The Incidence of Alkaptonuria: A study in Chemical Individuality

Garrod, Archibald E.

doi:10.1007/bf03401625

Cited by 226 publications

(226 citation statements)

References 12 publications

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“…Alkaptonuria (AKU) (Online Mendelian Inheritance in Man 203500) was the first human disorder recognised as conforming to the principles of Mendelian autosomal recessive inheritance by Archibald Garrod in 1902 1. Garrod introduced the concept of ‘inborn errors of metabolism’ to describe AKU,2 but it was another 50 years before AKU was revealed to be a deficiency of homogentisate 1,2 dioxygenase (HGD) (EC 1.13.11.5), an enzyme involved in the breakdown of tyrosine and phenylalanine 3.…”

Section: Introductionmentioning

confidence: 99%

Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone

et al. 2013

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The AKU mouse was established as a model of both the plasma biochemistry of AKU and its associated arthropathy. Early-stage treatment of AKU patients with nitisinone could prevent the development of associated joint arthropathies. The cellular pathology of ochronosis in AKU mice is identical to that observed in early human ochronosis and thus is a model in which the early stages of joint pathology can be studied and novel interventions evaluated.

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Section: Introductionmentioning

confidence: 99%

Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone

et al. 2013

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“…AKU was the first disease interpreted in terms of Mendelian inheritance 3. The HGO gene in humans is located on chromosome 3q21-23 1…”

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confidence: 99%

Novel mutations in the homogentisate- 1,2-dioxygenase gene identified in Slovak patients with alkaptonuria

Zaťková

2000

Journal of Medical Genetics

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“…Investigations of G×E interactions seek to define how “environmental” and genetic factors, in parallel, impact manifestation of abnormal organ phenotype and disease. Since the time of publication of Sir Archibald Garrod's classic work of intuition, on the incidence of alkaptonuria, it has been gradually comprehended that the etiology of various common diseases points to not only distinct genetic and/or “environmental” causes, but also to subtle but potent interactions between the two [9]. …”

Section: Introduction and Clinical Perspectivementioning

confidence: 99%

Mechanotransduction Mechanisms for Intraventricular Diastolic Vortex Forces and Myocardial Deformations: Part 2

Pasipoularides

2015

J. of Cardiovasc. Trans. Res.

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Epigenetic mechanisms are fundamental in cardiac adaptations, remodeling, reverse remodeling, and disease. A primary goal of translational cardiovascular research is recognizing whether disease related changes in phenotype can be averted by eliminating or reducing the effects of environmental epigenetic risks. There may be significant medical benefits in using gene-by-environment interaction knowledge to prevent or reverse organ abnormalities and disease. This survey proposes that “environmental” forces associated with diastolic RV/LV rotatory flows exert important, albeit still unappreciated, epigenetic actions influencing functional and morphological cardiac adaptations. Mechanisms analogous to Murray's law of hydrodynamic shear-induced endothelial cell modulation of vascular geometry are likely to link diastolic vortex-associated shear, torque and “squeeze” forces to RV/LV adaptations. The time has come to explore a new paradigm in which such forces play a fundamental epigenetic role, and to work out how heart cells react to them. Findings are considered from various disciplines, imaging modalities, computational fluid dynamics, molecular cell biology and cytomechanics. Examined are, among others, structural dynamics of myocardial cells (endocardium, cardiomyocytes, and fibroblasts), cytoskeleton, nucleoskeleton, and extracellular matrix, mechanotransduction and signaling, and mechanical epigenetic influences on genetic expression. To help integrate and focus relevant pluridisciplinary research, rotatory RV/LV filling flow is placed within a working context that has a cytomechanics perspective. This new frontier in contemporary cardiac research should uncover versatile mechanistic insights linking filling vortex patterns and attendant forces to variable expressions of gene regulation in RV/LV myocardium. In due course, it should reveal intrinsic homeostatic arrangements that support ventricular myocardial function and adaptability.

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The Incidence of Alkaptonuria: A study in Chemical Individuality

Cited by 226 publications

References 12 publications

Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone

Ochronotic osteoarthropathy in a mouse model of alkaptonuria, and its inhibition by nitisinone

Novel mutations in the homogentisate- 1,2-dioxygenase gene identified in Slovak patients with alkaptonuria

Mechanotransduction Mechanisms for Intraventricular Diastolic Vortex Forces and Myocardial Deformations: Part 2

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