RESUMEN
Lung adenocarcinoma against the background of idiopathic pulmonary fibrosis according to the world literature ranges from 2.7% to 48%, the incidence increases every year after the diagnosis of idiopathic pulmonary fibrosis. We present a clinical and morphological analysis of an autopsy observation of lung adenocarcinoma that developed against the background of corticosteroid-treated usual interstitial pneumonia in a 78-year-old woman. According to the results of histological and immunohistochemical studies, the diagnosis was formulated as: multicentric non-mucinous invasive adenocarcinoma of the right and left lungs with a lepidic growth pattern with background of usual interstitial pneumonia.
Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Fibrosis Pulmonar Idiopática , Adenocarcinoma/patología , Adenocarcinoma del Pulmón/patología , Anciano , Femenino , Humanos , Fibrosis Pulmonar Idiopática/diagnóstico , Fibrosis Pulmonar Idiopática/patología , Pulmón/patología , Tomografía Computarizada por Rayos X/métodosRESUMEN
Cardiac myxoma is the most common primary benign cardiac tumor (up to 50% of all primary cardiac neoplasms). The implementation of the modern imaging techniques into the clinical practice, particularly, 2D echocardiography, computed tomography and magnetic resonance tomography (MRI) results to the prompt diagnosis of the myxoma. However, the absence of specific clinical features, insufficient awareness of this condition among the physicians along with a rare prevalence, may lead to a misdiagnosis. This case report is notable for the relatively late diagnosis of a giant left atrial myxoma due to a number of circumstances but with successful surgical treatment.
RESUMEN
AIM: In a retrospective study, we evaluated factors associated with the early development of septic shock in patients with severe COVID-19. MATERIALS AND METHODS: We collected medical records of the intensive care unit patients submitted by the local COVID-19 hospitals across Russia to the Federal Center for the Critical Care at the Sechenov First Moscow State Medical University (Sechenov University). Septic shock in crticially ill patients requiring mechanical ventilation was defined as a need in vasopressors to maintain blood pressure. RESULTS: We studied 1078 patients with severe COVID-19 who were admitted to the intensive care units for respiratory support. There were 611 males and 467 females. The mean age was 61.013.7 years. Five hundred twenty five medical records (48.7%) were received from the Moscow hospitals, 159 (14.7%) from the Moscow region, and 394 (36.5%) from the hospitals located in 58 regions of the Russian Federation. In 613 (56.9%) patients, diagnosis of SARS-CoV-2 infection was confirmed by PCR, and in the other cases it was established on the basis of the clinical picture and the results of the chest CT scan. Septic shock developed in 214 (19.9%) of 1078 patients. In the logistic regression model, the risk of septic shock in patients older than 50 years was higher than in patients of a younger age (OR 2.34; 95% CI 1.533.67; p0.0001). In patients with more severe SARS-CoV-2 infection, there was an increase in the prevalence of cardiovascular diseases, including coronary heart disease and atrial fibrillation, type 2 diabetes and malignant tumors. The risk of septic shock in patients with three or more concomitant diseases was higher than in patients without any concomitant chronic diseases (OR 1.76; 95% CI 1.762.70). CONCLUSION: The risk of septic shock in patients with acute respiratory distress syndrome induced by SARS-CoV-2 is higher in patients older than 50 years with concomitant diseases, although a severe course of the disease is also possible in younger patients without any concomitant disorders.
Asunto(s)
COVID-19 , Diabetes Mellitus Tipo 2 , Choque Séptico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Moscú/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Federación de Rusia/epidemiología , SARS-CoV-2 , Choque Séptico/diagnóstico , Choque Séptico/epidemiología , Choque Séptico/etiologíaRESUMEN
Primary sarcomas of the pericardium are extremely rare malignant tumors of the heart. The incidence of sarcoma increases after radiation therapy in the field of breast. The specific features of this case report are the difficulties in diagnostics of undifferentiated spindle-cell sarcoma of the pericardium and the connection between the disease and the radiation therapy for Hodgkin's lymphoma.
Asunto(s)
Neoplasias Cardíacas/etiología , Enfermedad de Hodgkin/terapia , Neoplasias Inducidas por Radiación/etiología , Pericardio/efectos de la radiación , Radioterapia/efectos adversos , Sarcoma/etiología , Ecocardiografía , Resultado Fatal , Femenino , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/terapia , Humanos , Imagen por Resonancia Magnética , Persona de Mediana Edad , Neoplasias Inducidas por Radiación/diagnóstico por imagen , Neoplasias Inducidas por Radiación/terapia , Sarcoma/diagnóstico por imagen , Sarcoma/terapiaRESUMEN
The present work provides results of a number of biotechnological studies aimed at creating cell lines and entire plants resistant to anaerobic stress. Developed biotechnological approaches were based on earlier fundamental researches into anaerobic stress in plants, so "Introduction" briefly covers the importance of the problem and focuses on works considering two main strategies of plants adaptation to anaerobic stress. Those are adaptation at molecular level where key factor is anaerobic metabolism of energy (true tolerance) and adaptation of the entire plant via formation of aerenchyma and facilitated transportation of oxygen (apparent tolerance). Thus, sugarcane and wheat cells resistant to anaerobic stress were obtained through consecutive in vitro selection under conditions of anoxia and absence of exogenous carbohydrates. Tolerant wheat cells were used to regenerate entire plants of higher resistance to root anaerobiosis. It has been demonstrated that cells tolerance to anoxia is significantly supported by their ability to utilize exogenous nitrate. Cells tolerance established itself at the genetic level and was inherited by further generations. Apart from that, other successful attempts to increase tolerance of plants to anaerobic stress by means of stimulation of glycolysis and overexpression of genes responsible for cytokinin synthesis and programmed cell death are also discussed. The presented data proved the notion of two main strategies of plants adaptation to anaerobic stress proposed earlier on the base of fundamental studies.
RESUMEN
Structure and properties of the recently discovered aspartate-specific cell death-related plant proteases named phytaspases are reviewed and compared to those of animal apoptotic proteases, caspases. Caspases (cysteine-dependent proteases) and phytaspases (serine-dependent proteases) are structurally very different, yet they share cleavage specificity and a role in programmed cell death. We demonstrate here that the distinctions in structural organization of animal and plant death proteases define differences in the strategies to regulate functioning of these proteolytic enzymes in the two kingdoms.
Asunto(s)
Caspasas/metabolismo , Péptido Hidrolasas/química , Células Vegetales/enzimología , Proteínas de Plantas/química , Animales , Apoptosis/genética , Ácido Aspártico/química , Ácido Aspártico/metabolismo , Caspasas/química , Péptido Hidrolasas/metabolismo , Proteínas de Plantas/metabolismo , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismo , Especificidad por SustratoRESUMEN
The objective of the present investigation was to study the influence of diseases of the nasal cavity (NC) and paranasal sinuses (PNS) concomitant with bronchial asthma (BA) on the development of peculiar features of the patients' immune status. Phenotypic characteristics of the main lymphocyte subpopulations from peripheral blood of 101 patients were obtained by means of flow cytometry with the use of fluorescein isocyanate- or phycoerythrin-labeled monoclonal antibodies. Special emphasis was laid on the elucidation of characteristics of humoral and cell-mediated immunity in the patients presenting with BA and concomitant NC and PNS diseases and their comparison with the respective parameters in the patients with isolated lesions in the upper respiratory tract (allergic rhinitis and polypous rhinosinusitis) and lower respiratory tract (bronchial asthma). It was shown that the patients with concurrent lesions of the upper and lower respiratory tracts experience marked intensification of the immune reactions in the form of the elevated number of activated B-lymphocytes (CD23+), serum IgE level, and peripheral eosinophil count.
Asunto(s)
Asma/epidemiología , Asma/inmunología , Enfermedades de los Senos Paranasales/epidemiología , Enfermedades de los Senos Paranasales/inmunología , Rinitis Alérgica Perenne/epidemiología , Rinitis Alérgica Perenne/inmunología , Adulto , Linfocitos B/inmunología , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Cavidad Nasal/inmunología , Senos Paranasales/inmunología , Linfocitos T/inmunología , Adulto JovenRESUMEN
The modern concepts of programmed cell death (PCD) in plants are reviewed as compared to PCD (apoptosis) in animals. Special attention is focused on considering the potential mechanisms of implementation of this fundamental biological process and its participants. In particular, the proteolytic enzymes involved in PCD in animals (caspases) and plants (phytaspases) are compared. Emphasis is put on elucidation of both common features and substantial differences of PCD implementation in plants and animals.
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Apoptosis , Células Vegetales/fisiología , Animales , Caspasas/genética , Caspasas/metabolismo , Humanos , Células Vegetales/enzimología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas/enzimología , Plantas/genéticaRESUMEN
Activities displaying caspase cleavage specificity have been well documented in various plant programmed cell death (PCD) models. However, plant genome analyses have not revealed clear orthologues of caspase genes, indicating that enzyme(s) structurally unrelated yet possessing caspase specificity have functions in plant PCD. Here, we review recent data showing that some caspase-like activities are attributable to the plant subtilisin-like proteases, saspases and phytaspases. These proteases hydrolyze a range of tetrapeptide caspase substrates following the aspartate residue. Data obtained with saspases implicate them in the proteolytic degradation of ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) during biotic and abiotic PCD, whereas phytaspase overproducing and silenced transgenics provide evidence that phytaspase regulates PCD during both abiotic (oxidative and osmotic stresses) and biotic (virus infection) insults. Like caspases, phytaspases and saspases are synthesized as proenzymes, which are autocatalytically processed to generate a mature enzyme. However, unlike caspases, phytaspases and saspases appear to be constitutively processed and secreted from healthy plant cells into the intercellular space. Apoplastic localization presumably prevents enzyme-mediated protein fragmentation in the absence of PCD. In response to death-inducing stimuli, phytaspase has been shown to re-localize to the cell interior. Thus, plant PCD-related proteases display both common (D-specific protein fragmentation during PCD) and distinct (enzyme structure and activity regulation) features with animal PCD-related proteases.
Asunto(s)
Caspasas/metabolismo , Proteínas de Plantas/metabolismo , Plantas/enzimología , Subtilisina/metabolismo , Animales , Apoptosis/fisiología , Caspasas/química , Caspasas/clasificación , Caspasas/genética , Dominio Catalítico , Inhibidores de Cisteína Proteinasa/química , Inhibidores de Cisteína Proteinasa/metabolismo , Isoenzimas/química , Isoenzimas/clasificación , Isoenzimas/genética , Isoenzimas/metabolismo , Modelos Moleculares , Filogenia , Proteínas de Plantas/química , Proteínas de Plantas/clasificación , Proteínas de Plantas/genética , Conformación Proteica , Subtilisina/química , Subtilisina/clasificación , Subtilisina/genéticaRESUMEN
Several novel functions of the well-known and intensively studied protein prothymosin alpha have recently been revealed. In addition to such traditional functions of this protein as immunomodulatory activity and stimulation of cellular proliferation, prothymosin alpha was shown to be involved in protection of cells against apoptosis and in regulation of expression of the oxidative stress-protective genes. Methods and approaches used for revelation of prothymosin alpha novel functions are described in this review.
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Apoptosis , Estrés Oxidativo , Precursores de Proteínas/fisiología , Timosina/análogos & derivados , Secuencia de Aminoácidos , Animales , Humanos , Datos de Secuencia Molecular , Mutación , Precursores de Proteínas/genética , Timosina/genética , Timosina/fisiología , Activación TranscripcionalRESUMEN
The authors review current knowledge on pathogenesis of allergic rhinosinusitis and bronchial asthma and their relations, show the role of leukotriens in development of respiratory allergy, characterize antileukotrienic medicines. Eleven patients with allergic rhinosinusitis and bronchial asthma received monotherapy with zafirlucast (acolapt) which is a blocker of leukotrienic receptors. Eight patients benefited from the treatment. The positive effect consisted in improvement of nasal respiration, reduction of rhinorrhea, edema of nasal mucosa, size of polyps.
Asunto(s)
Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Antagonistas de Leucotrieno/uso terapéutico , Rinitis Alérgica Perenne/tratamiento farmacológico , Compuestos de Tosilo/uso terapéutico , Adulto , Femenino , Humanos , Indoles , Masculino , Persona de Mediana Edad , Fenilcarbamatos , SulfonamidasRESUMEN
The divalent cation binding properties of human prothymosin alpha, an abundant nuclear protein involved in cell proliferation, were evaluated. By using prothymosin alpha retardation on a weak cation chelating resin charged with various divalent cations, specific binding of Zn2+ ions by prothymosin alpha was observed. This finding was further confirmed by the equilibrium dialysis analysis which demonstrated that, within the micromolar range of Zn2+ concentrations, prothymosin alpha could bind up to three zinc ions in the presence of 100 mM NaCl and up to 13 zinc ions in the absence of NaCl. Equilibrium dialysis analysis also revealed that prothymosin alpha could bind Ca2+, although the parameters of Ca2+ binding by prothymosin alpha were less pronounced than those of Zn2+ binding in terms of the number of metal ions bound, the KD values, and the resistance of the bound metal ions to 100 mM NaCl. The effects of Zn2+ and Ca2+ on the interaction of prothymosin alpha with its putative partners, Rev of HIV type 1 and histone H1, were examined. We demonstrated that Rev binds prothymosin alpha, and that prothymosin alpha binding to Rev but not to histone H1 was significantly enhanced in the presence of zinc and calcium ions. Our data suggest that the modes of prothymosin alpha interaction with Rev and histone H1 are distinct and that the observed zinc and calcium-binding properties of prothymosin alpha might be functionally relevant.
Asunto(s)
Cationes , Precursores de Proteínas/metabolismo , Timosina/análogos & derivados , Calcio/metabolismo , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Productos del Gen rev/metabolismo , VIH-1/metabolismo , Histonas/metabolismo , Humanos , Cinética , Magnesio/metabolismo , Plásmidos/metabolismo , Unión Proteica , Proteínas Recombinantes de Fusión/metabolismo , Timosina/metabolismo , Factores de Tiempo , Zinc/metabolismo , Productos del Gen rev del Virus de la Inmunodeficiencia HumanaRESUMEN
A proliferation-related human protein prothymosin alpha displays exclusively nuclear localization when produced in human and Saccharomyces cerevisiae cells, whereas its isolated bipartite NLS confers nuclear targeting of the GFP reporter in human but not in yeast cells. To test whether this observation is indicative of the existence of specific requirements for nuclear targeting of proteins in yeast, a set of prothymosin alpha deletion mutants was constructed. Subcellular localization of these mutants fused to GFP was determined in yeast and compared with their ability to bind yeast importin alpha (Srp1p) in vitro. The NLS of prothymosin alpha turned out to be both necessary and sufficient to provide protein recognition by importin alpha. However, the NLS-importin alpha interaction did not ensure nuclear targeting of prothymosin alpha derivatives. This defect could be complemented by adding distinct prothymosin alpha sequences to the NLS-containing import substrate, possibly by providing binding site(s) for additional components of the yeast nuclear import machinery.
Asunto(s)
Núcleo Celular/metabolismo , Proteínas Fúngicas/metabolismo , Proteínas de Choque Térmico/metabolismo , Señales de Localización Nuclear/fisiología , Proteínas Nucleares/metabolismo , Precursores de Proteínas/metabolismo , Proteínas de Saccharomyces cerevisiae , Timosina/análogos & derivados , Timosina/metabolismo , Antígenos Virales de Tumores/metabolismo , Transporte Biológico , Cromatografía de Afinidad , Citoplasma/metabolismo , Proteínas Fluorescentes Verdes , Humanos , Carioferinas , Proteínas Luminiscentes/genética , Mutagénesis Sitio-Dirigida , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Unión Proteica/genética , Precursores de Proteínas/genética , Estructura Terciaria de Proteína/genética , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Saccharomyces cerevisiae , Eliminación de Secuencia/genética , Timosina/genéticaRESUMEN
We observed fragmentation of an essential proliferation-related human nuclear protein prothymosin alpha in the course of apoptosis induced by various stimuli. Prothymosin alpha cleavage occurred at the DDVD(99) motif. In vitro, prothymosin alpha could be cleaved at D(99) by caspase-3 and -7. Caspase hydrolysis disrupted the nuclear localization signal of prothymosin alpha and abrogated the ability of the truncated protein to accumulate inside the nucleus. Prothymosin alpha fragmentation may therefore be proposed to disable intranuclear proliferation-related function of prothymosin alpha in two ways: by cleaving off a short peptide containing important determinants, and by preventing active nuclear uptake of the truncated protein.
Asunto(s)
Apoptosis , Precursores de Proteínas/genética , Timosina/análogos & derivados , Sitios de Unión , Caspasa 3 , Caspasa 7 , Caspasas , Fragmentación del ADN , Células HeLa , Humanos , Señales de Localización Nuclear , Precursores de Proteínas/química , Timosina/química , Timosina/genética , TransfecciónAsunto(s)
ADN/metabolismo , Desoxirribonucleasas de Localización Especificada Tipo II/metabolismo , Ácidos Nucleicos Heterodúplex , ARN/metabolismo , Secuencia de Bases , Dicroismo Circular , Cartilla de ADN , Desoxirribonucleasas de Localización Especificada Tipo II/química , Electroforesis en Gel de Poliacrilamida , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismoRESUMEN
A covalent complex formed by bacterial tRNAs and prothymosin alpha, an abundant acidic nuclear protein involved in proliferation of mammalian cells, upon production of the recombinant rat protein in Escherichia coli cells was studied. Several tRNA attachment sites were identified in the prothymosin alpha molecule using a combination of deletion analysis of prothymosin alpha and site-specific fragmentation of the protein moiety of the prothymosin alpha-tRNA complex. The electrophoretic mobilities of the tRNA-linked prothymosin alpha and its derivatives are consistent with one tRNA molecule attached to one prothymosin alpha molecule, thus suggesting that alternative tRNA linking to one of several available attachment sites occurs. The possible effect of tRNA attachment on the nuclear uptake of prothymosin alpha is discussed.
Asunto(s)
Precursores de Proteínas/metabolismo , ARN de Transferencia/metabolismo , Timosina/análogos & derivados , Secuencia de Aminoácidos , Animales , Sitios de Unión , Escherichia coli/metabolismo , Modelos Biológicos , Datos de Secuencia Molecular , Mutagénesis , Unión Proteica , Precursores de Proteínas/química , Ratas , Timosina/química , Timosina/metabolismoRESUMEN
Mutants of human prothymosin alpha with impaired ability to inhibit yeast Saccharomyces cerevisiae. cerevisiae cell growth were characterized. Two types of prothymosin alpha-inactivating mutations were observed. Mutations that belong to the first type compromised the nuclear entry of prothymosin alpha by affecting its nuclear localization signal. Analysis of subcellular distribution of GFP-prothymosin alpha fusions revealed a bipartite nuclear localization signal that is both necessary and sufficient for nuclear import of the protein in human cells. Mutations of the second type abrogated the inhibitory action of prothymosin alpha through an unknown mechanism, without influencing the nuclear import of the protein.
Asunto(s)
Señales de Localización Nuclear/genética , Proteínas Nucleares/genética , Precursores de Proteínas/genética , Timosina/análogos & derivados , Secuencia de Aminoácidos , Compartimento Celular/genética , División Celular/genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Células Cultivadas , Humanos , Datos de Secuencia Molecular , Mutagénesis , Mutación , Saccharomyces cerevisiae , Timosina/genéticaRESUMEN
The examination covered 44 patients (16 males and 28 females) with chronic bronchitis (CB) associated with diseases of the nose and paranasal sinuses. Most of the patients (63.6%) had allergic rhinosinusopathy (ARSP). The kind of nasal and sinus affection varied with CB form (catarrhal or purulent). Aggravation of ENT disorders provoked deterioration of external respiration. Bronchial and maxillary mucosa showed identical changes in CB patients with purulent affection of the paranasal sinuses. Cytological examinations of the smear, lavage and sputum discovered a tendency to increased count of eosinophil leukocytes in all the samples from CB plus ARSP patients. On cytograms of bronchial lavage from patients with polypous-purulent ARSP there were also low counts of macrophages and lymphocytes. This is likely to reflect pronounced defects of local defense of the bronchi promoting progressive inflammatory and allergic processes.
Asunto(s)
Bronquitis/diagnóstico , Enfermedades Nasales/diagnóstico , Enfermedades de los Senos Paranasales/diagnóstico , Sistema Respiratorio/fisiopatología , Adolescente , Adulto , Bronquitis/fisiopatología , Líquido del Lavado Bronquioalveolar/citología , Líquido del Lavado Bronquioalveolar/microbiología , Enfermedad Crónica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/citología , Mucosa Nasal/metabolismo , Enfermedades Nasales/fisiopatología , Enfermedades de los Senos Paranasales/fisiopatología , Espirometría , Esputo/citología , Esputo/microbiologíaRESUMEN
The examination of 56 patients (35 females and 21 males) with bronchial asthma (BA) associated with nasal and paranasal diseases revealed allergic rhinosinusopathy (ARSP) in 87.5% of the examinees. Nasal and paranasal affections in BA of bacterial and atopic genesis differed. The study of external respiration showed that its volume and rate abnormality increased with growing severity of nasal and paranasal affections. The results of cytological investigations of impression smears of the nasal mucosa, sputum and bronchial lavage (portion I and II) suggest that elevated levels of eosinophilic leukocytes in all the studied specimens in BA patients with ARSP may evidence for common character of allergic reactions in the above nasal and bronchial diseases.
Asunto(s)
Asma/complicaciones , Enfermedades Otorrinolaringológicas/complicaciones , Adolescente , Adulto , Asma/diagnóstico , Asma/inmunología , Lavado Broncoalveolar , Broncoscopía , Eosinófilos/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mucosa Nasal/inmunología , Enfermedades Otorrinolaringológicas/diagnóstico , Enfermedades Otorrinolaringológicas/inmunología , Respiración , Rinitis Alérgica Perenne/complicaciones , Rinitis Alérgica Perenne/diagnóstico , Rinitis Alérgica Perenne/inmunología , Sinusitis/complicaciones , Sinusitis/diagnóstico , Sinusitis/inmunología , Esputo/inmunologíaRESUMEN
A bacterial strain overproducing human prothymosin alpha was constructed based on the efficient T7 RNA polymerase transcription of human prothymosin alpha cDNA. The highest yield of the human prothymosin alpha, up to 30% of the total bacterial protein, was achieved with constructions containing 6-10 nucleotides between the Shine-Dalgarno sequence and initiation ATG codon. Unexpectedly, cells grown in the presence of inducer of T7 RNA polymerase synthesis produced substantially lower levels of prothymosin alpha than those grown in the absence of inducer. A simple procedure for prothymosin alpha isolation was elaborated, resulting in large amounts of electrophoretically pure and immunoactive protein.