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Dai Qi-Run and Zhao Shu-Song. "Bose-Einstein关联与Q-vKv(Q)分布." Acta Physica Sinica 44, no. 8 (1995): 1203. http://dx.doi.org/10.7498/aps.44.1203.
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Agustina, Lili, and Isna Kasmilawati. "Pemerolehan Fonologi pada Kasus Azzahra (0-2 Tahun)." STILISTIKA: Jurnal Bahasa, Sastra, dan Pengajarannya 5, no. 1 (April 30, 2020): 66–77. http://dx.doi.org/10.33654/sti.v5i1.983.
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Perkembangan anak dalam memperoleh bahasa di lingkungannya sangat luar biasa. Anak dengan mudah mengucapkan dan meniru apa yang didengarkan bahkan dapat menyusun sebuah rangkaian bahasa yang tidak pernah anak tersebut dengar. Pemerolehan bahasa (language acquisition) merupakan proses anak memperoleh bahasanya. Pemerolehan bahasa seperti yang dijelaskan oleh para ahli adalah identik dengan pemerolehan bahasa pertama atau bahasa ibu.
Pendekatan yang digunakan adalah pendekatan kualitatif. Teknik pengumpulan data yang dilakukan dalam penelitian ini adalah teknik simak dan teknik cakap setiap bunyi yang diucapkan oleh Azzahra. Dengan penggunaan kedua metode ini dapat membantu peneliti untuk mendapatkan data yang diperlukan. Teknik simak yang dilakukan secara alami (natural) setiap bunyi yang diucapkan oleh Azzahra.
Hasil penelitian pemerolehan bunyipada kasus Azzahra pada usia (0-1 tahun)yaitupemerolehanbunyivokal, seperti[a], [i], [e], [ꞓ],[u]. Bunyi konsonan yang terdapat padausiainiadalah[b], [p], [m], [n], [d], [k], [y], [t]. Polatersebut berbentuk unit suku kata yang pertama kali muncul adalah KV (konsonan dan vokal). Berdasarkan data suku kata padausiainimemiliki struktur KV,VV, KVK, KV-KV, VKV, KV-KVK. Struktur yang paling banyak ditemukan adalah KVKV. Memasukiusia (2:0) dalam pemerolehan bunyi, Zahra mampu mengucapkan fonem [o], yaitu pada kata /onti aunty/. Fonem bunyi konsonan juga bertambah dengan adanya fonem [j], [w], [s], dan [ή].Pemerolehan suku kata atau silaba pada tahun kedua juga hampir sama dengan tahun pertama. Silaba yang digunakan adalah VK, KV, VKV, KV-KV, VK-VK, VK-KV, KVK, KV-KVK. Bunyi satu suku kata lebih dominan pada tahun kedua, dengan mengucapkan suku kata terakhir setiap kata, misalnya /cing/ ‘kucing’, /pu/ ‘sapu’, /num/ ‘minum’, /kan/ ‘makan’.Berdasarkan data yang telah dikumpulkan pada kasus Azzahra, secara signifikan pemerolehan bahasa umur 2:0 tidak mengalami peningkatan yang pesat. Pada kasus Azzahra lebih banyak menunjuk untuk mengatakan sesuatu, memahami apa yang disampaikankepadanya tetapi tidak secara aktif untuk berkomunikasi di lingkunganya
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Isaev, A. Yu, E. V. Rubtsova, E. V. Kotova, and M. N. Sutyagin. "RESEARCH OF PROPERTIES OF GLUES AND GLUE BINDING, MADE WITH USE OF MODERN DOMESTIC COMPONENT BASE." Proceedings of VIAM, no. 3 (2021): 58–67. http://dx.doi.org/10.18577/2307-6046-2021-0-3-58-67.
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Properties of epoxy glues of cold curing VK-9 and VKV-9, the components received with use which are let out by modern producers, depending on the filler used in their structure are considered. Tests of glued joints on VK-9 glue in wider interval of temperatures are carried out. Properties of VK-36 glue and its updating’s on the basis of components let out now are shown. Properties of glue binding brands VSK-14-1, VSK-14-2, VSK-14-4, VSK-14-4m and VSK-14-4k received, under production conditions by VIAM Federal State Unitary Enterprise are given. It is shown that on the properties they completely meet the requirements of existing normative documentation.
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Jüdt, Eberhard. "Lediglich ein »Mauerblümchen« des Unterhaltsrechts? – Überlegungen zum VKV unter besonderer Berücksichtigung der Rückzahlungspflicht und der Kostenfestsetzung." Familie und Recht 26, no. 6 (June 1, 2015): 331–38. http://dx.doi.org/10.1515/fur-2015-0607.
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Erniati, Erniati, and Yohanis Sanjoko. "DESKRIPSI POLA SUKU KATA BAHASA WEMALE A Description of Syllabic Patterns of Wemale Language." Jurnal Lingko : Jurnal Kebahasaan dan Kesastraan 2, no. 1 (June 28, 2020): 37–50. http://dx.doi.org/10.26499/jl.v2i1.48.
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Abstrak Bahasa Wemale dipakai sebagai bahasa pertama oleh penutur asli masyarakat Suku Wemale di Pulau Seram, Maluku, tepatnya di Negeri Hunitetu, Kecamatan Kairatu, Kabupaten Seram Bagian Barat. Bahasa Wemale memilki dua dialek yaitu dialek Wemale Utara dan Wemale Selatan.Hingga saaat ini, bahasa Wemale masih digunakan sebagai alat komunikasi secara lisan oleh kalangan tertentu dalam kehidupan masyarakat penuturnya. Meskipun demikian, bahasa Wemale dapat dikategorikan sebagai bahasa daerah yang hampir punah, karena tidak ada proses pewarisan kepada generasi mudanya. Untuk mencegah hal tersebut, perlu dilakukan berbagai upaya penyelamatan yang salah satu diantaranya melalui penelitian.Penelitian ini memberikan gambaran tentang pola suku kata bahasa Wemale. Penelitian ini bertujuan untuk mendiskripsikan pola suku kata bahasa Wemale, dialek Wemale Selatan. Meode yang digunakan adalah meode kualitatif deskriptif. Data diperoleh dari ucapan langsung penutur asli bahasa tersebut dan penutur yang dianggap mampu. Hasil analisis menunjukkan bahwa pola suku kata bahasaWemale terdiri atas V, KV, VKV, KVV, dan ½ KV. Kata kunci: suku kata, pola suku kata, bahasa Wemale Abstract Wemale is used as the first language by native speakers of the Wemale tribe on Seram Island, Maluku, precisely in the village of Hunitetu, Kairatu District, West Seram Regency. Wemale has two dialects namely North Wemale and South Wemale. Until now, Wemale is still used as an oral communication tool by certain groups in the life of the speaker community. However, Wemale language can be categorized as a regional language that is almost extinct, because there is no inheritance process to the younger generation. To prevent this, various rescue efforts need to be done, one of which is through research. This research provides an overview of the Wemale syllable patterns. This study aims to describe the syllabic patterns of the Wemale language, South Wemale dialect. The method used is descriptive qualitative method. Data obtained from the direct speech of native speakers of the language and speakers who are considered capable. The results of the analysis show that the syllabic syllable patterns consist of V, KV, VKV, KVV,and ½ KV. Keywords: syllables, syllable patterns, Wemale language
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Erniati, Erniati. "POLA SUKU KATA BAHASA LISABATA [Lisabata Syllabe Pattern Language]." TOTOBUANG 5, no. 2 (January 28, 2018): 315. http://dx.doi.org/10.26499/ttbng.v5i2.44.
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The language of Lisabata is used as the first language by native speakers of the Lisabata community on Seram Island, Maluku, precisely in the border area of West Seram and East Seram, West Lisabata Village, Nualiali Village, Desa Sukaraja, and Kawa Village. SIL (2006: 16—17) identified this language as the dialect of dialect, the dialect of the Eastern Lisabata, Nuniani, Sukaraja, and Kawa, Austronesian classes. Until now, the language of Lisabata has still been used as an oral communication tool by certain circles in life community speakers. Nevertheless, the language of Lisabata can be categorized as an almost extinct local language, since there has no inheritance process to the younger generation. To prevent this, it is necessary to make a variety of rescue efforts that one of them through research. This research provided an overview of the pattern of the Lisabata language syllables. This study aimed to describe the pattern of the Lisabata syllable, the Eastern Lisabata dialect. The method used descriptive qualitative method. Data was obtained from the direct speech of the native speakers of the language and speakers who were considered capable. The results showed that the Lisabata syllabic pattern consists of V, VK, KV, KVK, VKV, KKVK, , 1 / 2KV.Bahasa Lisabata dipakai sebagai bahasa pertama oleh penutur asli masyarakat Lisabata di Pulau Seram, Maluku, tepatnya di daerah perbatasan Seram Barat dan Seram Timur, Desa Lisabata Barat, Desa Nualiali, Desa Sukaraja, dan Desa Kawa. SIL (2006:16—17) mengidentifikasi bahasa ini sebagai bahasa dengan tempat dialeknya, yaitu dialek Lisabata Timur, Nuniani, Sukaraja, dan Kawa, kelas Austronesia. Hingga saaat ini, bahasa Lisabata masih digunakan sebagai alat komunikasi secara lisan oleh kalangan tertentu dalam kehidupan masyarakat penuturnya. Meskipun demikian, bahasa Lisabata dapat dikategorikan sebagai bahasa daerah yang hampir punah, karena tidak ada proses pewarisan kepada generasi mudanya. Untuk mencegah hal tersebut, perlu dilakukan berbagai upaya penyelamatan yang salah satu diantaranya melalui penelitian. Penelitian ini memberikan gambaran tentang pola suku kata bahasa Lisabata. Penelitian ini bertujuan untuk mendiskripsikan pola suku kata bahasa Lisabata, dialek Lisabata Timur. Metode yang digunakan adalah meode kualitatif deskriptif. Data diperoleh dari ucapan langsung penutur asli bahasa tersebut dan penutur yang dianggap mampu. Hasil analisis menunjukkan bahwa pola suku kata bahasa Lisabata terdiri atas V,VK, KV, KVK, VKV, KKVK, 1/2KV,.
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Jones, Larry Eugene. "Edgar Julius Jung: The Conservative Revolution in Theory and Practice." Central European History 21, no. 2 (June 1988): 142–74. http://dx.doi.org/10.1017/s0008938900012723.
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Of the conservative theorists who rose to prominence during the last years of the Weimar Republic, none stood more directly in the eye of the storm that descended upon Germany in 1933–34 than Edgar Julius Jung (1894–1934). His Die Herrschaft der Minderwertigen, first published in 1927 and then again in a revised and expanded edition in 1930, has been called the bible of German neo-conservatism and played a major role in crystallizing antidemocratic sentiment against the Weimar Republic. But Jung was more than a theorist; he was also a political activist deeply committed to a conservative regeneration (Erneuerung) of the German state. In 1930–31, for example, Jung was actively involved in the efforts of the People's Conservative Association (Volkskonservative Vereinigung or VKV) to create a new conservative movement to the left of the German National People's Party (Deutschnationale Volkspartei or DNVP) after its takeover by film and press magnate Alfred Hugenberg.
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Pudota, B. Nirmala, Eric L. Hommema, Kevin W. Hallgren, Beth A. McNally, Susan Lee, and Kathleen L. Berkner. "Identification of Sequences within the γ-Carboxylase That Represent a Novel Contact Site with Vitamin K-dependent Proteins and That Are Required for Activity." Journal of Biological Chemistry 276, no. 50 (October 8, 2001): 46878–86. http://dx.doi.org/10.1074/jbc.m108696200.
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The vitamin K-dependent (VKD) carboxylase converts clusters of Glu residues to γ-carboxylated Glu residues (Glas) in VKD proteins, which is required for their activity. VKD precursors are targeted to the carboxylase by their carboxylase recognition site, which in most cases is a propeptide. We have identified a second tethering site for carboxylase and VKD proteins that is required for carboxylase activity, called the vitamin K-dependent protein site of interaction (VKS). Several VKD proteins specifically bound an immobilized peptide comprising amino acids 343–355 of the human carboxylase (CVYKRSRGKSGQK) but not a scrambled peptide containing the same residues in a different order. Association with the 343–355 peptide was independent of propeptide binding, because the VKD proteins lacked the propeptide and because the 343–355 peptide did not disrupt association of a propeptide factor IX-carboxylase complex. Analysis with peptides that overlapped amino acids 343–355 indicated that the 343–345 CVY residues were necessary but not sufficient for prothrombin binding. Ionic interactions were also suggested because peptide-VKD protein binding could be disrupted by changes in ionic strength or pH. Mutagenesis of Cys343to Ser and Tyr345to Phe resulted in 7–11-fold decreases in vitamin K epoxidation and peptide (EEL) substrate and carboxylase carboxylation, and kinetic analysis showed 5–6-fold increases inKmvalues for the Glu substrate. These results suggest that Cys343and Tyr345are near the catalytic center and affect the active site conformation required for correct positioning of the Glu substrate. The 343–355 VKS peptide had a higher affinity for carboxylated prothrombin (Kd= 5 μm) than uncarboxylated prothrombin (Kd= 60 μm), and the basic VKS region may also facilitate exiting of the Gla product from the catalytic center by ionic attraction. Tethering of VKD proteins to the carboxylase via the propeptide-binding site and the VKS region has important implications for the mechanism of VKD protein carboxylation, and a model is proposed for how the carboxylase VKS region may be required for efficient and processive VKD protein carboxylation.
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Kulneva, N. G., V. A. Fedoruk, N. A. Matvienko, and E. M. Ponomareva. "Improving the massecuite crystallization in sugar production." Proceedings of the Voronezh State University of Engineering Technologies 83, no. 1 (June 3, 2021): 86–93. http://dx.doi.org/10.20914/2310-1202-2021-1-86-93.
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The article discusses the concepts of continuous vacuum apparatus operation: vertical VKT (VKT – Verdampfungs-Kristallisations-Turm) and horizontal cascade of VKH vacuum apparatus (VKH —horizontal vacuum pan) from BMA (Germany). The advantages and features of the vertical continuous vacuum apparatus VKT are shown, as well as the possibilities for increasing the efficiency of the product department of sugar factories. Thanks to the special design of the crystallization chambers, the low massecuite level above the heating chamber and the use of mechanical stirrers in each chamber, the VKT apparatus can operate without difficulty with a very small temperature difference between heating steam and massecuite, as well as with an absolute heating steam pressure well below 1 bar. With optimal use of VKT vacuum apparatus, a variety of energy-saving schemes can be implemented, for example, double-effect evaporation in the crystallization section. Part of the secondary crystallization steam is used to heat one of the VKT units, which saves the heating steam of the evaporator unit used for this purpose. With an increase in the productivity of the sugar factory, it is possible to quickly equip the VKT apparatus with an additional chamber. The device works continuously throughout the season, especially with products with massecuite purity of more than 94%. The chambers are cleaned without stopping the entire apparatus. The boiling of massecuite of all stages of crystallization in VKT devices ensures a uniform operating mode of the food compartment, allows to achieve an increase in sugar yield and helps to reduce steam consumption at the plant.
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Meylani, Vita, and Rinaldi Rizal Putra. "DETEKSI BAKTERI GENUS VIBRIO SEBAGAI CAUSATIVE AGENT PADA IKAN LELE SANGKURIANG (CLARIAS GARIEPINUS VAR. SANGKURIANG) DI KOTA TASIKMALAYA." BIOLINK (Jurnal Biologi Lingkungan, Industri, Kesehatan) 5, no. 1 (August 8, 2018): 42. http://dx.doi.org/10.31289/biolink.v5i1.1689.
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<em>Sangkuriang catfish (Clarias gariepinus var Sangkuriang) is the main commodity that widely cultivated in Tasikmalaya City. However, farmers have difficulty because of the disease which causes death in fish. High mortality is suspected as a vibriosis disease by genus Vibrio because redness wounds on dead fish. The purpose of this study is to know the genus Vibrio which causes of disease in Sangkuriang catfish. 10 samples of fish were taken from Sangkuriang catfish pond culture in Kelurahan Kersanagara Tasikmalaya City which were potentially suspected of vibriosis disease. Isolation of bacteria were done on TCBS medium. Bacterial isolates were collected from fish lesion on the body surface, liver, and kidneys of catfish. Isolation were able to gained 21 isolates and then 5 isolates (VK1, VK5, VK7, VK17, and VK21) were selected based on colony morphology and Postulates Koch’s were tested. The results showed that the clinical symptoms of catfish infected by vibriosis were redness lesions/ulcers on the body surface, hemorrhagic, fluid inside stomach, and fin eroded with redness wound. Bacterial identification through biochemical test revealed the causative agent of catfish disease at brackish pond area were bacteria of the genus Vibrio (VK 1, VK 5, and VK 7), Vibrio vulnificus (VK 17 and VK 21).</em>
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Babenko, L. P., L. M. Lazarenko, R. V. Bubnov, and M. J. Spivak. "Prophylactic effect of lactobacilli and bifidobacteria probiotic strains on experimental bacterial vaginitis." Biosystems Diversity 27, no. 2 (April 3, 2019): 170–76. http://dx.doi.org/10.15421/011923.
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The objective of the study was determining the prophylactic effect of Lactobacillus casei IMV B-7280, L. acidophilus IMV B-7279, L. delbrueckii subsp. bulgaricus IMV B-7281, Bifidobacterium animalis VKL and B. animalis VKB probiotic strains on experimental vaginitis in BALB/c mice induced by Staphylococcus aureus 8325-4. The infection with S. aureus 8325-4 caused an imbalance of microbiota in the vagina and intestine, as evidenced by an increase in the number of opportunistic microorganisms and a decrease in the amount of lactobacilli and bifidobacteria. L. casei IMV B-7280, B. animalis VKL and B. animalis VKB probiotic strains altered the microbiota spectrum of the vagina and intestine of Staphylococcus-infected mice: the amount of Lactobacillus and bifidobacteria increased with the reduction of the number of opportunistic microorganisms. Also under the influence of these strains, the normalization of the microbiota spectrum typical for vagina and intestine was observed in different periods of observation – in the intestines of mice the number of coliform bacteria increased, the number of microscopic fungi, streptococci and staphylococci decreased; in the vagina, the number of coliform bacteria and microscopic fungi decreased, the number of streptococci normalized. Rapid elimination of S. aureus 8325-4 from the vagina and prevention of the spread of infection to the intestine were observed after use of probiotics. Preventive effect of L. acidophilus IMV B-7279 and L. delbrueckii subsp. bulgaricus IMV B-7281 for bacterial vaginitis in mice was less effective. So, the target probiotic strains L. casei IMV B-7280, B. animalis VKL and B. animalis VKB are promising for the creation of highly effective novel probiotic drugs that can be used for directed prevention of infectious and inflammatory diseases of the genitourinary system caused by pathogenic and opportunistic microorganisms.
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Cranenburg, Ellen, Ralf Koos, Leon Schurgers, Elke Magdeleyns, Thea Schoonbrood, Robert Landewé, Vincent Brandenburg, Otto Bekers, and Cees Vermeer. "Characterisation and potential diagnostic value of circulating matrix Gla protein (MGP) species." Thrombosis and Haemostasis 104, no. 10 (2010): 811–22. http://dx.doi.org/10.1160/th09-11-0786.
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SummaryMatrix γ-carboxyglutamate (Gla) protein (MGP) is an important local inhibitor of vascular calcification, which can undergo two post-translational modifications: vitamin K-dependent γ-glutamate carboxylation and serine phosphorylation. While carboxylation is thought to have effects upon binding of calcium-ions, phosphorylation is supposed to affect the cellular release of MGP. Since both modifications can be exerted incompletely, various MGP species can be detected in the circulation. MGP levels were measured with two commercially available competitive and two novel sandwich assays in healthy controls, in patients with rheumatic disease, aortic valve disease, and end-stage renal disease, as well as in volunteers after vitamin K supplementation (VKS) and treatment with vitamin K antagonists (VKA). Major differences were found between the MGP assays, including significantly different behaviour with regard to vascular disease and the response to VKA and VKS. The dual-antibody assay measuring non-phosphorylated, non-carboxylated MGP (dp-ucMGP) was particularly sensitive for these changes and would be suited to assess the vascular vitamin K status. We conclude that the different assays for particular circulating MGP species allows the assessment of various aspects of the MGP system.
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Kawano, Masashi, Takuya Araki, Hideaki Yashima, Tomonori Nakamura, and Koujirou Yamamoto. "The Reductive Activity of Human Liver Microsomes for Vitamin K Epoxides." Indonesian Journal of Pharmaceutics 2, no. 1 (February 13, 2020): 7. http://dx.doi.org/10.24198/idjp.v2i1.25302.
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Vitamin K (VK) is oxidized to vitamin K epoxide (VK-O) during the production of VK-dependent blood clotting factors. Thereafter, VK-O is reduced to VK by vitamin K epoxide reductase (VKOR) in the liver and reused. This reductive reaction is inhibited by warfarin, an oral anticoagulant. VK in nature is roughly divided into two types, VK1 (phylloquinone) and VK2 (menaquinone). Although their bioavailabilities and elimination half-lives from human blood differ, information on the influence of each VK on the effectiveness of warfarin is limited. In this study, the difference in the metabolism of VK1-O and MK4-O by VKOR was evaluated in an in vitro study using human liver microsomes. The results showed that the substrate affinity (1/Km), and the maximum reaction rate (Vmax) of the VKOR reduction was around 7 and 4 times higher for MK4-O than for VK1-O, respectively. The intrinsic clearance of MK4-O, obtained by dividing the Vmax value by the Km value, was about 30 times greater than that of VK1-O. According to these data, the production of VK-dependent blood coagulation factors can be considered to be dominated mainly by MK4-O, at least under normal conditions. We may thus have to be more careful about controlling the intake of MK4 than VK1 in patients receiving warfarin therapy.Keywords: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), VKOR, warfarin
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Chen, Xuejie, Caihong Li, Da-Yun Jin, Brian Ingram, Zhenyu Hao, Xue Bai, Darrel W. Stafford, Keping Hu, and Jian-Ke Tie. "A cell-based high-throughput screen identifies drugs that cause bleeding disorders by off-targeting the vitamin K cycle." Blood 136, no. 7 (August 13, 2020): 898–908. http://dx.doi.org/10.1182/blood.2019004234.
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Abstract Drug-induced bleeding disorders contribute to substantial morbidity and mortality. Antithrombotic agents that cause unintended bleeding of obvious cause are relatively easy to control. However, the mechanisms of most drug-induced bleeding disorders are poorly understood, which makes intervention more difficult. As most bleeding disorders are associated with the dysfunction of coagulation factors, we adapted our recently established cell-based assay to identify drugs that affect the biosynthesis of active vitamin K–dependent (VKD) coagulation factors with possible adverse off-target results. The National Institutes of Health (NIH) Clinical Collection (NCC) library containing 727 drugs was screened, and 9 drugs were identified, including the most commonly prescribed anticoagulant warfarin. Bleeding complications associated with most of these drugs have been clinically reported, but the pathogenic mechanisms remain unclear. Further characterization of the 9 top-hit drugs on the inhibition of VKD carboxylation suggests that warfarin, lansoprazole, and nitazoxanide mainly target vitamin K epoxide reductase (VKOR), whereas idebenone, clofazimine, and AM404 mainly target vitamin K reductase (VKR) in vitamin K redox cycling. The other 3 drugs mainly affect vitamin K availability within the cells. The molecular mechanisms underlying the inactivation of VKOR and VKR by these drugs are clarified. Results from both cell-based and animal model studies suggest that the anticoagulation effect of drugs that target VKOR, but not VKR, can be rescued by the administration of vitamin K. These findings provide insights into the prevention and management of drug-induced bleeding disorders. The established cell-based, high-throughput screening approach provides a powerful tool for identifying new vitamin K antagonists that function as anticoagulants.
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Lowenstein, Charles J. "Vav-Vav-Vav-voom!" Blood 117, no. 21 (May 26, 2011): 5557–59. http://dx.doi.org/10.1182/blood-2011-04-345561.
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Onundarson, Pall T., Brynja R. Gudmundsdottir, and Charles W. Francis. "Critical Role of Factors II and X During Coumarin Anticoagulation and Their Combined Measurement with a New Prothrombin Time Variant (Fiix-PT),." Blood 118, no. 21 (November 18, 2011): 3354. http://dx.doi.org/10.1182/blood.v118.21.3354.3354.
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Abstract Abstract 3354 Introduction: Vitamin K antagonists (VKA) are monitored with prothrombin time (PT) based assays that are equally sensitive to reductions in factors II, VII or X. However, previous studies suggest that the anticoagulant effect of VKA depends primarily on reductions in factors II and X and not VII. Aim and methods: We compared the effect of vitamin K dependent (VKD) coagulation factors on PT (Quick and Owren methods) and also on rotational thromboelastometric (ROTEM) parameters. The experiments used normal platelet poor plasma (PPP) and PPP selectively immunodepleted of individual VKD factors, with and without added platelet phospholipid or washed platelets. Results: The PT was equally sensitive to reductions in factors II, VII or X. However, ROTEM parameters correlated poorly with the PT in anticoagulated patients` plasmas. ROTEM experiments showed that the clotting time, maximum velocity of clot formation and the maximum clot firmness were more affected by reductions in FII or FX than by FVII or FIX concentrations which had little influence except at very low concentrations. We developed a modified PT that was sensitive only to reductions in factors II and X by using factor II and X (Fiix) depleted plasma in the PT system. The Fiix-PT (Fiix-INR) correlated well with PT (INR) but the Fiix-INR fluctuated less than the INR in anticoagulated patients reflecting its insensitivity to FVII. Conclusion: The ROTEM results suggest that mild to moderate reductions in factors II or X are more important in clot formation than factors VII or IX at therapeutically relevant factor concentrations. Reductions in FII and X may therefore better reflect anticoagulation with VKA than FVII or IX. FVII may be a confounding source of unwanted variation in PT-INR. The new Fiix-PT that is sensitive only to FII and FX may more accurately reflect the degree of therapeutic anticoagulation in patients treated with VKA than do the current PT assays which may overestimate the fluctuation in anticoagulation. Disclosures: Onundarson: See i. other: Patent application for Fiix method in process. Gudmundsdottir:Other, see i: patent applicaiton filed for Fiix method.
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Spivak, MIa, LM Lazarenko, TM Falalieieva, OV Virchenko, and KS Neporada. "Prophylactic effect of probiotic strains Bifidobacterium animalis VKL and VKB on stress-induced lesions in the gastric mucosa of rats." Fiziolohichnyĭ zhurnal 59, no. 2 (May 15, 2013): 23–30. http://dx.doi.org/10.15407/fz59.02.023.
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Pinakhin, I. A., V. A. Chernigovskii, A. A. Bratsikhin, M. A. Yagmurov, and Kh R. Sugarov. "Investigation into Physicomechanical Properties of VK6, VK8, and T5K10 Hard Alloys after Volumetric Pulsed Laser Hardening." Inorganic Materials 54, no. 15 (December 2018): 1487–90. http://dx.doi.org/10.1134/s0020168518150177.
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Gancheva, Silvia, Martina Kitanova, Peter Ghenev, and Maria Zhelyazkova-Savova. "Experimental Model of Subclinical Vitamin K Deficiency." Folia Medica 62, no. 2 (June 30, 2020): 378–84. http://dx.doi.org/10.3897/folmed.62.e47510.
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Introduction: Vitamin K (VK) is a co-factor in the post-translational gamma glutamic carboxylation of Gla-proteins. VK-dependent coagulation factors are carboxylated in the liver by VK1. Osteocalcin and Matrix-Gla protein (MGP) are carboxylated in extrahepatic tissues by VK2. A model of VK deficiency would be suitable for studying extrahepatic Gla-proteins provided that severe bleeding is prevented. Aim: The aim of this work was to adapt an established protocol of vascular calcification by warfarin-induced inactivation of MGP as a calcification inhibitor, in an attempt to create a broader state of subclinical VK deficiency and to verify its safety. Materials and methods: Two consecutive experiments, each lasting 4 weeks, were required to modify the dosing schedule of warfa­rin and VK1 and to adapt it to the Wistar rats used. The original high doses of warfarin used initially had to be halved and the protective dose of VK1 to be doubled, in order to avoid treatment-induced hemorrhagic deaths. The second experiment aimed to confirm the efficacy and safety of the modified doses. To verify the VK deficiency, blood vessels were examined histologically for calcium deposits and serum osteocalcin levels were mea­sured. Results: The original dosing schedule induced VK deficiency, manifested by arterial calcifications and dramatic changes in carboxyl­ated and uncarboxylated osteocalcin. The modified dosing regimen caused similar vascular calcification and no bleeding. Conclusion: The modified protocol of carefully balanced warfarin and VK1 doses is an effective and safe way to induce subclinical VK deficiency that can be implemented to investigate VK-dependent proteins like osteocalcin.
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Rykin, P. O. "Reflexes of the *VgV and *VxV groups in the Mongol dialect of the glossary “Dada yu / Beilu yiyu” (late 16th - early 17th century)." Sibirskiy filologicheskiy zhurnal, no. 1 (March 1, 2019): 161–84. http://dx.doi.org/10.17223/18137083/66/14.
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Pinahin, I. A., V. A. Chernigovskij, A. A. Bracihin, and M. A. Yagmurov. "Improvement of wear resistance of VK6, VK8, T5K10, and T15K6 hard alloys by volume pulsed laser hardening." Journal of Friction and Wear 36, no. 4 (July 2015): 330–33. http://dx.doi.org/10.3103/s1068366615040145.
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Huang, Deli, Robert K. Abbott, Colin Havenar-Daughton, Patrick D. Skog, Rita Al-Kolla, Bettina Groschel, Tanya R. Blane, et al. "B cells expressing authentic naive human VRC01-class BCRs can be recruited to germinal centers and affinity mature in multiple independent mouse models." Proceedings of the National Academy of Sciences 117, no. 37 (September 1, 2020): 22920–31. http://dx.doi.org/10.1073/pnas.2004489117.
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Animal models of human antigen-specific B cell receptors (BCRs) generally depend on “inferred germline” sequences, and thus their relationship to authentic naive human B cell BCR sequences and affinities is unclear. Here, BCR sequences from authentic naive human VRC01-class B cells from healthy human donors were selected for the generation of three BCR knockin mice. The BCRs span the physiological range of affinities found in humans, and use three different light chains (VK3-20, VK1-5, and VK1-33) found among subclasses of naive human VRC01-class B cells and HIV broadly neutralizing antibodies (bnAbs). The germline-targeting HIV immunogen eOD-GT8 60mer is currently in clinical trial as a candidate bnAb vaccine priming immunogen. To attempt to model human immune responses to the eOD-GT8 60mer, we tested each authentic naive human VRC01-class BCR mouse model under rare human physiological B cell precursor frequency conditions. B cells with high (HuGL18HL) or medium (HuGL17HL) affinity BCRs were primed, recruited to germinal centers, and they affinity matured, and formed memory B cells. Precursor frequency and affinity interdependently influenced responses. Taken together, these experiments utilizing authentic naive human VRC01-class BCRs validate a central tenet of germline-targeting vaccine design and extend the overall concept of the reverse vaccinology approach to vaccine development.
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Gawne, Timothy J., and Julie M. Martin. "Responses of Primate Visual Cortical Neurons to Stimuli Presented by Flash, Saccade, Blink, and External Darkening." Journal of Neurophysiology 88, no. 5 (November 1, 2002): 2178–86. http://dx.doi.org/10.1152/jn.00151.200.
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Our visual experience constitutes an unending chain of transient events, including those caused by saccadic eye movements, by blinks, and by localized or global changes in the external world. The categorical perception of objects is maintained across different classes of transient events, suggesting that the neural circuitry underlying visual perception responds to different transient events in a similar manner. However, different sorts of transients do have different perceptual impacts: for example, the sudden changes in a scene due to a saccade or a blink do not disturb our perceptual continuity of a visual scene as much as an external change does. We recorded the responses of 103 single visual cortical neurons in two rhesus monkeys (V1: n = 38, V2: n = 19, V3V/VP: n = 30, V4V: n = 16) to the onset and offset of a visual stimulus that was elicited by four different conditions: 1) stimulus flashed on and off while the eyes remain fixed; 2) stimulus turned on and off along with the entire scene (external darkening); 3) stimulus constant, onset and offset induced by rapid saccadic eye movements; and 4) offset induced by an eyeblink. For most neurons the onset and offset of a visual stimulus elicited qualitatively similar responses regardless of condition. We found no systematic effect of different conditions across the neuronal population. Previously we have shown that when the visual scene is occluded by a blink V1 neuronal firing declines in a similar manner as when the external scene is darkened and the eyes left open. Here we show that this is also the case in V2, V3V/VP, and V4V. However, for a substantial minority of neurons, the response varied strongly as a function of the transient event. This overall pattern was the same in all four cortical areas studied here. We hypothesize that most neurons in visual cortex constitute a passive “filter bank”, analyzing the scene for specific details regardless of condition. However, there are neurons that respond in a qualitatively different manner depending on how a stimulus is presented, and we hypothesize that these signals may be important for determining the perceptual salience of a visual event.
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Spivak, Mykola Ya, L. M. Lazarenko, Tetyana M. Falalyeyeva, O. V. Virchenko, and K. S. Neporada. "Prophylactic Effect of Probiotic Strains Bifidobacterium Animalis VKL and VKB on Stress-Induced Lesions in the Gastric Mucosa of Rats." International Journal of Physiology and Pathophysiology 5, no. 1 (2014): 73–82. http://dx.doi.org/10.1615/intjphyspathophys.v5.i1.80.
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Kraus, Tanja, and Michael Novak. "VKO 2020." Pädiatrie & Pädologie 55, no. 1 (February 2020): 1–3. http://dx.doi.org/10.1007/s00608-020-00749-6.
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Leshchenko, I., O. Virchenko, O. Gadiliya, T. Falalyeyeva, and L. Lazarenko. "Сarbohydrate metabolism parameters under the glutamate-induced obesity in rats and concominant correction with probiotic strains of lactobacilli and bifidobacteria." Bulletin of Taras Shevchenko National University of Kyiv. Series: Biology 70, no. 2 (2015): 20–23. http://dx.doi.org/10.17721/1728_2748.2015.70.20-23.
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To find out the effect of probiotic strains on insulin resistance induced by glutamate-induced obesity in rats. Obesity was induced by neonatal administration of monosodium glutamate (4 mg/g,s.c.) at 2, 4, 6, 8, 10-day life. The introduction of probiotics started at the end of 4 week after birth and continued intermittently for 2-week courses. After 4 months, the rats of all groups glucose and insulin levels and insulin resistance index HOMA were analyzed. Neonatal administration of monosodium glutamate leads to the development of insulin resistance in rats 4 months of age. The periodic introduction of the combined probiotics prevented the development insulin resistance in rats. The most significant effect was revealed in the group of animals treated with the combined probiotic strains Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, Bifidobacterium animalis VKB. The results suggest the effectiveness of the use of probiotic strains of bifidobacteria and to prevent the development of insulin resistance.
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Oberst, M. "Neuordnung des Verletzungsartenverfahrens (VAV) aus Sicht einer VAV-Klinik." Trauma und Berufskrankheit 16, S3 (June 26, 2014): 227–30. http://dx.doi.org/10.1007/s10039-014-2081-7.
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Poberezhnikov, Igor, and Andrey Speranskiy. "V.V. Alekseyev's Anniversary." Rossiiskaia istoriia, no. 5 (2019): 245–48. http://dx.doi.org/10.31857/s086956870006396-6.
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Bonini, Stefano, and Sergio Bonini. "Vernal Keratoconjunctivitis (VKC)." Ocular Immunology and Inflammation 1, no. 1-2 (January 1993): 13–17. http://dx.doi.org/10.3109/09273949309086530.
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Schinzel, H. "Heparine – DOAKs – VKA." Onkologische Welt 07, no. 05 (2016): 206–16. http://dx.doi.org/10.1055/s-0037-1618984.
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ZusammenfassungBei Tumorpatienten bestehen ein erhöhtes Thromboembolierisiko und nicht selten gleichzeitig ein erhöhtes Blutungsrisiko. Dies macht die Antikoagulation nicht ganz einfach. Es muss stets eine individuelle Nutzen-Risiko-Abwägung erfolgen. Stationäre Tumorpatienten erhalten in der Regel eine medikamentöse VTE-Prophylaxe meist mit einem niedermolekularen Heparin (NMH) in der Hochrisikoprophylaxedosierung. Bei ambulanten Tumorpatienten ist das VTE-Risiko deutlich geringer, sie erhalten nur dann eine medikamentöse Prophylaxe, wenn zusätzliche prothrombogene Risikofaktoren vorliegen. Tumorpatienten mit akuter VTE werden mindesten 3–6 Monate mit NMH in therapeutischer (gewichtsadaptierter) Dosis behandelt, erst danach kann man ggf. auf Vitamin-K-Antagonisten umsetzen. Neben den etablierten Antikoagulanzien wie Heparinen, Vitamin-K-Antagonisten, Fondaparinux sind in den letzten Jahren die direkten oralen Antikoagulantien (DOAKs) hinzugekommen. Die Zulassung der DOAKs erstreckt sich aktuell auf die Thromboembolieprophylaxe nach elektiver Hüft- und Knietotalendoprothese, der Schlaganfallprophylaxe bei nicht-valvulärem Vorhofflimmern und der Initial- und Folgetherapie nach tiefer Beinvenenthrombose und Lungenembolie. In den Phase-III-Studien waren ca. 4–10 % Tumorpatienten integriert. Die DOAKs haben hierbei gezeigt, dass sie mindestens gleichwertig sind im Vergleich zur Standardtherapie bezüglich Rezidiv-VTE bei vergleichbarer Blutungsrate. Dies ist ermutigend. Die Datenlage reicht aktuell jedoch noch nicht aus, um sie bei Tumorpatienten einzusetzen. Entsprechende Studien speziell für Tumorpatienten stehen noch aus.
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Schinzel, H. "Heparins – DOACS – VKA." Phlebologie 44, no. 06 (November 2015): 307–15. http://dx.doi.org/10.12687/phleb2289-6-2015.
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SummaryPatients with cancer are at increased risk of venous thromboembolism (VTE). At the same time they have often an underlying bleeding risk. That can often make decisions surrounding the administration of anticoagulants complicate. Individual risk-benefit calculation is necessary. During hospital stage the patients get, if there are no contraindications, a medical VTE prophylaxis with low molecular weight heparin (LMWH). Whereas out-patients don’t get a prophylaxis because they are at low risk of thromboembolism. If additional risk factor for VTE exists a decision for medical VTE prophylaxis should be taken into account. In patients with cancer and acute VTE, LMWH is recommended as treatment of choice for initial and long-term management in a body weight adapted dosage. After a period of 3–6 month and if a prolonged treatment is necessary, guidelines allow to switch from LMWH to VKA for further anticoagulant therapy. Beside the established anticoagulants like heparin, vitamin K antagonists, fondaparinux new oral direct anticoagulants (DOACs) were established in the last years. These substances are evaluated in in clinical trials. They are approved for treatment of acute VTE, for secondary prophylaxis and for prevention of ischemic stroke in patients with arterial fibrillation. In the VTE trials, 4–10 % of the enrolled patients had a history of cancer. The data shows that DOACs can prevent recurrent VTE as good as standard therapy with enoxaparin/warfarin without more bleeding complications. The results are encouraging. Because of the limited data the direct oral anticoagulants are not recommended for treatment of VTE at this time. Further studies are necessary.
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Collins, Tassie L., Marcel Deckert, and Amnon Altman. "Views on Vav." Immunology Today 18, no. 5 (May 1997): 221–25. http://dx.doi.org/10.1016/s0167-5699(97)01037-2.
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NAKAI, K. "OCT for VKH." Acta Ophthalmologica 91 (August 2013): 0. http://dx.doi.org/10.1111/j.1755-3768.2013.2253.x.
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Puil, Lorri, and Tony Pawson. "Vagaries of Vav." Current Biology 2, no. 5 (May 1992): 275–77. http://dx.doi.org/10.1016/0960-9822(92)90396-r.
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Weimar, Christian. "NOAK oder VKA?" InFo Neurologie & Psychiatrie 21, no. 12 (December 2019): 23. http://dx.doi.org/10.1007/s15005-019-0235-7.
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Navas, Francisco, and Vicente Milanés. "Mixing V2V- and non-V2V-equipped vehicles in car following." Transportation Research Part C: Emerging Technologies 108 (November 2019): 167–81. http://dx.doi.org/10.1016/j.trc.2019.08.021.
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Ihle, Christoph, H. Nakayama, Christoph Gonser, Ulrich Stöckle, Stefan Döbele, Steffen Schröter, Marc-Daniel Ahrend, and Atesch Ateschrang. "Die Naht der frischen vorderen Kreuzbandruptur mit dynamischer intraligamentärer Stabilisierung – eine Alternative zur vorderen Kreuzbandersatzplastik bei sportlich aktiven jungen Patienten." Zeitschrift für Orthopädie und Unfallchirurgie 156, no. 01 (February 2018): 100–102. http://dx.doi.org/10.1055/s-0043-120576.
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Zusammenfassung Zielsetzung Der Ersatz des vorderen Kreuzbands (VKB) mit autologem Sehnentransplantat ist derzeit der Goldstandard zur Behandlung der VKB-Ruptur. Gute Ergebnisse wurden berichtet, wobei Langzeitresultate erhöhte Arthroseraten zeigten. Als Ursachen werden verbleibende Instabilitäten und der Propriozeptionsverlust trotz und durch den VKB-Ersatz diskutiert. Eine neue Alternative zur Behandlung frischer VKB-Rupturen stellt die VKB-Naht mit temporärer dynamischer intraligamentärer Stabilisierung (DIS) dar, wobei das readaptierte und heilende VKB durch die DIS über einen Zeitraum von ca. 3 – 5 Monaten biomechanisch geschützt wird. Nach längstens 6 Monaten hat die DIS keine Funktion mehr und das verheilte VKB übernimmt die gesamte Stabilisierung. Dieser Videobeitrag soll das operative Verfahren zum Erhalt des VKB demonstrieren. Indikation Die Indikation zum VKB-Erhalt beinhaltet frische (< 21 Tage) VKB-Rupturen des femurnahen Drittels mit einer sagittalen Translation von > 5 mm im Seitenvergleich bzw. einem positiven Pivot-Shift-Test. Der VKB-Erhalt kann jungen und sportlich aktiven Patienten angeboten werden, wobei die Wachstumsfuge am Tibiakopf weitestgehend verschlossen sein sollte. Methode Ein 22-jähriger Patient mit VKB-Läsion wurde 3 Wochen nach Kniegelenksdistorsion mit VKB-Naht und DIS versorgt. Schlussfolgerung Die VKB-Naht mit DIS ist eine operative Option zum Erhalt des VKB sowie möglicherweise der Propriozeption.
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Basiev, Tasoltan T. "Spectroscopy of new SRS-active crystals and solid-state SRS lasers." Uspekhi Fizicheskih Nauk 169, no. 10 (1999): 1149. http://dx.doi.org/10.3367/ufnr.0169.199910f.1149.
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Wang, Jian, Qiang Zheng, Fang Mei, Weiwen Deng, and Yuming Ge. "A Novel Method to Enable the Awareness Ability of Non-V2V-Equipped Vehicles in Vehicular Networks." Sensors 19, no. 9 (May 11, 2019): 2187. http://dx.doi.org/10.3390/s19092187.
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Autonomous vehicles need to have sufficient perception of the surrounding environment to produce appropriate driving behavior. The Vehicle-to-Vehicle (V2V) communication technology can exchange the speed, position, direction, and other information between autonomous vehicles to improve the sensing ability of the traditional on-board sensors. For example, V2V communication technology does not have a blind spot like a conventional on-board sensor, and V2V communication is not easily affected by weather conditions. However, it is almost impossible to make every vehicle a V2V-equipped vehicle in the real environment due to reasons such as policy and user choice. Low penetration of V2V-equipped vehicles greatly reduces the performance of the traditional V2V system. In this paper, however, we propose a novel method that can extend the awareness ability of the traditional V2V system without adding much extra investment. In the traditional V2V system, only a V2V-equipped vehicle can broadcast its own location information. However, the situation is somewhat different in our V2V system. Although non-V2V-equipped vehicles cannot broadcast their own location information, we can let V2V-equipped vehicle with radar and other sensors detect the location information of the surrounding non-V2V-equipped vehicles and then broadcast it out. Therefore, we think that a non-V2V-equipped vehicle can also broadcast its own location information. In this way, we greatly extend the awareness ability of the traditional V2V system. The proposed method is validated by real experiments and simulation experiments.
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Leonardi, Andrea, Daniela Lazzarini, Alvise La Gloria Valerio, Tania Scalora, and Iva Fregona. "Corneal staining patterns in vernal keratoconjunctivitis: the new VKC-CLEK scoring scale." British Journal of Ophthalmology 102, no. 10 (January 24, 2018): 1448–53. http://dx.doi.org/10.1136/bjophthalmol-2017-311171.
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AimTo propose a new scoring system in the assessment of ocular surface epithelial damage in vernal keratoconjunctivitis (VKC).Methods25 consecutive patients with VKC (50 eyes) were evaluated using the Quality of Life in children with VKC (QUICK) questionnaire and objective clinical measures: fluorescein and lissamine green staining and cornea confocal microscopy (Heidelberg Retina Tomography 3). Oxford, Van Bljsterweld and a new system, the VKC-Collaborative Longitudinal Evaluation of Keratoconus study (CLEK) (VKC-CLEK) scores, were used to evaluate the epithelial damage after staining.ResultsMean Oxford and VKC-CLEK scores were significantly different after fluorescein staining (P<0.001), but significantly correlated (P<0.001; r=0.649). The same data were obtained comparing Van Bljsterweld and VKC-CLEK after lissamine green staining (P<0.001; r=0.760). In patient with limbal VKC, a statistically significant difference was found comparing new VKC-CLEK scores and Oxford or Van Bljsterweld scores (P<0.001), but not in tarsal VKC. A statistically superior concordance was found between QUICK and VKC-CLEK scores compared with standard staining scores values (P<0.001).ConclusionsOxford and Van Bijsterveld scores are not adequate for the evaluation of the epithelial damage in patients with limbal VKC because the staining patterns considered for these tests do not correspond to the staining patterns in patients with VKC. We propose a new scoring system, VKC-CLEK, to better evaluate both limbal and tarsal epithelial damage in patients with VKC.
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Manckoundia, Patrick, Clémentine Rosay, Didier Menu, Valentine Nuss, Anca-Maria Mihai, Jérémie Vovelle, Gilles Nuémi, Philippe d’Athis, Alain Putot, and Jérémy Barben. "The Prescription of Vitamin K Antagonists in a Very Old Population: A Cross-Sectional Study of 8696 Ambulatory Subjects Aged Over 85 Years." International Journal of Environmental Research and Public Health 17, no. 18 (September 14, 2020): 6685. http://dx.doi.org/10.3390/ijerph17186685.
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We compared very elderly people taking vitamin K antagonists (VKA) and those not taking VKA (noVKA). Individuals were included in the noVKA group if there was no VKA on their reimbursed prescriptions during the study period. We also compared three subgroups, constituted by VKA type (fluindione, warfarin, or acenocoumarol). We included individuals aged over 85 years, affiliated to Mutualité Sociale Agricole of Burgundy, who were refunded for prescribed VKA in September 2017. The VKA and noVKA groups were compared in terms of demographic conditions, registered chronic diseases (RCD), number of drugs per prescription and cardiovascular medications. The three VKA subgroups were compared for the same items plus laboratory monitoring, novel and refill VKA prescriptions, and prescriber specialty. Of the 8696 included individuals, 1157 (13.30%) were prescribed VKA. Mean age was 90 years. The noVKA group had fewer women (53.67 vs 66.08%), more RCD (93.43 vs. 71.96%) and more drugs per prescription (6.65 vs. 5.18) than the VKA group (all p < 0.01). Except for direct oral anticoagulants and platelet aggregation inhibitors, the VKA group took significantly more cardiovascular medications. The most commonly prescribed VKA was fluindione (59.46%). Mean age was higher in the warfarin (90.42) than in the acenocoumarol (89.83) or fluindione (89.71) subgroups (p < 0.01). No differences were observed for sex (women were predominant) or RCD. 13% of subjects in this population had a VKA prescription. Fluindione was the most commonly prescribed VKA.
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Tanahashi, Toshiyuki, Shinji Osada, Hisashi Imai, Yoshiyuki Sasaki, Takao Takahashi, Kazuya Yamaguchi, and Kazuhiro Yoshida. "Signal transduction of vitamin K3 for pancreas cancer therapy." Oncology Reviews 5, no. 1 (October 25, 2011): 57. http://dx.doi.org/10.4081/oncol.2011.57.
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We characterized molecular mechanisms of vitamin K3 (VK3)-induced inhibition of proliferation to evaluate VK3 effectiveness in treating advanced pancreatic cancer. A novel endoscopic drug delivery system, ultrasound injection technique, was used to study local effects of VK3. VK3 inhibited pancreas cancer cell growth by rapid phosphorylation of growth factor receptor and cellular signal factors such as extracellular signal-regulated kinase. VK3 also activated apoptosis, and apoptosis inhibitor antagonized the apoptosis pathway without inhibiting cell growth. Thiol antioxidant treatment completely abrogated VK3-induced ERK but not JNK phosphorylation or inhibition of proliferation. Non-thiol antioxidant did not affect ERK phosphorylation or growth inhibitory actions. Arylation was considered the main mechanism of VK3-induced growth inhibition through ERK activation. VK3 may lead to favorable outcomes in the treatment of pancreatic tumors. Detection of ERK phosphorylation in tissue is important to predict VK3 effect. Endoscopic ultrasound-guided fine-needle injection may be beneficial for treating pancreatic cancer with VK3.
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López-Lago, Miguel, Hyunmi Lee, Cristina Cruz, Nieves Movilla, and Xosé R. Bustelo. "Tyrosine Phosphorylation Mediates Both Activation and Downmodulation of the Biological Activity of Vav." Molecular and Cellular Biology 20, no. 5 (March 1, 2000): 1678–91. http://dx.doi.org/10.1128/mcb.20.5.1678-1691.2000.
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ABSTRACT Vav works as a GDP/GTP exchange factor for Rac GTPases, thereby facilitating the transition of these proteins from the inactive (GDP-bound) into the active (GTP-bound) state. The stimulation of Vav exchange activity during cell signaling is mediated by tyrosine phosphorylation. To understand the roles of phosphorylation in the regulation of Vav activity, we have initiated the characterization of the residues of Vav that are phosphorylated during signal transduction. Here we show that a Y-to-F mutation in one of these residues, Y174, leads to the oncogenic activation of Vav and to the enhancement of other Vav-mediated signals such as those for cytoskeletal reorganization, JNK activation, and stimulation of the nuclear factor of activated T cells. The effect induced by the Y174F mutation is further accentuated by mutations in residue Y142 or Y160. The Y174F mutation has no effect on the exchange activity of Vav in vitro but results in higher levels of phosphorylation in vivo. Using a phosphospecific antibody, we found that Y174 is phosphorylated following stimulation of mitogenic and antigenic receptors. This phosphorylation event is conserved in Vav-2 and Vav-3, the other two members of the Vav family. These results identify a previously unknown mechanism for the oncogenic activation of Vav and suggest that the activity of this exchange factor is modulated by two antagonistic phosphorylation events, one involved in Vav activation and a second one implicated in Vav inactivation.
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Sada, Eriko, Yasunobu Abe, Rie Ohba, Yoshimichi Tachikawa, Eriko Nagasawa, Shiratshuchi Motoaki, Ryoichi Takayanagi, and Tsukuru Umemura. "Vitamin K2 Modulates Differentiation and Apoptosis of Both Myeloid and Erythroid Lineages." Blood 116, no. 21 (November 19, 2010): 3993. http://dx.doi.org/10.1182/blood.v116.21.3993.3993.
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Abstract Abstract 3993 Myelodysplastic syndrome (MDS) is a stem cell disorder characterized by ineffective hematopoiesis eventually leading to maturation arrest and leukemic transformation. It is well-known that VK2 induces differentiation and apoptosis in acute myeloid leukemia (AML) cell lines such as HL-60 and U937. Based on the studies of AML cell lines, several clinical trials of VK2 therapy for MDS patients have been conducted, and they showed improvement of cytopenia and reductions in blastic cells. Interestingly, hematological improvement was also observed in MDS patients with low percentage of blasts, and a differentiation/apoptosis-inducing effect on blasts alone could not explain this fact. Thus, the effects of VK2 on primary hematopoietic progenitors were examined from the perspective of differentiation and apoptosis. Mobilized CD34-positive cells from peripheral blood were used for the examination of myeloid lineage cells, and were cultured in IMDM containing 20% FCS, 20 ng/mL rhSCF, 20 ng/mL rhIL-3, with or without VK2. VK2 induced significant increase of CD11b-positive cells on day 4 (35.8% ± 12.3% with 10 μM VK2 vs. 10.7% ± 1.9% without VK2, P=0.0034) and day 6 (42.7% ± 6.3% with 10 μM VK2 vs. 24.1% ± 8.6% without VK2, P=0.0235). CD14-positive cells also increased significantly on day 4 (8.0% ± 0.3% with 10 μM VK2 vs. 4.1% ± 1.5% without VK2, P=0.008). Furthermore, after treatment with VK2, mRNA expression levels of both C/EBPα and PU.1 were elevated in a dose-dependent manner, and a significant increase was shown at 10 μM of VK2 on day 6. These results indicate that VK2 promotes the differentiation of myeloid progenitors through the upregulation of transcriptional factors C/EBPα and PU.1. The effect of VK2 on the apoptosis of myeloid progenitors was also examined. VK2 increased the number of apoptotic cells determined by Annexin V assay transiently on day 4 (58.9% ± 6.3% with 10 μM VK2 vs. 36.1% ± 2.8% without VK2, P<0.0001), but no significant increase was found on day 6. Next, human erythroid colony forming cells (ECFCs) purified from peripheral blood were used for the examination of erythroid lineage cells. ECFCs were cultured in IMDM containing 15% FCS, 15% human AB serum, 2 U/ml rhEPO, 20 ng/mL rhSCF, 10 ng/mL rhIL-3 (depleted on day 3), with or without VK2 (added on day 3). In ECFCs, VK2 did not affect the expressions of transferrin receptor (TfR) and glycophorin A (GPA) or the expression level of β-globin mRNA. However, the expression of GATA-1 mRNA increased significantly on day 7 with 10 μM of VK2. VK2 seems to have the potential to promote the differentiation of ECFCs through the upregulation of transcriptional factor GATA-1, although this differentiating effect on ECFCs was much smaller than that on myeloid progenitors. Furthermore, VK2 exhibited an anti-apoptotic effect on day 7 ECFCs under erythropoietin (EPO) -depletion. The percentage of apoptotic cells after 24 hours of EPO-depletion, which was determined by Annexin V-positivity, was significantly reduced with VK2 at low concentrations (0.5-2 μM) (76.9% ± 4.7% with 1 μM VK2 vs. 88.3% ± 1.7% without VK2, P=0.0019). VK2 lost its anti-apoptotic effect at concentrations greater than 5 μM. This anti-apoptotic effect was not shown in erythroleukemic cell line AS-E2. Finally, the expression of steroid and xenobiotic receptor (SXR), which was recently identified as a receptor of VK2, on primary hematopoietic cells was examined. SXR was expressed on myeloid progenitors, but not on erythroid progenitors. SXR agonist rifampicin also upregulated the expressions of CD11b and CD14 on myeloid progenitors. The differentiation-promoting effect of VK2 on myeloid progenitors seems to be mediated partly through SXR signaling. These results indicate that the effect of VK2 varies by cell type. The major effect on myeloid progenitors was promoting differentiation, whereas its anti-apoptotic effect seemed to be dominant in erythroid progenitors. Although the detailed mechanism of VK2's effect on differentiation or apoptosis of hematopoietic progenitors remains unknown, the effect of VK2 therapy in MDS patients could be partly explained by these mechanisms. Disclosures: No relevant conflicts of interest to declare.
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Samykutty, Abhilash, Aditya V. Shetty, Gajalakshmi Dakshinamoorthy, Ramaswamy Kalyanasundaram, Gouxing Zheng, Aoshuang Chen, Maarten C. Bosland, André Kajdacsy-Balla, and Munirathinam Gnanasekar. "Vitamin K2, a Naturally Occurring Menaquinone, Exerts Therapeutic Effects on Both Hormone-Dependent and Hormone-Independent Prostate Cancer Cells." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–15. http://dx.doi.org/10.1155/2013/287358.
Full textAbstract:
In recent years, several studies have shown that vitamin k2 (VK2) has anticancer activity in a variety of cancer cells. The antitumor effects of VK2 in prostate cancer are currently not known. In the present study, we sought to characterize the anticancer potential of VK2 in both androgen-dependent and -independent prostate cancer cells. Our investigations show that VK2 is able to suppress viability of androgen-dependent and androgen-independent prostate cancer cells via caspase-3 and -8 dependent apoptosis. We also show that VK2 treatment reduces androgen receptor expression and PSA secretion in androgen-dependent prostate cancer cells. Our results also implicate VK2 as a potential anti-inflammatory agent, as several inflammatory genes are downregulated in prostate cancer cells following treatment with VK2. Additionally, AKT and NF-kB levels in prostate cancer cells are reduced significantly when treated with VK2. These findings correlated with the results of the Boyden chamber and angiogenesis assay, as VK2 treatment reduced cell migration and angiogenesis potential of prostate cancer cells. Finally, in a nude mice model, VK2 administration resulted in significant inhibition of both androgen-dependent and androgen-independent tumor growth. Overall, our results suggest that VK2 may be a potential therapeutic agent in the treatment of prostate cancer.
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Gulbins, E., K. M. Coggeshall, G. Baier, D. Telford, C. Langlet, G. Baier-Bitterlich, N. Bonnefoy-Berard, P. Burn, A. Wittinghofer, and A. Altman. "Direct stimulation of Vav guanine nucleotide exchange activity for Ras by phorbol esters and diglycerides." Molecular and Cellular Biology 14, no. 7 (July 1994): 4749–58. http://dx.doi.org/10.1128/mcb.14.7.4749.
Full textAbstract:
We recently identified Vav as a Ras-activating guanine nucleotide exchange factor (GEF) stimulated by a T-cell antigen receptor-coupled protein tyrosine kinase (PTK). Here, we describe a novel, protein kinase-independent alternative pathway of Vav activation. Phorbol ester, 1,2-diacylglycerol, or ceramide treatment of intact T cells, Vav immunoprecipitates, or partially purified Vav generated by in vitro translation or COS-1 cell transfection stimulated the Ras exchange activity of Vav in the absence of detectable tyrosine phosphorylation. GEF activity of gel-purified Vav was similarly stimulated by phorbol myristate acetate (PMA). Stimulation was resistant to PTK and protein kinase C inhibitors but was blocked by calphostin, a PMA and diacylglycerol antagonist. In vitro-translated Vav lacking its cysteine-rich domain, or mutated at a single cysteine residue within this domain (C528A), was not stimulated by PMA but was fully activated by p56lck. This correlated with increased binding of radiolabeled phorbol ester to COS-1 cells expressing wild-type, but not C528A-mutated, Vav. Thus, Vav itself is a PMA-binding and -activated Ras GEF. Recombinant interleukin-1 alpha stimulated Vav via this pathway, suggesting that diglyceride-mediated Vav activation may couple PTK-independent receptors which stimulate production of lipid second messengers to Ras in hematopoietic cells.
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Gulbins, E., K. M. Coggeshall, G. Baier, D. Telford, C. Langlet, G. Baier-Bitterlich, N. Bonnefoy-Berard, P. Burn, A. Wittinghofer, and A. Altman. "Direct stimulation of Vav guanine nucleotide exchange activity for Ras by phorbol esters and diglycerides." Molecular and Cellular Biology 14, no. 7 (July 1994): 4749–58. http://dx.doi.org/10.1128/mcb.14.7.4749-4758.1994.
Full textAbstract:
We recently identified Vav as a Ras-activating guanine nucleotide exchange factor (GEF) stimulated by a T-cell antigen receptor-coupled protein tyrosine kinase (PTK). Here, we describe a novel, protein kinase-independent alternative pathway of Vav activation. Phorbol ester, 1,2-diacylglycerol, or ceramide treatment of intact T cells, Vav immunoprecipitates, or partially purified Vav generated by in vitro translation or COS-1 cell transfection stimulated the Ras exchange activity of Vav in the absence of detectable tyrosine phosphorylation. GEF activity of gel-purified Vav was similarly stimulated by phorbol myristate acetate (PMA). Stimulation was resistant to PTK and protein kinase C inhibitors but was blocked by calphostin, a PMA and diacylglycerol antagonist. In vitro-translated Vav lacking its cysteine-rich domain, or mutated at a single cysteine residue within this domain (C528A), was not stimulated by PMA but was fully activated by p56lck. This correlated with increased binding of radiolabeled phorbol ester to COS-1 cells expressing wild-type, but not C528A-mutated, Vav. Thus, Vav itself is a PMA-binding and -activated Ras GEF. Recombinant interleukin-1 alpha stimulated Vav via this pathway, suggesting that diglyceride-mediated Vav activation may couple PTK-independent receptors which stimulate production of lipid second messengers to Ras in hematopoietic cells.
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Gulbins, E., K. M. Coggeshall, C. Langlet, G. Baier, N. Bonnefoy-Berard, P. Burn, A. Wittinghofer, S. Katzav, and A. Altman. "Activation of Ras in vitro and in intact fibroblasts by the Vav guanine nucleotide exchange protein." Molecular and Cellular Biology 14, no. 2 (February 1994): 906–13. http://dx.doi.org/10.1128/mcb.14.2.906.
Full textAbstract:
We recently identified Vav, the product of the vav proto-oncogene, as a guanine nucleotide exchange factor (GEF) for Ras. Vav is enzymatically activated by lymphocyte antigen receptor-coupled protein tyrosine kinases or independently by diglycerides. To further evaluate the physiological role of Vav, we assessed its GDP-GTP exchange activity against several Ras-related proteins in vitro and determined whether Vav activation in transfected NIH 3T3 fibroblasts correlates with the activity status of Ras and mitogen-activated protein (MAP) kinases. In vitro translated purified Vav activated by phorbol myristate acetate (PMA) or phosphorylation with recombinant p56lck displayed GEF activity against Ras but not against recombinant RacI, RacII, Ral, or RhoA proteins. Expression of vav or proto-vav in stably transfected NIH 3T3 cells led to a approximately 10-fold increase in basal or PMA-stimulated Ras exchange activity, respectively, in total-cell lysates and Vav immunoprecipitates. Elevated GEF activity was paralleled in each case by a significant increase in the proportion of active, GTP-bound Ras. PMA had a minimal effect on the low Ras. GTP level in untransfected control fibroblasts but increased it from 20 to 37% in proto-vav-transfected cells. vav-transfected cells displayed a constitutively elevated Ras. GTP level (35%), which was not increased further by PMA treatment. MAP kinases, known downstream intermediates in Ras-dependent signaling pathways, similarly exhibited increased basal or PMA-stimulated activity in Vav-expressing cells by comparison with normal NIH 3T3 cells. These results demonstrate a physiologic interaction between Vav and its target, Ras, leading to MAP kinase activation.
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Gulbins, E., K. M. Coggeshall, C. Langlet, G. Baier, N. Bonnefoy-Berard, P. Burn, A. Wittinghofer, S. Katzav, and A. Altman. "Activation of Ras in vitro and in intact fibroblasts by the Vav guanine nucleotide exchange protein." Molecular and Cellular Biology 14, no. 2 (February 1994): 906–13. http://dx.doi.org/10.1128/mcb.14.2.906-913.1994.
Full textAbstract:
We recently identified Vav, the product of the vav proto-oncogene, as a guanine nucleotide exchange factor (GEF) for Ras. Vav is enzymatically activated by lymphocyte antigen receptor-coupled protein tyrosine kinases or independently by diglycerides. To further evaluate the physiological role of Vav, we assessed its GDP-GTP exchange activity against several Ras-related proteins in vitro and determined whether Vav activation in transfected NIH 3T3 fibroblasts correlates with the activity status of Ras and mitogen-activated protein (MAP) kinases. In vitro translated purified Vav activated by phorbol myristate acetate (PMA) or phosphorylation with recombinant p56lck displayed GEF activity against Ras but not against recombinant RacI, RacII, Ral, or RhoA proteins. Expression of vav or proto-vav in stably transfected NIH 3T3 cells led to a approximately 10-fold increase in basal or PMA-stimulated Ras exchange activity, respectively, in total-cell lysates and Vav immunoprecipitates. Elevated GEF activity was paralleled in each case by a significant increase in the proportion of active, GTP-bound Ras. PMA had a minimal effect on the low Ras. GTP level in untransfected control fibroblasts but increased it from 20 to 37% in proto-vav-transfected cells. vav-transfected cells displayed a constitutively elevated Ras. GTP level (35%), which was not increased further by PMA treatment. MAP kinases, known downstream intermediates in Ras-dependent signaling pathways, similarly exhibited increased basal or PMA-stimulated activity in Vav-expressing cells by comparison with normal NIH 3T3 cells. These results demonstrate a physiologic interaction between Vav and its target, Ras, leading to MAP kinase activation.
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Miyazawa, Keisuke, Kazuma Ohyashiki, Nobu Akiyama, Yoshinobu Kanda, Kaoru Tohyama, Mistuhiro Omine, and Kinuko Mitani. "Vitamin K2 (VK2) Monotherapy and VK2 Plus D3 Combination Therapy in Low-Risk Myelodysplastic Syndrome: A Prospective Japanese Study." Blood 106, no. 11 (November 16, 2005): 2528. http://dx.doi.org/10.1182/blood.v106.11.2528.2528.
Full textAbstract:
Abstract Vitamin K2 (VK2) analogs, including menaquinone-4 (MK4) but not vitamin K1, effectively induce apoptosis in acute myeloid leukemia cells (AML). Apoptosis induction by VK2 is specific toward leukemia cells, and almost no effect is observed in normal hematopoietic progenitor cells (Miyazawa K, Leukemia 1999, 2000, 2001). Combined treatment with VK2 plus 1α, 25-dihydroxy-vitamin D3 (D3) dramatically enhanced differentiation of leukemia cells as compared to the cells treated with D3 alone. Concomitant with the induction of differentiation and final maturation by VK2 plus D3, the cells became resistant to various apoptotic stimuli (Funato K, Leukemia, 2002). VK2 has been shown to improve the supportive hematopoietic functions of bone marrow stromal cells (Miyazawa K, Stem Cell Dev. 2004). Since VK2 (MK4, GlakayR) has been used to treat patients with osteoporosis in Japan, its non-toxicity and safety for long-term daily administration have already been well established. Case reports demonstrating the clinical benefits of using VK2 with or without D3 for treating patients with myelodysplastic syndrome (MDS) and AML have been accumulating, i.e. improving cytopenias in refractory anemia (RA) and reduction of blast cells in AML. We performed a multicenter prospective trial to determine the therapeutic benefit of VK2 with or without D3 in MDS. Patients with RA/RCMD with low/ int-1 by IPSS received VK2 (Glakay, 45 mg/day, po) for 16 weeks. The therapeutic response was assessed according to the International Working Group Criteria. Patients who did not respond to VK2 were sequentially re-registered and received a combination of VK2 plus D3 (alfacalcidol, AlfarolR, 0.75 microgram/day, po) for 16 weeks. Patients showing response to VK2 alone or VK2 plus D3 after 16 weeks continued to receive therapy for a total of 12 months. Forty-three patients have been enrolled and 29 patients were evaluable for their response to VK2. Five patients (17.2 %) showed improvement of cytopenia (major HI-E (1), minor HI-E (2), major HI-P (3), and minor HI-P (1)). Twenty out of 24 patients who showed no response to VK2 alone subsequently received VK2 plus D3. Eleven patients were eligible for evaluation and 4 patients (36.4%) showed improvement of cytopenia in response to VK2 plus D3 (major HI-E (3), minor HI-E (1) and major HI-P (1)). Four out of 7 patients (57 %) with anemia showed hematologic response. No adverse events were observed, except for one case of skin rash (Grade I) during VK2 plus D3 therapy. These data suggest that the therapeutic response rate is improved by combined treatment with VK2 plus D3 as compared with that by VK2 monothrapy. Safety and low price also support the therapeutic benefit of VK2 with D3 for improving cytopenia in RA.