RESUMEN

Preeclampsia (PE) is a severe complication of pregnancy accompanied by arterial hypertension, edema, or proteinuria with impaired functioning of various organs and systems. It is also an important medical and social problem, which has been one of the leading causes of maternal and perinatal mortality and morbidity worldwide. Despite the achievements of modern medicine, the etiology of this pathology is still unknown. Recently, many scientists have especially focused on the study of genetic factors underlying the etiopathogenesis of PE, namely, the contribution of individual polymorphic loci of various candidate genes. The current study aimed to investigate the clinical characteristics of PE and the contribution of the polymorphic loci rs1042838 of Progesterone Receptor (PGR) gene and rs8068318 of the T-Box Transcription Factor 2 (TBX2) gene to the development of PE. The study was conducted on 219 women with PE with the mean±SD age of 26.52±5.51 years and 329 women with the physiological course of pregnancy as the control group with the mean±SD age of 26.27±4.88 years. In total, 64.20%, 68.29%, 16.44%, 98.63%, and 35.48% of women with PE had increased systolic and normal diastolic blood pressure (SBP and DBP) values, proteinuria, edema, and overweight (BMI≥25), respectively. In the control group, 100%, 1.53%, 1.12%, and 35.48% of cases had normal SBP values with no proteinuria, DBP>90 mm Hg, edema, and overweight (BMI≥25), respectively. An association was observed between the CC genotype of the rs8068318 polymorphism of the TBX2 gene with the risk of developing PE in women with PE (OR=2.12, 95%CI: 1.14-3.92, P=0.02). In addition, there was an association between the rs8068318 TBX2 polymorphic locus with lower SBP (Me=140, Q25 - Q75 130 - 142.5, P=0.01) and PBP (Me=50, Q25 - Q75 40 - 55, P<0.01). According to the GeneCards database, the TBX2 gene, a member of a phylogenetically conserved gene family, is located on the long arm of chromosome 17 and encodes the TBX2 T-box transcription factor protein, which is a regulator of the transcriptional activity of various genes (i.e., it suppresses the expression of CDKN2A (p19/ARF), inhibits cyclin-dependent kinase p21 Cip1 (CDKN1A), and affects the expression of MYC, RAS, BRCA1, and BRCA2 genes).

Asunto(s)

Preeclampsia , Adulto , Femenino , Humanos , Sobrepeso , Preeclampsia/genética , Embarazo , Receptores de Progesterona/genética , Proteínas de Dominio T Box/genética , Factores de Transcripción/genética , Adulto Joven

RESUMEN

Ovarian hyperstimulation syndrome (OHSS) is the most severe and life-threatening complication of assisted reproductive technologies (ART). OHSS is based on an excessive ovarian response to ovarian stimulation; however, the pathogenesis has not been fully understood yet. The most serious complications of OHSS are thromboembolic complications and ovarian torsion. The current study describes the risk factors for the development of ovarian hyperstimulation syndrome and proposes a method for specific prediction of this syndrome. This study was designed to investigate 671 therapeutic cycles in the IVF program during 2009-2018. All patients were divided into two groups. Group one (n=56) included women who developed OHSS during the IVF procedure. Group two (n=615) consisted of women who did not have this complication during the IVF procedure. All the observation and examination outcomes were entered into a specially developed questionnaire, and then into a Microsoft Excel spreadsheet. The data were processed by variable statistics using Statistica 10.0. Analyzing of the recorded data revealed that the rate of OHSS was higher in the group of younger women, aged 30.76±3.67 years, in comparison with those aged 32.78±4.40 years in the group of patients without OHSS (p<0.05). The analysis of the initial phase of the reproductive system has confirmed that the group of patients with OHSS had a higher level of prolactin, 462.84±191.56 mIU/L in comparison with 363.43±187.84 mIU/L, which corresponded to the group of women without OHSS (p<0.05). In our results, 7.15±1.04% of cases with OHSS had obesity, while of the patients from the group without OHSS suffered from it (p<0.05). OHSS is the most severe iatrogenic complication of ART, therefore it is extremely important to consider its risk factors and take timely preventive measures. This study has established a high relationship between the studied risk factors and ovarian hyperstimulation syndrome and proposed a model for predicting this syndrome.

Asunto(s)

Síndrome de Hiperestimulación Ovárica , Adulto , Femenino , Fertilización In Vitro/efectos adversos , Humanos , Síndrome de Hiperestimulación Ovárica/etiología , Factores de Riesgo

RESUMEN

Organ-on-chip devices are intensively studied in academia and industry due to their high potential in pharmaceutical and biomedical applications. However, most of the existing organ-on-chip models focus on proof of concept of individual functional units without the possibility of testing multiple experimental stimuli in parallel. Here we developed a polydimethylsiloxane (PDMS) multiplexed chip with eight parallel channels branching from a common access port through which all eight channels can be addressed simultaneously without the need for extra pipetting steps thus increasing the reproducibility of the experimental results. At the same time, eight outlets provide individual entry to each channel with the opportunity to create eight different experimental conditions. A multiplexed chip can be assembled as a one-layer device for studying monocultures or as a two-layer device for studying barrier tissue functions. For a two-layer device, a ∼2 µm thick transparent PDMS membrane with 5 µm through-hole pores was fabricated in-house using a soft lithography technique, thereby allowing visual inspection of the cell-culture in real-time. The functionality of the chip was studied by recapitulating the blood-brain barrier. For this, human cerebral microvascular endothelial cells (hCMEC/D3) were cultured in mono- or coculture with human astrocytes. Immunostaining revealed a cellular monolayer with the expression of tight junction ZO-1 and adherence junction VE-cadherin proteins in endothelial cells as well as glial fibrillary acidic protein (GFAP) expression in astrocytes. Furthermore, multiplexed permeability studies of molecule passage through the cellular barrier exhibited expected high permeability coefficients for smaller molecules (4 kDa FITC-dextran) whereas larger molecules (20 kDa) crossed the barrier at a lower rate. With these results, we show that our device can be used as an organ-on-chip model for future multiplexed drug testing.

Asunto(s)

Barrera Hematoencefálica , Células Endoteliales , Técnicas de Cocultivo , Humanos , Dispositivos Laboratorio en un Chip , Reproducibilidad de los Resultados

RESUMEN

Activity of telomerase catalytic subunit hTERT (human Telomerase Reverse Transcriptase) can be regulated by alternative splicing of its mRNA. At present time exact mechanism of hTERT splicing is not fully understood. Apoptotic endonuclease EndoG is known to participate this process. EndoG expression is induced by DNA damages. The aim of this work was to investigate the ability of DNA-damaging agents with different mechanism of action to induce EndoG expression and inhibit telomerase activity due to the activation of hTERT alternative splicing in normal activated human CD4+ and CD8+ T-lymphocytes. All investigated DNA-damaging agents were able to induce EndoG expression. Cisplatin, a therapeutic compound, producing DNA cross-links induced the highest level of DNA damages and EndoG expression. Incubation of CD4+ and CD8+ T-cells with cisplatin caused the changes in proportion of hTERT splice variants and inhibition of telomerase activity.

Asunto(s)

Empalme Alternativo , Linfocitos T CD4-Positivos/enzimología , Linfocitos T CD8-positivos/enzimología , Daño del ADN , Endodesoxirribonucleasas/metabolismo , Telomerasa/genética , Células Cultivadas , Cisplatino , Humanos

RESUMEN

The activity of telomerase catalytic subunit hTERT (human telomerase reverse transcriptase) can be regulated by alternative splicing of its mRNA. The mechanism of hTERT splicing is not understood in detail. Apoptotic endonuclease EndoG is known to participate in this process. In the present work, the intracellular colocalization and mRNA levels of EndoG and hTERT splice-variants in normal and apoptotic cancer cells were studied. We found that the development of apoptosis increased the expression of EndoG and changed the ratio of hTERT splice-variants, which decreased the telomerase activity in the cells. The development of apoptosis was accompanied by changes in the amount of mRNA and in the localization of EndoG and hTERT splice-variants in the cytoplasm, nuclei, and mitochondria of the cells. The suppression of EndoG expression using RNA interference prevented induction of the α+ß- splice-variant of hTERT and inhibition of the telomerase activity. A high degree of the intracellular colocalization of EndoG and hTERT was shown. The changes in the expression and localization of EndoG corresponded with changes in the amount and localization of hTERT splice-variants. These data confirm the participation of EndoG in the alternative splicing of mRNA of the telomerase catalytic subunit and in regulation of the telomerase activity.

Asunto(s)

Endonucleasas/metabolismo , Telomerasa/metabolismo , Empalme Alternativo , Apoptosis , Células CACO-2 , Dominio Catalítico , Endonucleasas/antagonistas & inhibidores , Endonucleasas/genética , Humanos , Transporte de Proteínas , Interferencia de ARN , ARN Mensajero/metabolismo , ARN Interferente Pequeño/metabolismo , Telomerasa/química , Telomerasa/genética

RESUMEN

Telomerase activity is regulated by an alternative splicing of mRNA of the telomerase catalytic subunit hTERT (human telomerase reverse transcriptase). Increased expression of the inactive spliced hTERT results in inhibition of telomerase activity. Little is known about the mechanism of hTERT mRNA alternative splicing. This study was aimed at determining the effect of an apoptotic endonuclease G (EndoG) on alternative splicing of hTERT and telomerase activity in CD4+ human T lymphocytes. Overexpression of EndoG in CD4+ T cells downregulated the expression of the active full-length hTERT variant and upregulated the inactive alternatively spliced variant. Reduction of full-length hTERT levels caused downregulation of the telomerase activity, critical telomere shortening during cell division that converted cells into the replicative senescence state, activation of apoptosis, and finally cell death. Some cells survive and undergo a malignant transformation. Transformed cells feature increased telomerase activity and proliferative potential compared to the original CD4+ T cells. These cells have phenotype of T lymphoblastic leukemia cells and can form tumors and cause death in experimental mice.

Asunto(s)

Empalme Alternativo , Linfocitos T CD4-Positivos/enzimología , Transformación Celular Neoplásica/metabolismo , Endodesoxirribonucleasas/biosíntesis , Regulación Enzimológica de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Proteínas de Neoplasias/biosíntesis , Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimología , Telomerasa/biosíntesis , Homeostasis del Telómero , Animales , Linfocitos T CD4-Positivos/patología , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Endodesoxirribonucleasas/genética , Femenino , Xenoinjertos , Humanos , Masculino , Ratones , Proteínas de Neoplasias/genética , Trasplante de Neoplasias , Leucemia-Linfoma Linfoblástico de Células T Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Telomerasa/genética

RESUMEN

Alternative splicing of telomerase catalytic subunit hTERT pre-mRNA (human Telomerase Reverse Transcriptase) regulates telomerase activity. Increased expression of non-active splice variant hTERT results in inhibition of telomerase. Apoptotic endonuclease EndoG is known to participate in hTERT alternative splicing. Expression of EndoG can be induced in response to DNA damages. The aim of this study was to determine the ability of a DNA-damaging compound, cisplatin, to induce EndoG and its influence on alternative splicing of hTERT and telomerase activity in human CD4+ Т lymphocytes. Overexpression of EndoG in CD4+ T cells downregulated the expression of active full-length hTERT variant and upregulated its non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. Few cells survived and underwent malignant transformation. Transformed cells have increased telomerase activity and proliferative potential compare to initial CD4+ T cells. These cells have phenotype of T lymphoblastic leukemic cells and are able to form tumors and cause death in experimental mice.

Asunto(s)

Antineoplásicos/toxicidad , Linfocitos T CD4-Positivos/efectos de los fármacos , Transformación Celular Neoplásica/genética , Cisplatino/toxicidad , Endodesoxirribonucleasas/genética , Telomerasa/genética , Empalme Alternativo/efectos de los fármacos , Animales , Apoptosis , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/patología , Linfocitos T CD4-Positivos/trasplante , Proliferación Celular/efectos de los fármacos , Transformación Celular Neoplásica/inducido químicamente , Transformación Celular Neoplásica/inmunología , Transformación Celular Neoplásica/patología , Endodesoxirribonucleasas/metabolismo , Humanos , Linfoma/genética , Linfoma/inmunología , Linfoma/mortalidad , Linfoma/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Cultivo Primario de Células , Análisis de Supervivencia , Telomerasa/antagonistas & inhibidores , Telomerasa/metabolismo , Telómero/química , Telómero/efectos de los fármacos , Acortamiento del Telómero/efectos de los fármacos

RESUMEN

The diversity of Lb. rhamnosus and Lb. fermentum strains isolated from feces, saliva, and the vaginal cavity of 18-22-year-old healthy women residing in central regions of the Russian Federation has been characterized. The results obtained using multilocus sequence typing were identical to those obtained with the analysis of genetic and genomic polymorphism in TA systems. Different as well as identical Lb. rhamnosus and Lb. fermentum sequence types (ST) were isolated from various parts of the body of the same person. Identical ST were also isolated from different women, suggesting that such strains belong to a common pool of strains circulating among the population members. Our results demonstrate that TAs are suitable for characterizing intra-specific diversity of Lb. rhamnosus and Lb. fermentum strains. The advantage of using polymorphisms in TA systems for genotyping is based on the weak number of genes used, and consequently, less time is required for the analysis.

Asunto(s)

Antitoxinas/genética , Toxinas Bacterianas/genética , Heces/microbiología , Lacticaseibacillus rhamnosus/genética , Limosilactobacillus fermentum/genética , Saliva/microbiología , Vagina/microbiología , Adolescente , Adulto , Femenino , Genotipo , Humanos , Limosilactobacillus fermentum/clasificación , Limosilactobacillus fermentum/aislamiento & purificación , Lacticaseibacillus rhamnosus/clasificación , Lacticaseibacillus rhamnosus/aislamiento & purificación , Tipificación de Secuencias Multilocus , Polimorfismo Genético/genética , Federación de Rusia , Adulto Joven

RESUMEN

Human telomerase catalytic subunit hTERT is subjected to alternative splicing results in loss of its function and leads to decrease of telomerase activity. However, very little is known about the mechanism of hTERT pre-mRNA alternative splicing. Apoptotic endonuclease EndoG is known to participate this process. The aim of this study was to determine the role of EndoG in regulation of hTERT alternative splicing. Increased expression of b-deletion splice variant was determined during EndoG over-expression in CaCo-2 cell line, after EndoG treatment of cell cytoplasm and nuclei and after nuclei incubation with EndoG digested cell RNA. hTERT alternative splicing was induced by 47-mer RNA oligonucleotide in naked nuclei and in cells after transfection. Identified long non-coding RNA, that is the precursor of 47-mer RNA oligonucleotide. Its size is 1754 nucleotides. Based on the results the following mechanism was proposed. hTERT pre-mRNA is transcribed from coding DNA strand while long non-coding RNA is transcribed from template strand of hTERT gene. EndoG digests long non-coding RNA and produces 47-mer RNA oligonucleotide complementary to hTERT pre-mRNA exon 8 and intron 8 junction place. Interaction of 47-mer RNA oligonucleotide and hTERT pre-mRNA causes alternative splicing.

Asunto(s)

Empalme Alternativo/fisiología , Endodesoxirribonucleasas/metabolismo , Exones , ARN no Traducido/biosíntesis , Telomerasa/biosíntesis , Células CACO-2 , Endodesoxirribonucleasas/genética , Humanos , ARN no Traducido/genética , Telomerasa/genética

RESUMEN

Gamma-amino butyric acid (GABA) is an active biogenic substance synthesized in plants, fungi, vertebrate animals and bacteria. Lactic acid bacteria are considered the main producers of GABA among bacteria. GABA-producing lactobacilli are isolated from food products such as cheese, yogurt, sourdough, etc. and are the source of bioactive properties assigned to those foods. The ability of human-derived lactobacilli and bifidobacteria to synthesize GABA remains poorly characterized. In this paper, we screened our collection of 135 human-derived Lactobacillus and Bifidobacterium strains for their ability to produce GABA from its precursor monosodium glutamate. Fifty eight strains were able to produce GABA. The most efficient GABA-producers were Bifidobacterium strains (up to 6 g/L). Time profiles of cell growth and GABA production as well as the influence of pyridoxal phosphate on GABA production were studied for L. plantarum 90sk, L. brevis 15f, B. adolescentis 150 and B. angulatum GT102. DNA of these strains was sequenced; the gadB and gadC genes were identified. The presence of these genes was analyzed in 14 metagenomes of healthy individuals. The genes were found in the following genera of bacteria: Bacteroidetes (Bacteroides, Parabacteroides, Alistipes, Odoribacter, Prevotella), Proteobacterium (Esherichia), Firmicutes (Enterococcus), Actinobacteria (Bifidobacterium). These data indicate that gad genes as well as the ability to produce GABA are widely distributed among lactobacilli and bifidobacteria (mainly in L. plantarum, L. brevis, B. adolescentis, B. angulatum, B. dentium) and other gut-derived bacterial species. Perhaps, GABA is involved in the interaction of gut microbiota with the macroorganism and the ability to synthesize GABA may be an important feature in the selection of bacterial strains - psychobiotics.

Asunto(s)

Proteínas Bacterianas/genética , Bifidobacterium/genética , Microbioma Gastrointestinal/genética , Glutamato Descarboxilasa/genética , Lactobacillus/genética , Proteínas de la Membrana/genética , Ácido gamma-Aminobutírico/biosíntesis , Proteínas Bacterianas/metabolismo , Bacteroidetes/efectos de los fármacos , Bacteroidetes/genética , Bacteroidetes/aislamiento & purificación , Bacteroidetes/metabolismo , Bifidobacterium/efectos de los fármacos , Bifidobacterium/aislamiento & purificación , Bifidobacterium/metabolismo , ADN Bacteriano/genética , Firmicutes/efectos de los fármacos , Firmicutes/genética , Firmicutes/aislamiento & purificación , Firmicutes/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/microbiología , Expresión Génica , Glutamato Descarboxilasa/metabolismo , Humanos , Lactobacillus/efectos de los fármacos , Lactobacillus/aislamiento & purificación , Lactobacillus/metabolismo , Proteínas de la Membrana/metabolismo , Metagenoma , Proteobacteria/efectos de los fármacos , Proteobacteria/genética , Proteobacteria/aislamiento & purificación , Proteobacteria/metabolismo , Fosfato de Piridoxal/metabolismo , Fosfato de Piridoxal/farmacología , Glutamato de Sodio/metabolismo , Glutamato de Sodio/farmacología

RESUMEN

Telomerase activity is known to be regulated by alternative splicing of its catalytic subunit hTERT (human Telomerase Reverse Transcriptase) mRNA. Induction of non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. Strong correlation was found between expression of EndoG and hTERT splice-variants in 12 colon cancer cell lines. Overexpression of EndoG in СаСо-2 cells downregulated the expression of active full-length hTERT variant and upregulated non-active spliced variant. Reduction of full-length hTERT caused downregulation of telomerase activity, dramatically shortening of telomeres length during cell divisions, converting cells to the replicative senescence state, activation of apoptosis and finally cell death. These data indicated the participation of EndoG in alternative splicing of mRNA of telomerase catalytic subunit, regulation of telomerase activity and cell fate.

Asunto(s)

Empalme Alternativo , Apoptosis , Endodesoxirribonucleasas/metabolismo , Telomerasa/genética , Células CACO-2 , Endodesoxirribonucleasas/genética , Células HCT116 , Células HT29 , Humanos , Telomerasa/metabolismo

RESUMEN

The effects of fetal calf serum (FCS) growth factor concentration and cell growth phase on production of angiogenic mediators by mesenchymal stromal cells (MSCs) at different O2 levels (20 and 5%) was studied. For this purpose vascular endothelial growth factor (VEGF-A) production was measured in MSC-conditioned medium (CM); besides, branching vessels as well as vessel end points (ramification) in the chorioallantoic membrane of Japanese quail eggs (Coturnix coturnix japonica) were counted following MSC-CM application. During the standard cultivation (20% O2; 10% FCS) the total number of vessels was 1.6 times higher comparing with hypoxic condition (5% O2; 10% FCS) due to increase in ramification, the number of branching vessels did not change. Maximal (double) increase in the total vessel number was observed when CM from MSCs after hypoxia plus serum deprivation was added. VEGF-A synthesis linearly increased with FCS concentration both at 20% and 5% O2. In all cases VEGF-A level was higher at hypoxia. No direct correlation between the VEGF-A concentration and total number of vessels was noted indicating that hypoxia possibly stimulates synthesis of additional angiogenic factors to enhance vascular growth despite the drastic serum deprivation. At 20% oxygen, exponentially growing MSCs showed the highest angiogenic activity and the ramification increased in 1.6 times. Depending on O2, MSCs produced angiogenic factors required at different stages of vascularization. Specifically, mediators of ramification were accumulated in the standard conditions (20% O2) and factors stimulating growth of branching vessels--in hypoxia.

Asunto(s)

Endotelio Vascular/metabolismo , Hipoxia/metabolismo , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Células Madre Mesenquimatosas/metabolismo , Neovascularización Patológica/metabolismo , Oxígeno/metabolismo , Células del Estroma/metabolismo , Animales , Bovinos , Proliferación Celular , Células Cultivadas , Endotelio Vascular/patología , Humanos , Hipoxia/patología , Células Madre Mesenquimatosas/patología , Neovascularización Patológica/patología , Células del Estroma/patología

RESUMEN

Trichoderma harzianum Rifai F-180, an organism producing the antitumor enzyme L-lysine-alpha-oxidase was cultivated and the enzyme was isolated and purified under the manufacturing conditions. The effect of L-lysine-alpha-oxidase on oxidation of L-lysine was investigated for the first time by capillary electrophoresis and the procedure conditions were developed. The reaction of L-lysine oxidative deamination is described and location of the reaction components picks on the elecrophoregrams was identified. The average rate of the catalytic reaction of L-lysine oxidation equal to 0.46 RU/min (7.7 x 10(-3) RU/sec) was determined. The use of the antitumor enzyme L-lysine-alpha-oxidase is recommended as a drug for the treatment of superficial tumors and tissue relative oxygen excess.

Asunto(s)

Aminoácido Oxidorreductasas/química , Antineoplásicos/química , Proteínas Fúngicas/química , Lisina/química , Trichoderma/química , Aminoácido Oxidorreductasas/aislamiento & purificación , Antineoplásicos/aislamiento & purificación , Electroforesis Capilar , Electroforesis en Gel de Poliacrilamida , Pruebas de Enzimas , Proteínas Fúngicas/aislamiento & purificación , Cinética , Oxidación-Reducción , Trichoderma/enzimología

RESUMEN

The paper presents the results of comparative characterization of the effects of low oxygen levels (10 ± 0.5 and 14.5 ± 0.5%) on developing organism. Four-day old embryos of the Japanese quail (Coturnix coturnix japonica) were chosen for the object of investigation as this is the age when avians acquire their organs and systems. Acute hypoxia (10 ± 0.5% oxygen) caused a general death of the embryos, and serious abnormalities of the eye and brain, and ectopy. Embryos that developed in the low-oxygen atmosphere (14.5 ± 0.5%) did not exhibit many of these morphological abnormalities and yet their growth was retarded apparently. Such abnormalities in acute hypoxia are ascribed to disturbance in development of extra-embryonic membranes, amnion in particular, desynchronization of morphogenetic processes and movement of embryo's tissue layers.

Asunto(s)

Coturnix/embriología , Desarrollo Embrionario/genética , Oxígeno/metabolismo , Animales , Hipoxia

RESUMEN

This paper describes physiochemical and biological properties of 3 immunologically active compounds extracted by acetone from porcine skin. High pressure gel chromatography confirmed their heterogeneity. RP-HPLC of compound 2 (C2 or K-activin) also characterizes it as a heterogeneous entity. It was shown to inhibit proliferation of cultured fibroblasts from human fetuses and exhibit weak activity in general anaphylactic reaction (anaphylactic shock) and skin anaphylactic reaction. A summary of data on immunologically active compounds are presented with special emphasis laid on acetone-extractable K-activin.

Asunto(s)

Factores Biológicos/aislamiento & purificación , Piel/química , Acetona , Anafilaxia/inmunología , Animales , Factores Biológicos/inmunología , Factores Biológicos/farmacología , Proliferación Celular/efectos de los fármacos , Fibroblastos/citología , Fibroblastos/efectos de los fármacos , Cobayas , Humanos , Piel/efectos de los fármacos , Piel/inmunología , Solventes , Porcinos

Asunto(s)

Colelitiasis/cirugía , Neoplasias Intestinales/cirugía , Intestino Delgado/cirugía , Laparoscopía/métodos , Colecistectomía Laparoscópica , Colelitiasis/diagnóstico por imagen , Humanos , Neoplasias Intestinales/diagnóstico por imagen , Intestino Delgado/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Ultrasonografía

RESUMEN

The relationship between MRI-parameters of frontal lobes and levels of autoantibodies to nerve growth factor (Aab-NGF) in the blood serum of patients with schizophrenia and their relatives was studied. The negative correlation between the Aab-NGF level and the total volume of frontal lobes (r= -0,59; p<0,01) was found in the group of patients. No significant correlations were found in the control groups of healthy subjects without family history of schizophrenia and relatives of patients. The authors concede that Aab-NGF may play a substantial role in the development of neuromorphological changes in schizophrenia.

Asunto(s)

Autoanticuerpos/sangre , Autoinmunidad/inmunología , Lóbulo Frontal/patología , Factor de Crecimiento Nervioso/sangre , Esquizofrenia/sangre , Adulto , Progresión de la Enfermedad , Femenino , Humanos , Técnicas para Inmunoenzimas , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pronóstico , Esquizofrenia/diagnóstico , Esquizofrenia/inmunología , Índice de Severidad de la Enfermedad

RESUMEN

Eighty-four families with schizophrenia: 84 patients (probands) and 73 their first-degree unaffected relatives as well as 37 normals and their relatives have been studied using pathopsychological (pictogram) and Luria's neuropsychological tests. The most prominent abnormalities both in patients and relatives were global characteristics of auditory-speech memory predominantly related to left subcortical and left temporal regions. Abnormalities of immediate recall of short logic story (SLS) were connected with dysfunction of the same brain regions. Less prominent delayed recall abnormalities of SLS were revealed only in patients and connected with left subcortical, left subcortical-frontal and left subcortical-temporal zones. This abnormality was absent in relatives and age-matched controls. The span of mediated retention was decreased in patients and, to a less degree, in relatives. A quantitative psychological analysis has demonstrated the disintegration ("schizys") between semantic conception and image memory structure in patients and, to a less degree, in relatives. Data obtained show primary memory abnormalities in families with schizophrenia related to the impairment of decoding information process in the subcortical structures, the left-side dysfunction of brain structures being predominantly typical.

Asunto(s)

Familia , Memoria/fisiología , Esquizofrenia/fisiopatología , Adulto , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Psicometría/métodos , Estudios Retrospectivos , Esquizofrenia/genética

RESUMEN

MicroRNAs (miRNAs) are a class of small regulatory RNAs that control a level of expression of protein encoding genes. Their role in brain pathologies is unknown. We made a first attempt to carry out a genetic study coupled with gene expression analysis of microRNA in human neuropsychiatric pathology. Presumably, at least one third of known miRNA genes are expressed in the brain. Mutations disrupting MECP2 protein lead to abnormal development of the brain and resulting behavior. MiR-130b expressed in the brain and potentially targeting MECP2 is located in the susceptibility locus for schizophrenia (22q11). We performed a comparative analysis of the expression of miR-130b in 24 brain neocortex samples from schizophrenic and normal individuals. The stability and effective detection of mature microRNA in postmortem tissues using Real-time PCR have been shown. Screening for mutations has identified a population polymorphism in the 5 -upstream miR-130b gene region containing DNA elements for putative transcription factors. Genetic association analysis of 300 schizophrenia and 316 normal control individuals revealed no statistically significant association of any of the miR-130b allelic variants with schizophrenia. The data demonstrated feasibility and perspective of convergent genetic and expression analysis of human microRNA genes in testing their role in human diseases.

Asunto(s)

Proteína 2 de Unión a Metil-CpG/genética , MicroARNs/genética , Mutación , Esquizofrenia/genética , Adolescente , Adulto , Secuencia de Bases , Encéfalo/metabolismo , Cromosomas Humanos Par 22/genética , Femenino , Perfilación de la Expresión Génica , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Datos de Secuencia Molecular , Neocórtex/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Proyectos Piloto , Polimorfismo Genético

Asunto(s)

Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas/genética , Racemasas y Epimerasas/genética , Esquizofrenia/genética , Estudios de Casos y Controles , Femenino , Genética de Población , Humanos , Masculino , ARN Mensajero/genética