Ornythonym component and phraseological meaning

The paper represents the results of the research into phraseological and paremiological units with ornythonym component. According to the level of complexity of their semantic structure phraseological units are divided into 3 groups. Detecting the status of ornythonym components one should refer to this classification, because these two phenomena, i.e. the level of semantic complexity of the phraseological unit semantic structure and status of its component parts, are closely related to each other. Within the framework of this research studying symbolic meanings different birds are endowed in the English linguistic culture is given appropriate attention too, because most ornythonym components of phraseological units realize their symbolic meaning. Appearance, behavior, relations with other birds and different other characteristics of birds also serve as basis for metaphoric meaning realized in phraseology

Клозапин: механизмы токсичности и побочных эффектов

Clozapine is an atypical antipsychotic agent with a confirmed effectiveness which is widely used in the clinical practice. However, its administration is associated with a high risk of serious adverse events. Life-threatening conditions related to administration of clozapine may be a result of idiosyncrasy, acute poisoning resulting from unintentional overdose of the prescribed dug, suicidal behavior, and criminal actions. The review presents current data on the mechanism of therapeutic and toxic effect of clozapine. It describes the effect of clozapine on cell receptors and ultracellular structures. It dwells on the contribution of major and intermediate metabolites of this medicinal agent to the development of toxic effects.Клозапин – атипичное антипсихотическое средство с доказанной эффективностью, которое широко используется в клинической практике. Однако, его применение сопряжено с высоким риском развития серьезных побочных эффектов. Угрожающие жизни состояния при приеме клозапина могут быть следствием идиосинкразии, острого отравления в результате непреднамеренной передозировки назначенного препарата, суицидального поведения, криминальных действий. В обзоре представили современные данные о механизмах терапевтического и токсического действия клозапина. Описали воздействие клозапина на клеточные рецепторы и ультраклеточные структуры. Рассмотрели роль основных и промежуточных метаболитов данного лекарственного средства в развитии токсических эффектов

Морфологические изменения головного мозга при острых комбинированных отравлениях азалептином и этиловым алкоголем

Objective: to study brain morphological changes in acute combined intoxication with asaleptin and ethyl alcohol. Material and methods. The cerebral cortex (the parietal region) was histologically examined in 26 patients (19 men and 7 women, 22 to 63 years old) who had died of acute (first 24hour) combined intoxication with asaleptin and ethyl alcohol. Blood ethyl alcohol concentrations varied from 1.4 to 4.1%o. Brain pieces were fixed in 10% formalin and embedded in paraffin. Histologic specimens were stained with hematoxilin and eosin by Nissl and analyzed using the Olympus BX 41 microscope. Morphological changes in the nerve cells were assessed according to existing classification and protocols («Histopathology of the central nervous system», Meditsina Publishers, Moscow, 1969). Results. In cases of death from acute combined intoxication with asaleptin and ethyl alcohol morphological patterns of acute brain neuronal damages were detected. They included (a) nonspecific reversible and irreversible neuronal damages and (b) circulatory disorders comprising of vascular plethora in the microcircula-tory bed and developed perivascular and pericellulary edema. Conclusion. Detection of brain neuronal damage patterns in acute combined intoxications with asaleptin and ethyl alcohol might aid in justification of an immediate death cause as a supplement to forensic chemical analysis. Key words: brain morphological changes, intoxications, asaleptin, ethyl alcohol.Цель исследования — изучение морфологических изменений головного мозга при острых комбинированных отравлениях азалептином и этиловым алкоголем. Материал и методы. Гистологическое исследование коры головного мозга (теменная область) проведено у 26 умерших людей в результате острого (в течении первых суток) комбинированного отравления азалептином и этиловым алкоголем. Из них мужчин 19, женщин 7. Возраст умерших составил от 22 до 63 лет. Концентрация этилового спирта в крови составляла от 1,4%о, до 4,1%о. Кусочки мозга фиксировали в 10% формалине и заливали в парафин. Гистологические срезы окрашивали гематоксилином и эозином и по Нисслю с последующим анализом морфологических изменений с помощью микроскопа Olympus ВХ 41. Морфологические изменения нервных клеток оценивали в соответствии с существующей классификацией («Гистопатология центральной нервной системы». «Медицина». М., 1969 г.). Результаты. В случаях смерти от острого комбинированного отравления азалептином и этиловым алкоголем выявляются признаки острых повреждений нейронов головного мозга. Они характеризуются неспецифическими обратимыми и необратимыми повреждениями нейронов и нарушениями кровообращения: полнокровием сосудов микроциркуляторного русла, развитием периваскулярного и перицеллюлярного отека. Заключение. Выявление признаков повреждения нейронов головного мозга при острых комбинированных отравлениях азалептином и этиловым алкоголем позволяет использовать эти данные, наряду с результатами судебно-химического анализа, в обосновании непосредственной причины смерти

Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial

Combination treatment with pegylated-interferon-alpha (PEG IFN-Α) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-Α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2 -2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 -2256 carried the A variant compared with 68 of 120 (57%) nonresponders ( P = 0.006). Conclusion: Genetic polymorphisms in the interferon-Α pathway may affect responses to antiviral therapy of chronic hepatitis C. (H EPATOLOGY 2009.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63061/1/22877_ftp.pd

Changes in the parameters of free radical fluid oxidation in young people with chronic gastroduodenitis, depending on the duration of the underlying disease

The article presents the results of chemiluminescence of oral fluid in 155 patients of young age (from 19 to 25 years) with chronic gastroduodenitis. Depending on the duration of chronic gastroduodenitis, changes in the luminous sum of radiation and its maximum value in these patients were revealed. The relationship between the chemiluminescence of the oral fluid and the degree of inflammation of the gastroduodenal zone was determined.В статье приведены результаты хемилюминесценции ротовой жидкости 155 пациентов молодого возраста (от 19 до 25 лет) с хроническим гастродуоденитом. В зависимости от длительности хронического гастродуоденита выявлена изменения в показателях светосуммы излучения и ее максимального значения у данных пациентов. определена взаимосвязь между хемилюминесценцией ротовой жидкости и степенью воспаления гастродуоденальной зоны

An Sp1/Sp3 Binding Polymorphism Confers Methylation Protection

Hundreds of genes show aberrant DNA hypermethylation in cancer, yet little is known about the causes of this hypermethylation. We identified RIL as a frequent methylation target in cancer. In search for factors that influence RIL hypermethylation, we found a 12-bp polymorphic sequence around its transcription start site that creates a long allele. Pyrosequencing of homozygous tumors revealed a 2.1-fold higher methylation for the short alleles (P<0.001). Bisulfite sequencing of cancers heterozygous for RIL showed that the short alleles are 3.1-fold more methylated than the long (P<0.001). The comparison of expression levels between unmethylated long and short EBV-transformed cell lines showed no difference in expression in vivo. Electrophorectic mobility shift assay showed that the inserted region of the long allele binds Sp1 and Sp3 transcription factors, a binding that is absent in the short allele. Transient transfection of RIL allele-specific transgenes showed no effects of the additional Sp1 site on transcription early on. However, stable transfection of methylation-seeded constructs showed gradually decreasing transcription levels from the short allele with eventual spreading of de novo methylation. In contrast, the long allele showed stable levels of expression over time as measured by luciferase and ∼2–3-fold lower levels of methylation by bisulfite sequencing (P<0.001), suggesting that the polymorphic Sp1 site protects against time-dependent silencing. Our finding demonstrates that, in some genes, hypermethylation in cancer is dictated by protein-DNA interactions at the promoters and provides a novel mechanism by which genetic polymorphisms can influence an epigenetic state

Structural and regulatory diversity shape HLA-C protein expression levels

Expression of HLA-C varies widely across individuals in an allele-specific manner. This variation in expression can influence efficacy of the immune response, as shown for infectious and autoimmune diseases. MicroRNA binding partially influences differential HLA-C expression, but the additional contributing factors have remained undetermined. Here we use functional and structural analyses to demonstrate that HLA-C expression is modulated not just at the RNA level, but also at the protein level. Specifically, we show that variation in exons 2 and 3, which encode the α1/α2 domains, drives differential expression of HLA-C allomorphs at the cell surface by influencing the structure of the peptide-binding cleft and the diversity of peptides bound by the HLA-C molecules. Together with a phylogenetic analysis, these results highlight the diversity and long-term balancing selection of regulatory factors that modulate HLA-C expression

Characterization of killer immunoglobulin-like receptor genetics and comprehensive genotyping by pyrosequencing in rhesus macaques

<p>Abstract</p> <p>Background</p> <p>Human killer immunoglobulin-like receptors (KIRs) play a critical role in governing the immune response to neoplastic and infectious disease. Rhesus macaques serve as important animal models for many human diseases in which KIRs are implicated; however, the study of KIR activity in this model is hindered by incomplete characterization of <it>KIR </it>genetics.</p> <p>Results</p> <p>Here we present a characterization of <it>KIR </it>genetics in rhesus macaques (<it>Macaca mulatta)</it>. We conducted a survey of <it>KIRs </it>in this species, identifying 47 novel full-length <it>KIR </it>sequences. Using this expanded sequence library to build upon previous work, we present evidence supporting the existence of 22 <it>Mamu-KIR </it>genes, providing a framework within which to describe macaque <it>KIRs</it>. We also developed a novel pyrosequencing-based technique for <it>KIR </it>genotyping. This method provides both comprehensive <it>KIR </it>genotype and frequency estimates of transcript level, with implications for the study of <it>KIRs </it>in all species.</p> <p>Conclusions</p> <p>The results of this study significantly improve our understanding of macaque <it>KIR </it>genetic organization and diversity, with implications for the study of many human diseases that use macaques as a model. The ability to obtain comprehensive KIR genotypes is of basic importance for the study of KIRs, and can easily be adapted to other species. Together these findings both advance the field of macaque KIRs and facilitate future research into the role of KIRs in human disease.</p

Genetic Epidemiology of Glioblastoma Multiforme: Confirmatory and New Findings from Analyses of Human Leukocyte Antigen Alleles and Motifs

Human leukocyte antigen (HLA) class I genes mediate cytotoxic T-lymphocyte responses and natural killer cell function. In a previous study, several HLA-B and HLA-C alleles and haplotypes were positively or negatively associated with the occurrence and prognosis of glioblastoma multiforme (GBM).As an extension of the Upper Midwest Health Study, we have performed HLA genotyping for 149 GBM patients and 149 healthy control subjects from a non-metropolitan population consisting almost exclusively of European Americans. Conditional logistic regression models did not reproduce the association of HLA-B*07 or the B*07-Cw*07 haplotype with GBM. Nonetheless, HLA-A*32, which has previously been shown to predispose GBM patients to a favorable prognosis, was negatively associated with occurrence of GBM (odds ratio=0.41, p=0.04 by univariate analysis). Other alleles (A*29, A*30, A*31 and A*33) within the A19 serology group to which A*32 belongs showed inconsistent trends. Sequencing-based HLA-A genotyping established that A*3201 was the single A*32 allele underlying the observed association. Additional evaluation of HLA-A promoter and exon 1 sequences did not detect any unexpected single nucleotide polymorphisms that could suggest differential allelic expression. Further analyses restricted to female GBM cases and controls revealed a second association with a specific HLA-B sequence motif corresponding to Bw4-80Ile (odds ratio=2.71, p=0.02).HLA-A allelic product encoded by A*3201 is likely to be functionally important to GBM. The novel, sex-specific association will require further confirmation in other representative study populations