Time filter

Source Type

Chumachenko A.G.,V A Negovsky Research Institute Of General Reanimatology | Myazin A.E.,V A Negovsky Research Institute Of General Reanimatology | Kuzovlev A.N.,V A Negovsky Research Institute Of General Reanimatology | Gaponov A.M.,V A Negovsky Research Institute Of General Reanimatology | And 4 more authors.
Obshchaya Reanimatologiya | Year: 2016

Aim of the study. To elucidate the association of allelic variants of single nucleotide polymorphism in NRF2 (rs6726395, 177238501A>G) and TLR9 (rs352162, 52218953T>C) genes, each gene separately and in their com bination, with peculiarities of the course of critical conditions during lung infection. Materials and methods. DNA from 86 post-operative patients and oncologic patients was genotyped in an allele specific fashion using tetra-primer polymerase chain reaction followed by gel electrophoresis analysis of products. Results. It has been found that septic shock patients with NRF2 177238501A>G GG genotype had increased mortality and higher APACHE II score and developed non-responsive edema more frequently. Patients with NRF2 177238501A>G GG/TLR9 52218953T>C CC genotype combination developed septic shock and nosocomial pneumonia more rarely. Conclusion. The homozygous NRF2 177238501A>G (GG) allele combination is unfavorable for the course and outcome of critical conditions only in combination with TLR9 52218953T>C СT or TLR9 52218953T>C TT alleles in septic shock patients. At the same time, the combination of TLR9 52218953T>C СС alleles in the same patients with ‘unfavorable’ NRF2 177238501A>G GG protects against development of septic shock and nosoco mial pneumonia. © 2016, V.A. Negovsky Research Institute of General Reanimatology. All Rights reserved.


Lyubchenko L.N.,Nnblokhin Russian Cancer Research Center Moscow | Karpukhin A.V.,Medical Genetics Research Center | Muzaffarova T.A.,Medical Genetics Research Center
Voprosy Onkologii | Year: 2013

About 3% of cases of gastric cancer (GC) cases are due to hereditary predisposition. Molecular causes of inherited predisposition to diffuse GC among Russian patients have not been studied. In the present work there was performed the molecular genetics study in 9 probands with signet-ring cell GC. Search of hereditary mutations was conducted in a suppressor gene of diffuse GC - the gene CDH1. We have discovered a new hereditary mutation (c.1005delA) and one rare variant (s.2253C> T). Frequency of hereditary mutations in sample of patients Russian was 1/9 (11,1%).


Nukuzuma S.,Kobe Institute of Health | Sugiura S.,Medical Genetics Research Center | Nakamichi K.,Japan National Institute of Infectious Diseases | Kameoka M.,Kobe University | And 3 more authors.
Microbiology and Immunology | Year: 2015

It has been difficult to study JCV replication because of its restricted host range. In this study, JCV replication was examined using different clones in 293cells. RT-PCR assay revealed that large T antigen expression in cells transfected with IMR-32-adapted JCVs was significantly greater than in those transfected with Mad-1 or CY. DNA replication assay and viral load verified that the IMR-32-adapted JCVs were replication-competent in 293cells, but not Mad-1 or CY JCVs. These results suggest that a 293 culture system with IMR-32-adapted JCVs may be a useful tool for assessing replication of JCV in vitro. © 2015 The Societies and Wiley Publishing Asia Pty Ltd.


Moghaddasian M.,Mashhad University of Medical Sciences | Moghaddasian M.,Medical Genetics Research Center | Arab H.,Dental Research Center | Dadkhah E.,Mashhad University of Medical Sciences | And 5 more authors.
Gene | Year: 2014

Background: Papillon-Lefèvre syndrome (PLS) is a rare autosomal recessive disorder characterized by hyperkeratosis involving the palms, soles, elbows, and knees followed by periodontitis, destruction of alveolar bone, and loss of primary and permanent teeth. Mutations of the lysosomal protease cathepsin C gene (CTSC) have been shown to be the genetic cause of PLS. This study analyzed CTSC mutations in five Iranian families with PLS and modeled the protein for mutations found in two of them. Methods: DNA analysis was performed by direct automated sequencing of genomic DNA amplified from exonic regions and associated splice intron site junctions of CTSC. RFLP analyses were performed to investigate the presence of previously unidentified mutation(s) in control groups. Protein homology modeling of the deduced novel mutations (P35 delL and R272P) was performed using the online Swiss-Prot server for automated modeling and analyzed and tested with special bioinformatics tools to better understand the structural effects caused by mutations in cathepsin C protein (CTSC). Results: Six Iranian patients with PLS experienced premature tooth loss and palm plantar hyperkeratosis. Sequence analysis of CTSC revealed a novel mutation (P35delL) in exon 1 of Patient 1, and four previously reported mutations; R210X in Patient 2, R272P in Patient 3, Q312R in two siblings of family 4 (Patients 4 and 5), and CS043636 in Patient 6. RFLP analyses revealed different restriction fragment patterns between 50 healthy controls and patients for the P35delL mutation. Modeling of the mutations found in CTSC, P35delL in Patient 1 and R272P in Patient 3 revealed structural effects, which caused the functional abnormalities of the mutated proteins. Conclusions: The presence of this mutation in these patients provides evidence for founder CTSC mutations in PLS. This newly identified P35delL mutation leads to the loss of a leucine residue in the protein. The result of this study indicates that the phenotypes observed in these two patients are likely due to CTSC mutations. Also, structural analyses of the altered proteins identified changes in energy and stereochemistry that likely alter protein function. © 2014 Elsevier B.V.


PubMed | George Mason University, Mashhad University of Medical Sciences, Dental Research Center and Medical Genetics Research Center
Type: Case Reports | Journal: Gene | Year: 2014

Papillon-Lefvre syndrome (PLS) is a rare autosomal recessive disorder characterized by hyperkeratosis involving the palms, soles, elbows, and knees followed by periodontitis, destruction of alveolar bone, and loss of primary and permanent teeth. Mutations of the lysosomal protease cathepsin C gene (CTSC) have been shown to be the genetic cause of PLS. This study analyzed CTSC mutations in five Iranian families with PLS and modeled the protein for mutations found in two of them.DNA analysis was performed by direct automated sequencing of genomic DNA amplified from exonic regions and associated splice intron site junctions of CTSC. RFLP analyses were performed to investigate the presence of previously unidentified mutation(s) in control groups. Protein homology modeling of the deduced novel mutations (P35 delL and R272P) was performed using the online Swiss-Prot server for automated modeling and analyzed and tested with special bioinformatics tools to better understand the structural effects caused by mutations in cathepsin C protein (CTSC).Six Iranian patients with PLS experienced premature tooth loss and palm plantar hyperkeratosis. Sequence analysis of CTSC revealed a novel mutation (P35delL) in exon 1 of Patient 1, and four previously reported mutations; R210X in Patient 2, R272P in Patient 3, Q312R in two siblings of family 4 (Patients 4 and 5), and CS043636 in Patient 6. RFLP analyses revealed different restriction fragment patterns between 50 healthy controls and patients for the P35delL mutation. Modeling of the mutations found in CTSC, P35delL in Patient 1 and R272P in Patient 3 revealed structural effects, which caused the functional abnormalities of the mutated proteins.The presence of this mutation in these patients provides evidence for founder CTSC mutations in PLS. This newly identified P35delL mutation leads to the loss of a leucine residue in the protein. The result of this study indicates that the phenotypes observed in these two patients are likely due to CTSC mutations. Also, structural analyses of the altered proteins identified changes in energy and stereochemistry that likely alter protein function.


Moghbeli M.,Mashhad University of Medical Sciences | Moaven O.,Harvard University | Memar B.,Omeed Hospital | Raziei H.R.,Mashhad University of Medical Sciences | And 7 more authors.
Journal of Gastrointestinal Cancer | Year: 2014

Introduction: Gastric cancer (GC) is one of the leading causes of cancer-related death in Iran. Genome stability is one of the main genetic issues in cancer biology which is governed via the different repair systems such as DNA mismatch repair (MMR). A clear correlation between MMR defects and tumor progression has been shown. Beside the genetic mutations, epigenetic changes also have a noticeable role in MMR defects. Methods: Here, we assessed promoter methylation status and the level of hMLH1mRNA expression as the main component of MMR system in 51 GC patients using the methylation-specific PCR and real-time PCR, respectively. Moreover, we performed a promoter methylation study of the E-cadherin gene promoter. Results: It was observed that, 12 out of 39 cases (23.5 %) had hMLH1 overexpression. Hypermethylation of hMLH1 and E-cadherin promoter regions were observed in 25.5 and 36.4 %, respectively. Although, there was no significant correlation between hMLH1 mRNA expression and clinicopathological features, there are significant correlations between E-cadherin promoter methylation and tumor stage (p=0.028) and location (p=0.025). The rate of hMLH1 promoter methylation in this study was lower than that in the other population, showing the importance of the other mechanisms, in gastric tumorigenesis. Conclusion: The results of this study indicate that DNA repair system is adversely affected by hypermethylation of hMLH1 in a fraction of gastric cancer patients. Additionally, E-cadherin hypermethylation seen in a subset of our gastric cancer patients is consistent with other reports showing correlation with aggressiveness and metastasis of gastric cancer. © 2013 Springer Science+Business Media.


Manschreck T.C.,Beth Israel Deaconess Medical Center | Chun J.,Beth Israel Deaconess Medical Center | Merrill A.M.,Beth Israel Deaconess Medical Center | Maher B.A.,Beth Israel Deaconess Medical Center | And 7 more authors.
Schizophrenia Research | Year: 2015

Background: The Harvard Adolescent Family High Risk (FHR) Study examined multiple domains of function in young relatives of individuals diagnosed with schizophrenia to identify precursors of the illness. One such area is motor performance, which is deviant in people with schizophrenia and in children at risk for schizophrenia, usually offspring. The present study assessed accuracy of motor performance and degree of lateralization in FHR adolescents and young adults. Methods: Subjects were 33 non-psychotic, first-degree relatives of individuals diagnosed with schizophrenia, and 30 non-psychotic comparison subjects (NpC), ranging in age from 13 to 25 who were compared using a line-drawing task. Results: FHR individuals exhibited less precise and coordinated line drawing but greater degree of lateralization than controls. Performance on the linedrawing task was correlated with degree of genetic loading, a possible predictor of higher risk for schizophrenia in the pedigree. Conclusions: The observation of increased motor deviance and increased lateralization in FHR can be utilized in identification and initiation of the treatment in those at high risk in order to prevent or delay the full manifestation of this devastating condition. The use of a rigorously quantified measure is likely to add to the sensitivity of measuring motor performance, especially when impairments may be subtle. © 2015 Elsevier B.V.


Alexeeva I.S.,Central Research Institute of Dental and Maxillofacial Surgery | Volkov A.V.,Central Research Institute of Dental and Maxillofacial Surgery | Kulakov A.A.,Central Research Institute of Dental and Maxillofacial Surgery | Goldshtein D.V.,Medical Genetics Research Center
Cellular Transplantation and Tissue Engineering | Year: 2012

The clinical and experimental study on the restoration of bone tissue with tissue engineering scaffold based on stem cells of adipose tissue and resorbable osteoplastic matrix. In a pilot study proved the effectiveness of the transplant, founded the dates of dental implantation. Use of tissue engineering scaffold led to organotypic reconstruction of bone tissue in the field of transplantation in patients with severe atrophy of the alveolar process of the maxilla and mandible. As part of a clinical trial were treated 20 patients.


Mglinets V.A.,Medical Genetics Research Center
Russian Journal of Genetics | Year: 2015

The paper discusses the current data on the genetics of the lens development. Genetically based processes of the formation of the lens anlage, as well as its specification and differentiation, are considered. The main genes responsible for these consecutive processes of lens development are presented. Their mutational disorders can lead to the absence or underdevelopment of the lens or multiple types of cataracts. © 2015, Pleiades Publishing, Inc.

Loading Medical Genetics Research Center collaborators
Loading Medical Genetics Research Center collaborators