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The auxin-inducible degron (AID) system degrades target proteins rapidly in a controllable manner. Although this is a highly versatile technique for studying protein functionality, protein degradation with spatiotemporal resolution is not currently possible. Herein we describe a photoswitchable AID using a light-active auxin derivative for reversible and site-specific protein degradation with temporal resolution.
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Degrones , Ácidos Indolacéticos , Proteolisis , Degrones/efectos de la radiación , Ácidos Indolacéticos/química , Ácidos Indolacéticos/efectos de la radiación , Luz , Procesos Fotoquímicos , Proteolisis/efectos de la radiaciónRESUMEN
Mosaic valve shows higher pressure gradient after aortic valve replacement compared to other same size labeled prostheses in postoperative echocardiogram. The purpose of this study was to evaluate the mid-term echocardiogram findings and long-term clinical outcomes of patients receiving a 19 mm Mosaic. Forty-six aortic stenosis patients receiving 19 mm Mosaic and 112 patients receiving either 19 mm Magna or Inspiris, who underwent mid-term follow-up echocardiogram were included in the study. Mid-term hemodynamic measurements evaluated by trans-thoracic echocardiogram and long-term outcomes were compared. Patients receiving Mosaic were significantly older (Mosaic: 76 ± 5.1 years vs. Magna/Inspiris: 74 ± 5.5 years, p = 0.046) and had smaller body surface area (Mosaic: 1.40 ± 0.114m2 vs. Magna/Inspiris: 1.48 ± 0.143m2, p < 0.001). There were no significant differences in comorbidities and medications. Post-operative echocardiogram performed at 1 week after the surgery showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 38 ± 13.5 mmHg vs. Magna/Inspiris: 31 ± 10.7 mmHg, p = 0.002). Furthermore, mid-term echocardiogram follow-up performed at median duration of 53 ± 14.9 months after the surgery continuously showed higher maximum pressure gradient in patients receiving Mosaic (Mosaic: 45 ± 15.6 mmHg vs. Magna/Inspiris: 32 ± 13.0 mmHg, p < 0.001). However, there were no significant difference in changes in left ventricular mass from baseline in both groups. Kaplan-Meyer curve also showed no difference in long-term mortality and major adverse cardiac and cerebrovascular event between the two groups. Although the pressure gradient across the valve evaluated by echocardiogram was higher in 19 mm Mosaic compared to 19 mm Magna/Inspiris, there were no significant differences in left ventricular remodeling and long-term outcomes between the two groups.
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Estenosis de la Válvula Aórtica , Bioprótesis , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Humanos , Remodelación Ventricular , Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Hemodinámica , Resultado del Tratamiento , Diseño de PrótesisRESUMEN
PURPOSE: To investigate the morphological characteristics and operative outcomes of acute type A aortic dissection (ATAAD) in patients with aortic arch variants. METHODS: Of 616 patients with ATAAD, 97 (15.7%) had aortic arch variants, including bovine aortic arch (BAA, n = 66), isolated left vertebral artery (ILVA, n = 25), and aberrant subclavian artery (ASA, n = 6). The characteristics and outcomes were compared between the normal branching group (control, n = 519) and the total/individual arch variant groups. RESULTS: Compared to the control group, arch entry was more prevalent in the BAA (18.5% vs. 31.8%) and ILVA groups (44%) (both, P < 0.05), and right common carotid arterial occlusion was less common in the arch variant group (6.7% vs. 0%, P = 0.017). The in-hospital mortality (9.2% vs. 9.3%), new-onset stroke (7.3% vs. 7.2%), and 5-year survival (81.7% vs. 78.8%) did not differ markedly between the control and arch variant groups. Arch repair was performed in 28.9% (28/97) of the arch variant group using 3-4 vessel antegrade cerebral perfusion, with 3.8% in-hospital mortality and a 15.4% stroke rate, which were comparable to those of the control group. CONCLUSIONS: Aortic arch variants may influence tear location and involvement of the supra-arch vessels but may not affect postoperative outcomes.
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Tetraploidy is a hallmark of broad cancer types, but it remains largely unknown which aspects of cellular processes are influenced by tetraploidization in human cells. Here, we found that tetraploid HCT116 cells manifested severe cell shape instability during cytokinesis, unlike their diploid counterparts. The cell shape instability accompanied the formation of protrusive deformation at the cell poles, indicating ectopic contractile activity of the cell cortex. While cytokinesis regulators such as RhoA and anillin correctly accumulated at the equatorial cortex, myosin II was over-accumulated at the cell poles, specifically in tetraploid cells. Suppression of myosin II activity by Y27632 treatment restored smooth cell shape in tetraploids during cytokinesis, indicating dysregulation of myosin II as a primary cause of the cell shape instability in the tetraploid state. Our results demonstrate a new aspect of the dynamic cellular process profoundly affected by tetraploidization in human cells, which provides a clue to molecular mechanisms of tetraploidy-driven pathogenic processes.
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Citocinesis , Tetraploidía , Humanos , Forma de la Célula , Células HCT116 , Proteínas del CitoesqueletoRESUMEN
The development of a dismantlable adhesion technology that allows switching between bonding and debonding states using external stimuli is important for realizing renewable and sustainable material cycles. Controlling the adhesion interface is an effective approach to manipulate the adhesion strength; however, research on dismantlable systems focusing on the interface has not been proceeded. Recently, we demonstrated a novel dismantlable system based on a stimuli-responsive molecular layer comprising cleavable anthracene dimers, which strengthen the initial adhesive force by forming chemical bonds between the substrate and adhesive and can be dismantled when required via stimulation-induced bond breaking. Here, we evaluate the use of the anthracene-based molecular layer with different components for verifying its versatility in the adhesive/dismantling system. The formation of the cleavable molecular layer by the stacking of relevant molecules enabled its usage with two types of adhesives, an epoxy adhesive and a silane-modified polymer adhesive. The initial adhesive strengths were improved in both types of molecular layers by creating chemical bonds at the adhesion interfaces. Light irradiation or heating stimuli for 1 min reduced the peel strength by up to 65%, and dismantling occurred in the cleavable photodimer layer. This study expands the versatile applicability of the molecular layer-based dismantling system.
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We aimed to clarify the effect of nafamostat mesilate (nafamostat) on intestinal mucositis as well as the potentiation of intestinal 5-hydroxytryptamine (5-HT) dynamics induced by methotrexate, an anti-cancer drug, in rats. Rats received intraperitoneal methotrexate at 12.5 mg/kg/day for 4 days. In addition, 1, 3, or 10 mg/kg/day of nafamostat was given subcutaneously for 4 days. Ninety-six hours after the first administration of methotrexate, jejunal tissues were collected for analysis. The results showed that 1 mg/kg, but not 3 or 10 mg/kg, of nafamostat significantly ameliorated the methotrexate-induced body weight loss. Moreover, 1 mg/kg of nafamostat significantly improved methotrexate-induced mucositis, including villus atrophy. Nafamostat (1 mg/kg) significantly inhibited the methotrexate-induced mRNA expression of pro-inflammatory cytokines and cyclooxygenase-2, as well as methotrexate-induced 5-HT content and tryptophan hydroxylase (TPH) activity. In addition, it tended to inhibit the number of anti-TPH antibody-positive cells and significantly inhibited the number of anti-substance P antibody-positive cells. These findings suggest that low-dose nafamostat ameliorates tissue injury and 5-HT and substance P synthesis in methotrexate-induced mucositis. Nafamostat may be a novel therapeutic strategy for the prevention and treatment of mucositis as well as 5-HT- and/or substance P-related adverse effects in cancer chemotherapy.
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Metotrexato , Mucositis , Ratas , Animales , Metotrexato/efectos adversos , Serotonina/metabolismo , Mucositis/inducido químicamente , Intestinos , Guanidinas/farmacologíaRESUMEN
Retroviral infection requires reverse transcription, and the reverse transcriptase (RT) uses cellular tRNA as its primer. In humans, the TRMT6-TRMT61A methyltransferase complex incorporates N1-methyladenosine modification at tRNA position 58 (m1A58); however, the role of m1A58 as an RT-stop site during retroviral infection has remained questionable. Here, we constructed TRMT6 mutant cells to determine the roles of m1A in HIV-1 infection. We confirmed that tRNA3Lys m1A58 was required for in vitro plus-strand strong-stop by RT. Accordingly, infectivity of VSV-G pseudotyped HIV-1 decreased when the virus contained m1A58-deficient tRNA3Lys instead of m1A58-modified tRNA3Lys. In TRMT6 mutant cells, the global protein synthesis rate was equivalent to that of wild-type cells. However, unexpectedly, plasmid-derived HIV-1 expression showed that TRMT6 mutant cells decreased accumulation of HIV-1 capsid, integrase, Tat, Gag, and GagPol proteins without reduction of HIV-1 RNAs in cells, and fewer viruses were produced. Moreover, the importance of 5,2'-O-dimethyluridine at U54 of tRNA3Lys as a second RT-stop site was supported by conservation of retroviral genome-tRNALys sequence-complementarity, and TRMT6 was required for efficient 5-methylation of U54. These findings illuminate the fundamental importance of tRNA m1A58 modification in both the early and late steps of HIV-1 replication, as well as in the cellular tRNA modification network.
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VIH-1/fisiología , Procesamiento Postranscripcional del ARN , ARN de Transferencia de Lisina/metabolismo , Replicación Viral , Animales , Células HEK293 , Células HeLa , Humanos , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Metilación , Ratones , Mutación , ARN de Transferencia de Lisina/químicaRESUMEN
PURPOSE: A Lactobacillus-dominated microbiota in the endometrium was reported to be associated with favorable reproductive outcomes. We investigated in this study whether 16S ribosomal RNA (rRNA) gene sequencing analysis of the uterine microbiome improves pregnancy outcomes. METHODS: This prospective cohort study recruited a total of 195 women with recurrent implantation failure (RIF) between March 2019 and April 2021 in our fertility center. Analysis of the endometrial microbiota by 16S rRNA gene sequencing was suggested for all patients who had three or more failed embryo transfers (ETs). One hundred and thirty-one patients underwent microbial 16S rRNA gene sequencing (study group) before additional transfers, while 64 patients proceeded to ET without that analysis (control group). The primary outcome was to compare the cumulative clinical pregnancy rate of two additional ETs. MAIN RESULTS: An endometrial microbiota considered abnormal was detected in 30 patients (22.9%). All but one of these 30 patients received antibiotics according to the bacterial genus detected in their sample, followed by treatment with probiotics. As a result, the cumulative clinical pregnancy rate (study group: 64.5% vs. control group: 33.3%, p = 0.005) and the ongoing pregnancy rate (study group: 48.9% vs. control group: 32.8%, p = 0.028) were significantly increased in the study group compared to the control group. CONCLUSION: Personalized treatment recommendations based on the microbial 16S rRNA gene sequencing of the uterine microbiota can improve IVF outcomes of patients with RIF. TRIAL REGISTRATION: The University Hospital Medical Information Network (UMIN) Clinical Trial Registry: UMIN000036050 (date of registration: March 1, 2019).
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Fertilización In Vitro , Microbiota , Resultado del Embarazo , ARN Ribosómico 16S , Femenino , Humanos , Embarazo , Endometrio/microbiología , Microbiota/genética , Estudios Prospectivos , ARN Ribosómico 16S/genéticaRESUMEN
A 44-year old man with a history of Stanford type B acute aortic dissection was admitted for the treatment of acute aortic dissection. Computed tomography( CT) scan showed a descending entry-type non-A non-B aortic dissection with a maximum diameter of 65 mm occurring in a patient with Edwards typeâ ¢ right aortic arch whose left subclavian artery was obliterated. The patient was initially treated conservatively and underwent one-stage extended aortic repair from the ascending aorta to the descending thoracic aorta via median sternotomy 22 days after the symptom onset. Although the patient suffered from right empyema postoperatively, he was discharged from the hospital on postoperative day 64 after 4 weeks antibiotics therapy. The patient was also complicated by right recurrent nerve palsy, hoarseness improved over the 8 months after surgery.
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Aneurisma de la Aorta Torácica , Disección Aórtica , Implantación de Prótesis Vascular , Masculino , Humanos , Adulto , Aorta Torácica/diagnóstico por imagen , Aorta Torácica/cirugía , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico por imagen , Disección Aórtica/cirugía , Aorta/cirugía , Procedimientos Quirúrgicos Vasculares , Esternotomía , Stents , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Resultado del TratamientoRESUMEN
Controlling the alignment of single-walled carbon nanotubes (SWCNTs) on the macroscopic scale is critical for practical applications because SWCNTs are extremely anisotropic materials. One efficient technique is to create an effective SWCNT dispersion, which shows a liquid crystal (LC) phase. A strong acid treatment can realize SWCNT liquid crystalline dispersions. However, strong acids pose a substantial safety risk, which renders the process unfit for mass production. Herein, an isolated SWCNT dispersion displaying an LC behavior is prepared using sodium cholate without an acid treatment, and its phase transition behaviors are systematically investigated across the isotropic to biphasic to nematic phases. As the SWCNT concentration increases, the dispersion undergoes an isotropic-to-nematic phase transition in which the spindle-shaped LC droplets, or the so-called tactoids, and the Schlieren textures can be observed in the intermediate biphasic state and the nematic phase, respectively. The arrangements of SWCNTs in the tactoids and the Schlieren structures are directly investigated by polarized optical microscopy. The clear LC behaviors of the CNT dispersion suggest that the CNT orientations can be controlled by the normal surfactant-assisted method, which is a crucial advantage for the liquid-phase processing of CNT fibers and films.
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INTRODUCTION: The most detrimental factor preventing the use of oral iron in the treatment of iron deficiency anemia is gastrointestinal side effects accompanied by nausea and vomiting. Anorexia is a known secondary effect of nausea and vomiting. The important gastrointestinal signaling molecule 5-hydroxytryptamine (5-HT) is critically involved in not only physiological function but also nausea and vomiting. The present study was designed to compare the effects of the administration of sodium ferrous citrate (SF) and ferric citrate hydrate (FC) to rats on anorexia and hyperplasia of enterochromaffin cells, which mainly synthesize and store 5-HT. METHODS: Rats received either SF (3 or 30 mg/kg/day) or FC (30 mg/kg/day) orally for 4 days. Food and water intakes were measured every 24 h during the study. At 96 h after the first administration of the oral iron preparation, the duodenal and jejunal tissues were collected for analysis. Enterochromaffin cells were detected by immunohistochemical analysis. RESULTS: Administration of 3 mg/kg SF had no effect on anorexia but led to increased hyperplasia of enterochromaffin cells in the duodenum (p < 0.1). Administration of 30 mg/kg SF significantly decreased food and water intakes and significantly increased hyperplasia of enterochromaffin cells in the duodenum and jejunum. Alternatively, administration of 30 mg/kg FC had no significant effect on food and water intakes or hyperplasia of enterochromaffin cells. CONCLUSION: The lower impact on the hyperplasia of enterochromaffin cells of FC compared to SF may contribute to the maintenance of rats' physical condition.
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Células Enterocromafines , Serotonina , Ratas , Animales , Hiperplasia , Anorexia , Hierro , Intestino Delgado , Vómitos , Náusea , AguaRESUMEN
Rapid deployment valve has expanded surgical indication for high-risk patients with aortic stenosis despite its accommodated risk for conduction disorder (CD). The purpose of this study was to evaluate the degree of oversizing in association with postoperative CD. During June 2019 to September 2021, 25 patients underwent aortic valve replacement with Edwards INTUITY. Device size selection was evaluated intraoperatively using provided sizers. Oversizing was evaluated retrospectively by measuring the difference of the dimension of the annulus and left ventricular outflow tract (LVOT) compared to the dimensions of the device used by preoperative-computed tomography. Although there was no incidence of pacemaker implantation, seven patients (28.0%) experienced CD after surgery. There was no difference in device area and annulus area (CD: - 37 ± 22.7 mm2 vs. no CD: - 56 ± 63.6 mm2, p = 0.47), and device circumference and annulus circumference (CD: - 4.4 ± 2.77 mm vs. no CD: - 6.9 ± 5.60 mm, p = 0.26) in patients with and without CD. However, there was a significant difference in area of the device skirt and sub-annular area at the LVOT (CD: 114 ± 28.4 mm2 vs. no CD: - 8 ± 80.0 mm2, p < 0.001), and circumference of device skirt and the LVOT (CD: 3.9 ± 2.08 mm vs. no CD: - 4.6 ± 5.24 mm, p < 0.001) between the two groups. Receiver operating characteristic curve analysis showed that an area difference of 77.7 mm2 and circumference difference of 0.91 mm at LVOT were associated with postoperative CD with specificities of 0.83, 0.78 and sensitivity of 1.0, 1.0, respectively. Preoperative measurement of the LVOT may be useful in evaluating the risk of postoperative CD in patients receiving rapid deployment valve.
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Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/patología , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Prótesis Valvulares Cardíacas/clasificación , Prótesis Valvulares Cardíacas/normas , Humanos , Diseño de Prótesis , Curva ROC , Estudios Retrospectivos , Reemplazo de la Válvula Aórtica Transcatéter , Resultado del TratamientoRESUMEN
Spider dragline silk is a biopolymer with excellent mechanical properties. The development of recombinant spider silk protein (RSP)-based materials with these properties is desirable. Formic acid (FA) is a spinning solvent for regenerated Bombyx mori silk fiber with excellent mechanical properties. To use FA as a spinning solvent for RSP with the sequence of major ampullate spider silk protein from Araneus diadematus, we determined the conformation of RSP in FA using solution NMR to determine the role of FA as a spinning solvent. We assigned 1H, 13C, and 15N chemical shifts to 32-residue repetitive sequences, including polyAla and Gly-rich regions of RSP. Chemical shift evaluation revealed that RSP is in mainly random coil conformation with partially type II ß-turn structure in the Gly-Pro-Gly-X motifs of the Gly-rich region in FA, which was confirmed by the 15N NOE data. In addition, formylation at the Ser OH groups occurred in FA. Furthermore, we evaluated the conformation of the as-cast film of RSP dissolved in FA using solid-state NMR and found that ß-sheet structure was predominantly formed.
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Formiatos/química , Proteínas de Insectos/química , Espectroscopía de Resonancia Magnética/métodos , Proteínas Recombinantes/química , Seda/química , Animales , Bombyx , Conformación ProteicaRESUMEN
Hemorrhage arising from the coronary sinus is very rare and can be lethal. It has historically been treated surgically. The present patient had coronary sinus rupture secondary to esophageal cancer and an abscess in the pericardium. Due to her poor general status, this patient was contraindicated for surgery and underwent endovascular therapy. The hemorrhage was treated by stent graft deployment and the patient was temporarily discharged. Two months later, CT showed that the stent graft was occluded by thrombosis. The patient died without hemorrhage 2.5 months thereafter.
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Implantación de Prótesis Vascular , Seno Coronario , Neoplasias Esofágicas , Neoplasias Esofágicas/complicaciones , Neoplasias Esofágicas/cirugía , Femenino , Hemorragia , Humanos , Stents , Resultado del TratamientoRESUMEN
The loss-of-function variants of the human asparagine synthetase (ASNS) gene cause asparagine synthetase deficiency (ASNSD). Diagnosis of ASNSD requires genetic tests because a specific biochemical diagnostic for ASNSD is not available. There are a few reports describing the functional evaluation of ASNS variants. Therefore, in vitro methods are needed to evaluate the detected variants in patients. In this report, five types of human ASNS proteins (wild-type and our reported four variants: p.Leu145Ser, p.Leu247Trp, p.Val489Asp, and p.Trp541Cysfs*5) were expressed in silkworm using a baculoviral expression system. An enzymatic activity assay of ASNS was performed, and the concentration of asparagine by ninhydrin and High Performance Liquid Chromatography methods using the purified recombinant proteins was measured. We established ASNS deficient HEK293 cells using the CRISPR/Cas9 method and evaluated the growth of cells without asparagine after transduction of ASNS variants with a lentiviral expression system. The four ASNS variants displayed significantly low enzymatic activity. The ASNS deficient HEK293 cells transduced with wild-type ASNS grew without asparagine, whereas cells transduced with the variants did not grow or showed significantly slower growth than cells transduced with wild-type ASNS. Herein, we established a method for evaluating the enzymatic activity of the recombinant human ASNS variants. The results of the cell-based assay corroborated the results of the enzymatic activity. These methods should enable the evaluation of the pathogenicity of ASNS variants.
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Ligasas de Carbono-Nitrógeno con Glutamina como Donante de Amida-N/genética , Asparagina/metabolismo , Sistemas CRISPR-Cas , Ligasas de Carbono-Nitrógeno con Glutamina como Donante de Amida-N/deficiencia , Variación Genética , Células HEK293 , HumanosRESUMEN
Polyunsaturated fatty acids (PUFAs), esterified to phospholipids, are susceptible to oxidation. They form oxidized phospholipids (OxPLs) by oxygenases or reactive oxygen species (ROS), or both. These OxPLs are associated with various diseases, such as atherosclerosis, pulmonary injuries, neurodegenerative diseases, cancer, and diabetes. Since many types of OxPLs seem to be generated in vivo, precise determination of their structural diversity is required to understand their potential structure-specific functions. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) is a powerful method to quantitatively measure the structural diversity of OxPLs present in biological samples. This review outlines recent advances in analytical methods for OxPLs and their physiological relevance in health and diseases.
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Fosfolípidos/química , Cromatografía Liquida , Oxidación-Reducción , Espectrometría de Masas en TándemRESUMEN
RBM10 is an RNA-binding protein that regulates alternative splicing (AS). It localizes to the extra-nucleolar nucleoplasm and S1-1 nuclear bodies (NBs) in the nucleus. We investigated the biological significance of this localization in relation to its molecular function. Our analyses, employing deletion mutants, revealed that RBM10 possesses two S1-1 NB-targeting sequences (NBTSs), one in the KEKE motif region and another in the C2H2 Zn finger (ZnF). These NBTSs act synergistically to localize RBM10 to S1-1 NBs. The C2H2 ZnF not only acts as an NBTS, but is also essential for AS regulation by RBM10. Moreover, RBM10 does not participate in S1-1 NB formation, and without alterations of RBM10 protein levels, its NB-localization changes, increasing as cellular transcriptional activity declines, and vice versa. These results indicate that RBM10 is a transient component of S1-1 NBs and is sequestered in NBs via its NBTSs when cellular transcription decreases. We propose that the C2H2 ZnF exerts its NB-targeting activity when RBM10 is unbound by pre-mRNAs, and that NB-localization of RBM10 is a mechanism to control its AS activity in the nucleus.
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Empalme Alternativo , Núcleo Celular/metabolismo , Señales de Localización Nuclear/metabolismo , Proteínas de Unión al ARN/metabolismo , Secuencias de Aminoácidos , Núcleo Celular/genética , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Señales de Localización Nuclear/genética , Dominios Proteicos , Transporte de Proteínas , Proteínas de Unión al ARN/genéticaRESUMEN
A 75-year-old man was admitted for cerebral infarction. Magnetic resonance imaging revealed parietal lobe cerebral infarction. Transesophageal echo and contrast-enhanced computed tomography indicated mobile and speckled mass arising from left atrium. He was diagnosed with cardiogenic cerebral embolism. Under cardiopulmonary bypass, resection of the mass including endocardium tissue was per formed. The resected specimen showed multiple small fronds resembling a sea anemone. Microscopic examination showed multiple branching fronds of paucicellular and avascular fibroelastic tissue lined by a single layer of endocardium. Pathological diagnosis was papillary fibroelastoma. Three years passed without recurrence.
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Fibroelastoma Papilar Cardíaco , Fibroma , Neoplasias Cardíacas , Anciano , Fibroma/diagnóstico por imagen , Fibroma/cirugía , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/cirugía , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Humanos , Masculino , Recurrencia Local de NeoplasiaRESUMEN
A 26-year-old man with relapsing polychondritis was admitted for the treatment of multiple thoracic aortic aneurysms in the ascending and descending aorta. Descending thoracic aortic aneurysm showed rapid expansion, therefore, the patient underwent an extended thoracic aortic repair from the ascending aorta to the descending aorta via anterolateral thoracotomy and partial sternotomy. Although postoperative course was uneventful, aortic root enlargement and severe aortic insufficiency progressed over the next two years. He and his family refused redo surgical intervention and the patient died of heart failure. Careful perioperative follow-up may be mandatory in a patient with relapsing polychondritis complicated by cardiovascular disease.
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Aneurisma de la Aorta Torácica , Implantación de Prótesis Vascular , Policondritis Recurrente , Adulto , Aorta/cirugía , Aorta Torácica/cirugía , Aneurisma de la Aorta Torácica/complicaciones , Aneurisma de la Aorta Torácica/diagnóstico por imagen , Aneurisma de la Aorta Torácica/cirugía , Humanos , Masculino , Policondritis Recurrente/complicaciones , ToracotomíaRESUMEN
Pseudomonas putida KT2440 retains three homologs (PplR1 to PplR3) of the LitR/CarH family, an adenosyl B12-dependent light-sensitive MerR family transcriptional regulator. Transcriptome analysis revealed the existence of a number of photoinducible genes, including pplR1, phrB (encoding DNA photolyase), ufaM (furan-containing fatty acid synthase), folE (GTP cyclohydrolase I), cryB (cryptochrome-like protein), and multiple genes without annotated/known function. Transcriptional analysis by quantitative reverse transcription-PCR with knockout mutants of pplR1 to pplR3 showed that a triple knockout completely abolished the light-inducible transcription in P. putida, which indicates the occurrence of ternary regulation of PplR proteins. A DNase I footprint assay showed that PplR1 protein specifically binds to the promoter regions of light-inducible genes, suggesting a consensus PplR1-binding direct repeat, 5'-T(G/A)TACAN12TGTA(C/T)A-3'. The disruption of B12 biosynthesis cluster did not affect the light-inducible transcription; however, disruption of ppSB1-LOV (where LOV indicates "light, oxygen, or voltage") and ppSB2-LOV, encoding blue light photoreceptors adjacently located to pplR3 and pplR2, respectively, led to the complete loss of light-inducible transcription. Overall, the results suggest that the three PplRs and two PpSB-LOVs cooperatively regulate the light-inducible gene expression. The wide distribution of the pplR/ppSB-LOV cognate pair homologs in Pseudomonas spp. and related bacteria suggests that the response and adaptation to light are similarly regulated in the group of nonphototrophic bacteria.IMPORTANCE The LitR/CarH family is a new group of photosensor homologous to MerR-type transcriptional regulators. Proteins of this family are distributed to various nonphototrophic bacteria and grouped into at least five classes (I to V). Pseudomonas putida retaining three class II LitR proteins exhibited a genome-wide response to light. All three paralogs were functional and mediated photodependent activation of promoters directing the transcription of light-induced genes or operons. Two LOV (light, oxygen, or voltage) domain proteins, adjacently encoded by two litR genes, were also essential for the photodependent transcriptional control. Despite the difference in light-sensing mechanisms, the DNA binding consensus of class II LitR [T(G/A)TA(C/T)A] was the same as that of class I. This is the first study showing the actual involvement of class II LitR in light-induced transcription.