scholarly journals Molecular genetic aspects of keratoconus pathogenesis

2017 ◽  
Vol 10 (2) ◽  
pp. 62-71
Author(s):  
Alexey N Kulikov ◽  
Sergey V Churashov ◽  
Tatiana A Kamilova ◽  
Vladimir A Reituzov
Keyword(s):  
Current Knowledge ◽  
Strong Association ◽  
Molecular Genetic ◽  
Corneal Transplantation ◽  
Young Generation ◽  
Corneal Curvature ◽  
Complex Segregation Analysis ◽  
Genetic Abnormalities ◽  
Number Of Genes ◽  
Genetic And Environmental Factors

Keratoconus is a bilateral, progressive corneal disease affecting all ethnic groups around the world. It is one of the major ocular problems with significant social impacts as the disease affects young generation, and is the leading cause of corneal transplantation. Although keratoconus is associated with genetic and environmental factors, its precise etiology is not yet established. Results from complex segregation analysis and patterns of gene expression show that genetic abnormalities may play an essential role in the susceptibility to keratoconus. There is a strong association between the polymorphism of a number of genes and corneal curvature. These polymorphisms explain only a small percentage of keratoconus cases, so genetic influences on keratoconus are most likely complex and varied. The aim of this review is to briefly provide the current knowledge on the genetic keratoconus basis - to understand the disease pathogenesis.

HLA Genotype of Patients with Severe Haemophilia A due to Intron 22 Inversion with and without Inhibitors of Factor VIII

1997 ◽  
Vol 77 (02) ◽  
pp. 238-242 ◽  
Author(s):  
J Oldenburg ◽  
J K Picard ◽  
R Schwaab ◽  
H H Brackmann ◽  
E G D Tuddenham ◽  
...  
Keyword(s):  
Factor Viii ◽  
Major Gene ◽  
Statistical Significance ◽  
Strong Association ◽  
Molecular Genetic ◽  
Single Mutation ◽  
Severe Haemophilia ◽  
Extended Haplotype ◽  
Intron 22 Inversion ◽  
Hla Genotype

SummaryMolecular genetic studies have shown that development of antibodies to factor VIII (inhibitors) occurs most frequently in patients with severe haemophilia due to major gene lesions including inversions, stop codons and large deletions. Previous studies of HLA type were performed on inhibitor and non-inhibitor patients with diverse uncharacterised mutations which may have confounded detection of significant associations. We therefore selected a group of patients with a single mutation type, the prevalent intron 22 inversion, with or without inhibitors, to determine HLA genotype. Seventy-one such patients, 42 without and 29 with inhibitors (13 high, 9 low and 7 transient responders) were genotyped for MHC Class I HLA-A, -B, -C and Class II HLA-DQA, -DQB and -DRB loci. No strong correlation of any HLA-allele to inhibitor or non-inhibitor status was found. However, alleles of the haplotype HLA-A3, HLA-B7, HLA-C7, HLA-DQA0102, HLA-DQB0602, HLA-DR15 occurred more often in inhibitor patients. Since the alleles of this extended haplotype are common in the North European population only a very strong association would achieve statistical significance. Further studies of groups of patients similar to those studied here will be needed to confirm or exclude this association.

The Role of the Endothelium in Premature Atherosclerosis: Molecular Mechanisms

2020 ◽  
Vol 27 (7) ◽  
pp. 1041-1051 ◽  
Author(s):  
Michael Spartalis ◽  
Eleftherios Spartalis ◽  
Antonios Athanasiou ◽  
Stavroula A. Paschou ◽  
Christos Kontogiannis ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Low Density Lipoprotein ◽  
Critical Role ◽  
Density Lipoprotein ◽  
Number Of Genes ◽  
Causes Of Mortality ◽  
Artery Disease ◽  
Genetic And Environmental Factors ◽  
Made In

Atherosclerotic disease is still one of the leading causes of mortality. Atherosclerosis is a complex progressive and systematic artery disease that involves the intima of the large and middle artery vessels. The inflammation has a key role in the pathophysiological process of the disease and the infiltration of the intima from monocytes, macrophages and T-lymphocytes combined with endothelial dysfunction and accumulated oxidized low-density lipoprotein (LDL) are the main findings of atherogenesis. The development of atherosclerosis involves multiple genetic and environmental factors. Although a large number of genes, genetic polymorphisms, and susceptible loci have been identified in chromosomal regions associated with atherosclerosis, it is the epigenetic process that regulates the chromosomal organization and genetic expression that plays a critical role in the pathogenesis of atherosclerosis. Despite the positive progress made in understanding the pathogenesis of atherosclerosis, the knowledge about the disease remains scarce.

scholarly journals Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes

2021 ◽  
Vol 10 (5) ◽  
pp. 1759-1771
Author(s):  
Xuefen Yan ◽  
Lu Wang ◽  
Lingxu Jiang ◽  
Yingwan Luo ◽  
Peipei Lin ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Myelodysplastic Syndromes ◽  
Molecular Genetic ◽  
Chinese Patients ◽  
Genetic Abnormalities

scholarly journals Eye Rubbing and Keratoconus: A Literature Review

2014 ◽  
Vol 3 (3) ◽  
pp. 118-121 ◽  
Author(s):  
Elizabeth Hawkes ◽  
Mayank A Nanavaty
Keyword(s):  
Environmental Factors ◽  
Literature Review ◽  
Visual Loss ◽  
Current Knowledge ◽  
Common Cause ◽  
Genetic And Environmental Factors ◽  
Developed World

ABSTRACT Keratoconus is a progressive corneal ectactic condition that can lead to visual loss. Despite being the most common cause for keratoplasty in the developed world the aetiology is unknown. It is thought to be multifactorial, with genetic and environmental factors implicated. The association of eye rubbing and pathogenesis of keratoconus has been well documented. In this review, we collate the existing literature and summarize the current knowledge of the role of eye rubbing in the pathogenesis of keratoconus. How to cite this article Hawkes E, Nanavaty MA. Eye Rubbing and Keratoconus: A Literature Review. Int J Kerat Ect Cor Dis 2014;3(3):118-121.

Recent Atmospheric Variability at Kibo Summit, Kilimanjaro, and Its Relation to Climate Mode Activity

2018 ◽  
Vol 31 (10) ◽  
pp. 3875-3891 ◽  
Author(s):  
Emily Collier ◽  
Thomas Mölg ◽  
Tobias Sauter
Keyword(s):  
Indian Ocean ◽  
Current Knowledge ◽  
Southern Oscillation ◽  
Strong Association ◽  
Atmospheric Modeling ◽  
High Mountain ◽  
Atmospheric Variability ◽  
Rain Season ◽  
The Indian Ocean ◽  
The Impact

Abstract Accurate knowledge of the impact of internal atmospheric variability is required for the detection and attribution of climate change and for interpreting glacier records. However, current knowledge of such impacts in high-mountain regions is largely based on statistical methods, as the observational data required for process-based assessments are often spatially or temporally deficient. Using a case study of Kilimanjaro, 12 years of convection-permitting atmospheric modeling are combined with an 8-yr observational record to evaluate the impact of climate oscillations on recent high-altitude atmospheric variability during the short rains (the secondary rain season in the region). The focus is on two modes that have a well-established relationship with precipitation during this season, El Niño–Southern Oscillation and the Indian Ocean zonal mode, and demonstrate their strong association with local and mesoscale conditions at Kilimanjaro. Both oscillations correlate positively with humidity fluctuations, but the association is strongest with the Indian Ocean zonal mode in the air layers near and above the glaciers because of changes in zonal circulation and moisture transport, emphasizing the importance of the moisture signal from this basin. However, the most anomalous conditions are found during co-occurring positive events because of the combined effects of the (i) extended positive sea surface temperature anomalies, (ii) enhanced atmospheric moisture capacity from higher tropospheric temperatures, (iii) most pronounced weakening of the subsiding branch of the Indian Ocean Walker circulation over East Africa, and (iv) stronger monsoonal moisture fluxes upstream from Kilimanjaro. This study lays the foundation for unraveling the contribution of climate modes to observed changes in Kilimanjaro’s glaciers.

scholarly journals The Biological Bases of Group 2 Pulmonary Hypertension

2019 ◽  
Vol 20 (23) ◽  
pp. 5884 ◽  
Author(s):  
Ana I. Fernández ◽  
Raquel Yotti ◽  
Ana González-Mansilla ◽  
Teresa Mombiela ◽  
Enrique Gutiérrez-Ibanes ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Current Knowledge ◽  
Molecular Genetic ◽  
Pressure Overload ◽  
Pulmonary Vasculature ◽  
World Population ◽  
Pulmonary Hemodynamics ◽  
Ongoing Research ◽  
Therapeutic Implications ◽  
Group 2

Pulmonary hypertension (PH) is a potentially fatal condition with a prevalence of around 1% in the world population and most commonly caused by left heart disease (PH-LHD). Usually, in PH-LHD, the increase of pulmonary pressure is only conditioned by the retrograde transmission of the left atrial pressure. However, in some cases, the long-term retrograde pressure overload may trigger complex and irreversible biomechanical and biological changes in the pulmonary vasculature. This latter clinical entity, designated as combined pre- and post-capillary PH, is associated with very poor outcomes. The underlying mechanisms of this progression are poorly understood, and most of the current knowledge comes from the field of Group 1-PAH. Treatment is also an unsolved issue in patients with PH-LHD. Targeting the molecular pathways that regulate pulmonary hemodynamics and vascular remodeling has provided excellent results in other forms of PH but has a neutral or detrimental result in patients with PH-LHD. Therefore, a deep and comprehensive biological characterization of PH-LHD is essential to improve the diagnostic and prognostic evaluation of patients and, eventually, identify new therapeutic targets. Ongoing research is aimed at identify candidate genes, variants, non-coding RNAs, and other biomarkers with potential diagnostic and therapeutic implications. In this review, we discuss the state-of-the-art cellular, molecular, genetic, and epigenetic mechanisms potentially involved in PH-LHD. Signaling and effective pathways are particularly emphasized, as well as the current knowledge on -omic biomarkers. Our final aim is to provide readers with the biological foundations on which to ground both clinical and pre-clinical research in the field of PH-LHD.

Enteric Nervous System: Development and Developmental Disturbances—Part 2

2002 ◽  
Vol 5 (4) ◽  
pp. 329-349 ◽  
Author(s):  
Donald Newgreen ◽  
Heather M. Young
Keyword(s):  
Nervous System ◽  
Enteric Nervous System ◽  
System Development ◽  
Molecular Genetic ◽  
Nervous System Development ◽  
Developmental Disturbances ◽  
Genetic Abnormalities ◽  
A Cell ◽  
Cells Of Cajal ◽  
Enteric Nervous System Development

This review, which is presented in two parts, summarizes and synthesizes current views on the genetic, molecular, and cell biological underpinnings of the early embryonic phases of enteric nervous system (ENS) formation and its defects. Accurate descriptions of the phenotype of ENS dysplasias, and knowledge of genes which, when mutated, give rise to the disorders (see Part 1 in the previous issue of this journal), are not sufficient to give a real understanding of how these abnormalities arise. The often indirect link between genotype and phenotype must be sought in the early embryonic development of the ENS. Therefore, in this, the second part, we provide a description of the development of the ENS, concentrating mainly on the origin of the ENS precursor cells and on the cell migration by which they become distributed throughout the gastrointestinal tract. This section also includes experimental evidence on the controls of ENS formation derived from classic embryological, cell culture, and molecular genetic approaches. In addition, for reasons of completeness, we also briefly describe the origins of the interstitial cells of Cajal, a cell population closely related anatomically and functionally to the ENS. Finally, a brief sketch is presented of current notions on the developmental processes between the genes and the morphogenesis of the ENS, and of the means by which the known genetic abnormalities might result in the ENS phenotype observed in Hirschsprung's disease.

scholarly journals Molecular and Histopathological Changes Associated with Keratoconus

2017 ◽  
Vol 2017 ◽  
pp. 1-16 ◽  
Author(s):  
Mariam Lotfy Khaled ◽  
Inas Helwa ◽  
Michelle Drewry ◽  
Mutsa Seremwe ◽  
Amy Estes ◽  
...  
Keyword(s):  
Structural Changes ◽  
Corneal Transplantation ◽  
Leading Indicators ◽  
Histopathological Changes ◽  
Molecular Defects ◽  
Research Areas ◽  
Fourth Decade ◽  
Genetic And Environmental Factors ◽  
Opening Up ◽  
Corneal Thinning

Keratoconus (KC) is a corneal thinning disorder that leads to loss of visual acuity through ectasia, opacity, and irregular astigmatism. It is one of the leading indicators for corneal transplantation in the Western countries. KC usually starts at puberty and progresses until the third or fourth decade; however its progression differs among patients. In the keratoconic cornea, all layers except the endothelium have been shown to have histopathological structural changes. Despite numerous studies in the last several decades, the mechanisms of KC development and progression remain unclear. Both genetic and environmental factors may contribute to the pathogenesis of KC. Many previous articles have reviewed the genetic aspects of KC, but in this review we summarize the histopathological features of different layers of cornea and discuss the differentially expressed proteins in the KC-affected cornea. This summary will help emphasize the major molecular defects in KC and identify additional research areas related to KC, potentially opening up possibilities for novel methods of KC prevention and therapeutic intervention.

Genetic and immunophenotypical diagnostics for acute myeloid leukemia and their implication on treatment strategy

2012 ◽  
Vol 0 (0) ◽  
pp. -
Author(s):  
Sabine Kayser ◽  
Richard F. Schlenk
Keyword(s):  
Acute Myeloid Leukemia ◽  
Treatment Strategy ◽  
Myeloid Leukemia ◽  
Molecular Genetic ◽  
Treatment Strategies ◽  
Disease Classification ◽  
Novel Drugs ◽  
Genetic Abnormalities ◽  
Binding Factor ◽  
Acute Myeloid

AbstractCytogenetic and molecular genetic abnormalities in acute myeloid leukemia (AML) play an important role in the pathogenesis, are absolutely necessary for disease classification, are the most important prognostic factors for induction success and survival, and are increasingly used for specific genotype-adapted treatment approaches. In particular, molecular-targeted treatment strategies are evolving within clinical trials in the AML entities core-binding factor AML, characterized by t(8;21) and inv(16)/t(16;16), and AML with mutated NPM1, as well as AML with an internal tandem duplication of the FMS-related tyrosine kinase 3 (FLT3) gene. The link between the leukemogenic importance of genetic abnormalities and their role as a potential target for well-known and novel drugs will contribute to the stepwise replacement of purely risk-adapted therapy to a more and more genotype-adapted treatment strategy.

The Decrease of JAK2 V617F Allele Burden in Leukemia Transformation of An Elderly Patient with Myelofibrosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4990-4990
Author(s):  
Su-Jiang Zhang ◽  
Jianyong Li ◽  
Wei Xu
Keyword(s):  
Conflicts Of Interest ◽  
Molecular Genetic ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Jak2 V617f Mutation ◽  
Leukemia Cells ◽  
Elderly Aml ◽  
Genetic Abnormalities ◽  
V617f Mutation

Abstract Abstract 4990 Recently there were two different model about clone genesis of acute myeloid leukemia (AML) transformed from pre-existing JAK2 V617F positive myeloproliferative neoplasm (MPN). One model showed the leukemia cells were come from JAK2 V617F negative clone, however, the other indicated that the leukemia cells were still developed from JAK2 V617F positive clone. Here, we report a elderly AML patient who was developed from pre-existing myelofibrosis (MF) with homozygous JAK2 V617F mutation. In leuekmic transformation phase, heterozygous JAK2 V617F mutation was identified, supported the idea that the leukemia cells may be come from JAK2 V617F negative clone. Moreover, no other cytogenetic and molecular genetic abnormalities were further found. After one course of CAG regimen, complete remission was achieved. Further follow-up is still in progress. Disclosures No relevant conflicts of interest to declare.

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