun, M. L. Zeidel, and S. C. Hebert. "Cellular NH4+/K+ transport pathways in mouse medullary thick limb of Henle. Regulation by intracellular pH." Journal of General Physiology 99, no. 3 (March 1, 1992): 435–61. http://dx.doi.org/10.1085/jgp.99.3.435.
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Fluorescence and electrophysiological methods were used to determine the effects of intracellular pH (pHi) on cellular NH4+/K+ transport pathways in the renal medullary thick ascending limb of Henle (MTAL) from CD1 mice. Studies were performed in suspensions of MTAL tubules (S-MTAL) and in isolated, perfused MTAL segments (IP-MTAL). Steady-state pHi measured using 2,7-biscarboxyethyl-5(6)-carboxyfluorescein (BCECF) averaged 7.42 +/- 0.02 (mean +/- SE) in S-MTAL and 7.26 +/- 0.04 in IP-MTAL. The intrinsic cellular buffering power of MTAL cells was 29.7 +/- 2.4 mM/pHi unit at pHi values between 7.0 and 7.6, but below a pHi of 7.0 the intrinsic buffering power increased linearly to approximately 50 mM/pHi unit at pHi 6.5. In IP-MTAL, NH4+ entered cells across apical membranes via both Ba(2+)-sensitive pathway and furosemide-sensitive Na+:K+(NH4+):2Cl- cotransport mechanisms. The K0.5 and maximal rate for combined apical entry were 0.5 mM and 83.3 mM/min, respectively. The apical Ba(2+)-sensitive cell conductance in IP-MTAL (Gc), which reflects the apical K+ conductance, was sensitive to pHi over a pHi range of 6.0-7.4 with an apparent K0.5 at pHi approximately 6.7. The rate of cellular NH4+ influx in IP-MTAL due to the apical Ba(2+)-sensitive NH4+ transport pathway was sensitive to reduction in cytosolic pH whether pHi was changed by acidifying the basolateral medium or by inhibition of the apical Na+:H+ exchanger with amiloride at a constant pHo of 7.4. The pHi sensitivities of Gc and apical, Ba(2+)-sensitive NH4+ influx in IP-MTAL were virtually identical. The pHi sensitivity of the Ba(2+)-sensitive NH4+ influx in S-MTAL when exposed to (apical+basolateral) NH4Cl was greater than that observed in IP-MTAL where NH4Cl was added only to apical membranes, suggesting an additional effect of intracellular NH4+/NH3 on NH4+ influx. NH4+ entry via apical Na+:K+ (NH4+):2Cl- cotransport in IP-MTAL was somewhat more sensitive to reductions in pHi than the Ba(2+)-sensitive NH4+ influx pathway; NH4+ entry decreased by 52.9 +/- 13.4% on reducing pHi from 7.31 +/- 0.17 to 6.82 +/- 0.14. These results suggest that pHi may provide a negative feedback signal for regulating the rate of apical NH4+ entry, and hence transcellular NH4+ transport, in the MTAL. A model incorporating these results is proposed which illustrates the role of both pHi and basolateral/intracellular NH4+/NH3 in regulating the rate of transcellular N H4+ transport in the MTAL.
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Dienstmann, Rodrigo, Gessami Sanchez-Olle, Danila Serpico, Jordi Rodon Ahnert, Cristina Saura, Teresa Macarulla, Maria Elena Elez Fernandez, et al. "Molecular profiling of patients (pts) with colorectal cancer (CRC) and matched targeted therapy (MTA) in phase I clinical trials." Journal of Clinical Oncology 30, no. 15_suppl (May 20, 2012): 3014. http://dx.doi.org/10.1200/jco.2012.30.15_suppl.3014.
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3014 Background: Molecular prescreening and biomarker enrichment strategies in Phase 1 trials with targeted therapies are anticipated to improve the outcomes of affected pts. Methods: As part of our personalized oncology program, tumors from pts with advanced chemorefractory CRC were analyzed for specific molecular aberrations (KRAS/ BRAF/ PIK3CA mutations [mut], PTEN and pMET expression) at the Vall d'Hebron Molecular Pathology and Genomics Labs. Those whose tumors were found to have a dysregulation were offered a Phase 1 trial with MTA. Results: During 2010 and 2011, tumor molecular analysis was performed in 254 pts: KRAS mut (80/254, 31.5%), BRAF mut (24/196, 12.2%), PIK3CA mut (15/114, 13.2%), KRAS+PIK3CA mut (9/114, 7.9%), PTEN low (97/183, 53.0% - HSCORE<50; 45/183, 24.6% - PTEN null), KRAS mut + PTEN low (38/138, 20.8%), pMET high (38/64, 59.4% with HSCORE>30). In total, 68 pts (median, age 63 yrs; prior therapies 3), received 82 different matched therapies. Type of MTA: PI3K pathway inh (if PIK3CA mut, n=10; or PTEN low, n=32), MEK+PI3K pathway inh (if KRAS mut, n=10; or BRAF mut, n=1), second-generation anti-EGFR mAbs (if KRAS wild-type, n=11), anti-HGF mAb (if pMET high, n=10), mTOR inh + anti-IGFR-1R mAb (if PTEN low, n=5) and BRAF inh (if BRAF mut, n=3). Median time to treatment failure (TTF) with MTA was 7.9 weeks (CI95%:7.6-8.1) vs. 16.3 weeks (CI95%:13.9-18.7) for their prior systemic antitumor therapy (p<0.001). If prior therapy non-standard (according to NCCN guidelines, n=39), TTF with MTA 7.9 weeks (CI95%:6.8-8.9) vs. TTF with prior therapy 8.7 weeks (CI95%:7.3-10.1). If an approved standard regimen (n=43), TTF with MTA 7.9 weeks (CI95%:7.6-8.1) vs. TTF with prior therapy 21.9 weeks (CI95%:15.0-28.7). Partial response was seen in one pt (1.2%, PI3K inh with PIK3CA mut) and stable disease > 16 weeks in 10 cases (12.2%). Clinical benefit, defined as a TTF ratio ≥ 1.3 (TTF on MTA/ TTF on prior therapy), was seen with 15.9% of the therapies (13/82). Conclusions: Preliminary results suggest that matching chemorefractory CRC patients with targeted agents in early clinical trials based on the current molecular profile does not result in longer TTF compared to their prior therapy.
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Gaviño-Orduña, José F., Javier Caviedes-Bucheli, María C. Manzanares-Céspedes, Sophie Román-Richon, Benjamín Martin-Biedma, Juan J. Segura-Egea, Esther Berástegui-Jimeno, and José López-López. "Dentin Growth after Direct Pulp Capping with the Different Fractions of Plasma Rich in Growth Factors (PRGF) vs. MTA: Experimental Study in Animal Model." Journal of Clinical Medicine 10, no. 15 (July 31, 2021): 3432. http://dx.doi.org/10.3390/jcm10153432.
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Background: This study aimed to evaluate the area of dentin growth in rabbit incisors after pulp capping with plasma rich in growth factors (PRGF) compared with mineral trioxide aggregate (MTA) by fluorescence. Methods: twenty-seven upper and lower incisors of rabbits were divided into 4 groups: poor PRGF (F1) (n = 9 teeth), rich PRGF (F2) (n = 8 teeth), ProRoot MTA (positive control, n = 5 teeth), and untreated (NC) (negative control, n = 5). Fluorochrome markers were injected 24 h before surgery and the day before euthanasia, 28 days after the vital pulp therapy (VPT). Two transverse cuts were performed to every tooth: the first cut (A), 1 mm incisal to the gingival margin, and the second cut (B), 5 mm apical to the first cut. The sections were assessed with histomorphometric evaluation by fluorescence microscopy, comparing the dentin area between fluorescence marks and the total mineralized area. Results: The higher percentage of dentin growth was observed in the F2 group (B = 63.25%, A = 36.52%), followed by F1 (B = 57.63%, A = 30,12%) and MTA (B = 38.64%, A = 15,74%) The group with lowest percentage of dentin growth was the NC group (B = 29.22%, A = 7.82%). Significant difference (p < 0.05) was found between F2 group and MTA, also statistically significant difference has been observed comparing dentin growth areas of NC group with F1 and F2 groups. Conclusions: The application of PRGF rich and poor fraction as a pulp capping material stimulated dentin formation more intensively than MTA and NC.
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Berger, B., P. E. Hunziker, C. R. Hauer, N. Birchler, and R. Dallinger. "Mass spectrometry and amino acid sequencing of two cadmium-binding metallothionein isoforms from the terrestrial gastropod Arianta arbustorum." Biochemical Journal 311, no. 3 (November 1, 1995): 951–57. http://dx.doi.org/10.1042/bj3110951.
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1. Two cadmium-binding metallothionein (Mt) isoforms, called Mta and Mtb, were isolated from terrestrial snails (Arianta arbustorum), using various chromatographic techniques, such as gel-permeation chromatography and reversed-phase HPLC. The purified proteins were S-methylated and cleaved by means of different enzymes (trypsin, endoproteinase Glu-C, and endoproteinase Asp-N). Amino acid sequences were determined by automated Edman degradation and collision-induced dissociation (CID) tandem MS. According to their primary structures, both isoforms should be attributed to class-I Mts. 2. The two forms are structurally identical, differing only by one amino acid exchange in position 60 of the peptide chain. Both isoproteins consist of 66 amino acids, 18 of which are cysteine residues. Most of the cysteine residues are arranged in seven Cys-Xaa-Cys motifs. Mta and Mtb possess an N-terminal acetylated-serine residue and contain a short N-terminal motif which shows a high degree of similarity with the N-termini of histones H4 and H2A. 3. A comparison of Mta and Mtb with other invertebrate Mts shows a very high degree of sequence similarity with a cadmium-binding Mt from Helix pomatia, a species that is closely related to Arianta arbustorum. Moreover, Mta and Mtb, as expected, also exhibit structural similarities with Mts from other molluscan species, such as mussels and oysters. It is suggested that Mta and Mtb represent two allelic isoforms, reflecting the genetic polymorphism of Mt in Arianta arbustorum.
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O'Connor, Paul M., Limin Lu, Carlos Schreck, and Allen W. Cowley. "Enhanced amiloride-sensitive superoxide production in renal medullary thick ascending limb of Dahl salt-sensitive rats." American Journal of Physiology-Renal Physiology 295, no. 3 (September 2008): F726—F733. http://dx.doi.org/10.1152/ajprenal.00137.2008.
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The aims of the present study were to determine whether superoxide (O2−) production is enhanced in medullary thick ascending limb (mTAL) of Dahl salt-sensitive (SS) rats compared with a salt-resistant consomic control strain (SS.13BN) and to elucidate the cellular pathways responsible for augmented O2− production. Studies were carried out in 7- to 10-wk-old male SS and SS.13BN rats fed either a 0.4% NaCl diet or a 4.0% NaCl diet for 3 days before tissue harvest. Tissue strips containing mTAL were isolated from the left kidney, loaded with the O2−-sensitive fluorescent dye dihydroethidium, superfused with modified Hanks’ solution, and imaged at ×60 magnification on a heated microscope stage. O2− production was stimulated in mTAL by incrementing superfusate NaCl concentration from 154 to 254 to 500 mM. O2− production was enhanced in mTAL of SS rats compared with SS.13BN rats in response to incrementing bath NaCl. Addition of N-methyl-amiloride (100 μM) or inhibition of NAD(P)H oxidase reduced O2− production in SS mTAL to levels observed in SS.13BN rats. Both amiloride- and ouabain-sensitive pathways of O2− production were elevated following 3 days of high (4.0%) NaCl feeding in mTAL of SS and SS.13BN rats. We conclude that mTAL from SS rats exhibit enhanced amiloride-sensitive O2− production. The amiloride-sensitive O2− response in mTAL is independent of active Na+ transport and appears to be mediated by NAD(P)H oxidase. Amiloride-sensitive O2− production is likely to contribute to augmented outer medullary O2− production observed in SS rats during both normal and high NaCl diets.
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Korkidis, Giorgos, Vasiliki Pavlidou, Konstantinos Tassis, Evangelia Ntormousi, Theodore N. Tomaras, and Konstantinos Kovlakas. "Turnaround radius of galaxy clusters in N-body simulations." Astronomy & Astrophysics 639 (July 2020): A122. http://dx.doi.org/10.1051/0004-6361/201937337.
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Aims. We use N-body simulations to examine whether a characteristic turnaround radius, as predicted from the spherical collapse model in a ΛCDM Universe, can be meaningfully identified for galaxy clusters in the presence of full three-dimensional effects. Methods. We use The Dark Sky Simulations and Illustris-TNG dark-matter-only cosmological runs to calculate radial velocity profiles around collapsed structures, extending out to many times the virial radius R200. There, the turnaround radius can be unambiguously identified as the largest nonexpanding scale around a center of gravity. Results. We find that: (a) a single turnaround scale can meaningfully describe strongly nonspherical structures. (b) For halos of masses M200 > 1013 M⊙, the turnaround radius Rta scales with the enclosed mass Mta as Mta1/3, as predicted by the spherical collapse model. (c) The deviation of Rta in simulated halos from the spherical collapse model prediction is relatively insensitive to halo asphericity. Rather, it is sensitive to the tidal forces due to massive neighbors when these are present. (d) Halos exhibit a characteristic average density within the turnaround scale. This characteristic density is dependent on cosmology and redshift. For the present cosmic epoch and for concordance cosmological parameters (Ωm ∼ 0.3; ΩΛ ∼ 0.7) turnaround structures exhibit a density contrast with the matter density of the background Universe of δ ∼ 11. Thus, Rta is equivalent to R11 – in a way that is analogous to defining the “virial” radius as R200 – with the advantage that R11 is shown in this work to correspond to a kinematically relevant scale in N-body simulations.
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Demiriz, Levent, and Ebru Hazar Bodrumlu. "Retrospective Evaluation of Healing of Periapical Lesions after Unintentional Extrusion of Mineral Trioxide Aggregate." Journal of Applied Biomaterials & Functional Materials 15, no. 4 (January 2017): e382-e386. http://dx.doi.org/10.5301/jabfm.5000359.
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Background During the apexification procedure for teeth with open apices, mineral trioxide aggregate (MTA) may be unintentionally extruded. The aim of the present study was the retrospective evaluation of the healing of periapical lesions in permanent incisor teeth with open apices after the unintentional extrusion of MTA. Methods The clinical and radiographic records of 55 maxillary permanent central teeth treated by MTA apexification were evaluated. Filled teeth with unintentionally extruded MTA were selected as group 1 (n = 21), whereas the teeth with no MTA extrusion were selected as group 2 (n = 34). For each tooth, the clinical and radiographic records from a 3-year follow-up were investigated. Results Complete healing (CH) was observed in 19 teeth (90.4%) in group 1, whereas the same type of healing was observed in all 34 teeth (100%) in group 2 (p>0.05). At the 6-month follow-up appointment, 25 teeth (73.5%) showed CH in group 2, whereas 15 teeth (71.4%) showed CH at the 1-year follow-up in group 1 (p<0.001). At the end of the 3-year follow-up period, the amount of MTA extrusion was reduced in 17 teeth (85%) (p<0.05), whereas it was almost absent in 2 teeth (10%). Conclusions The unintentional extrusion of MTA does not prevent the healing of periapical lesions, but may be a delaying factor for periapical healing.
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Zhu, Hai-Liang, Xiao-Lan Yu, and Xiao-Ming Chen. "Synthesis, Characterization and Crystal Structures of Monomeric and Imidazolate-Bridged Polymeric Copper(II) Complexes of 5-Methyl-1,5,9-triazanonane." Australian Journal of Chemistry 53, no. 10 (2000): 883. http://dx.doi.org/10.1071/ch00096.
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Two complexes [Cu(mtan)(H2O)(ClO4)](ClO4) (Im = imidazolate) (1) and [Cu(mtan)(Im)]n (ClO4)2n (mtan = 5-methyl-1,5,9-triazanonane) (2) have been prepared and characterized. Single-crystal X-ray analysis reveals that (1) crystallizes in the orthorhombic space group Pbcm, with a 8.906(5), b 12.255(6), c 14.821(4) Å and V 1618(1) Å3, and complex (2) crystallizes in the orthorhombic space group Pca21, with a 11.125(7), b 9.149(6), c 15.180(7) Å and 1545(1) Å3. The copper(II) atom in complex (1) is in a distorted square-pyramidal geometry, being coordinated by three nitrogen atoms from an mtan ligand and one oxygen atom from an aqua ligand at the basal plane and one perchlorate oxygen atom at the apical position. The structure of complex (2) features polymeric cationic chains composed of [Cu(mtan)(Im)]+ repeating units and discrete perchlorate anions. The Cu(1) atom in each unit has a severely distorted trigonal-bipyramidal geometry, being coordinated by three nitrogen atoms from one mtan ligand and two nitrogen atoms from two Im groups. The structural units are linked by -Im groups to give one-dimensional chains. The variable-temperature magnetic measurement on the powder sample of (2) reveals intrachain, medium antiferromagnetic interaction with g = 2.240 and J = –36.45 cm–1 through the -Im bridges.
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Ngoi, Natalie, Emma L. Scholefield, Vamsi Parini, Richard S. P. Huang, Tyler Janovitz, Natalie Danziger, Mia Alyce Levy, et al. "Genomic classification of clinically advanced pancreatic ductal adenocarcinoma (PDAC) based on methylthioadenosine phosphorylase (MTAP) genomic loss (MTAP loss)." Journal of Clinical Oncology 40, no. 4_suppl (February 1, 2022): 604. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.604.
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604 Background: MTAP loss is represented across a wide variety of cancer types including PDAC and is an emerging target for synthetic lethality-based cancer therapies. Preclinically, MTAP loss leads to the accumulation of 2-methylthioadenosine, reduced protein arginine N-methyltransferase 5 (PRMT5) methylation activity and increased vulnerability to targeting of the methionine adenosyltransferase IIα (MAT2A)/ PRMT5 axis. In addition, 9p21 loss, homozygous co-deletion of MTAP/CDKN2A or homozygous deletion of either gene have been associated with an immunologically “cold” tumor microenvironment, primary resistance to anti PD(L)1 immunotherapy (IO) and poor prognosis phenotype (Han G, Nat Commun 2021). We investigated concurrent mutations and immune biomarkers in clinical PDAC samples with MTAP-loss versus -intact status. Methods: From a series of 177705 consecutive cases, we performed comprehensive genomic profiling on 9423 cases of PDAC using an FDA-approved assay (F1CDx) to evaluate all classes of genomic alterations (GA). Tumor mutational burden (TMB) was determined on up to 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. PD-L1 expression was determined by immunohistochemistry (Dako 22C3). Furthermore, we correlated pertinent findings within a database of 16558 cases of clinically advanced cancer with MTAP loss. Results: 2003 (21.3%) of 9423 PDAC demonstrated MTAP-loss. Similar gender, age and number of GA per tumor were observed between MTAP-loss and -intact groups. Frequencies of TP53, CDKN2A/B, SMAD4, PTEN and ARID1A were significantly higher in MTAP-loss PDAC. However, previously-described biomarkers of IO efficacy (MSI, TMB, CD274 amplification and PD-L1 expression) and resistance ( STK11, KEAP1 and MDM2) were infrequent and similar in both groups. The frequencies of other potentially targetable GA including BRCA1/2, ATM, KRAS G12C, ERBB2, BRAF, FGFR1, NF1 and PIK3CA were also infrequent and similar in both groups of PDAC patients. Amongst a database of 16558 cases of clinically advanced cancer with MTAP loss, 1538 (9.3%) featured co-alterations in MTAP and SMAD4. 52% of the MTAP/SMAD4 co-altered cases were PDAC. Conclusions: MTAP loss is associated with a distinctive concurrent genomic profile in PDAC and represents a potential new synthetic lethality-based opportunity for treatment with PRMT5 and MAT2A inhibitors. Furthermore, MTAP loss may represent an independent negative predictive biomarker for immune checkpoint inhibition in PDAC.[Table: see text]
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Radeva, E., T. Usunov, I. Ivanov, and G. Genchev. "Apical Microleakage of four Materials after Root End Resection (In Vitro Study)." Acta Medica Bulgarica 43, no. 2 (October 1, 2016): 61–67. http://dx.doi.org/10.1515/amb-2016-0018.
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Summary Hermetic sealing of the apical area after root end resection is essential to the success of endodontic surgery. To compare microleakage after root end resection of the two bioceramic sealers without retrograde filling - Total Fill BC Sealer and MTA Fillapex, and two materials for retrograde filling-MTA and Biodentine, using the method of penetration of dye - 2% methylene blue. Forty eight extracted single-rooted human teeth were used in this study. The resection was made at 3 mm from the root tip at an angle of 90 degree to the long axis of the tooth. The teeth were divided into 4 groups: 1st group (n = 9) - root canal obturation with Total Fill BC Sealer without retrograde filling; 2nd group (n = 8) - root canal obturation with MTA Fillapex without retrograde filling. 3rd group (n = 10) - retrograde ultrasonic cavity preparation and filling with MTA. 4th group (n = 8) - retrograde ultrasonic cavity preparation and filling with Biodentine. The outer surface of the root was covered with two layers of varnish, with the exception of the apical 3 mm and then immersed in 2% methylene blue for 72 h. The degree of penetration of the dye is measured in millimeters. The data was entered and processed with the statistical package IBM SPSS Statistics 22.0. We reject the null hypothesis when p < 0.05. With significantly higher value is the arithmetic mean of the group with the root canal obturation with Total Fill BC Sealer without retrograde filling - 2,01 mm; versus a retrograde filling with MTA - 0,68 mm and Biodentin - 0,51 mm; and no statistically significant difference with the group root canal obturation with MTA Fillapex - 1,76 mm. In the four material microleakage dye was observed, but to varying degrees.
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Klingler, C., L. Preisser, M. B. Barrault, P. Lluel, L. Horgen, L. Teillet, N. Ancellin, and B. Corman. "Vasopressin V2 receptor mRNA expression and cAMP accumulation in aging rat kidney." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 272, no. 6 (June 1, 1997): R1775—R1782. http://dx.doi.org/10.1152/ajpregu.1997.272.6.r1775.
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The ability of the kidney to regulate water balance is impaired with age, although the secretion of vasopressin is maintained in senescent animals. This suggests that the cellular response to antidiuretic hormone is reduced in aging kidney. To test this hypothesis, the relationship between the expression of the vasopressin. V2 receptor mRNA and adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was investigated in the medullary thick ascending limb of Henle's loop (MTAL) of adult and aging rats. Tubular suspensions of MTAL were prepared from 10- and 30-mo-old female WAG/Rij rats. The accumulation of cAMP for maximal concentration of vasopressin was 34% larger in adult than in old animals (9.5 +/- 0.5 pmol/4 min, n = 16, and 7.1 +/- 0.6 pmol/4 min, n = 12, respectively). The concentration of vasopressin corresponding to half-maximal stimulation was similar in the two groups (0.66 +/- 0.20 and 0.52 +/- 0.09 nmol, n = 5, in adult and old animals), indicating comparable sensitivity of the renal cells with age. The age-related impaired response to vasopressin of the V2 receptor was specific for females and was not observed in males. Direct stimulation of adenylyl cyclase by forskolin induced a comparable accumulation of cAMP in adult and senescent rats. The V2 receptor mRNA level in the MTAL was constant between 10 and 30 mo whether the animals were normally hydrated or dehydrated for 2 days. These data indicate that, in MTAL, the age-related impaired cAMP accumulation by vasopressin would be linked to a change either in the translation of V2 mRNA or in posttranslational processing mechanisms or in the coupling between the V2 receptor and adenylyl cyclase.
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Giuroiu, Cristian Levente, Sorin Andrian, Aurelian Sorin Pasca, Ana Maria Fatu, and Mihai Bogdan Vascu. "Assessment of Physical and Chemical Parameters of Four Endodontic Sealants." Revista de Chimie 69, no. 9 (October 15, 2018): 2443–47. http://dx.doi.org/10.37358/rc.18.9.6550.
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The endodontic sealants have an essential role in the root canal filling. The aim of this study was to analyse and compare three physio-chemical properties (pH, solubility, viscosity). The most significant decrease of the viscosity was for MTA-Fillapex, followed by Endoflas FS and Acroseal. The best behavior was recorded for Endomethasone N. The total decrease of dry mass (reported to baseline) was 0.0113 for Acroseal. Endoflas FS had a total decrease of dry mass of 0.0377 (from 0,6864 to 0.6487) during the study. The total decrease of dry mass (reported to baseline) was 0.0047 for Endomethasone N. MTA Fillapex had a total decrease of 0.0226 (from 0.4805 to 0.4579) during the study period. MTA Fillapex had the highest pH values (pH 10.16), followed by Acroseal (pH 8.79), Endoflas FS (pH 7.98) and Endomethasone N (pH 7.73).