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1.
Eur J Haematol ; 113(2): 227-234, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38665060

RESUMEN

OBJECTIVES: Our aim was to describe the frequency and severity of infectious complications after chimeric antigen receptor (CAR) T-cell therapy in patients with large B-cell lymphoma (LBCL). METHODS: We retrospectively reviewed clinical records of LBCL patients treated with CD19-targeted CAR T-cell therapy from July/2018 to December/2021 at our institution, and identified all infectious episodes from CAR T-cell infusion until disease progression, death or last follow-up. RESULTS: Overall, 137 patients were included. Thirty six percent had received ≥3 previous lines of therapy and 26% an autologous hematopoietic cell transplantation (auto-HCT). Cytokine release syndrome occurred in 87 (64%) patients. Antibacterial prophylaxis was not used in any patient; only 38% received antifungal prophylaxis. Sixty three infectious events were observed in 41 (30%) patients. Fifty two (83%) of the infectious events had at least one pathogen identified (bacteria [n = 38], virus [n = 11], and fungi [n = 3]). Most of the infectious events occurred during hospitalization for CAR-T treatment. Infection-related mortality was observed in two patients. Independent risk factors for infection included male gender, previous auto-HCT, ≥3 lines of treatment and pre-lymphodepletion neutropenia. CONCLUSIONS: Infections after CAR T-cell therapy in patients with lymphoma are frequent but generally not severe. A conservative and tailored antimicrobial prophylaxis seems to be a safe approach.


Asunto(s)
Antifúngicos , Inmunoterapia Adoptiva , Humanos , Masculino , Femenino , Inmunoterapia Adoptiva/métodos , Inmunoterapia Adoptiva/efectos adversos , Persona de Mediana Edad , Anciano , Antifúngicos/uso terapéutico , Adulto , Estudios Retrospectivos , Profilaxis Antibiótica/métodos , Linfoma de Células B/terapia , Linfoma de Células B/inmunología , Estadificación de Neoplasias , Receptores Quiméricos de Antígenos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Linfoma de Células B Grandes Difuso/terapia , Antibacterianos/uso terapéutico , Micosis/prevención & control , Micosis/etiología , Factores de Riesgo
4.
Plant Foods Hum Nutr ; 72(3): 294-300, 2017 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-28831659

RESUMEN

Quinoa protein concentrate (QPC) was extracted and digested under in vitro gastrointestinal conditions. The protein content of QPC was in the range between 52.40 and 65.01% depending on the assay used. Quinoa proteins were almost completely hydrolyzed by pepsin at pH of 1.2, 2.0, and 3.2. At high pH, only partial hydrolysis was observed. During the duodenal phase, no intact proteins were visible, indicating their susceptibility to the in vitro simulated digestive conditions. Zebrafish larvae model was used to evaluate the in vivo ability of gastrointestinal digests to inhibit lipid peroxidation. Gastric digestion at pH 1.2 showed the highest lipid peroxidation inhibition percentage (75.15%). The lipid peroxidation activity increased after the duodenal phase. The digest obtained at the end of the digestive process showed an inhibition percentage of 82.10%, comparable to that showed when using BHT as positive control (87.13%).


Asunto(s)
Chenopodium quinoa/química , Peroxidación de Lípido/efectos de los fármacos , Proteínas de Plantas/farmacología , Animales , Digestión/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Concentración de Iones de Hidrógeno , Hidrólisis , Larva , Proteínas de Plantas/química , Pez Cebra
5.
Rev Gastroenterol Mex ; 82(3): 226-233, 2017.
Artículo en Inglés, Español | MEDLINE | ID: mdl-28298258

RESUMEN

INTRODUCTION: Enteropathogenic bacteria isolated in Mexico City have shown a high rate of resistance to different antibiotics, with the exception of rifaximin (RIF). RIF is a nonabsorbable antibiotic that reaches high fecal concentrations (≈ 8,000µg/g). Susceptibility to antimicrobials can vary in different geographic regions. AIM: To study the susceptibility to rifaximin and other antimicrobials of enteropathogenic bacteria isolated in patients with acute diarrhea in the southeastern region of Mexico. MATERIAL AND METHODS: A total of 614 strains of bacteria isolated from patients with acute diarrhea from 4 cities in Southeast Mexico were analyzed. An antibiogram with the following antibiotics was created: ampicillin (AMP), trimethoprim/sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), ciprofloxacin (CIP), chloramphenicol (CHL), and fosfomycin (FOS), assessed through the agar diffusion method at the standard concentrations recommended by the Clinical and Laboratory Standards Institute (CLSI) and the American Society for Microbiology (ASM), and RIF, assessed through microdilution at 4 concentrations. RESULTS: The bacteria were Escherichia coli (55%), as the majority, in all its pathogenic variants, Shigella (16.8%), Salmonella (15.3%), Aeromonas (7.8%), and less than 5% Campylobacter, Yersinia, Vibrio, and Plesiomonas. The accumulated overall susceptibility to RIF was 69.1, 90.8, 98.9, and 100% at concentrations of 100, 200, 400, and 800µg/ml, respectively. Overall susceptibility to other antibiotics was FOS 82.8%, CHL 76.8%, CIP 73.9%, FUR 64%, T-S 58.7%, NEO 55.8%, and AMP 23.8%. Susceptibility to RIF at 400 and 800µg was significantly greater than with the other antimicrobials (P<.001). CONCLUSIONS: The data of the present study were similar to those of a previous study carried out in Mexico City: susceptibility to RIF in > 98% of the bacterial strains and a high frequency of resistance to several common antimicrobials.


Asunto(s)
Antibacterianos/farmacología , Diarrea/microbiología , Farmacorresistencia Bacteriana , Gastroenteritis/microbiología , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/microbiología , Rifamicinas/farmacología , Enfermedad Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Bacterias Gramnegativas/aislamiento & purificación , Infecciones por Bacterias Gramnegativas/diagnóstico , Humanos , Lactante , Recién Nacido , Masculino , México , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Rifaximina , Adulto Joven
6.
Rev Gastroenterol Mex ; 81(1): 3-10, 2016.
Artículo en Inglés, Español | MEDLINE | ID: mdl-26525276

RESUMEN

BACKGROUND: Bacterial resistance may hamper the antimicrobial management of acute gastroenteritis. Bacterial susceptibility to rifaximin, an antibiotic that achieves high fecal concentrations (up to 8,000µg/g), has not been evaluated in Mexico. OBJECTIVE: To determine the susceptibility to rifaximin and other antimicrobial agents of enteropathogenic bacteria isolated from patients with acute gastroenteritis in Mexico. MATERIAL AND METHODS: Bacterial strains were analyzed in stool samples from 1,000 patients with diagnosis of acute gastroenteritis. The susceptibility to rifaximin (RIF) was tested by microdilution (<100, <200, <400 and <800µg/ml) and susceptibility to chloramphenicol (CHL), trimethoprim-sulfamethoxazole (T-S), neomycin (NEO), furazolidone (FUR), fosfomycin (FOS), ampicillin (AMP) and ciprofloxacin (CIP) was tested by agar diffusion at the concentrations recommended by the Clinical & Laboratory Standards Institute and the American Society for Microbiology. RESULTS: Isolated bacteria were: enteropathogenic Escherichia coli (E. coli) (EPEC) 531, Shigella 120, non-Typhi Salmonella 117, Aeromonas spp. 80, enterotoxigenic E. coli (ETEC) 54, Yersinia enterocolitica 20, Campylobacter jejuni 20, Vibrio spp. 20, Plesiomonas shigelloides 20, and enterohemorrhagic E. coli (EHEC 0:157) 18. The overall cumulative susceptibility to RIF at <100, <200, <400, and <800µg/ml was 70.6, 90.8, 99.3, and 100%, respectively. The overall susceptibility to each antibiotic was: AMP 32.2%, T-S 53.6%, NEO 54.1%, FUR 64.7%, CIP 67.3%, CLO 73%, and FOS 81.3%. The susceptibility to RIF <400 and RIF <800µg/ml was significantly greater than with the other antibiotics (p<0.001). CONCLUSIONS: Resistance of enteropathogenic bacteria to various antibiotics used in gastrointestinal infections is high. Rifaximin was active against 99-100% of these enteropathogens at reachable concentrations in the intestine with the recommended dose.


Asunto(s)
Antibacterianos/farmacología , Infecciones Bacterianas/microbiología , Gastroenteritis/microbiología , Rifamicinas/farmacología , Enfermedad Aguda , Humanos , México , Pruebas de Sensibilidad Microbiana , Rifaximina
7.
Rev Clin Esp (Barc) ; 223(1): 1-9, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36182538

RESUMEN

BACKGROUND AND OBJECTIVE: Available data support differences by gender in the leadership of clinical investigations (CI). This study analyzes to what extent women lead these investigations. MATERIALS AND METHODS: Observational-retrospective study in a tertiary university hospital associated with one of the most important health research institutes in Spain. We analyzed the principal investigators (PI) by gender from 2001 to 2020. MAIN OUTCOME: proportion of CI led by female doctors (FD) during the study period. SECONDARY OUTCOMES: differences in PI by gender according to the type of study: clinical trials (CT) or non-interventional-researches (NIR) and according to type of funding. DATA SOURCES: Research Ethics Committee (REC) and Human Resources Department registries. RESULTS: During the study, the REC approved 8466 protocols, 52% (4408/8466) were EC, the rest were NIR. Women led 39.7% (3360/8466) of the total. The gender gap was observed mainly in EC: FD were IP of 31.5% of them (1391/4408) and 48.5% (1969/4058) of NIR. This despite the increasing trend in the number of FD staff. By type of funding, when the studies were supported by private sector there was a wider gap markedly unfavorable for women. CONCLUSIONS: Our results show that there is underrepresentation of women in research leadership, mainly those with private financing. This study reinforces the idea that there is still a long way to go in this field. More studies are necessary to identify the existing differences that allow the implementation of actions at the institutional and cultural level that promote gender equality in the field of clinical research.


Asunto(s)
Liderazgo , Médicos , Humanos , Femenino , España , Estudios Retrospectivos , Recursos Humanos
8.
Rev Neurol ; 75(8): 247-250, 2022 10 16.
Artículo en Español | MEDLINE | ID: mdl-36218255

RESUMEN

INTRODUCTION: The massive vaccination against the SARS-CoV-2 virus has demonstrated to be one of the major measures for the reduction of the morbidity and mortality that this virus causes. However, during the last months the administration of the vaccine has been also associated with some rare, but life-threatening, adverse effects. CASE REPORT: In this article we describe the case of a patient that developed a Guillain-Barre syndrome and an Idiopathic thrombocytopenic purpura nine days after the vaccination with the third dose for the SARS-CoV-2 virus (Moderna). He had received previously two doses of the AstraZeneca vaccine. Moreover, the patient was positive for auto-antibodies anti-SSA/Ro60 and auto-antibodies IgG anti-GM1 and IgG anti-GM3. DISCUSSION: Even though it is not possible to stablish a clear relation of causality between the administration of the vaccine booster for SARS-CoV-2 and the diseases developed by the patient, the association of two concomitant autoimmune processes is remarkable. As well as the positivity for the auto-antibodies anti-SSA/Ro60, which have been described in the bibliography in cases of SARS-CoV-2 infection.


TITLE: Síndrome de Guillain-Barré y trombocitopenia tras la vacunación contra el SARS-CoV-2 con Moderna. Descripción de un caso.Introducción. La vacunación masiva contra el virus SARS-CoV-2 constituye una de las principales estrategias en la reducción de la morbimortalidad que presenta dicho virus. No obstante, a lo largo de los últimos meses, su administración también se ha relacionado con diversos efectos adversos raros, pero potencialmente graves. Caso clínico. En el presente artículo describimos el caso de un paciente que desarrolló un síndrome de Guillain-Barré y una púrpura trombocitopénica idiopática nueve días después de la vacunación con la tercera dosis contra el virus SARS-CoV-2 (Moderna), con dos dosis previas de AstraZeneca. Adicionalmente, destaca la presencia de positividad para autoanticuerpos anti-SSA/Ro60 y para anticuerpos inmunoglobulina G anti-GM1 e inmunoglobulina G anti-GM3. Conclusión. Aunque no es posible establecer una relación de causalidad entre la administración del booster de la vacuna y el desarrollo de la enfermedad, es destacable la asociación de dos procesos autoinmunes concomitantes, junto con la positividad en los autoanticuerpos anti-SSA/Ro60, lo cual se ha descrito en la bibliografía en casos de infección del virus SARS-CoV-2.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Síndrome de Guillain-Barré , Trombocitopenia , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Síndrome de Guillain-Barré/etiología , Humanos , Inmunoglobulina G , Masculino , SARS-CoV-2 , Trombocitopenia/etiología , Vacunación/efectos adversos , Vacunas Virales
9.
Ecol Appl ; 18(7): 1795-809, 2008 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-18839773

RESUMEN

Invasive species are a major threat to the sustainable provision of ecosystem products and services, both in natural and agricultural ecosystems. To understand the spatial arrangement of species successively introduced into the same ecosystem, we examined the tolerance to temperature and analyzed the field distribution of three potato tuber moths (PTM, Lepidoptera: Gelechiidae), that were introduced in Ecuador since the 1980s. We studied physiological responses to constant temperatures of the three PTM species under laboratory conditions and modeled consequences for their overall population dynamics. We then compared our predictions to field abundances of PTM adults collected in 42 sites throughout central Ecuador. Results showed that the three PTM species differed with respect to their physiological response to temperature. Symmetrischema tangolias was more cold tolerant while Tecia solanivora had the highest growth rates at warmer temperatures. Phthorimaea operculella showed the poorest physiological performance across the range of tested temperatures. Overall, field distributions agree with predictions based on physiological experiments and life table analyses. At elevations >3000 m, the most cold-tolerant species, S. tangolias, was typically dominant and often the only species present. This species may therefore represent a biological sensor of climate change. At low elevations (<2700 m), T. solanivora was generally the most abundant species, probably due to its high fecundity at high temperatures. At mid elevations, the three species co-occurred, but P. operculella was generally the least abundant species. Consistent with these qualitative results, significant regression analyses found that the best predictors of field abundance were temperature and a species x temperature interaction term. Our results suggest that the climatic diversity in agricultural landscapes can directly affect the community composition following sequential invasions. In the tropical Andes, as in other mountain ecosystems, the wide range of thermal environments found along elevational gradients may be one reason why the risks of invasion by successively introduced pest species could increase in the near future. More data on potential biological risks associated with climatic warming trends in mountain systems are therefore urgently needed, especially in developing nations where such studies are lacking.


Asunto(s)
Demografía , Mariposas Nocturnas/fisiología , Clima Tropical , Animales , Conservación de los Recursos Naturales , Ecuador , Larva/fisiología , Óvulo/fisiología , Pupa/fisiología , Temperatura
10.
Rev. enferm. neurol ; 21(3): 226-234, sep.-dic. 2022.
Artículo en Español | LILACS, BDENF - enfermagem (Brasil) | ID: biblio-1428428

RESUMEN

Introducción: El problema de la violencia no sólo afecta a quien la padece, pues tiene efectos colaterales en los hijos y otros familiares, lo cual deteriora su salud física, mental y emocional. Objetivo: Analizar la situación de desigualdad y la violencia de género en las mujeres. Metodología: El estudio se realizó bajo un enfoque cualitativo de tipo fenomenológico, aplicando la técnica de la entrevista a profundidad con previo consentimiento informado para su grabación, transcripción, análisis e interpretación. Resultados: Se identificaron formas de violencia física, sexual, psicológica, económica y patrimonial debido a las relaciones asimétricas dentro del hogar, producto del machismo y un sistema patriarcal que afectan la calidad de vida y el desarrollo social de las mujeres. Limitaciones: Las mujeres participantes eran vendedoras del mercado municipal y contaban con poco tiempo disponible para las entrevistas, pues el cierre de sus puestos de trabajo podía generar pérdidas económicas. Valor del estudio: La violencia y desigualdad de género son problemáticas en los países latinoamericanos que se deben abordar desde toda perspectiva para su identificación y prevención oportuna. Conclusiones: La situación de violencia y desigualdad de género ha tenido un impacto negativo no sólo en la vida de las mujeres entrevistadas, sino también de su núcleo familiar, sin embargo, cada una de ellas busca mejorar sus condiciones de vida a pesar de estas adversidades.


Introduction: Gender violence does not only affect the women who suffer it, since it causes collateral effects to children and other family members that deteriorates their physical, mental and emotional health. Objective: To analyze gender inequality and gender-based violence against women. Methodology: We carried out qualitative research of phenomenological type, applying in-depth interviews with previously informed consent for its recording, transcription, analysis and interpretation. Results: Physical, sexual, psychological, economic and patrimonial violence were identified in asymmetrical relationships as a result of sexism and the patriarchal system, which affects women's quality of life and social development. Limitations: Female participants were vendors from a local market and had limited time for the interviews, since the closing of their stands could cause economic losses. Value of the study: Gender-based violence and gender inequality constitute a problem in Latin American countries that should be thoroughly studied for its identification and timely prevention. Conclusions: Gender-based violence and gender inequality produces a negative impact not only on the lives of the women interviewed, but also on their families, however, every one of them tries to improve their life conditions and overcome adversities.


Asunto(s)
Humanos , Femenino , Adulto , Persona de Mediana Edad , Anciano , Adulto Joven , Mujeres Maltratadas , Delitos Sexuales , Violencia de Género , Abuso Emocional , Equidad de Género
11.
Rev. argent. endocrinol. metab ; 57(4): 1-10, dic. 2020. graf
Artículo en Español | LILACS-Express | LILACS | ID: biblio-1155670

RESUMEN

Es conocida la relación entre la diabetes y la demencia según numerosos estudios, siendo estas enfermedades crónicas no transmisibles de gran impacto en la salud pública. En la actualidad existen diversos estudios sobre el control glicémico en pacientes diabéticos adultos mayores, población en la cual se han encontrado controversias sobre esta temática, específicamente en el control glicémico estricto, en especial en población muy mayor. El objetivo del estudio es determinar la asociación entre trastornos neurocognitivos según MiniMental State Examination y control glicémico adecuado en adultos mayores diabéticos de 80 años en comparación a los no controlados, atendidos en el Centro Médico Naval entre 2017 y 2018. Se realizó un estudio analítico, transversal, retrospectivo, análisis secundario de base de datos. La muestra final fue de 66 participantes. Se evaluó el control glicémico y el grado de trastorno neuro cognitivo (TNC). Se realizó un análisis descriptivo de las variables principales y un análisis bivariado comparando las covariables con la variable dependiente. Finalmente, las variables significativas en el análisis bivariado fueron incluidas en el modelo de regresión de Poisson. En los resultados se observó que el 92.42% no tuvo un control glicémico adecuado y presentaron trastornos neurocognitivos el 22.73% de los participantes. El valor de glucosa promedio en el grupo sin TNC fue de 99.53 ± 16.26 y del grupo con TNC el cual fue de 117.40 ± 55.01; además el valor de hemoglobina glicosilada fue en promedio de 7.96% ± 0.55 en el grupo con TNC y de 5.81 ± 0.54% en grupo sin TNC. En el modelo de regresión ajustado se obtuvo un valor de 1.13 (1.11-1.26). Se concluye que los pacientes con mal control glicémico tuvieron más riesgo de sufrir deterioro de la función cognitiva.


The relationship between diabetes and dementia is well known according to múltiple studies. These non-transmissible chronic conditions have a great impact in public health. Nowadays there are several studies that discuss the glycemic control in elderly diabetic patients and there have been controversies about this topic, especially in the strict glycemic management in very old populations. The objective of the study is to determine the relationship between cognitive impairment according to MiniMental State Examination procedure in appropriately controlled glycemic index in 80 years old diabetic adults versus not appropriately controlled, who were monitored at the Navy Medical Center between 2017 and 2018. The research consisted of an analytical, transversal and retrospective secondary analysis of a database. The final sample consisted of 66 participants. The glycemic control and the degree of neurocognitive impairment were evaluated. A descriptive analysis of the main variables was made and a bivariate analysis comparing the covariables with the dependent variable. Finally, all the meaningful variables in the bivariate analysis were included in the Poisson regression model. In the results it was observed that 92.42% did not have and adequate glycemic control and 22.73% of those presented neurocognitive impairments (NCI). The mean glucose value in the group without NCI was 99.53 ±16.26 and the group with NCI 117.40 ± 55.01. Furthermore, the glycosylated hemoglobin was on average of 7.96% ± 0.55 in the NCI group and 5.81 ± 0.54 % in the group without NCI. In the adjusted regression model, the value obtained was 1.13 (1.11-1.26). It was concluded that the patients with an inadequate glycemic control were more at risk of suffering cognitive decline.

12.
Transplantation ; 67(4): 637-8, 1999 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-10071042

RESUMEN

High-dose administration of intravenous immunoglobulin is reported to be useful for inhibiting complement-dependent immune cytolysis. We have found that, among the proposed C1q-binding sites of the Fc portion of human IgG1, only residues 282-292 inhibited pig red blood cell lysis by human serum. Moreover, a hexadecemeric multiple antigen peptide of residues 282-292 from IgG showed significantly greater activity in suppressing complement-mediated immune cytolysis and can be used in place of high-dose intravenous immunoglobulin, which is extracted from donors and thus is expensive.


Asunto(s)
Proteínas del Sistema Complemento/inmunología , Hemólisis , Regiones Constantes de Inmunoglobulina/fisiología , Inmunoglobulina G/fisiología , Fragmentos de Péptidos/fisiología , Complemento C1q/metabolismo , Humanos
13.
Peptides ; 21(3): 327-30, 2000 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10793212

RESUMEN

In recent years, several endogenous mammalian antibacterial peptides have been described. An amphipathic cationicalpha-helix is a common feature in many cases; therefore, other peptides with this characteristic might also possess antibiotic activity. In fact, a 30-mer peptide of apoprotein E 133-162 (LRVRLASHLRKLRKRLLRDADDLQKRLAVY) was found to have antibiotic activity comparable to those of a classic antibiotic (Gentamicin) and a neutrophil-derived antibiotic peptide (CAP18). Calculation of cationicity, hydrophobicity, and hydrophobic moment and the helical wheel diagram of apoprotein E 133-162 revealed close similarities to CAP18.


Asunto(s)
Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos , Apolipoproteínas E/química , Apolipoproteínas E/farmacología , Bacterias/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Secuencia de Aminoácidos , Proteínas Portadoras/farmacología , Catelicidinas , Resistencia a Múltiples Medicamentos , Escherichia coli/efectos de los fármacos , Gentamicinas/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Fragmentos de Péptidos/síntesis química , Fragmentos de Péptidos/química , Estructura Secundaria de Proteína , Pseudomonas aeruginosa/efectos de los fármacos , Salmonella/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos
14.
Genome Inform ; 12: 113-22, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11791230

RESUMEN

In the present work we evaluate the performance of an algorithm for the automatic recognition of binding sites in proteins as well as in other macromolecules whose interactions are involved in many cellular and physiological processes. The algorithm is a combination of an unsupervised learning algorithm - based on Kohonen self organizing maps - to characterize the properties of patches of protein solvent accessible surfaces and a filtering algorithm to establish both the physical boundaries of the patches as well as the level of contribution of different and distant atoms involved in the interaction. We have found that the algorithm performs extremely well in a set of randomly selected protein complexes for which the interaction interfaces are extracted and compared with the results of the algorithm. A statistical evaluation of the algorithm is additionally performed by analysis of the degree of hydrophobicity and hydrophilicity of the output patches and comparison with that of the observed interface constituent amino acids.


Asunto(s)
Algoritmos , Proteínas/química , Proteínas/inmunología , Sitios de Unión , Biología Computacional , Epítopos , Sustancias Macromoleculares , Modelos Moleculares , Proteínas/metabolismo
15.
Leukemia ; 28(10): 1993-2004, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24618734

RESUMEN

Chronic lymphocytic leukemia (CLL) cells located in proliferation centers are constantly stimulated by accessory cells, which provide them with survival and proliferative signals and mediate chemotherapy resistance. Herein, we designed an experimental strategy with the aim of mimicking the microenvironment found in the proliferative centers to specifically target actively proliferating CLL cells. For this, we co-cultured CLL cells and bone marrow stromal cells with concomitant CD40 and Toll-like receptor 9 stimulation. This co-culture system induced proliferation, cell-cycle entry and marked resistance to treatment with fludarabine and bendamustine. Proliferating CLL cells clustered together showed a typical morphology of activated B cells and expressed survivin protein, a member of the inhibitor of apoptosis family that is mainly expressed by CLL cells in the proliferation centers. With the aim of specifically targeting actively proliferating and chemoresistant CLL cells, we investigated the effects of treatment with YM155, a small-molecule survivin inhibitor. YM155 treatment suppressed the co-culture-induced survivin expression and that was sufficient to inhibit proliferation and effectively induce apoptosis particularly in the proliferative subset of CLL cells. Interestingly, sensitivity to YM155 was independent from common prognostic markers, including 17p13.1 deletion. Altogether, these findings provide a rationale for clinical development of YM155 in CLL.


Asunto(s)
Antineoplásicos/química , Resistencia a Antineoplásicos , Proteínas Inhibidoras de la Apoptosis/metabolismo , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Clorhidrato de Bendamustina , Células de la Médula Ósea/citología , Antígenos CD40/metabolismo , Ciclo Celular , Proliferación Celular , Técnicas de Cocultivo , Femenino , Eliminación de Gen , Humanos , Imidazoles/química , Leucocitos Mononucleares/citología , Masculino , Persona de Mediana Edad , Naftoquinonas/química , Compuestos de Mostaza Nitrogenada/química , Células del Estroma/citología , Survivin , Receptor Toll-Like 9/metabolismo , Vidarabina/análogos & derivados , Vidarabina/química
17.
Rev. arg. morfol ; 3(1): 23-27, 2014. ilus
Artículo en Español | LILACS | ID: lil-776945

RESUMEN

El músculo subescapular es de forma triangular aplanada,situado profundamente en la cara anterior de la escápula,en la fosa subescapular, se inserta en el labioanterior del borde medial de la escápula por delante delserrato anterior; en toda la superficie anterior de la caraanterior del hueso. Es el más grande de los cuatro músculosdel manguito rotador. Clásicamente se analiza lafunción del subescapular así como las demás estructurasdel hombro de una forma muy simplificada, en gestosfuncionales las exigencias y la complejidad son elevadas.El músculo subescapular es una estructura blanda,esta condición determina que el dolor percibido anteuna lesión sea referido, es decir que existe una discrepanciaentre el sitio donde se percibe el dolor y el sitio dela lesión. La lesión en él puede ser difícil de localizar acausa de esto y debido a que suele estar asociada a lade otras estructuras del manguito rotador, aunque hayvarias estrategias semiológicas para identificarlo comoestructura afectada. El músculo subescapular es unaestructura estabilizadora clave en la función normal delhombro...


The subscapularis muscle has a triangular flattenislocated deep in the front of the scapula, in the subscapularfossa, is inserted into the anterior lip of the medial borderof the scapula ahead serratus anterior, across the anteriorsurface of the anterior bone.The subscapularismuscle is the biggest of the four muscles of the rotatorcuff. Traditionally, it is analysed as regards the function ofthe subscapularis, as well as the others structures of theshoulder in a very simplify way in functional gestures therequirement and the complexity are high. The subscapularis muscle is a soft structure, this conditiondetermines that the perceived pain before an injury bereferred to, that is to say, there is divergence between theplace where the pain is perceived and the place wherethe damage is. The injury in it can be difficult to pinpointas a result of this, because of this, the injure can beassociated to other structures to the rotator cuff; eventhough, there are some semiological strategies to identifythe structures involved. The subscapularis muscle is akey stabilising structure in the normal function of the shoulder...


Asunto(s)
Humanos , Masculino , Femenino , Músculos de la Espalda , Escápula/anatomía & histología , Escápula/patología
18.
Anim Genet ; 36(2): 146-51, 2005 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-15771726

RESUMEN

Bovine chromosome 20 (BTA20) is associated with several quantitative trait loci (QTL) for meat tenderness, birth weight, milk yield and composition. Fine mapping of these QTL requires the development of additional informative markers to increase the resolution of the BTA20 genetic and physical maps. A BTA20-specific library was constructed by means of microdissection and microcloning, and screened for dinucleotide repeats with (CA)16 and (GT)16 oligos. A total of 60 new microsatellites (MS) were developed and characterized for polymorphism using the U.S. Department of Agriculture (USDA)/Meat Animal Research Center (MARC) bovine reference family, of which 53 markers were informative in this family. The number of alleles for these loci varied from 1 to 14, with an average of 6.5. Thirty-three of these MSs, together with 105 markers previously mapped to BTA20, were scored on a 7000-rad cattle-hamster whole-genome radiation hybrid panel (SUNbRH), resulting in a high-resolution RH7000 rad map for BTA20.


Asunto(s)
Bovinos/genética , Cromosomas de los Mamíferos/genética , Biblioteca de Genes , Repeticiones de Microsatélite/genética , Mapeo de Híbrido por Radiación , Animales , Secuencia de Bases , Clonación Molecular/métodos , Cartilla de ADN , Microdisección , Datos de Secuencia Molecular , Análisis de Secuencia de ADN
19.
Artículo en Inglés | MEDLINE | ID: mdl-11700601

RESUMEN

We propose a parallel hybrid genetic algorithm for flexible protein-protein docking in order to improve the conventional rigid-body models to manipulate protein-protein interactions. The proposed hybrid algorithm is a combination of an evolutionary algorithm with a simulated annealing one, yielding a powerful protein-complex conformation-searching engine. Parallelization of the procedure makes possible to reach high algorithm performance, in both, execution times and size of treated monomers and complexes. Knowledge on side chain flexibility is extracted by means of an exhaustive analysis of crystallographic data on proteins and protein complexes. Results demonstrate the competency of the algorithm since comparison of calculated and crystallographic data accounts for a maximum of 2.5A in RMS difference, including side chain conformation. The system allows routine analysis of this fundamental molecular biology problem important to elucidate bio-macromolecular function in biophysical and biochemical mechanisms involving molecular recognition and interaction, yielding simultaneously clues for designing new proteins and enzymes directed to different purposes.


Asunto(s)
Algoritmos , Proteínas/química , Evolución Biológica , Biología Computacional , Simulación por Computador , Sustancias Macromoleculares , Modelos Genéticos , Modelos Moleculares , Mutación , Unión Proteica , Conformación Proteica , Proteínas/genética , Proteínas/metabolismo
20.
Rev. arg. morfol ; 2(3): 38-38, 2014. ilus
Artículo en Español | LILACS | ID: lil-777716

RESUMEN

Este artículo aborda una breve biografía al Prof. Dr. Pablo Luis Mirizzzi en econmemoración al 50 aniversario de su fallecimiento.


This article deals a brief biography of Prof. Dr. Pablo Luis Mirizzzi in econmemoración the 50th anniversary of his death.


Asunto(s)
Humanos , Masculino , Biografías como Asunto , Colangiografía , Médicos/historia , Médicos
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