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131.
132.
RuthMabel Boytz Mikołaj Słabicki Sita Ramaswamy J. J. Patten Charles Zou Chengcheng Meng Brett L. Hurst Jinhua Wang Radosław P. Nowak Priscilla L. Yang Martin Sattler Richard M. Stone James D. Griffin Nathanael S. Gray Suryaram Gummuluru Robert A. Davey Ellen Weisberg 《Journal of medical virology》2023,95(1):e28157
Coronavirus disease 2019 (COVID-19) remains a major public health concern, and vaccine unavailability, hesitancy, or failure underscore the need for discovery of efficacious antiviral drug therapies. Numerous approved drugs target protein kinases associated with viral life cycle and symptoms of infection. Repurposing of kinase inhibitors is appealing as they have been vetted for safety and are more accessible for COVID-19 treatment. However, an understanding of drug mechanism is needed to improve our understanding of the factors involved in pathogenesis. We tested the in vitro activity of three kinase inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including inhibitors of AXL kinase, a host cell factor that contributes to successful SARS-CoV-2 infection. Using multiple cell-based assays and approaches, gilteritinib, nintedanib, and imatinib were thoroughly evaluated for activity against SARS-CoV-2 variants. Each drug exhibited antiviral activity, but with stark differences in potency, suggesting differences in host dependency for kinase targets. Importantly, for gilteritinib, the amount of compound needed to achieve 90% infection inhibition, at least in part involving blockade of spike protein-mediated viral entry and at concentrations not inducing phospholipidosis (PLD), approached a clinically achievable concentration. Knockout of AXL, a target of gilteritinib and nintedanib, impaired SARS-CoV-2 variant infectivity, supporting a role for AXL in SARS-CoV-2 infection and supporting further investigation of drug-mediated AXL inhibition as a COVID-19 treatment. This study supports further evaluation of AXL-targeting kinase inhibitors as potential antiviral agents and treatments for COVID-19. Additional mechanistic studies are needed to determine underlying differences in virus response. 相似文献
133.
Barbara Biedziak Justyna Dąbrowska Anna Szponar-Żurowska Ewelina Bukowska-Olech Aleksander Jamsheer Ewa Mojs Jennifer Mulle Rafał Płoski Adrianna Mostowska 《American journal of medical genetics. Part A》2023,191(1):205-219
Many unbalanced large copy number variants reviewed in the paper are associated with syndromic orofacial clefts, including a 1.6 Mb deletion on chromosome 3q29. The current report presents a new family with this recurrent deletion identified via whole-exome sequencing and confirmed by array comparative genomic hybridization. The proband exhibited a more severe clinical phenotype than his affected mother, comprising right-sided cleft lip/alveolus and cleft palate, advanced dental caries, heart defect, hypospadias, psychomotor, and speech delay, and an intellectual disability. Data analysis from the 3q29 registry revealed that the 3q29 deletion increases the risk of clefting by nearly 30-fold. No additional rare and pathogenic nucleotide variants were identified that could explain the clefting phenotype and observed intrafamilial phenotypic heterogeneity. These data suggest that the 3q29 deletion may be the primary risk factor for clefting, with additional genomic variants located outside the coding sequences, methylation changes, or environmental exposure serving as modifiers of this risk. Additional studies, including whole-genome sequencing or methylation analyses, should be performed to identify genetic factors underlying the phenotypic variation associated with the recurrent 3q29 deletion. 相似文献
134.
Gasiorowski K Szyba K Brokos B Kołaczyńska B Jankowiak-Włodarczyk M Oszmiański J 《Cancer letters》1997,119(1):37-46
Anthocyanins belong to the flavonoid family and are ubiquitous in plants, especially in flower petals and fruit peels. We established that anthocyanins isolated from fruits of Aronia melanocarpa markedly inhibited the mutagenic activity of benzo(a)pyrene and 2-amino fluorene in the Ames test. In the Sister Chromatid Exchanges (SCEs) test with human blood-derived lymphocytes cultured in vitro, a significant decrease of SCEs frequency induced by benzo(a)pyrene was observed in the presence of anthocyanins. In the case of mitomycin C the effect of anthocyanins on SCEs frequency was smaller but still noticeable. Anthocyanins markedly inhibited the generation and release of superoxide radicals by human granulocytes. The results suggest that the antimutagenic influence of anthocyanins is exerted mainly by their free-radicals scavenging action as well as by the inhibition of enzymes activating promutagens and converting mutagens to the DNA-reacting derivatives. These preliminary data seem to be important in the aspect of a possible antimutagenic and anticarcinogenic potency of anthocyanins commonly present in fruits and vegetables. 相似文献
135.
Jastrzebska M Torbus-Lisiecka B Pieczul-Mróz J Chełstowski K Naruszewicz M 《Materia medica Polona. Polish journal of medicine and pharmacy》1997,29(1-4):3-7
The concentrations of fibrinogen (Fb) and the activities of factor VII (F VIIC) and antithrombin III (AT III) both in men less than 55 years old with a history of myocardial infarction (MI) and with normolipemia (MI-NLP) or hyperlipoproteinemia (MI-HLP) and in their sons have been measured. A significantly higher levels of Fb were found in both MI groups. Significantly higher levels of F VIIC and AT III were found only in the MI-NLP group. No lipid or haemostatic disorders were noted in sons. Furthermore, a positive correlation between the level of F VIIC and triglycerides (TG) or total cholesterol (TCh) in the patients and sons was revealed. A positive correlation was found between: (a) Fb levels in MI-HLP patients and in their sons; (b) TG levels in MI-HLP patients and in their sons; and (c) AT III activity in MI patients and in their sons. Fibrinogen appears to be associated with ischemic heart disease more closely than factor VII, the latter being strongly linked with hypertriglyceridemia. Elevated activities of AT III may reflect the haemostatic response to the prothrombotic state in IHD on the one hand whereas they may contribute to the development of IHD on the other. 相似文献
136.
Comparison of non-invasive approaches to red marrow dosimetry for radiolabelled monoclonal antibodies 总被引:1,自引:0,他引:1
Marian A. B. D. Plaizier Jan C. Roos Gerrit J. J. Teule Erik B. van Dieren Wim den Hollander Hidde J. Haisma Robert L. DeJager Arthur van Lingen 《European journal of nuclear medicine and molecular imaging》1994,21(3):216-222
Red marrow is usually the dose-limiting organ during radioimmunotherapy. Several non-invasive approaches to calculate the red marrow dose have been proposed. We compared four approaches to analyse the differences in calculated red marrow doses. The data were obtained from immunoscintigraphy of two antibodies with different red marrow kinetics [iodine-131-16.88 IgM and indium- 111-OV-TL-3 F(ab)2]. The approaches are based on, respectively, homogeneously distributed activity in the body, a red marrow-blood activity concentration ratio of 0.3, scintigraphic quantification, and a combination of the second and third approaches. This fourth approach may be more adequate because of its independence from the chosen antibody. In addition, the influence of activity accumulation in liver, kidneys or cancellous bone on red marrow dose was studied. The calculated red marrow dose varied between 0.14 and 0.42 mGy/MBq for 111 In-OV TL-3 and between 0.13 and 0.68 mGy/MBq for 131I-16-88. If the radiopharmaceutical shows high affinity for cancellous bone or another organ situated near the red marrow, the activity in these organs must be included in dose calculations. This study shows a large variation in calculated red marrow dose and selection of the definitive non-invasive approach awaits validation.
Correspondence to: M.A.B.D. Plaizier 相似文献
137.
Marian Degardin Jean Pierre Armand Bernard Chevallier Paul Cappelaere Marie-Ange Lentz Marc David Henri Roché 《Investigational new drugs》1995,13(3):253-255
Summary We evaluated the efficacy and tolerability of lobaplatin, a new platinum compound, given at the dose of 50 mg/m2 by i.v. bolus every 4 weeks, in 49 patients with advanced and/or metastatic squamous cell carcinoma of the head and neck (SCCHN). One complete and 2 partial responses were observed in 43 eligible patients for an overall response rate of 7% (95% confidence interval: 1–19%). The duration of responses was 11, 16 and 32 weeks. Toxicities of WHO grade 3 were hematologic: thrombocytopenia in 26%, granulocytopenia in 12% and anemia in 12% of patients. There was no therapy-related death. Nausea/vomiting, diarrhoea and paresthesia were mild and rare. In conclusion, lobaplatin was well tolerated, but its efficacy in advanced SCCHN at the presented dose and schedule, was marginal. 相似文献
138.
McCallion Orla N. M. Taylor Kevin M. G. Thomas Marian Taylor Anthony J. 《Pharmaceutical research》1995,12(11):1682-1688
Purpose. Empirical formulae relate the mean size of primary droplets from jet and ultrasonic nebulizers to a fluid's physicochemical properties. Although the size selective filtering effects of baffling and evaporation may modify the secondary aerosol produced, this research sought to evaluate whether viscosity and surface tension of nebulized fluids influenced the aerosol's size and output characteristics.
Methods. Fluid systems of different surface tension and viscosity (glycerol and propylene glycol solutions [10–50% (v/v)] and a range of silicone fluids [200/0.65 cs– l00cs]) were nebulized in three jet and two ultrasonic nebulizers. Secondary aerosol characteristics were measured with a Malvern 2600C laser diffraction sizer and the nebulization times, residual volumes and percentage outputs were determined.
Results. While the droplet size appeared to be inversely proportional to viscosity for jet nebulizers, it was directly proportional to viscosity for ultrasonic nebulizers. Although fluid systems with lower surface tensions generally produced slightly smaller MMDs, the relationship between surface tension and droplet size was complex. The more viscous fluids required longer nebulization times and were associated with increased residual amounts (lower outputs). The ultrasonic nebulizers did not effectively, and were on occasion unable to, nebulize the more viscous fluids.
Conclusions. It follows that there are cut-off values for viscosity and/or surface tension above or below which ultrasonic devices fail to operate. Moreover, jet nebulizers generated an aerosol with an optimum respirable output from median-viscosity fluids. 相似文献
139.
Szamatowicz Marian Grochowski Dariusz 《Journal of assisted reproduction and genetics》1994,11(4):182-184
Journal of Assisted Reproduction and Genetics - 相似文献
140.
Mercury concentration was determined in the caps and stalks of nine species of edible mushrooms collected at the area of Wieluńska Upland in district of Czestochowa in 1995-96. The mushroom species examined were such as: yellow-cracking bolete Xerocomus subtomentosus, brown birch scaber stalk Leccinum scabrum, slippery Jack Suillus luteus, larch bolete Suillus grevillei, gray knight-cap Tricholoma terreum, parasol mushroom Macrolepiota procera, horse mushroom Agaricus arvensis, fennel funnel cap Clitocybe odora, fairy-ring mushroom Marasmius oreades and tacky green brittle gills Russula aereuginea. The method of mercury measurement was cold-vapour atomic absorption spectroscopy (CV-AAS) after wet digestion of the samples with concentrated nitric acid in a whole glass system. The parasol mushroom and horse mushroom showed a highest mercury concentrations and contained, respectively, 4500 +/- 1700 and 4400 +/- 2400 ng/g dry wt in caps, and 2800 +/- 1300 and 2800 +/- 2100 ng/g dry wt in stalks. In the case of fennel funnel cap and fairy-ring mushroom the mean total mercury concentrations in caps was above 500 ng/g dry wt, and for other species were between 150 +/- 50 and 500 +/- 230 ng/g dry wt. The stalks of the mushroom species examined in all cases showed lower contamination with mercury than caps. The mean total mercury concentrations noted in caps and stalks of mushrooms examined were usually higher than was reported till now in the same species elsewhere in Poland, while a maximum values found in an individual fruiting bodies are within the range of the concentrations noted in specimens collected from an unpolluted areas. 相似文献