143 results match your criteria Pathogenetics [Journal]


Transgenic short-QT syndrome 1 rabbits mimic the human disease phenotype with QT/action potential duration shortening in the atria and ventricles and increased ventricular tachycardia/ventricular fibrillation inducibility.

Eur Heart J 2018 Nov 28. Epub 2018 Nov 28.

Department of Cardiology and Angiology I, Heart Center University of Freiburg, Hugstetter Str. 55, 79106 Freiburg, Germany.

Aims: Short-QT syndrome 1 (SQT1) is an inherited channelopathy with accelerated repolarization due to gain-of-function in HERG/IKr. Patients develop atrial fibrillation, ventricular tachycardia (VT), and sudden cardiac death with pronounced inter-individual variability in phenotype. We generated and characterized transgenic SQT1 rabbits and investigated electrical remodelling. Read More

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November 2018
3 Reads

HIF-1, Metabolism, and Diabetes in the Embryonic and Adult Heart.

Front Endocrinol (Lausanne) 2018 15;9:460. Epub 2018 Aug 15.

Laboratory of Molecular Pathogenetics, Institute of Biotechnology of the Czech Academy of Sciences, Prague, Czechia.

The heart is able to metabolize any substrate, depending on its availability, to satisfy its energy requirements. Under normal physiological conditions, about 95% of ATP is produced by oxidative phosphorylation and the rest by glycolysis. Cardiac metabolism undergoes reprograming in response to a variety of physiological and pathophysiological conditions. Read More

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[Progress of Clinical Application of SNP-A to MDS--Review].

Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018 Aug;26(4):1244-1247

Department of Clinical Laborotarial Examination, Qingdao Women & Children's Hospital,Qingdao 266011, Shandong Province, China

Cytogenetic abnormalities get wide attention for its guidance value for prognosis and therapy in myelodysplastic syndrome (MDS) and related malignancies. Cytogenetic analysis is also the key to clarify the molecular pathogenesis of these kinds of diseases. The traditional karyotyping technique including metaphase cytogenetic (MC) karyotype analysis and immune fluorescence in situ hybridization (FISH) can detect the chromosomal abnormalities to some degree while the positive rate detected by the techniques is low due to the low resolution, dependence on metaphase dividing cells or the limitation of specific sites on the chromosomes, respectively. Read More

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August 2018
8 Reads

Adverse effects of Hif1a mutation and maternal diabetes on the offspring heart.

Cardiovasc Diabetol 2018 05 12;17(1):68. Epub 2018 May 12.

Laboratory of Molecular Pathogenetics, Institute of Biotechnology CAS, BIOCEV, Center of Excellence, Prumyslova 595, 25250, Vestec, Czechia.

Background: Epidemiological studies show that maternal diabetes predisposes offspring to cardiovascular and metabolic disorders. However, the precise mechanisms for the underlying penetrance and disease predisposition remain poorly understood. We examined whether hypoxia-inducible factor 1 alpha, in combination with exposure to a diabetic intrauterine environment, influences the function and molecular structure of the adult offspring heart. Read More

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May 2018
3 Reads

Challenging tumour immunological techniques that help to track cancer stem cells in malignant melanomas and other solid tumours.

Contemp Oncol (Pozn) 2018 Mar 5;22(1A):41-47. Epub 2018 Mar 5.

Department of Pathogenetics, National Institute of Oncology, Budapest, Hungary.

Aim Of The Study: The arsenal of questions and answers about the minor cancer initiating cancer stem cell (CSC) population put responsible for cancer invasiveness and metastases, has left with an unsolved puzzle. Specific aims of a complex project were partly focused on revealing new biomarkers of cancer. We designed and set up novel techniques to facilitate the detection of cancerous cells. Read More

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March 2018
8 Reads

Inflammation role in sensory neuropathy in Chinese patients with diabetes/prediabetes.

Clin Neurol Neurosurg 2018 Mar 31;166:136-140. Epub 2018 Jan 31.

Rehabilitation Specialty, Jinan University, Guangzhou, 510632, China. Electronic address:

Objectives: Prediabetes involves people with glucose-metabolism impairment, and is related to different diabetic complications, like peripheral neuropathy. We aimed to explore the relationship among inflammatory (tumor necrosis factor alpha [TNFα]) and antiinflammatory (interleukin 10 [IL10]) cytokines as well as neuropathy of very distal-sensory-nerves in Chinese patients with prediabetes/diabetes.

Patients And Methods: In the present study, 55 patients having prediabetes, 55 patients having type 2 diabetes mellitus (DM), and 48 controls were included. Read More

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March 2018
3 Reads

Transcriptome analysis of inflammation-related gene expression in endothelial cells activated by complement MASP-1.

Sci Rep 2017 Sep 5;7(1):10462. Epub 2017 Sep 5.

Department 3rd of Internal Medicine, Semmelweis University, Budapest, Hungary.

Mannan-binding lectin-associated serine protease 1 (MASP-1), the most abundant enzyme of the complement lectin pathway, is able to stimulate human umbilical vein endothelial cells (HUVECs) to alter the expression of several cytokines and adhesion molecules. This study has assessed to what extent MASP-1 is able to modify the transcriptional pattern of inflammation-related (IR) genes in HUVECs. We utilized Agilent microarray to analyse the effects of recombinant MASP-1 (rMASP-1) in HUVECs, on a set of 884 IR genes. Read More

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September 2017
30 Reads

Retroviral envelope proteins: Involvement in neuropathogenesis.

J Neurol Sci 2017 Sep 22;380:151-163. Epub 2017 Jul 22.

Department of Biomedicine, Aarhus University, Bartholin Building, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark. Electronic address:

The primary disease caused by infection with the exogenous human retroviruses, human immunodeficiency virus 1 (HIV-1) or human T-cell lymphotropic virus 1 (HTLV-1), may overlay manifestations of additional autoimmune pathogenesis. Currently, a role for human endogenous retroviruses (HERVs) is also emerging in some autoimmune/immune-mediated diseases, particularly in multiple sclerosis (MS). Both exogenous and endogenous retroviruses have the potential to elicit the processes leading to autoimmune disease. Read More

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September 2017
3 Reads

Renal injury is accelerated by global hypoxia-inducible factor 1 alpha deficiency in a mouse model of STZ-induced diabetes.

BMC Endocr Disord 2017 Aug 3;17(1):48. Epub 2017 Aug 3.

Laboratory of Molecular Pathogenetics, Institute of Biotechnology CAS, BIOCEV, Center of Excellence, Prumyslova 595, Vestec, 25242, Czechia.

Background: Hypoxia inducible factor 1 (HIF-1) activates protective pathways to counteract hypoxia and prevent tissue damage in conjunction with renal injury. The aim of this study was to evaluate a role of HIF-1 in diabetes-induced kidney damage.

Methods: We used a streptozotocin-induced diabetes mouse model and compared biochemical, histological and molecular parameters associated with kidney damage in Hif1α deficient (Hif1α ) and wild-type mice. Read More

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August 2017
7 Reads

Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable β-catenin Overexpression and a β-catenin Mutation.

J Neurol Surg B Skull Base 2017 Aug 27;78(4):346-352. Epub 2017 Mar 27.

Department of Otolaryngology - Head and Neck Surgery, University of Michigan Medical School, Ann Arbor, Michigan, United States.

 Sinonasal teratocarcinosarcomas are rare, aggressive tumors of the skull base. Treatment options are limited and outcomes are poor. Little is known in regard to the genetic factors regulating these tumors. Read More

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August 2017
11 Reads

Transgenerational inheritance of susceptibility to diabetes-induced male subfertility.

Sci Rep 2017 Jul 10;7(1):4940. Epub 2017 Jul 10.

Laboratory of Reproductive Biology, Institute of Biotechnology CAS, BIOCEV, Vestec, Czechia.

Male infertility is a worldwide problem associated with genetic background, environmental factors, and diseases. One of the suspected contributing factors to male infertility is diabetes mellitus. We investigated the molecular and morphological changes in sperms and testicular tissue of diabetic males. Read More

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July 2017
16 Reads

Tuberous sclerosis and its rare association with macrodactyly and fibrous hamartomas.

Skeletal Radiol 2017 Sep 3;46(9):1293-1296. Epub 2017 Jun 3.

Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore.

Tuberous sclerosis complex is a genetic disease that results in abnormal cellular proliferation and hamartoma growths in multiple organ systems. However, macrodactyly and subcutaneous fibrous harmatomas are very uncommon associations with this disease. We see these rare manifestations in our case report of a 16-year-old female with tuberous sclerosis complex and discuss the imaging findings and pathogenetics of these manifestations. Read More

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September 2017
6 Reads

A unique haplotype of RCCX copy number variation: from the clinics of congenital adrenal hyperplasia to evolutionary genetics.

Eur J Hum Genet 2017 06 12;25(6):702-710. Epub 2017 Apr 12.

Molecular Medicine Research Group, Hungarian Academy of Sciences and Semmelweis University, Budapest, Hungary.

There is a difficulty in the molecular diagnosis of congenital adrenal hyperplasia (CAH) due to the c.955C>T (p.(Q319*), formerly Q318X, rs7755898) variant of the CYP21A2 gene. Read More

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June 2017
16 Reads

IMHOTEP-a composite score integrating popular tools for predicting the functional consequences of non-synonymous sequence variants.

Nucleic Acids Res 2017 02;45(3):e13

Institute of Medical Informatics and Statistics, Kiel University, Kiel, Germany.

The in silico prediction of the functional consequences of mutations is an important goal of human pathogenetics. However, bioinformatic tools that classify mutations according to their functionality employ different algorithms so that predictions may vary markedly between tools. We therefore integrated nine popular prediction tools (PolyPhen-2, SNPs&GO, MutPred, SIFT, MutationTaster2, Mutation Assessor and FATHMM as well as conservation-based Grantham Score and PhyloP) into a single predictor. Read More

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February 2017
13 Reads

Genetics and pathophysiology of mammalian sulfate biology.

J Genet Genomics 2017 01 13;44(1):7-20. Epub 2016 Aug 13.

Mater Research Institute, University of Queensland, Woolloongabba, 4102, Queensland, Australia. Electronic address:

Nutrient sulfate is essential for numerous physiological functions in mammalian growth and development. Accordingly, disruptions to any of the molecular processes that maintain the required biological ratio of sulfonated and unconjugated substrates are likely to have detrimental consequences for mammalian physiology. Molecular processes of sulfate biology can be broadly grouped into four categories: firstly, intracellular sulfate levels are maintained by intermediary metabolism and sulfate transporters that mediate the transfer of sulfate across the plasma membrane; secondly, sulfate is converted to 3'-phosphoadenosine 5'-phosphosulfate (PAPS), which is the universal sulfonate donor for all sulfonation reactions; thirdly, sulfotransferases mediate the intracellular sulfonation of endogenous and exogenous substrates; fourthly, sulfate is removed from substrates via sulfatases. Read More

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January 2017
2 Reads

Enteropathy-Associated T-Cell Lymphoma.

Curr Hematol Malig Rep 2016 12;11(6):504-513

Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA.

Enteropathy-associated T-cell lymphoma is a rare neoplasm with uniformly aggressive features that arises from intestinal T-cells. There is strong evidence supporting its association as a dire complication of celiac disease. The clinical presentation can vary from malabsorption and abdominal pain to an acute abdominal emergency. Read More

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December 2016
6 Reads

Kinase-Associated Phosphoisoform Assay: a novel candidate-based method to detect specific kinase-substrate phosphorylation interactions in vivo.

BMC Plant Biol 2016 Sep 21;16(1):204. Epub 2016 Sep 21.

Department of Plant Cell Biology, Centre for Agricultural Research of the Hungarian Academy of Sciences, H-2462, Brunszvik u. 2, Martonvásár, Hungary.

Background: Protein kinases are important components of signalling pathways, and kinomes have remarkably expanded in plants. Yet, our knowledge of kinase substrates in plants is scarce, partly because tools to analyse protein phosphorylation dynamically are limited. Here we describe Kinase-Associated Phosphoisoform Assay, a flexible experimental method for directed experiments to study specific kinase-substrate interactions in vivo. Read More

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September 2016
2 Reads

Base-Biased Evolution of Disease-Associated Mutations in the Human Genome.

Hum Mutat 2016 11 31;37(11):1209-1214. Epub 2016 Aug 31.

Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas.

Understanding the evolution of disease-associated mutations is fundamental to analyze pathogenetics of diseases. Mutation, recombination (by GC-biased gene conversion, gBGC), and selection have been known to shape the evolution of disease-associated mutations, but how these evolutionary forces work together is still an open question. In this study, we analyzed several human large-scale datasets (1000 Genomes, ESP6500, ExAC and ClinVar), and found that base-biased mutagenesis generates more GC→AT than AT→GC mutations, while gBGC promotes the fixation of AT→GC mutations to balance the impact of base-biased mutation on genome. Read More

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November 2016
7 Reads

Pathogenetics of the RASopathies.

Hum Mol Genet 2016 Oct 12;25(R2):R123-R132. Epub 2016 Jul 12.

Department of Pediatrics, Division of Genomic Medicine, University of California Davis, Sacramento, CA, USA UC Davis MIND Institute, Sacramento, CA 95817, USA

The RASopathies are defined as a group of medical genetics syndromes that are caused by germ-line mutations in genes that encode components or regulators of the Ras/mitogen-activated protein kinase (MAPK) pathway. Taken together, the RASopathies represent one of the most prevalent groups of malformation syndromes affecting greater than 1 in 1,000 individuals. The Ras/MAPK pathway has been well studied in the context of cancer as it plays essential roles in growth, differentiation, cell cycle, senescence and apoptosis, all of which are also critical to normal development. Read More

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October 2016
5 Reads

[Evolution of genetic diversity and human diseases].

Authors:
V A Stepanov

Genetika 2016 Jul;52(7):852-64

The problem of development and dispersion of complex diseases in human populations requires new views, approaches, hypotheses, and paradigms. Evolutionary medicine provides one of the promising approaches to this problem, putting the disease into an evolutionary context. Unlike classic approaches oriented to proximate issues on structure and mechanisms of a disease, evolutionary considerations are broader. Read More

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Complement MASP-1 enhances adhesion between endothelial cells and neutrophils by up-regulating E-selectin expression.

Mol Immunol 2016 07 21;75:38-47. Epub 2016 May 21.

3rd Department of Internal Medicine, Semmelweis University, 1125 Budapest, Hungary. Electronic address:

The complement system and neutrophil granulocytes are indispensable in the immune response against extracellular pathogens such as bacteria and fungi. Endothelial cells also participate in antimicrobial immunity largely by regulating the homing of leukocytes through their cytokine production and their pattern of cell surface adhesion molecules. We have previously shown that mannan-binding lectin-associated serine protease-1 (MASP-1), a complement lectin pathway enzyme, is able to activate endothelial cells by cleaving protease activated receptors, which leads to cytokine production and enables neutrophil chemotaxis. Read More

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July 2016
4 Reads

A novel transgenic rabbit model with reduced repolarization reserve: long QT syndrome caused by a dominant-negative mutation of the KCNE1 gene.

Br J Pharmacol 2016 06 19;173(12):2046-61. Epub 2016 May 19.

Rabbit Genome and Biomodel Group, NARIC - Agricultural Biotechnology Institute, Gödöllő, Hungary.

Background And Purpose: The reliable assessment of proarrhythmic risk of compounds under development remains an elusive goal. Current safety guidelines focus on the effects of blocking the KCNH2/HERG ion channel-in tissues and animals with intact repolarization. Novel models with better predictive value are needed that more closely reflect the conditions in patients with cardiac remodelling and reduced repolarization reserve. Read More

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June 2016
22 Reads

Pathogenetics of alveolar capillary dysplasia with misalignment of pulmonary veins.

Authors:
Przemyslaw Szafranski Tomasz Gambin Avinash V Dharmadhikari Kadir Caner Akdemir Shalini N Jhangiani Jennifer Schuette Nihal Godiwala Svetlana A Yatsenko Jessica Sebastian Suneeta Madan-Khetarpal Urvashi Surti Rosanna G Abellar David A Bateman Ashley L Wilson Melinda H Markham Jill Slamon Fernando Santos-Simarro María Palomares Julián Nevado Pablo Lapunzina Brian Hon-Yin Chung Wai-Lap Wong Yoyo Wing Yiu Chu Gary Tsz Kin Mok Eitan Kerem Joel Reiter Namasivayam Ambalavanan Scott A Anderson David R Kelly Joseph Shieh Taryn C Rosenthal Kristin Scheible Laurie Steiner M Anwar Iqbal Margaret L McKinnon Sara Jane Hamilton Kamilla Schlade-Bartusiak Dawn English Glenda Hendson Elizabeth R Roeder Thomas S DeNapoli Rebecca Okashah Littlejohn Daynna J Wolff Carol L Wagner Alison Yeung David Francis Elizabeth K Fiorino Morris Edelman Joyce Fox Denise A Hayes Sandra Janssens Elfride De Baere Björn Menten Anne Loccufier Lieve Vanwalleghem Philippe Moerman Yves Sznajer Amy S Lay Jennifer L Kussmann Jasneek Chawla Diane J Payton Gael E Phillips Erwin Brosens Dick Tibboel Annelies de Klein Isabelle Maystadt Richard Fisher Neil Sebire Alison Male Maya Chopra Jason Pinner Girvan Malcolm Gregory Peters Susan Arbuckle Melissa Lees Zoe Mead Oliver Quarrell Richard Sayers Martina Owens Charles Shaw-Smith Janet Lioy Eileen McKay Nicole de Leeuw Ilse Feenstra Liesbeth Spruijt Frances Elmslie Timothy Thiruchelvam Carlos A Bacino Claire Langston James R Lupski Partha Sen Edwina Popek Paweł Stankiewicz

Hum Genet 2016 May 12;135(5):569-86. Epub 2016 Apr 12.

Department of Molecular and Human Genetics, Baylor College of Medicine, One Baylor Plaza, Rm. R809, Houston, TX, 77030, USA.

Alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV) is a lethal lung developmental disorder caused by heterozygous point mutations or genomic deletion copy-number variants (CNVs) of FOXF1 or its upstream enhancer involving fetal lung-expressed long noncoding RNA genes LINC01081 and LINC01082. Using custom-designed array comparative genomic hybridization, Sanger sequencing, whole exome sequencing (WES), and bioinformatic analyses, we studied 22 new unrelated families (20 postnatal and two prenatal) with clinically diagnosed ACDMPV. We describe novel deletion CNVs at the FOXF1 locus in 13 unrelated ACDMPV patients. Read More

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May 2016
35 Reads

High-Throughput Microdissection for Next-Generation Sequencing.

PLoS One 2016 21;11(3):e0151775. Epub 2016 Mar 21.

Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Precision medicine promises to enhance patient treatment through the use of emerging molecular technologies, including genomics, transcriptomics, and proteomics. However, current tools in surgical pathology lack the capability to efficiently isolate specific cell populations in complex tissues/tumors, which can confound molecular results. Expression microdissection (xMD) is an immuno-based cell/subcellular isolation tool that procures targets of interest from a cytological or histological specimen. Read More

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August 2016
14 Reads

Deterioration of the Medial Olivocochlear Efferent System Accelerates Age-Related Hearing Loss in Pax2-Isl1 Transgenic Mice.

Mol Neurobiol 2016 May 20;53(4):2368-83. Epub 2015 May 20.

Laboratory of Molecular Pathogenetics, Institute of Biotechnology, CAS, Prague 4, CZ-142 20, Prague, Czechia.

The development, maturation, and maintenance of the inner ear are governed by temporal and spatial expression cascades of transcription factors that form a gene regulatory network. ISLET1 (ISL1) may be one of the major players in this cascade, and in order to study its role in the regulation of inner ear development, we produced a transgenic mouse overexpressing Isl1 under the Pax2 promoter. Pax2-regulated ISL1 overexpression increases the embryonic ISL1(+) domain and induces accelerated nerve fiber extension and branching in E12. Read More

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May 2016
10 Reads
6 Citations
5.140 Impact Factor

Rheumatoid arthritis susceptibility genes: An overview.

World J Orthop 2014 Sep 18;5(4):544-9. Epub 2014 Sep 18.

Izabela Korczowska, Department of Rheumatology and Clinical Immunology, University of Medical Sciences in Poznan, 61-701 Poznan, Poland.

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease sustained by genetic factors. Various aspects of the genetic contribution to the pathogenetics and outcome of RA are still unknown. Several genes have been indicated so far in the pathogenesis of RA. Read More

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September 2014

Principal component analysis characterizes shared pathogenetics from genome-wide association studies.

PLoS Comput Biol 2014 Sep 11;10(9):e1003820. Epub 2014 Sep 11.

Department of Biological Statistics & Computational Biology, Cornell University, Ithaca, New York, United States of America; Program in Computational Biology and Medicine, Cornell University, Ithaca, New York, United States of America.

Genome-wide association studies (GWASs) have recently revealed many genetic associations that are shared between different diseases. We propose a method, disPCA, for genome-wide characterization of shared and distinct risk factors between and within disease classes. It flips the conventional GWAS paradigm by analyzing the diseases themselves, across GWAS datasets, to explore their "shared pathogenetics". Read More

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September 2014

MLH1 and MSH2 mutation screening in HNPCC families of Hungary - Two new MMR gene mutations.

Eur J Surg Oncol 2014 Nov 24;40(11):1445-52. Epub 2014 Jul 24.

Institute of Surgery, University of Debrecen, Medical and Health Science Centre, Debrecen, Hungary.

Introduction: Hereditary Non-Polyposis Colorectal Cancer is an inherited disease with deleterious germline mutations in the DNA mismatch repair genes causing the development of colon cancer and other malignancies. This is the first study in Hungary screening the population of our colorectal cancer patients in order to identify the prevalence of the disease.

Methods: In families who met the Modified Amsterdam and Bethesda Criteria the removed tumor tissue was first examined by immunohistochemistry and microsatellite instability analysis. Read More

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November 2014

Multiplex quantitative measurement of mRNAs from fixed tissue microarray sections.

Appl Immunohistochem Mol Morphol 2014 May-Jun;22(5):323-30

*Pathogenetics Unit ‡Tissue Array Research Program, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda †Fischell Department of Bioengineering and the Institute for Systems Research §Department of Mechanical Engineering, University of Maryland, College Park, MD.

The development of prognostic and diagnostic biomarkers, such as those from gene expression studies, requires independent validation in clinical specimens. Immunohistochemical analysis on tissue microarrays (TMAs) of formalin-fixed paraffin-embedded tissue is often used to increase the statistical power, and it is used more often than in situ hybridization, which can be technically limiting. Herein, we introduce a method for performing quantitative gene expression analysis across a TMA using an adaptation of 2D-RT-qPCR, a recently developed technology for measuring transcript levels in a histologic section while maintaining 2-dimensional positional information of the tissue sample. Read More

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April 2015
6 Reads

Primary squamous cell carcinoma of the endometrium in elderly women: a report of four cases.

Aging Clin Exp Res 2014 Oct 11;26(5):543-5. Epub 2014 Mar 11.

Department of Obstetrics and Gynecology, University of Insubria, Del Ponte Hospital, Piazza Biroldi 1, 21100, Varese, Italy,

Pure squamous cell carcinoma arising in the endometrium represents a rare entity, accounting for <1 % of all endometrial malignancies. Limited data about pathogenetics' and behaviours' features are available. Of consequence, there is no consensus about classification and different therapeutic option. Read More

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October 2014
3 Reads
2 Citations
1.140 Impact Factor

NFκB induces overexpression of bovine FcRn: a novel mechanism that further contributes to the enhanced immune response in genetically modified animals carrying extra copies of FcRn.

MAbs 2013 Nov-Dec;5(6):860-71

ImmunoGenes Kft; Budakeszi, Hungary; Department of Immunology; Eötvös Loránd University; Budapest, Hungary.

Among the many functions of the neonatal Fc receptor (FcRn) for IgG, it binds to IgG-opsonized antigen complexes and propagates their traffic into lysosomes where antigen processing occurs. We previously reported that transgenic (Tg) mice and rabbits that carry multiple copies and overexpress FcRn have augmented humoral immune responses. Nuclear factor-kappa B (NFκB) is a critical molecule in the signaling cascade in the immune response. Read More

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January 2015
5 Reads

MASP-1 induces a unique cytokine pattern in endothelial cells: a novel link between complement system and neutrophil granulocytes.

PLoS One 2014 29;9(1):e87104. Epub 2014 Jan 29.

3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.

Microbial infection urges prompt intervention by the immune system. The complement cascade and neutrophil granulocytes are the predominant contributors to this immediate anti-microbial action. We have previously shown that mannan-binding lectin-associated serine protease-1 (MASP-1), the most abundant enzyme of the complement lectin pathway, can induce p38-MAPK activation, NFkappaB signaling, and Ca(2+)-mobilization in endothelial cells. Read More

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October 2014
7 Reads

Validation of esophageal squamous cell carcinoma candidate genes from high-throughput transcriptomic studies.

Am J Cancer Res 2013 14;3(4):402-10. Epub 2013 Aug 14.

Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health Bethesda, Maryland, USA.

In a recent study, a unique gene expression signature was observed when comparing esophageal squamous cell carcinoma (ESCC) epithelial cells to normal esophageal epithelial cells using laser capture microdissection (LCM) and cDNA microarray technology. To validate the expression of several intriguing genes from that study (KRT17, cornulin, CD44, and EpCAM), we employed two new technologies, expression microdissection (xMD) for high-throughput microdissection facilitating protein analysis and RNAscope for the evaluation of low abundant transcripts in situ. For protein measurements, xMD technology was utilized to specifically procure sufficient tumor and normal epithelium from frozen human tissue for immunoblot analysis of KRT17 (CK17) and cornulin. Read More

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August 2013
5 Reads

Cancer cell micronucleus: an update on clinical and diagnostic applications.

APMIS 2013 Jul 20;121(7):569-81. Epub 2012 Dec 20.

Department of Experimental Medicine & Biotechnology, PGIMER, Chandigarh, India.

Micronucleus (MN) is the small nucleus that forms whenever a chromosome or its fragment is not incorporated into one of the daughter nuclei during cell division. Any form of genotoxic stress due to extraneous or internal factors leads to formation of a MN, which serves as an indicator of chromosomal instability. Chromosomal damage and formation of MN are believed to play a significant role in the pathogenesis of many malignancies. Read More

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July 2013
4 Reads

Three-dimensional mRNA measurements reveal minimal regional heterogeneity in esophageal squamous cell carcinoma.

Am J Pathol 2013 Feb 3;182(2):529-39. Epub 2012 Dec 3.

Pathogenetics Unit, National Institutes of Health, Bethesda, Maryland 20892, USA.

The classic tumor clonal evolution theory postulates that cancers change over time to produce unique molecular subclones within a parent neoplasm, presumably including regional differences in gene expression. More recently, however, this notion has been challenged by studies showing that tumors maintain a relatively stable transcript profile. To examine these competing hypotheses, we microdissected discrete subregions containing approximately 3000 to 8000 cells (500 to 1500 μm in diameter) from ex vivo esophageal squamous cell carcinoma (ESCC) specimens and analyzed transcriptomes throughout three-dimensional tumor space. Read More

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February 2013
8 Reads

Mucinous breast carcinomas lack PIK3CA and AKT1 mutations.

Hum Pathol 2012 Dec 15;43(12):2207-12. Epub 2012 Jun 15.

Department of Pathology, Oregon Health & Science University, Portland, OR 97239, USA.

Activating point mutations in the phosphatidylinositol-3-kinase catalytic subunit (PIK3CA) are among the most common molecular defects in invasive breast cancer. Point mutations in the downstream kinase AKT1 are seen in a minority of carcinomas. These mutations are found preferentially in estrogen receptor-positive and Her2-positive breast carcinomas; however, special morphologic types of breast cancer have not been well studied. Read More

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December 2012
11 Reads

[Evolutionary ontogenetic aspects of pathogenetics of chronic human diseases].

Genetika 2011 Dec;47(12):1573-85

This article is a review of scientific publications, in which issues of pathogenetics of multifactorial diseases (MFDs) are considered from the viewpoint of evolution and ontogeny. Concepts explaining significance of evolutionary processes in the formation of genetic architecture of human chronic diseases ("thrifty" genomes and phenotypes, "drifting genes," decanalization) are analyzed. The roles of natural selection and genetic drift in the formation of hereditary diversity of genes for susceptibility to MFDs are considered. Read More

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December 2011

Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma.

BMC Res Notes 2012 Jan 26;5:73. Epub 2012 Jan 26.

Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, Bethesda, USA.

Background: Esophageal squamous cell carcinoma (ESCC), the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB), normal differentiated squamous epithelium (ND), and squamous cell cancer. Read More

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January 2012
4 Reads

[Phenome-genome relations and pathogenetics of multifactorial diseases].

Authors:
V P Puzyrev

Vestn Ross Akad Med Nauk 2011 (9):17-27

This study of phenome-genome relations in multifactorial diseases is focused on the principal notions and concepts, such as "arthritism", syntropies and syntropic gene, diseasome, orthologic phenotypes (phenologs). The results of original investigations into synthropic genes responsible for predisposition to multifactorial diseases are presented along with analysis of DNA methylation in atherosclerotic plaques and whole-genome analysis of asthma. A hypothesis is proposed that ischaemic preconditioning may be a mechanism underlying the stable cardiovascular disease continuum as a special form of synthropy. Read More

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January 2012
3 Reads

Squamous Cell Carcinoma - Similarities and Differences among Anatomical Sites.

Am J Cancer Res 2011 Jan;1(3):275-300

Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.

Squamous cell carcinoma (SCC) is an epithelial malignancy involving many anatomical sites and is the most common cancer capable of metastatic spread. Development of early diagnosis methods and novel therapeutics are important for prevention and mortality reduction. In this effort, numerous molecular alterations have been described in SCCs. Read More

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January 2011
1 Read

Genetic testing of the short child.

Horm Res Paediatr 2011 7;76 Suppl 3:13-6. Epub 2011 Sep 7.

Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.

Increased understanding of the pathogenetics of short stature and readily available genetic testing have changed the face of diagnostic endocrinology. It remains essential, however, that each short child undergoes detailed clinical, auxological and traditional endocrine assessment to determine which gene (or genes) to study. Diagnostic algorithms and clinical scoring systems are reviewed and the implications of genetic testing for determination of therapy type are discussed. Read More

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January 2012

MicroRNA analysis of microdissected normal squamous esophageal epithelium and tumor cells.

Am J Cancer Res 2011 ;1(5):574-584

Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research, Bethesda, MD, USA.

Previous studies have identified several dysregulated microRNAs in esophageal squamous cell carcinoma (ESCC); however, to date there are no ex vivo analyses comparing expression levels of these regulatory molecules in esophageal squamous cell tumors versus patient-matched normal epithelium. We describe here a technical strategy to evaluate microRNAs in normal esophageal basal cells (NB), normal esophageal differentiated cells (ND), and tumor cells (T). Laser capture microdissection was used to procure target populations from five cases and 18 ESCC-associated microRNAs were measured by RT-qPCR. Read More

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January 2011
7 Reads

Necroptosis: biochemical, physiological and pathological aspects.

Pathol Oncol Res 2011 Dec 21;17(4):791-800. Epub 2011 Jul 21.

Department of Pathogenetics, National Institute of Oncology, Ráth György street 7-9, Budapest H-1122, Hungary.

Programmed cell death is a key component of tissue homeostasis, normal development and wide variety of diseases. Conventional view refers to programmed cell death form as caspase-mediated apoptosis while necrosis is considered as an accidental and unwanted cell demise, carried out in a non-regulated manner and caused by extreme conditions. However, accumulating evidences indicate that necrotic cell death can also be a regulated process. Read More

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December 2011
10 Reads

Immunoguided microdissection techniques.

Methods Mol Biol 2011 ;755:57-66

Pathogenetics Unit and Laser Microdissection Core, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Over the past 15 years, laser-based microdissection has improved the precision by which scientists can procure cells of interest from a heterogeneous tissue section. However, for studies that require a large amount of material (e.g. Read More

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November 2011

Why is it crucial to reintegrate pathology into cancer research?

Bioessays 2011 Jul 17;33(7):490-8. Epub 2011 May 17.

Laser Capture Microdissection Core and Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

The integration of pathology with molecular biology is vital if we are to enhance the translational value of cancer research. Pathology represents a bridge between medicine and basic biology, it remains the gold standard for cancer diagnosis, and it plays an important role in discovery studies. In the past, pathology and cancer research were closely associated; however, the molecular biology revolution has shifted the focus of investigators toward the molecular alterations of tumors. Read More

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Behavioural variant frontotemporal dementia--defining genetic and pathological subtypes.

J Mol Neurosci 2011 Nov 11;45(3):583-8. Epub 2011 May 11.

Dementia Research Centre, Department of Neurodegenerative Disease, UCL Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK.

Behavioural variant frontotemporal dementia (bvFTD) is a clinically, genetically and pathologically heterogeneous neurodegenerative disorder caused by FTLD-tau, FTLD-TDP and FTLD-FUS pathologies. Clinically, patients present with behavioural symptoms that may include one or more of disinhibition, apathy/inertia, loss of sympathy/empathy, perseverative, stereotyped and compulsive/ritualistic behaviour or hyperorality/dietary changes. Cognitive deficits, particularly executive dysfunction, are also seen. Read More

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November 2011
1 Read

Effect of immunohistochemistry on molecular analysis of tissue samples: implications for microdissection technologies.

J Histochem Cytochem 2011 Jun 23;59(6):591-600. Epub 2011 Mar 23.

Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health (NIH), Bethesda, Maryland 20892, USA.

Laser-based tissue microdissection is an important tool for the molecular evaluation of histological sections. The technology has continued to advance since its initial commercialization in the 1990s, with improvements in many aspects of the process. More recent developments are tailored toward an automated, operator-independent mode that relies on antibodies as targeting probes, such as immuno-laser capture microdissection or expression microdissection (xMD). Read More

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June 2011
5 Reads

Layered electrophoretic transfer - A method for pre-analytic processing of histological sections.

Proteomics 2011 Mar 31;11(5):883-9. Epub 2011 Jan 31.

Pathogenetics Unit, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD, USA.

Current technologies for measuring protein expression across a tissue section are based on MS or in situ detection such as immunohistochemistry. However, due to the inherent molecular complexity of tissue samples and the large dynamic range of protein expression in cells, current approaches are often unable to measure moderate- and low-abundant proteins. In addition, they do not provide information on the physico-chemical properties of the proteins studied. Read More

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March 2011
2 Reads

Increased matrix metalloproteinase activation in esophageal squamous cell carcinoma.

J Transl Med 2010 Oct 5;8:91. Epub 2010 Oct 5.

Pathogenetics Unit, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.

Background: Esophageal squamous cell carcinomas (ESCC) are usually asymptomatic and go undetected until they are incurable. Cytological screening is one strategy to detect ESCC at an early stage and has shown promise in previous studies, although improvement in sensitivity and specificity are needed. Proteases modulate cancer progression by facilitating tumor invasion and metastasis. Read More

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October 2010
1 Read

Disease risk of missense mutations using structural inference from predicted function.

Curr Protein Pept Sci 2010 Nov;11(7):573-88

Department of Microbiology School of Medicine, University of Washington, 1959 NE Pacific St 357132, Seattle, WA 98195, USA.

Advancements in sequencing techniques place personalized genomic medicine upon the horizon, bringing along the responsibility of clinicians to understand the likelihood for a mutation to cause disease, and of scientists to separate etiology from nonpathologic variability. Pathogenicity is discernable from patterns of interactions between a missense mutation, the surrounding protein structure, and intermolecular interactions. Physicochemical stability calculations are not accessible without structures, as is the case for the vast majority of human proteins, so diagnostic accuracy remains in infancy. Read More

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November 2010