Дифференциальная диагностика острой и хронической тромбоэмболии легочной артерии по данным МСКТ

Introduction. One of the important problems of medical imaging is the differential diagnosis of patients with acute and chronic pulmonary embolism. The widely used minimally invasive technique of multispiral computed tomography with intravenous bolus contrast enhancement can serve to solve this problem, in particular, to assess the state of the parenchyma and vascular structures of the lungs.The purpose. To assess the state of bronchial arteries and parenchymal changes in the lungs in pulmonary thromboembolism based on the results of multispiral computed tomography and their role in the more precise diagnosis of this disease.Materials and methods. An analysis of CT-angiopulmonography of 600 patients with suspected PE was performed. 87 patients with confirmed pulmonary thromboembolism were selected and divided into groups according to the final diagnosis: group 1 — acute pulmonary embolism, group 2 — chronic pulmonary embolism. CT data were analyzed for the presence of pathologically changed bronchial arteries, as well as lung's parenchymal changes (including mosaic perfusion, fibrotic changes, bronchial dilatation with or without wall thickening).Results. Bronchial arteries were assessed in patients with acute and chronic pulmonary embolism and the diagnostic value of the detected changes was determined. Acute pulmonary embolism does not lead to such dilatation of the bronchial arteries as chronic pulmonary embolism. In diagnostically unclear cases, secondary parenchymal signs visible on CT (mosaic perfusion and dilated bronchi without wall thickening) can be useful in the differential diagnosis of acute and chronic pulmonary embolism.Conclusions. Most patients with chronic pulmonary embolism demonstrated dilated bronchial arteries, in contrast to patients with acute pulmonary embolism. Lung's parenchymal changes (a mosaic perfusion pattern and bronchial dilation without wall thickening) were more common in patients with chronic pulmonary embolism. These CT-signs can help differentiate acute from chronic pulmonary embolism in unclear clinical situations.Введение. Одной из важных проблем медицинской визуализации является дифференциальная диагностика пациентов с острой и хронической тромбоэмболией легочной артерии. Решению этой задачи, в частности оценке состояния паренхимы и сосудистых структур легких, может служить широко применяемая малоинвазивная методика мультиспиральной компьютерной томографии с внутривенным болюсным контрастированием.Цель: оценить состояние бронхиальных артерий и паренхиматозные изменения в легких при тромбоэмболии легочных артерий по результатам мультиспиральной компьютерной томографии и их роль в уточненной диагностике данного заболевания.Материалы и методы. Выполнен анализ данных МСКТ-ангиопульмонографии 600 пациентов с подозрением на тромбоэмболию легочной артерии. 87 пациентов с подтвержденной тромбоэмболией легочной артерии были отобраны и разделены на группы в соответствии с окончательным диагнозом: 1-я группа — острая ТЭЛА, 2-я группа — хроническая ТЭЛА. МСКТ-данные были проанализированы на предмет наличия измененных бронхиальных артерий, а также паренхиматозных изменений (таких как «мозаичная перфузия», очаги или участки уплотнения паренхимы легких, расширение бронхов с утолщением стенок и без).Результаты. Произведена оценка состояния бронхиальных артерий у пациентов с острой и хронической ТЭЛА и определена диагностическая ценность выявленных изменений. Установлено, что острая ТЭЛА не приводит к такому расширению бронхиальных артерий, как хроническая ТЭЛА. В диагностически неясных случаях вторичные паренхиматозные признаки, выявляемые при МСКТ (симптом мозаичной перфузии и расширенные бронхи без утолщения стенок), могут быть полезными в дифференциальной диагностике острой и хронической тромбоэмболии легочной артерии.Заключение. У большинства пациентов с хронической ТЭЛА выявлялись расширенные бронхиальные артерии, в отличие от пациентов с острой ТЭЛА. Паренхиматозные изменения в легких, которые были более характерны для пациентов с хронической ТЭЛА, включали в себя: паттерн «мозаичной перфузии» и расширение бронхов без утолщения стенок. Вышеперечисленные МСКТ-признаки могут помочь дифференцировать острую от хронической ТЭЛА в неясных клинических ситуациях

The Caenorhabditis elegans Gene mfap-1 Encodes a Nuclear Protein That Affects Alternative Splicing

RNA splicing is a major regulatory mechanism for controlling eukaryotic gene expression. By generating various splice isoforms from a single pre–mRNA, alternative splicing plays a key role in promoting the evolving complexity of metazoans. Numerous splicing factors have been identified. However, the in vivo functions of many splicing factors remain to be understood. In vivo studies are essential for understanding the molecular mechanisms of RNA splicing and the biology of numerous RNA splicing-related diseases. We previously isolated a Caenorhabditis elegans mutant defective in an essential gene from a genetic screen for suppressors of the rubberband Unc phenotype of unc-93(e1500) animals. This mutant contains missense mutations in two adjacent codons of the C. elegans microfibrillar-associated protein 1 gene mfap-1. mfap-1(n4564 n5214) suppresses the Unc phenotypes of different rubberband Unc mutants in a pattern similar to that of mutations in the splicing factor genes uaf-1 (the C. elegans U2AF large subunit gene) and sfa-1 (the C. elegans SF1/BBP gene). We used the endogenous gene tos-1 as a reporter for splicing and detected increased intron 1 retention and exon 3 skipping of tos-1 transcripts in mfap-1(n4564 n5214) animals. Using a yeast two-hybrid screen, we isolated splicing factors as potential MFAP-1 interactors. Our studies indicate that C. elegans mfap-1 encodes a splicing factor that can affect alternative splicing.National Natural Science Foundation (China) (Grant 30971639)United States. National Institutes of Health (Grant GM24663

The CUGBP2 Splicing Factor Regulates an Ensemble of Branchpoints from Perimeter Binding Sites with Implications for Autoregulation

Alternative pre-mRNA splicing adjusts the transcriptional output of the genome by generating related mRNAs from a single primary transcript, thereby expanding protein diversity. A fundamental unanswered question is how splicing factors achieve specificity in the selection of target substrates despite the recognition of information-poor sequence motifs. The CUGBP2 splicing regulator plays a key role in the brain region-specific silencing of the NI exon of the NMDA R1 receptor. However, the sequence motifs utilized by this factor for specific target exon selection and its role in splicing silencing are not understood. Here, we use chemical modification footprinting to map the contact sites of CUGBP2 to GU-rich motifs closely positioned at the boundaries of the branch sites of the NI exon, and we demonstrate a mechanistic role for this specific arrangement of motifs for the regulation of branchpoint formation. General support for a branch site-perimeter–binding model is indicated by the identification of a group of novel target exons with a similar configuration of motifs that are silenced by CUGBP2. These results reveal an autoregulatory role for CUGBP2 as indicated by its direct interaction with functionally significant RNA motifs surrounding the branch sites upstream of exon 6 of the CUGBP2 transcript itself. The perimeter-binding model explains how CUGBP2 can effectively embrace the branch site region to achieve the specificity needed for the selection of exon targets and the fine-tuning of alternative splicing patterns

Инвазивный аспергиллёз лёгких у больных COVID-19

A retrospective analysis of the medical data of 12 patients with COVID-19 was performed. For the diagnosis of invasive aspergillosis the international criteria ECMM/ISHAM 2020 were used. We analyzed the scientific literature data on the diagnosis and treatment of invasive aspergillosis in patients with COVID-19.Results. Among the 12 examined patients with a severe course of COVID-19, invasive aspergillosis was diagnosed in 5 patients. Four patients (80%) were treated in the ICU. Steroids or interleukin-6 inhibitors were used in 80% patients. Severe lymphocytopenia was in 80% patients, neutropenia 20%. A fever refractory to antibiotic therapy was noted in 80% patients, an increase in respiratory failure – 60%, acute respiratory distress syndrome – 60%. All patients showed negative dynamics of changes in the chest CT scan. Invasive aspergillosis was confirmed with a positive test for galactomannan in bronchoalveolar lavage and / or serum in 100% of cases. All patients received antifungal therapy with voriconazole and/or caspofungin. The overall 12-week survival rate was 80%.Conclusion. In ICU patients with severe COVID-19 and progressive pulmonary symptoms invasive aspergillosis should be excluded. Examination of substrates from the lower respiratory tract (BAL, tracheal aspirate, or nonbronchoscopic lavage) is necessary. Laboratory examination should include microscopy, culture and test for galactomannan. Voriconazole and isavuconazole are drugs of choice for the treatment of invasive aspergillosis in patients with COVID-19.Провели ретроспективный анализ медицинских данных 12 больных COVID-19. Для диагностики инвазивного аспергиллеза использовали международные критерии ECMM/ISHAM, 2020. Проанализировали данные научной литературы, посвященной диагностике и терапии инвазивного аспергиллеза у больных COVID-19.Результаты. Из 12 обследованных пациентов с тяжелым течением COVID-19 инвазивный аспергиллез был диагностирован у 5 больных, из них 4 пациента (80%) находились на лечении в ОРИТ. Глюкокортикостероиды или ингибиторы интерлейкина-6 применяли у 80% пациентов. Выраженная лимфоцитопения была у 80% больных, нейтропения – у 20%. Рефрактерную к антибиотикотерапии лихорадку отмечали у 80% пациентов, нарастание дыхательной недостаточности – у 60%, острый респираторный дистресс-синдром – у 60%. У всех пациентов выявляли отрицательную динамику изменений в легких при компьютерной томографии. Инвазивный аспергиллез был подтвержден положительным результатом теста на галактоманнан в бронхоальвеолярном лаваже и/или сыворотке крови в 100% случаев. Все больные получали антимикотическую терапию вориконазолом и/или каспофунгином. Общая 12-недельная выживаемость составила 80%.Заключение. У пациентов в ОРИТ с тяжелым течением COVID-19 и прогрессирующими симптомами поражения легких следует исключить инвазивный аспергиллёз. Необходимо исследование материала из нижних отделов респираторного тракта (БАЛ, трахеальный аспират или небронхоскопический лаваж), которое должно включать микроскопию, посев и тест на галактоманнан. Вориконазол и изавуконазол – препараты выбора для лечения инвазивного аспергиллеза у больных COVID-19

H2B ubiquitylation is part of chromatin architecture that marks exon-intron structure in budding yeast

<p>Abstract</p> <p>Background</p> <p>The packaging of DNA into chromatin regulates transcription from initiation through 3' end processing. One aspect of transcription in which chromatin plays a poorly understood role is the co-transcriptional splicing of pre-mRNA.</p> <p>Results</p> <p>Here we provide evidence that H2B monoubiquitylation (H2BK123ub1) marks introns in <it>Saccharomyces cerevisiae</it>. A genome-wide map of H2BK123ub1 in this organism reveals that this modification is enriched in coding regions and that its levels peak at the transcribed regions of two characteristic subgroups of genes. First, long genes are more likely to have higher levels of H2BK123ub1, correlating with the postulated role of this modification in preventing cryptic transcription initiation in ORFs. Second, genes that are highly transcribed also have high levels of H2BK123ub1, including the ribosomal protein genes, which comprise the majority of intron-containing genes in yeast. H2BK123ub1 is also a feature of introns in the yeast genome, and the disruption of this modification alters the intragenic distribution of H3 trimethylation on lysine 36 (H3K36me3), which functionally correlates with alternative RNA splicing in humans. In addition, the deletion of genes encoding the U2 snRNP subunits, Lea1 or Msl1, in combination with an <it>htb-K123R </it>mutation, leads to synthetic lethality.</p> <p>Conclusion</p> <p>These data suggest that H2BK123ub1 facilitates cross talk between chromatin and pre-mRNA splicing by modulating the distribution of intronic and exonic histone modifications.</p

Genetic depletion indicates a late role for U5 snRNP during in vitro spliceosome assembly.

The pre-mRNA splicing pathway is highly conserved from yeast (S. cerevisiae) to mammals. Of the four snRNPs involved in splicing three (U1, U2 and U4/U6) have been shown to be essential for in vitro splicing. To examine the remaining snRNP, we utilized our previously described genetic procedures (Seraphin and Rosbash, 1989) to prepare yeast extracts depleted of U5 snRNP. The results show that U5 snRNP is necessary for both steps of pre- mRNA splicing and for proper spliceosome assembly, i.e., addition of the U4/U5/U6 triple snRNP. The prior steps of U1 and U2 snRNP addition occur normally in the absence of U5 snRNP