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1.
Nature ; 606(7916): 1027-1031, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35580630

RESUMEN

Around 250 million people are infected with hepatitis B virus (HBV) worldwide1, and 15 million may also carry the satellite virus hepatitis D virus (HDV), which confers even greater risk of severe liver disease2. The HBV receptor has been identified as sodium taurocholate co-transporting polypeptide (NTCP), which interacts directly with the first 48 amino acid residues of the N-myristoylated N-terminal preS1 domain of the viral large protein3. Despite the pressing need for therapeutic agents to counter HBV, the structure of NTCP remains unsolved. This 349-residue protein is closely related to human apical sodium-dependent bile acid transporter (ASBT), another member of the solute carrier family SLC10. Crystal structures have been reported of similar bile acid transporters from bacteria4,5, and these models are believed to resemble closely both NTCP and ASBT. Here we have used cryo-electron microscopy to solve the structure of NTCP bound to an antibody, clearly showing that the transporter has no equivalent of the first transmembrane helix found in other SLC10 proteins, and that the N terminus is exposed on the extracellular face. Comparison of our structure with those of related proteins indicates a common mechanism of bile acid transport, but the NTCP structure displays an additional pocket formed by residues that are known to interact with preS1, presenting new opportunities for structure-based drug design.


Asunto(s)
Ácidos y Sales Biliares , Microscopía por Crioelectrón , Virus de la Hepatitis B , Transportadores de Anión Orgánico Sodio-Dependiente , Receptores Virales , Simportadores , Anticuerpos , Ácidos y Sales Biliares/metabolismo , Virus de la Hepatitis B/metabolismo , Hepatocitos/metabolismo , Humanos , Transportadores de Anión Orgánico Sodio-Dependiente/química , Transportadores de Anión Orgánico Sodio-Dependiente/metabolismo , Transportadores de Anión Orgánico Sodio-Dependiente/ultraestructura , Receptores Virales/química , Receptores Virales/metabolismo , Receptores Virales/ultraestructura , Simportadores/química , Simportadores/metabolismo , Simportadores/ultraestructura
2.
Cardiol Young ; 33(9): 1775-1776, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37042609

RESUMEN

Ornithine transcarbamylase deficiency is an X-linked disorder which results in the accumulation of ammonia causing irritability and vomiting. Acute hyperammonemia requires rapid and intensive intervention. However, as those clinical features are non-specific and commonly seen in peri-operative situation, ornithine transcarbamylase deficiency could be difficult to diagnose prior to and post-emergency cardiac surgery. We report a 2-day-old male neonate who was diagnosed with ornithine transcarbamylase deficiency presenting hyperammonemia and severe heart failure after total anomalous pulmonary venous connection repair.


Asunto(s)
Hiperamonemia , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa , Humanos , Recién Nacido , Masculino , Amoníaco , Hiperamonemia/diagnóstico , Hiperamonemia/etiología , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/complicaciones , Enfermedad por Deficiencia de Ornitina Carbamoiltransferasa/diagnóstico , Procedimientos Quirúrgicos Vasculares , Vómitos
3.
Genes Dev ; 29(15): 1649-60, 2015 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-26215567

RESUMEN

The pre-mRNA splicing reaction of eukaryotic cells has to be carried out extremely accurately, as failure to recognize the splice sites correctly causes serious disease. The small subunit of the U2AF heterodimer is essential for the determination of 3' splice sites in pre-mRNA splicing, and several single-residue mutations of the U2AF small subunit cause severe disorders such as myelodysplastic syndromes. However, the mechanism of RNA recognition is poorly understood. Here we solved the crystal structure of the U2AF small subunit (U2AF23) from fission yeast, consisting of an RNA recognition motif (RRM) domain flanked by two conserved CCCH-type zinc fingers (ZFs). The two ZFs are positioned side by side on the ß sheet of the RRM domain. Further mutational analysis revealed that the ZFs bind cooperatively to the target RNA sequence, but the RRM domain acts simply as a scaffold to organize the ZFs and does not itself contact the RNA directly. This completely novel and unexpected mode of RNA-binding mechanism by the U2AF small subunit sheds light on splicing errors caused by mutations of this highly conserved protein.


Asunto(s)
Modelos Moleculares , Proteínas Nucleares/química , Sitios de Empalme de ARN , Ribonucleoproteínas/química , Schizosaccharomyces/fisiología , Dedos de Zinc/fisiología , Secuencias de Aminoácidos , Sitios de Unión , Análisis Mutacional de ADN , Unión Proteica , Estructura Cuaternaria de Proteína , Estructura Terciaria de Proteína , Schizosaccharomyces/química , Factor de Empalme U2AF
4.
BMC Urol ; 22(1): 130, 2022 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-36008830

RESUMEN

BACKGROUND: To develop a nomogram of urinary volume and flow based on the data of Japanese men without lower urinary tract symptoms and multiple flows per participant whose characteristics were clear. METHODS: Overall, 101 Japanese male volunteers without lower urinary tract symptoms aged between 20 and 59 years were enrolled. A portable uroflowmeter (P-Flowdiary®) was used to record urinary information (flow rate and volume) for 2 successive days. The model (quadratic, linear, or logarithmic regression) most fit for the relationship between maximum flow rate and voided volume was determined. The maximum flow rate at > 150 mL was compared among the 20-29-, 30-39-, 40-49-, and 50-59-year age groups. Nomograms appropriate for the age groups were created. RESULTS: The mean age, International Prostate Symptom Score, and Overactive Bladder Symptom Score were 38.5 years, 0.42, and 0.24, respectively. The quadratic regression model was the most fit because its mean coefficient determination was 0.93 ± 0.06. The mean maximum flow rate was significantly lower in the 50-59-year age group (21.8 ± 5.05 mL/s, P < 0.01) than in the younger groups (24.14 ± 4.94, 24.05 ± 6.99, and 24.64 ± 5.72 mL/s). The 2 nomograms are Y = 28.99 {1 - exp(- 0.01 × X)} and Y = 25.67 {1 - exp(- 0.01 × X)} for the 20-49- and 50-59-year age groups, respectively. CONCLUSIONS: The nomogram can predict maximum flow rate based on voided volume in Japanese men aged 20-59 years without lower urinary tract symptoms.


Asunto(s)
Síntomas del Sistema Urinario Inferior , Urodinámica , Adulto , Humanos , Japón , Síntomas del Sistema Urinario Inferior/diagnóstico , Síntomas del Sistema Urinario Inferior/etiología , Masculino , Persona de Mediana Edad , Nomogramas , Micción , Adulto Joven
5.
J Mol Evol ; 84(5-6): 267-278, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28589220

RESUMEN

The C-terminal domain of methionyl-tRNA synthetase (MetRS-C) from Nanoarchaeum equitans is homologous to a tRNA-binding protein consisting of 111 amino acids (Trbp111) from Aquifex aeolicus. The crystal structure of MetRS-C showed that it existed as a homodimer, and that each monomer possessed an oligonucleotide/oligosaccharide-binding fold (OB-fold). Analysis using a quartz crystal microbalance indicated that MetRS-C freshly isolated from N. equitans was bound to tRNA. However, binding of the split 3'-half tRNA species was stronger than that of the 5'-half species. The T-loop and the 3'-end regions of the split 3'-half tRNA were found to be responsible for the binding. The minimum structure for binding to MetRS-C might be a minihelix-like stem-loop with single-stranded 3'-terminus. After successive duplications of such a small hairpin structure with the assistance of a Trbp-like structure, the interaction of the T-loop region of the 3'-half with a Trbp-like structure could have been evolutionarily replaced by RNA-RNA interactions, along with many combinational tertiary interactions, to form the modern tRNA structure.


Asunto(s)
Nanoarchaeota/genética , ARN de Transferencia/metabolismo , Secuencia de Aminoácidos , Sitios de Unión , Dimerización , Metionina-ARNt Ligasa/metabolismo , Nanoarchaeota/metabolismo , Dominios Proteicos , Estructura Terciaria de Proteína , ARN/metabolismo
6.
Nature ; 454(7208): 1127-31, 2008 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-18660801

RESUMEN

Influenza A virus is a major human and animal pathogen with the potential to cause catastrophic loss of life. The virus reproduces rapidly, mutates frequently and occasionally crosses species barriers. The recent emergence in Asia of avian influenza related to highly pathogenic forms of the human virus has highlighted the urgent need for new effective treatments. Here we demonstrate the importance to viral replication of a subunit interface in the viral RNA polymerase, thereby providing a new set of potential drug binding sites entirely independent of surface antigen type. No current medication targets this heterotrimeric polymerase complex. All three subunits, PB1, PB2 and PA, are required for both transcription and replication. PB1 carries the polymerase active site, PB2 includes the capped-RNA recognition domain, and PA is involved in assembly of the functional complex, but so far very little structural information has been reported for any of them. We describe the crystal structure of a large fragment of one subunit (PA) of influenza A RNA polymerase bound to a fragment of another subunit (PB1). The carboxy-terminal domain of PA forms a novel fold, and forms a deep, highly hydrophobic groove into which the amino-terminal residues of PB1 can fit by forming a 3(10) helix.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A/enzimología , Subunidades de Proteína/química , Subunidades de Proteína/metabolismo , ARN Polimerasa Dependiente del ARN/química , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas Virales/química , Proteínas Virales/metabolismo , Sitios de Unión , Línea Celular , Cristalización , Cristalografía por Rayos X , Humanos , Subtipo H1N1 del Virus de la Influenza A/genética , Unión Proteica , Subunidades de Proteína/genética , ARN Polimerasa Dependiente del ARN/genética , Proteínas Virales/genética , Replicación Viral
7.
Ann Thorac Surg ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38936589

RESUMEN

BACKGROUND: This study investigated the long-term outcomes of physiological and anatomical repair for corrected transposition of the great arteries and double-outlet right ventricle with discordant atrioventricular connection. METHODS: This single-center retrospective study included 146 patients who underwent biventricular repair of corrected transposition of the great arteries or double-outlet right ventricle with discordant atrioventricular connections from 1972 to 2023. Survival rate, freedom from reoperation, New York Heart Association (NYHA) Functional Classification, and incidence of systemic ventricular dysfunction in the long-term were compared between physiological repair (PR) and anatomical repair (AR) groups. RESULTS: The PR group consisted of 55 patients, with median age at repair of 10.3 years. Thirty-one patients underwent conventional Rastelli procedure, and 24 patients underwent atrial and/or ventricular septal defect closure. The AR group consisted of 91 patients, with median age at repair of 5.8 years. Seventy-two patients underwent atrial switch plus Rastelli procedure and 19 patients underwent atrial plus arterial switch operation. The 30-year survival was 63.5% in the PR group and 72.3% in the AR group (P = .448). The 30-year freedom from reoperation was 71.9% in the PR group and 62.2% in the AR group (P = .220). There was a significant difference in the incidence of systemic ventricular dysfunction between the groups (87.5% in the PR group and 35.3% in the AR group, P < .001) and in the NYHA classification of long-term survivors (mean NYHA class of 1.9 in the PR group and 1.5 in the AR group, P = .009). CONCLUSIONS: The systemic ventricular function and general status in the long-term were significantly better in AR patients, suggesting the potential advantage of AR.

8.
Acta Crystallogr D Biol Crystallogr ; 69(Pt 1): 44-51, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23275162

RESUMEN

Bacterial biofilm formation is an extremely widespread phenomenon involving the secretion of a protective exopolysaccharide matrix which helps the bacteria to attach to surfaces and to overcome a variety of stresses in different environments. This matrix may also include proteins, lipids, DNA and metal ions. Its composition depends on the bacterial species and growth conditions, but one of the most widely found components is polymeric ß-1,6-N-acetyl-D-glucosamine (PGA). Several studies have suggested that PGA is an essential component of biofilm and it is produced by numerous bacteria, including Escherichia coli, Staphylococcus epidermis, Yersinia pestis, Bordetella spp. and Actinobacillus spp. In E. coli, PGA production and export are dependent on four genes that form a single operon, pgaABCD, which appears to have been transferred between various species. Biofilms themselves are recognized as environments in which such horizontal gene transfer may occur. The pga operon of E. coli, which is even found in innocuous laboratory strains, is highly homologous to that from the plague bacterium Yersinia pestis, and biofilm is believed to play an important role in the transmission of Yersinia. The crystal structure of the N-terminal domain of PgaB, which has deacetylase activity, is described and compared with models of other deacetylases.


Asunto(s)
Acetilesterasa/química , Amidohidrolasas/química , Biopelículas/crecimiento & desarrollo , Carboxilesterasa/química , Proteínas de Escherichia coli/química , Histona Desacetilasas/química , Histona Desacetilasas/fisiología , Acetilesterasa/genética , Amidohidrolasas/antagonistas & inhibidores , Amidohidrolasas/genética , Carboxilesterasa/genética , Carboxilesterasa/fisiología , Dominio Catalítico/genética , Cristalografía por Rayos X , Proteínas de Escherichia coli/antagonistas & inhibidores , Proteínas de Escherichia coli/genética , Histona Desacetilasas/genética , Modelos Químicos , Operón/genética , Estructura Terciaria de Proteína/genética
9.
JTCVS Open ; 15: 382-393, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37808018

RESUMEN

Objective: The purpose of this study is to compare the long-term outcomes of 2 different tricuspid surgeries including valvuloplasty and replacement for significant tricuspid regurgitation in patients with systemic right ventricle. Method: This is a retrospective study of 34 patients with dextro-transposition of the great arteries or levo-transposition of the great arteries with biventricular circulation and systemic right ventricle undergoing tricuspid valve surgery between April 1979 and April 2022. Patients were divided into 2 groups based on the procedure: tricuspid valvuloplasty (n = 11) and tricuspid valve replacement (n = 23). These groups were compared in terms of survival, tricuspid valve dysfunction, and tricuspid valve-related reoperation. Results: There was no significant difference between the groups in operative age, body weight, the proportion of dextro-transposition of the great arteries, Ebstein-like tricuspid dysplasia, and preoperative right ventricular volume/function. During the median follow-up of 9.7 years, there was 1 early death (tricuspid valvuloplasty group) and 4 late deaths (3 in tricuspid valvuloplasty group and 1 in tricuspid valve replacement group). There were 7 tricuspid valve dysfunctions, including 6 significant tricuspid regurgitations in the tricuspid valvuloplasty group and 1 prosthetic valve dysfunction in the tricuspid valve replacement group, and 4 tricuspid valve-related reoperations (3 in the tricuspid valvuloplasty group and 1 in the tricuspid valve replacement group) were performed. There were significant differences between the groups in survival (tricuspid valvuloplasty vs tricuspid valve replacement: 72.7 vs 94.7% at 10 years after surgery, P = .0328) and cumulative incidence of tricuspid valve dysfunction at 10 years after tricuspid surgery (tricuspid valvuloplasty vs tricuspid valve replacement: 27.3% vs 0%, P = .0121). Conclusions: Tricuspid valve replacement provided better long-term survival and tricuspid function in patients with systemic right ventricle compared with tricuspid valvuloplasty.

10.
World J Pediatr Congenit Heart Surg ; 13(4): 451-457, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35757952

RESUMEN

BACKGROUND: This study aimed to evaluate the long-term outcomes of partial and transitional atrioventricular septal defect repair, focusing on left atrioventricular valve reoperation. METHODS: We conducted a retrospective review of 104 children who underwent partial or transitional atrioventricular septal defect repair between August 1983 and January 2021. The major outcomes included patient survival and left atrioventricular valve reoperation. RESULTS: Median age at repair was 4.0 (0.1-17.0) years, with 17 patients being infants (age ≤ 1 year; 16.3%). All but eight patients (92.3%) underwent left atrioventricular valve cleft closure. After initial repair, there were 18 cases of moderate-to-severe left atrioventricular valve regurgitation (17.3%). Three in-hospital deaths (2.9%) and four late deaths (3.8%) occurred. At follow-up (median 14.3 years), actuarial survival was 95.1% and 93.0% at 1 and 20 years, respectively, and 16 patients (15.4%) had undergone a total of 19 left atrioventricular valve reoperations. Initial repair performed during infancy was associated with significantly higher mortality than a repair performed after infancy (35.3% vs 1.5%, P < .01, hazard ratio = 26.4). On multivariable analysis, repair during infancy was associated with mortality (P < .01, hazard ratio = 27.4, 95% confidence interval = 2.7-283). Partial or no cleft closure of left atrioventricular valve (P = .03, hazard ratio = 4.7, 95% confidence interval = 1.2-18.8) and moderate-to-severe left atrioventricular valve regurgitation after repair (P < .01, hazard ratio = 9.9, 95% confidence interval = 3.0-32.2) were associated with left atrioventricular valve reoperation. CONCLUSIONS: Partial and transitional atrioventricular septal defect repair outcomes were generally satisfactory. However, repair during infancy had worse survival outcomes, and moderate-to-severe left atrioventricular valve regurgitation after a repair was associated with future left atrioventricular valve reoperation.


Asunto(s)
Defectos de los Tabiques Cardíacos , Insuficiencia de la Válvula Mitral , Reoperación , Adolescente , Niño , Preescolar , Humanos , Lactante , Insuficiencia de la Válvula Mitral/cirugía , Gravedad del Paciente , Complicaciones Posoperatorias/cirugía , Estudios Retrospectivos , Resultado del Tratamiento
11.
Interact Cardiovasc Thorac Surg ; 34(3): 438-445, 2022 02 21.
Artículo en Inglés | MEDLINE | ID: mdl-34849934

RESUMEN

OBJECTIVES: Patients who have achieved Fontan circulation may require reoperation. We reviewed the outcomes of reoperation after Fontan completion and assessed the risk factors for poor outcomes. METHODS: This was a retrospective study of 106 patients undergoing open-heart reoperations after Fontan completion in 2003 at a single institution. RESULTS: The mean age at reoperation was 24.6 ± 8.3 years. A history of Fontan failure or end-organ dysfunction was noted in 30 patients. The reoperations included 73 total cavopulmonary connection conversions, 29 atrioventricular or semilunar valve operations (17 with total cavopulmonary connection conversions) and 4 other operations. Eight early deaths occurred. During a median follow-up of 5.5 (0.01-16.2) years, there were 3 late deaths and 9 second cardiac operations. The 10-year survival rate after reoperation was 89.8%, and the 5-year second cardiac operation-free survival was 84.3%. The 10-year survival rates were significantly lower in patients who underwent surgery before 2011 (75.8% vs 100%), had a history of Fontan failure or end-organ dysfunction (71.7% vs 97.3%), had preoperative central venous pressure >15 mmHg (64.9% vs 96.5%) and were operated on with deep hypothermic circulatory arrest (DHCA) (60.0% vs 91.3%). A history of Fontan failure or end-organ dysfunction, preoperative central venous pressure >15 mmHg and requirement of DHCA were identified as risk factors for mortality. CONCLUSIONS: Reoperation after Fontan completion resulted in excellent mid-term outcomes. A history of failed Fontan circulation and the requirement of DHCA negatively affected survival outcomes.


Asunto(s)
Procedimiento de Fontan , Cardiopatías Congénitas , Procedimiento de Fontan/efectos adversos , Procedimiento de Fontan/métodos , Cardiopatías Congénitas/cirugía , Humanos , Reoperación , Estudios Retrospectivos , Resultado del Tratamiento
12.
Biomed Phys Eng Express ; 8(4)2022 06 30.
Artículo en Inglés | MEDLINE | ID: mdl-35728581

RESUMEN

This study investigates the equivalence or compatibility between U-Net and visual segmentations of fibroglandular tissue regions by mammography experts for calculating the breast density and mean glandular dose (MGD). A total of 703 mediolateral oblique-view mammograms were used for segmentation. Two region types were set as the ground truth (determined visually): (1) one type included only the region where fibroglandular tissue was identifiable (called the 'dense region'); (2) the other type included the region where the fibroglandular tissue may have existed in the past, provided that apparent adipose-only parts, such as the retromammary space, are excluded (the 'diffuse region'). U-Net was trained to segment the fibroglandular tissue region with an adaptive moment estimation optimiser, five-fold cross-validated with 400 training and 100 validation mammograms, and tested with 203 mammograms. The breast density and MGD were calculated using the van Engeland and Dance formulas, respectively, and compared between U-Net and the ground truth with the Dice similarity coefficient and Bland-Altman analysis. Dice similarity coefficients between U-Net and the ground truth were 0.895 and 0.939 for the dense and diffuse regions, respectively. In the Bland-Altman analysis, no proportional or fixed errors were discovered in either the dense or diffuse region for breast density, whereas a slight proportional error was discovered in both regions for the MGD (the slopes of the regression lines were -0.0299 and -0.0443 for the dense and diffuse regions, respectively). Consequently, the U-Net and ground truth were deemed equivalent (interchangeable) for breast density and compatible (interchangeable following four simple arithmetic operations) for MGD. U-Net-based segmentation of the fibroglandular tissue region was satisfactory for both regions, providing reliable segmentation for breast density and MGD calculations. U-Net will be useful in developing a reliable individualised screening-mammography programme, instead of relying on the visual judgement of mammography experts.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Mamografía , Tejido Adiposo , Mama/diagnóstico por imagen , Densidad de la Mama
13.
Clin Case Rep ; 9(8): e04674, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-34457293

RESUMEN

Acute aortic dissection with coronary malperfusion is a life-threatening disease, resulting in demanding postoperative management. We report a successful insertion of percutaneous heart pump Impella through the intact true lumen in a patient with residual aortic dissection after the graft replacement. Careful evaluation of the access site and the Impella size selection is required.

14.
World J Pediatr Congenit Heart Surg ; 12(4): 508-515, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34278861

RESUMEN

BACKGROUND: The purpose of this study was to assess autograft function after the Ross procedure and to review surgical outcomes associated with autograft reoperations. METHODS: This is a retrospective study of patients undergoing the Ross procedure since 1993. Autograft function and autograft reoperation were studied. Autograft failure was defined as more than moderate autograft regurgitation or autograft dilatation to more than 50 mm diameter or z-score of more than +4 in children. One hospital death was excluded from analysis as were patients with unknown late autograft status. RESULTS: Among 75 patients analyzed, preoperative diagnosis before the Ross procedure included aortic regurgitation in 26, aortic stenosis in 19, combined lesions in 28, and 2 mechanical valve malfunctions. Median age at the Ross procedure was 12.1 (0.4-43.6) years with 44 children less than 15 years old. Six patients had greater than mild autograft regurgitation at post-Ross hospital discharge. During median follow-up of 14.9 years, there were 23 autograft failures. Eighteen autograft reoperations were performed on 17 patients (13 children), including 12 aortic valve replacements, 5 aortic root replacements (including 1 valve-sparing root replacement), and 1 Konno procedure. Freedom from autograft failure and autograft reoperation at 20 years after the Ross procedure was 52.0% and 66.3%, respectively. Multivariate analysis identified greater than mild autograft regurgitation at hospital discharge from Ross procedure as a risk factor for autograft failure (P < .01). All patients who underwent autograft reoperation survived and had good health status at a median of 6.9 years after the reoperation. CONCLUSIONS: The Ross procedure is effective in delaying prosthetic aortic valve replacement, although the time-related risk of autograft failure is a real consideration.


Asunto(s)
Insuficiencia de la Válvula Aórtica , Estenosis de la Válvula Aórtica , Válvula Pulmonar , Adolescente , Válvula Aórtica/cirugía , Insuficiencia de la Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Autoinjertos , Niño , Estudios de Seguimiento , Humanos , Válvula Pulmonar/cirugía , Reoperación , Estudios Retrospectivos , Trasplante Autólogo , Resultado del Tratamiento
15.
Ann Thorac Surg ; 112(3): 831-837, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-32946840

RESUMEN

BACKGROUND: Excellent outcomes of right ventricle to pulmonary artery conduits with expanded polytetrafluoroethylene (ePTFE) valves have been reported. The purpose of this study was to evaluate the outcomes of the different material conduits with tricuspid ePTFE valves. METHODS: Forty-one consecutive patients who received right ventricle to pulmonary artery conduit with tricuspid ePTFE valves for biventricular repair between April 2004 and December 2016 were studied. The conduits made of autologous pericardial roll or xenograft roll were used in 22 patients (group P) and the conduits made of ePTFE tube were used in 19 patients (group G). The conduit reoperation and the conduit dysfunction were analyzed. RESULTS: During the median follow-up of 5.8 years, no death related to the conduit was observed. There were four reoperations (three in group P and one in group G). Freedom from conduit reoperation at 5 years was 100% in both groups (P = .30). Freedom from more than moderate conduit stenosis at 5 years after operation was not significantly different between groups (46.9% in group P vs 76.3% in group G, P = .23) even though the group G conduits were significantly smaller and freedom from more than moderate conduit regurgitation at 5 years was significantly better in group G (63.3% in group P vs 94.1% in group G, P = .04). CONCLUSIONS: The conduit with ePTFE valves in the ePTFE tubes had better conduit function compared with the conduit with autologous pericardial or xenograft roll, especially in terms of conduit regurgitation.


Asunto(s)
Prótesis Valvulares Cardíacas , Ventrículos Cardíacos/cirugía , Politetrafluoroetileno , Diseño de Prótesis , Arteria Pulmonar/cirugía , Válvula Tricúspide/cirugía , Adolescente , Adulto , Procedimientos Quirúrgicos Cardíacos/métodos , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven
16.
BMC Plant Biol ; 10: 124, 2010 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-20573275

RESUMEN

BACKGROUND: Low-molecular-weight glutenin subunits (LMW-GS) play a crucial role in determining end-use quality of common wheat by influencing the viscoelastic properties of dough. Four different methods - sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), two-dimensional gel electrophoresis (2-DE, IEF x SDS-PAGE), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and polymerase chain reaction (PCR), were used to characterize the LMW-GS composition in 103 cultivars from 12 countries. RESULTS: At the Glu-A3 locus, all seven alleles could be reliably identified by 2-DE and PCR. However, the alleles Glu-A3e and Glu-A3d could not be routinely distinguished from Glu-A3f and Glu-A3g, respectively, based on SDS-PAGE, and the allele Glu-A3a could not be differentiated from Glu-A3c by MALDI-TOF-MS. At the Glu-B3 locus, alleles Glu-B3a, Glu-B3b, Glu-B3c, Glu-B3g, Glu-B3h and Glu-B3j could be clearly identified by all four methods, whereas Glu-B3ab, Glu-B3ac, Glu-B3ad could only be identified by the 2-DE method. At the Glu-D3 locus, allelic identification was problematic for the electrophoresis based methods and PCR. MALDI-TOF-MS has the potential to reliably identify the Glu-D3 alleles. CONCLUSIONS: PCR is the simplest, most accurate, lowest cost, and therefore recommended method for identification of Glu-A3 and Glu-B3 alleles in breeding programs. A combination of methods was required to identify certain alleles, and would be especially useful when characterizing new alleles. A standard set of 30 cultivars for use in future studies was chosen to represent all LMW-GS allelic variants in the collection. Among them, Chinese Spring, Opata 85, Seri 82 and Pavon 76 were recommended as a core set for use in SDS-PAGE gels. Glu-D3c and Glu-D3e are the same allele. Two new alleles, namely, Glu-D3m in cultivar Darius, and Glu-D3n in Fengmai 27, were identified by 2-DE. Utilization of the suggested standard cultivar set, seed of which is available from the CIMMYT and INRA Clermont-Ferrand germplasm collections, should also promote information sharing in the identification of individual LMW-GS and thus provide useful information for quality improvement in common wheat.


Asunto(s)
Glútenes/química , Triticum/química , Alelos , ADN de Plantas/genética , Electroforesis en Gel Bidimensional , Electroforesis en Gel de Poliacrilamida , Glútenes/genética , Glútenes/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , Triticum/genética
17.
Nat Commun ; 11(1): 4744, 2020 09 21.
Artículo en Inglés | MEDLINE | ID: mdl-32958768

RESUMEN

The accurate exclusion of introns by RNA splicing is critical for the production of mature mRNA. U2AF1 binds specifically to the 3´ splice site, which includes an essential AG dinucleotide. Even a single amino acid mutation of U2AF1 can cause serious disease such as certain cancers or myelodysplastic syndromes. Here, we describe the first crystal structures of wild-type and pathogenic mutant U2AF1 complexed with target RNA, revealing the mechanism of 3´ splice site selection, and how aberrant splicing results from clinically important mutations. Unexpected features of this mechanism may assist the future development of new treatments against diseases caused by splicing errors.


Asunto(s)
Sitios de Empalme de ARN/genética , Factor de Empalme U2AF/genética , Factor de Empalme U2AF/metabolismo , Secuencia de Bases , Cristalografía por Rayos X , Exones/genética , Humanos , Mutación , Neoplasias/química , Neoplasias/genética , Nucleótidos , Motivo de Reconocimiento de ARN , Empalme del ARN/genética , Factor de Empalme U2AF/química , Dedos de Zinc
18.
Biomedicines ; 8(12)2020 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-33327466

RESUMEN

Nucleus accumbens-associated protein 1 (NAC1) is a nuclear protein that harbors an amino-terminal BTB domain and a carboxyl-terminal BEN domain. NAC1 appears to play significant and diverse functions in cancer and stem cell biology. Here we demonstrated that the BEN domain of NAC1 is a sequence-specific DNA-binding domain. We selected the palindromic 6 bp motif ACATGT as a target sequence by using a PCR-assisted random oligonucleotide selection approach. The interaction between NAC1 and target DNA was characterized by gel shift assays, pull-down assays, isothermal titration calorimetry (ITC), chromatin-immunoprecipitation assays, and NMR chemical shifts perturbation (CSP). The solution NMR structure revealed that the BEN domain of human NAC-1 is composed of five conserved α helices and two short ß sheets, with an additional hitherto unknown N-terminal α helix. In particular, ITC clarified that there are two sequential events in the titration of the BEN domain of NAC1 into the target DNA. The ITC results were further supported by CSP data and structure analyses. Furthermore, live cell photobleaching analyses revealed that the BEN domain of NAC1 alone was unable to interact with chromatin/other proteins in cells.

19.
Photodermatol Photoimmunol Photomed ; 25(1): 41-4, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-19152515

RESUMEN

BACKGROUND: Narrow-band ultraviolet B (NB-UVB) for the treatment of refractory skin diseases, such as psoriasis and atopic dermatitis, requires an adequate irradiation protocol based on the minimal erythema dose (MED) to establish an optimal dosage schedule. Although MED can be measured using a systemic-type irradiation unit, there are difficulties associated with this device. There is no standardized device available to determine the MED for NB-UVB. Here, we compared a conventional device with a newly developed device for measuring MED. METHOD: MED was measured in 16 psoriasis patients using both a conventional measuring device and the newly developed device, which comprised a hand-held NB-UVB (311-313 nm) flat-type fluorescent lamp with neutral density filters having different transmittances ranging from 10% to 90%. This device was designed to be stably maintained on the skin surface and to provide a highly accurate measurement with only one UV irradiation exposure while also preventing UV radiation from leaking to nonirradiated areas. RESULTS: The MED values obtained from each patient were the same using both devices. CONCLUSION: One-time irradiation using the new hand-held device with the NB-UVB flat-type fluorescent lamp is feasible and accurate for determining the MED to use in calculating the UV irradiation treatment dose.


Asunto(s)
Eritema/terapia , Fluorescencia , Iluminación , Fototerapia/instrumentación , Fototerapia/métodos , Relación Dosis-Respuesta en la Radiación , Eritema/diagnóstico , Estudios de Factibilidad , Humanos , Psoriasis/diagnóstico , Psoriasis/terapia , Piel/patología , Piel/efectos de la radiación
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