RESUMEN
BACKGROUND: Acute respiratory distress syndrome (ARDS) with COVID-19 has a worse prognosis than ARDS with other diseases. Mortality from ARDS with COVID-19 is 26.0 - 61.5%, and due to other causes - 35.3-37.2%. OBJECTIVE: To find of the correlation between polymorphonuclear leukocytes (PMNs), lymphocytes, and macrophages in the cellular composition of the inflammatory infiltrate at different stages and phases of diffuse alveolar damage (DAD) with COVID-19, analyzing the autopsy material. MATERIAL AND METHODS: The lung tissue of 25 patients who died from ARDS with COVID-19 without a secondary bacterial or mycotic infection, another thanatologically significant pathology of the lungs, was studied. To study the cellular composition of the inflammatory infiltrate and the dynamics of its changes a double immunohistochemical analysis of the expression of antibodies to CD15, CD3, and CD68 was used. RESULTS: The inflammatory infiltrate and intraalveolar exudate in the exudative phase of DAD was represented by 56.8% of PMNs (CD15-positive cells; hereinafter - the average value of the percentage of positive cells to the total number of cells of the inflammatory infiltrate), 6.9% - lymphocytes (CD3-positive cells) and 19.5% macrophages (CD68-positive cells). In the early stage of the proliferative phase: 14.1% PMNs, 38.7% lymphocytes and 13.5% macrophages. In the late stage of the proliferative phase: 11.3% PMNs, 14.5% lymphocytes and 39.3% macrophages. CONCLUSIONS: In the exudative phase of DAD a statistically significant predominance of PMN was revealed, which could determine the main volume of lung damage and the severity of ARDS with COVID-19. In the early stage of the proliferative phase of DAD, a statistically significant change in the composition of the inflammatory infiltrate was revealed to compare with the exudative phase: a significant decrease in the content of PMNs relative to the total number of cells in the inflammatory infiltrate; an increase in the number of lymphocytes, which is probably associated with the start of organization and repair processes. In the late stage of the proliferative phase of DAD, compared with its early stage, was revealed a statistically significant increase in the number of macrophages in ratio.
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COVID-19 , Síndrome de Dificultad Respiratoria , Autopsia , Humanos , Pulmón/patología , Alveolos Pulmonares/patologíaRESUMEN
We studied biocompatibility and bioresorption of 3D-printed polylactide and polyglycolide tissue membranes. Ultrasound microscopy and histological examination showed that membranes fabricated of a copolymer of lactic and glycolic acids in a mass ratio of 1:9 are bioresorbed and have good biocompatibility with soft tissues (connective tissue, adipose tissue, and epithelium). An important feature of the copolymer membranes, which differs them from pure polylactide membranes, is the formation of a thin fibrous capsule that did not interfere its destruction by the mechanism of hydrolytic resorption.
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Materiales Biocompatibles/química , Poliésteres/química , Ácido Poliglicólico/química , Membranas Artificiales , Impresión TridimensionalRESUMEN
AIM: To improve the results of treatment of a widespread purulent peritonitis in children by optimizing fluid therapy includes the use of combined treatment: reamberin and remaxol. MATERIAL AND METHODS: We studied 269 patients aged 1 to 15 years with a widespread purulent peritonitis treated at the children's surgical departments in Samara from 2001 to 2015. The study group included 179 children who used the optimized infusion therapy. In the study group was allocated to 2 groups: 69 children in infusion therapy which used reamberin and 110 patients in which treatment was applied reamberin and remaxol. The surgical treatment used laparoscopic sanation of the abdomen. Comprehensive survey included a study of dynamics of the white blood cell count, leukocyte index Kalf-Caliph, erythrocyte sedimentation rate, temperature, total albumin concentration, transaminase levels. Catamnesis studied 48 patients with the definition of complex intima-media thickness in the projection of basilar, brachial and femoral arteries. RESULTS: A study compared indicators of both groups, revealed a more rapid reduction of intoxication symptomps (leukocytosis, LII, body temperature), the disappearance of enteric disease, recovery of protein-synthetic function of the liver, decrease of cytolytic and mesenchymal-inflammatory syndromes in the main group, especially in the subgroup in which treatment was included remaxol. CONCLUSION: The use of reamberin and remaxol in infusion therapy led to improvement of the results of the treatment of common purulent peritonitis in children. Study catamnesis with the study of the intima-media revealed that children undergoing widespread purulent peritonitis further develop signs of endothelial dysfunction. The developed clinical recommendations to significantly reduce the risk of developing signs of endothelial dysfunction, thereby reducing the possible appearance of vascular pathology in patients who underwent childhood widespread purulent peritonitis.
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Arterias/diagnóstico por imagen , Fluidoterapia/métodos , Peritonitis/terapia , Succinatos/uso terapéutico , Enfermedades Vasculares/prevención & control , Adolescente , Arterias/fisiopatología , Niño , Preescolar , Terapia Combinada , Endotelio Vascular/diagnóstico por imagen , Humanos , Lactante , Laparoscopía , Peritonitis/tratamiento farmacológico , Enfermedades Vasculares/etiologíaRESUMEN
Informative capacity analysis of immunohistochemistry (IHC) and flow cytometry (FCM) in the assessment of estrogen receptor α (ERα) expression in breast cancer tissue was performed. Similar frequencies of expression were shown by both methods: 27% of ERα-negative and 73% ERα-positive cases. However, IHC evaluation detected low levels in only 20% of ERα-positive cases, whereas low levels of ERα detected by FCM were 2 times more often (48%). Moreover, FCM revealed positive expression (23-60%) in 33% of IHC ERα-negative cases. Among IHC ER-positive cases, zero ERα expression was detected by FCM in 12.5%. The approaches to minimize errors in routine clinical determination of the estrogen receptor status were proposed.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/diagnóstico , Receptor alfa de Estrógeno/metabolismo , Biomarcadores de Tumor/genética , Receptor alfa de Estrógeno/genética , Femenino , Citometría de Flujo , Humanos , InmunohistoquímicaRESUMEN
The paper reviews the literature on primary paratesticular tumors. It describes the classification, brief characteristics of liposarcomas and the morphological pattern of the tumor with an immunohistochemical profile. A clinical case of differentiated liposarcoma of the spermatic cord with myxoid and rhabdomyoblastic differentiation is depicted in a 61-year-old man.
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Liposarcoma/metabolismo , Liposarcoma/patología , Cordón Espermático/metabolismo , Cordón Espermático/patología , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/patología , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana EdadRESUMEN
It was retrospectively analyzed clinicopathological features of 529 breast cancer patients treated at the Ulyanovsk Oncology Center. Of 529 patients 235 (44.4%) had at least one positive axillary lymph node. Tumor size (p = 0,0005), histological grade (p = 0004), lymphovascular invasion (p < 0,0001), HER2-status (p = 0,014) and total score of malignancy (p < 0,0001) were significant independent predictors for lymph nodes metastases. By univariate and multivariate regression analysis it was created the graphic variant of nomogram which could predict the risk of lymph nodes metastases in breast cancer patients. An area under ROC-curve in our nomogram reached 0,737 that demonstrated high prediction level of accuracy of the developed model. Thus new nomogram is a useful tool in planning axillary surgery in breast cancer patients.
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Neoplasias de la Mama/diagnóstico , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico , Nomogramas , Adulto , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/patología , Femenino , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Invasividad Neoplásica , Valor Predictivo de las Pruebas , Pronóstico , Curva ROC , Receptor ErbB-2/análisis , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Neoplasias Vasculares/secundarioRESUMEN
THE PURPOSE OF THE STUDY: Improving the treatment of advanced peritonitis via use in therapy antihypoxant Reamberin and hepatoprotector Remaxol, nutritional support, sanitation laparoscopic abdominal cavity. SUBJECTS: A total of 232 children aged 1 to 15 years with generalized purulent peritonitis treated at the children's surgical departments of Samara from 2001 to 2014. A study group comprised 148 patients who used the optimized pathogenetic therapy. In the study group was allocated two groups: 64 patients in the pathogenetic therapy that used antihypoxant reamberin, and 84 children in the treatment of which reamberin and hepatoprotector remaxol. All the children of the main group received nutritional support (trophic feedings), used in the surgical treatment of abdominal laparoscopic sanitation. Comprehensive survey includes the study of the dynamics of the level of white blood cells, leukocyte index on Kalf-Caliph, erythrocyte sedimentation rate, temperature, total albumin concentration, transaminase levels. RESULTS: Comparison of the studied parameters in the study and control groups, showed a more rapid decrease in the symptoms and signs of intoxication (leukocytosis, LII, body temperature), relief of enteric disease, recovery of protein-synthetic function of the liver, a decrease of cytolytic and mesenchymal-inflammatory syndrome in the study group, especially in the subgroup in which therapy was included remaxol. CONCLUSIONS: Optimization of treatment involving the application of the combined drugs--antihypoxant reamberin, hepatoprotector remaxol, nutritional support and implementation of laparoscopic abdominal sanitation led to improved results of therapy common purulent peritonitis in children.
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Drenaje/métodos , Laparoscopía/métodos , Meglumina/análogos & derivados , Apoyo Nutricional/métodos , Peritonitis/terapia , Succinatos/uso terapéutico , Adolescente , Niño , Preescolar , Quimioterapia Combinada , Femenino , Humanos , Lactante , Masculino , Meglumina/uso terapéutico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
The bleeding of intraoperative period is one of the actual problem in surgery. There aren't any universal hemostatic means in spite of large variety of modern hemostatic methods. An experimental research studied the results of hemostatic activity of different forms of materials on the basis of oxidize cellulose (a gauze, a powder) as compared with their foreign analog (a hemostatic gauze "SurgiceI"). Median of hemostasis time consisted of (120 ± 59.9) and (73 ± 46.8) s, in case of application of gauze and powder preparations, respectively. The rate of group using the hemostatic gauze "Surgicel" was (142 ± 77.4) s. The authors made a conclusion on the basis of given research, that the hemostatic material based on oxidize cellulose (the powder form) showed a more expressed hemostatic activity and reliably twice reduced the time of hemostasis as compared with their analog forms of gauze (p < 0.05).
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Vendajes , Pérdida de Sangre Quirúrgica/prevención & control , Celulosa Oxidada/farmacología , Hemostasis Quirúrgica , Hemostáticos/farmacología , Animales , Modelos Animales de Enfermedad , Hemostasis Quirúrgica/instrumentación , Hemostasis Quirúrgica/métodos , Técnicas Hemostáticas , Ensayo de Materiales/métodos , Polvos , Ratas , Ratas Wistar , Resultado del TratamientoRESUMEN
The molecular profile of a tumor is associated with its histological type and can be used both to study the mechanisms of tumor progression and to diagnose it. In this work, changes in the lipid profile of a malignant breast tumor and the adjacent tissue were studied. The potential possibility of determining the histological type of the tumor by its lipid profile was evaluated. Lipid profiling was performed by reverse-phase chromato-mass-spectrometric analysis the tissue of lipid extract with identification of lipids by characteristic fragments. Potential lipid markers of the histological type of tumor were determined using the Kruskal-Wallis test. Impact of lipid markers was calculated by MetaboAnalyst. Classification models were built by support vector machines with linear kernel and 1-vs-1 architecture. Models were validated by leave-one out cross-validation. Accuracy of models based on microenvironment tissue, were 99% and 75%, accuracy of models, based on tumor tissue, were 90% and 40% for the positive ion mode and negative ion mode respectively. The lipid profile of marginal (adjacent) tissue can be used for identification histological types of breast cancer. Glycerophospholipid metabolism pathway changes were statistically significant in the adjacent tissue and tumor tissue.
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Neoplasias de la Mama , Lipidómica , Humanos , Femenino , Neoplasias de la Mama/patología , Lípidos/análisis , Espectrometría de Masas , Biomarcadores , Microambiente TumoralRESUMEN
Research of cancer progression mechanisms and their impact on metabolism of tumor cells and tumor microenvironment cells is an important element in drug development for cancer target therapy. In this study, changes in tumor tissue and margin tissue lipid profiles, were associated with the following clinical and morphological characteristics: tumor size, cancer stage, multifocalite, tumor grade, number of lymph node metastasis, Nottingham prognostic index, total malignancy score, level of Ki67 protein. Lipid profiling was performed by reverse-phase chromato-mass spectrometry analysis of lipid tissue extract with lipid identification by characteristic fragments. In the lipid profile of tumor tissue 13 characteristic lipids were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Eight of 13 belonged to phosphatidylcholines. In lipid profile of tumor microenviroment tissue 13 lipid features were selected. Their levels significantly correlated with at least 5 clinical and morphological features. Four of 13 belonged to oxidized lipids, 4 lipid features belonged to sphingomyelins, four of 13 belonged to phosphatidylethanolamines. The tumor microenvironment tissue lipid profile correlated with tumor size, cancer stage, tumor grade, number of axillary metastases, Nottingham prognostic index. The tumor tissue lipid profile correlated with tumor size, tumor grade, total malignant score, and number of axillary metastases.
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Neoplasias de la Mama , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Lipidómica , Metástasis Linfática , Estadificación de Neoplasias , Pronóstico , Microambiente TumoralRESUMEN
Aberrant methylation is strongly associated with development of cancer, but limited data exist on correlation between methylation and regional lymph node metastasis (RLNM). The aim of this research was to study using of methylation levels of WIF1, RASSF1A, CDO1 and MEST aberrant methylated genes in a primary breast cancer for prediction of regional lymph node metastases. We used MS-HRM (Methylation Sensitive High Resolution Melting) to assess methylation levels. The results were confirmed by pyrosequencing. The study included 66 women with LumA and 46 women with HER2- (LumB-), 22 and 26 of them had metastasis in at least one lymph node respectively. It was found that methylation levels between LumA and LumB subtypes differed significantly in genes: WIF1 (p<0.001), CDO1 (p=0.002) and MEST (p=0.033). In the Lum A subtype statistically significant differences in level of methylation of WIF1 gene between patients with metastases in RLNM and patients without metastases were found (p=0.03). Analysis of tumors longer than 2 cm in the LumA subtype, revealed an increase of statistical significance of WIF1 gene - p=0.009 (AUC (95%CI) = 0.76 (0.59-0.93)). In LumB- subtype RASSF1A, CDO1 and MEST had statistically significant differences in methylation level between groups (p=0.03, p=0.048 and p=0.045 respectively). ROC analysis showed that combining of three genes by logistic regression, AUC (95%CI) was 0.74 (0.6-0.88). Analysis of tumors longer than 2 cm, did not increase statistical significance for these genes (p=0.046; p=0.089 and p=0.076, respectively). Thus, the study of methylation in primary tumors may be useful for prediction of lymph node metastasis, as well as for better understanding of biological process inside breast cancer.
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Neoplasias de la Mama , Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Metilación de ADN , Femenino , Humanos , Metástasis Linfática , Fenobarbital , Receptores de Estrógenos/metabolismoRESUMEN
We have studied the dynamics of microtubules in black tetra (Gymnocorymbus ternetzi) melanophores to test the possible correlation of microtubule stability and intracellular particle transport. X-rhodamine-or caged fluorescein-conjugated tubulin were microinjected and visualized by fluorescence digital imaging using a cooled charge coupled device and videomicroscopy. Microtubule dynamics were evaluated by determining the time course of tubulin incorporation after pulse injection, by time lapse observation, and by quantitation of fluorescence redistribution after photobleaching and photoactivation. The time course experiments showed that the kinetics of incorporation of labeled tubulin into microtubules were similar for cells with aggregated or dispersed pigment with most microtubules becoming fully labeled within 15-20 min after injection. Quantitation by fluorescence redistribution after photobleaching and photoactivation confirmed that microtubule turnover was rapid in both states, t1/2 = 3.5 +/- 1.5 and 6.1 +/- 3.0 min for cells with aggregated and dispersed pigment, respectively. In addition, immunostaining with antibodies specific to posttranslationally modified alpha-tubulin, which is usually enriched in stable microtubules, showed that microtubules composed exclusively of detyrosinated tubulin were absent and microtubules containing acetylated tubulin were sparse. We conclude that the microtubules of melanophores are very dynamic, that their dynamic properties do not depend critically on the state of pigment distribution, and that their stabilization is not a prerequisite for intracellular transport.
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Melanóforos/ultraestructura , Microtúbulos/metabolismo , Animales , Transporte Biológico/fisiología , Biopolímeros/metabolismo , Células Cultivadas , Peces , Técnica del Anticuerpo Fluorescente , Melanóforos/metabolismo , Microinyecciones , Fotoquímica , Rodaminas , Tubulina (Proteína)/metabolismoRESUMEN
We examined the association of a 34-kD light chain component to the heavy chains of MAP-1 using a monoclonal antibody that specifically binds the 34-kD component and labels neuronal microtubules in a specific and saturable manner. Immunoprecipitation of MAP-1 heavy chains together with the 34-kD component by the antibody indicates that the 34-kD polypeptide forms a complex with MAP-1 heavy chains. Both major isoforms of MAP-1 heavy chains (MAP-1A and MAP-1B) were found in the immunoprecipitate. Digestion of MAP-1 with alpha-chymotrypsin and analysis of the chymotryptic peptides reveals a 120-kD fragment of the MAP-1 heavy chain that binds to microtubules and is precipitable with the 34-kD light chain antibody, suggesting that the 34-kD light chain also binds to this domain of the molecule. Since microtubules that contain the 120-kD fragment lack the long lateral projections characteristic of microtubules with intact MAP-1, the 34-kD light chains may be localized at or near the microtubule surface.
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Proteínas Asociadas a Microtúbulos/metabolismo , Microtúbulos/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Especificidad de Anticuerpos , Química Encefálica , Bovinos , Péptido Hidrolasas , Péptidos/inmunología , Péptidos/aislamiento & purificación , Péptidos/metabolismo , Unión Proteica , Tubulina (Proteína)/metabolismoRESUMEN
One of the major functions of cytoplasmic microtubules is their involvement in maintenance of asymmetric cell shape. Microtubules were considered to perform this function working as rigid structural elements. At the same time, microtubules play a critical role in intracellular organelle transport, and this fact raises the possibility that the involvement of microtubules in maintenance of cell shape may be mediated by directed transport of certain cellular components to a limited area of the cell surface (e.g., to the leading edge) rather than by their functioning as a mechanical support. To test this hypothesis we microinjected cultured human fibroblasts with the antibody (called HD antibody) raised against kinesin motor domain highly conserved among the different members of kinesin superfamily. As was shown before this antibody inhibits kinesin-dependent microtubule gliding in vitro and interferes with a number of microtubule-dependent transport processes in living cells. Preimmune IgG fraction was used for control experiments. Injections of fibroblasts with HD antibody but not with preimmune IgG significantly reduced their asymmetry, resulting in loss of long processes and elongated cell shape. In addition, antibody injection suppressed pseudopodial activity at the leading edge of fibroblasts moving into an experimentally made wound. Analysis of membrane organelle distribution showed that kinesin antibody induced clustering of mitochondria in perinuclear region and their withdrawal from peripheral parts of the cytoplasm. HD antibody does not affect either density or distribution of cytoplasmic microtubules. The results of our experiments show that many changes of phenotype induced in cells by microtubule-depolymerizing agents can be mimicked by the inhibition of motor proteins, and therefore microtubule functions in maintaining of the cell shape and polarity are mediated by motor proteins rather than by being provided by rigidity of tubulin polymer itself.
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Anticuerpos/farmacología , Cinesinas/fisiología , Microtúbulos/fisiología , Animales , Línea Celular , Células Cultivadas , Drosophila melanogaster , Fibroblastos/citología , Fibroblastos/fisiología , Fibroblastos/ultraestructura , Células HeLa , Humanos , Cinesinas/inmunología , Microinyecciones , Microtúbulos/ultraestructura , Células PC12 , PielRESUMEN
In vivo, cytoplasmic microtubules are nucleated and anchored by their minus ends at the centrosome and are believed to turn over by a mechanism termed dynamic instability: depolymerization and repolymerization at their plus ends. In cytoplasmic fragments of fish melanophores, microtubules were shown to detach from their nucleation site and depolymerize from their minus ends. Free microtubules moved toward the periphery by treadmilling-growth at one end and shortening from the opposite end. Frequent release from nucleation sites may be a general property of centrosomes and permit a minus-end mechanism of microtubule turnover and treadmilling.
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Microtúbulos/fisiología , Animales , Membrana Celular/metabolismo , Células Cultivadas , Centrosoma/metabolismo , Citoplasma/metabolismo , Citoplasma/ultraestructura , Peces , Cinética , Melanóforos/ultraestructura , Microtúbulos/metabolismo , Microtúbulos/ultraestructura , Movimiento , Pigmentos Biológicos/metabolismo , PolímerosRESUMEN
The goal of the present study was to apply the oscillatory brain dynamics model to the structural and quantitative analysis of neurocognitive functions considered as a potential marker of schizophrenia. This was achieved in tests of the detection of auditory events deviating in the regular auditory stream (oddball paradigm, MMN effect). It was hypothesized that the post-stimulus peaks of the oscillation power localized in post-stimulus time in the definite EEG oscillators represented neuro-electrical 'events' evoked in the specific neuronal nets characterized by this oscillation frequency band. We suggest that the time-frequency destination of these events related to the activation of the functional neuronal nets could be used for the determination of specific neurocognitive functions. Thus it was an attempt to distinguish the different neuro-functional parts of auditory processing and to compare these results between healthy subjects and patients with schizophrenia. The present results demonstrate the significant difference between the frontal averaged EEG oscillatory dynamics in healthy subjects and patients with schizophrenia related to neurocognitive function marked by the MMN and orienting response N200/P300a.
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Trastornos del Conocimiento/fisiopatología , Electroencefalografía , Potenciales Evocados Auditivos , Esquizofrenia/fisiopatología , Estimulación Acústica/métodos , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Trastornos del Conocimiento/etiología , Lóbulo Frontal/fisiopatología , Humanos , Masculino , Red Nerviosa/metabolismo , Adulto JovenRESUMEN
BACKGROUND: It is shown that each type of human malignancies has a unique set of expressed miRNAs, and tumor-specific miRNAs in biological tissues of a patient are stable. The aim of this study was to determine the differences in the expression of miRNAs in tumor tissue of invasive breast carcinoma compared to normal tissue, as well as to analyze the variable expression of miRNAs in molecular genetic subtypes of breast cancer. METHODS: We determined differences in mRNA expression in 35 biopsies of tumor tissue of various molecular genetic subtypes of breast cancer and 35 biopsies of adjacent conventionally normal breast tissue by RT-PCR in real time. We assessed the expression levels of miRNA-21, 221, 222, 155, 205, 20a , 125b and 200a. RESULTS: A significant increase in the level of expression of the oncogenic miRNA-20a (p=0.000141) and miRNA-221 (p=0.037777) in the triple negative cancer in comparison with the luminal A and luminal B/HER2/neu-negative breast cancer subtypes was established. Assessment of significance of the results was conducted using ROC analysis. For miRNA-221 AUC value was 0.772, for miRNA-20a AUC value was 0.949. The obtained results suggest the possibility of using the levels of miRNA-21, 155, 205, 125b expression in tumor tissue to assess a malignant potential of a breast carcinoma. The levels of expression of oncogenic miRNA-221 and miRNA-20a are increased in TNBC compared with luminal A and luminal B/HER2/neu-negative breast cancer subtypes, supporting the characteristic of TNBC as the most aggressive subtype of breast cancer. MiRNA-20a is a marker of TNBC compared with luminal subtypes of breast cancer. MICRO ABSTRACT: To identify markers for breast cancer with triple-negative phenotype, we evaluated expression levels of siRNA-21, 221, 222, 155, 205, 20a, 125b, 200a and 146b in the tumor tissue of 35 patients by RT-PCR. AUC value equal to 0.949 in the ROC-analysis allows us to recommend the miRNA-20a as a marker of triple negative breast cancer to differentiate it from the luminal subtypes.
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Biomarcadores de Tumor , Neoplasias de la Mama/genética , Regulación Neoplásica de la Expresión Génica , MicroARNs/genética , Adulto , Anciano , Anciano de 80 o más Años , Biopsia , Neoplasias de la Mama/diagnóstico , Femenino , Perfilación de la Expresión Génica , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Curva ROC , Transcriptoma , Carga TumoralRESUMEN
The fish melanophore has been considered the exemplar of microtubule-based organelle transport. In this system, a radial array of uniformly polarized microtubules [1] provides a framework on which dynein-related and kinesin-related motors drive pigment granules toward the minus or plus ends, respectively [2-4]. Stimulation of minus-end motors accounts satisfactorily for aggregation of granules at the cell center. Rapid dispersion is clearly microtubule-dependent; however, the uniform distribution of granules throughout the cytoplasm is paradoxical because stimulation of plus-end motors is predicted to drive the granules to the cell margin. This paradox suggested that the transport system was incompletely understood. Here, we report the discovery of a microtubule-independent motility system in fish melanophores. The system is based on actin filaments and is required for achieving uniform distribution of pigment granules. When it is abrogated, granules accumulate at the cell's margin as predicted for microtubule plus-end motors acting alone. The results presented here demonstrate the functional coordination of microtubule and actin filament systems, a finding that may be of general significance for organelle motility in cytoplasm.
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Actinas/fisiología , Melanocitos/fisiología , Melanóforos/fisiología , Microtúbulos/fisiología , Citoesqueleto de Actina/efectos de los fármacos , Citoesqueleto de Actina/fisiología , Actinas/antagonistas & inhibidores , Adenosina Trifosfato/fisiología , Animales , Transporte Biológico Activo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacología , Cipriniformes/fisiología , Citocalasina D/farmacología , Microtúbulos/efectos de los fármacos , Miosinas/fisiología , Nocodazol/farmacología , Tiazoles/farmacología , TiazolidinasRESUMEN
In this study, we examined the activation of natural killer(NK)-lymphocytes mediated by Toll-like receptor 3(TLR3), in the group of children with recurrent infections and the group of children with invasive bacterial infections. We examined level of CD69 (marker, of activation) expression on NK - lymphocytes after incubation with TLR3 ligand. There was a significant decrease in the level of an activation marker - 36,3±4,4% in the group of children with recurrent infections, compared with a control group of healthy children (56,5±4,9%) and the group of children with invasive bacterial infections (55,9±4,4%). Also, decreased was an activation potential of NK-lymphocytes - 24,9±L4,5% which was calculated as the difference between the percentage of CD69+ NK - lymphocytes after incubation and spontaneous value (without the addition of activator). There were no correlations between markers of TLR3 mediated activation of NK-cells and the age. Thus, the ability to activate NK - lymphocyte mediated by TLR3, independent of age and reduced in the group of children with recurrent infections. Reduced activation of NK-lymphocytes may contribute to increased susceptibility to viral infections and bacterial complications.
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Antígenos CD/genética , Antígenos de Diferenciación de Linfocitos T/genética , Infecciones Bacterianas/inmunología , Células Asesinas Naturales/efectos de los fármacos , Lectinas Tipo C/genética , Infecciones del Sistema Respiratorio/inmunología , Receptor Toll-Like 3/genética , Adolescente , Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Infecciones Bacterianas/genética , Infecciones Bacterianas/microbiología , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Regulación de la Expresión Génica , Humanos , Lactante , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/microbiología , Lectinas Tipo C/inmunología , Activación de Linfocitos , Masculino , Poli I-C/farmacología , Cultivo Primario de Células , Recurrencia , Infecciones del Sistema Respiratorio/genética , Infecciones del Sistema Respiratorio/microbiología , Receptor Toll-Like 3/inmunologíaRESUMEN
In acute experiments on cats anaesthetized with ketamine (25 mg/kg, i.m.) and immobilized with myorelaxine (2 mg/kg, i.v.) the activity of two groups of motor thalamic (nucleus ventralis anterior thalami-nucleus ventralis lateralis thalami) relay neurons was studied. The neurons (n = 7) receiving afferents from deep cerebellar nuclei and projecting to the motor area 4 gamma were included in the first group, and those (n = 12) receiving afferents from nucleus entopeduncularis and projecting to the supplementary motor area 6 were included in the second one. All changes in the background activity and reactions to cerebellothalamic or nucleus entopeduncularis stimulation developing under the influence of D2 receptor antagonist haloperidol (1.5-1.7 mg/kg, i.v.) have been studied in the same cell. Under haloperidol influence both groups of neurons showed a reliable decrease of background activity and generation of high frequency discharges accompanied by a shift in the mode of interspike interval histograms. A regular decrease of probability and increase of response latencies after stimulation of afferent input were observed in neurons receiving afferents from the cerebellum. In nucleus ventralis anterior thalami-nucleus ventralis lateralis thalami neurons with an inhibitory input from nucleus entopeduncularis, a shortening of inhibition from 17.5 +/- 3.6 to 9.1 +/- 1.8 ms (P < 0.05) under the haloperidol influence was evident. If the inhibition evoked by nucleus entopeduncularis stimulation consisted of two phases separated by a period of excitation (n = 4), the duration of the second phase of inhibition after haloperidol injection regularly increased and the excitation separating the phase of inhibition after haloperidol injection regularly increased and the excitation separating the phases of inhibition became more prominent. Observation on the spontaneous activity and reactions of the same neuron for 2 h or more showed a gradual moderation of the changes evoked by haloperidol. On the basis of data obtained it is concluded that the blockade of D2 receptors is followed by the increase of inhibitory processes in the relay neurons of motor thalamic nuclei. The suggestion is discussed that during the blockade of D2 receptors afferent impulsation to the motor cortex is being restricted and its influence on segmental apparatus of the spinal cord decreases. These conditions are beneficial for the development of spasticity (rigidity). At the same time, hyperpolarization of the relay neurons promotes the development of oscillatory processes at least in part of them and creates conditions for forming of tremor generators.