Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microcysts of the iris pigment epithelium have been described in association with diabetes mellitus, systemic mucopolysaccharidoses. Menkes's syndrome, and in neonates. Our study covers 68 cases obtained at necropsy. We specifically examined the iris pigment epithelium for vacuolation. We found that microcysts are more widespread than previously thought. In our series 57.3% of the cases reviewed by the light microscope showed microcysts. Of interest was the relationship of malignant neoplasm to iris pigment epithelium microcyst: 69.4% of cases with malignancy showed microcyst, whereas only 30% of the cases without neoplasms showed microcysts. Patients treated with exogenous steroid also had a raised incidence of microcysts.
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PMID:Microcysts of the human iris pigment epithelium. 50 90

Genetic defects in copper metabolism highlight the delicate balance mammalian systems have developed to maintain normal copper homeostasis. Menkes disease, the mottled mouse, the Atox-1-deficient mouse and the ctr1 knockout mouse reveal the importance of adequate copper intake during embryogenesis and early development, especially in the central nervous system. The toxicity associated with excess copper as manifest in Wilson disease, the toxic milk mouse, the LEC rat and copper toxicosis in the Bedlington terrier demonstrate the profound cellular susceptibility to copper overload, in particular, in the brain and liver. Ceruloplasmin (Cp) contains 95% of the copper found in human serum, and inherited loss of this protein results in diabetes, retinal degeneration and neurodegeneration. Despite normal copper metabolism, aceruloplasminemic patients and the Cp knockout mouse have disturbed iron homeostasis and mild hepatic copper retention. These genetic disorders of copper metabolism provide valuable insight into the mechanisms regulating copper homeostasis and models to further dissect the role of this essential metal in health and disease.
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PMID:Genetic defects in copper metabolism. 1273 Apr 58

The homeostasis of all self-renewing tissues is dependent on adult stem cells. As undifferentiated stem cells undergo asymmetric divisions, they generate daughter cells that retain the stem cell phenotype and transit-amplifying cells (TA cells) that migrate from the stem cell niche, undergo rapid proliferation and terminally differentiate to repopulate the tissue. Epithelial stem cells have been identified in the epidermis, hair follicle, and intestine as cells with a high in vitro proliferative potential and as slow-cycling label-retaining cells in vivo (1-3). Adult, tissue-specific stem cells are responsible for the regeneration of the tissues in which they reside during normal physiologic turnover as well as during times of stress (4-5). Moreover, stem cells are generally considered to be multi-potent, possessing the capacity to give rise to multiple cell types within the tissue (6). For example, rodent hair follicle stem cells can generate epidermis, sebaceous glands, and hair follicles (7-9). We have shown that stem cells from the human hair follicle bulge region exhibit multi-potentiality (10). Stem cells have become a valuable tool in biomedical research, due to their utility as an in vitro system for studying developmental biology, differentiation, tumorigenesis and for their possible therapeutic utility. It is likely that adult epithelial stem cells will be useful in the treatment of diseases such as ectodermal dysplasias, monilethrix, Netherton syndrome, Menkes disease, hereditary epidermolysis bullosa and alopecias (11-13). Additionally, other skin problems such as burn wounds, chronic wounds and ulcers will benefit from stem cell related therapies (14,15). Given the potential for reprogramming of adult cells into a pluripotent state (iPS cells)(16,17), the readily accessible and expandable adult stem cells in human skin may provide a valuable source of cells for induction and downstream therapy for a wide range of disease including diabetes and Parkinson's disease.
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PMID:Isolation and culture of adult epithelial stem cells from human skin. 2149 May 79

Oxidative stress and mitochondrial dysfunction have been identified by many workers as key pathogenic mechanisms in ageing-related metabolic, cardiovascular and neurodegenerative diseases (for example diabetes mellitus, heart failure and Alzheimer's disease). However, although numerous molecular mechanisms have been advanced to account for these processes, their precise nature remains obscure. This author has previously suggested that, in such diseases, these two mechanisms are likely to occur as manifestations of a single underlying disturbance of copper regulation. Copper is an essential but highly-toxic trace metal that is closely regulated in biological systems. Several rare genetic disorders of copper homeostasis are known in humans: these primarily affect various proteins that mediate intracellular copper transport processes, and can lead either to tissue copper deficiency or overload states. These examples illustrate how impaired regulation of copper transport pathways can cause organ damage and provide important insights into the impact of defects in specific molecular processes, including those catalyzed by the copper-transporting ATPases, ATP7A (mutated in Menkes disease), ATP7B (Wilson's disease), and the copper chaperones such as those for cytochrome c oxidase, SCO1 and SCO2. In diabetes, impaired copper regulation manifests as elevations in urinary CuII excretion, systemic chelatable-CuII and full copper balance, in increased pro-oxidant stress and defective antioxidant defenses, and in progressive damage to the blood vessels, heart, kidneys, retina and nerves. Linkages between dysregulated copper and organ damage can be demonstrated by CuII-selective chelation, which simultaneously prevents/reverses both copper dysregulation and organ damage. Pathogenic structures in blood vessels that contribute to binding and localization of catalytically-active CuII probably include advanced glycation end products (AGEs), as well as atherosclerotic plaque: the latter probably undergoes AGE-modification itself. Defective copper regulation mediates organ damage through two general processes that occur simultaneously in the same individual: elevation of CuII-mediated pro-oxidant stress and impairment of copper-catalyzed antioxidant defence mechanisms. This author has proposed that diabetes-evoked copper dysregulation is an important new target for therapeutic intervention to prevent/reverse organ damage in diabetes, heart failure, and neurodegenerative diseases, and that triethylenetetramine (TETA) is the first in a new class of anti-diabetic molecules, which function by targetting these copper-mediated pathogenic mechanisms. TETA prevents tissue damage and causes organ regeneration by acting as a highly-selective CuII chelator which suppresses copper-mediated oxidative stress and restores anti-oxidant defenses. My group has employed TETA in a comprehensive programme of nonclinical studies and proof-of-principle clinical trials, thereby characterizing copper dysregulation in diabetes and identifying numerous linked cellular and molecular mechanisms though which TETA exerts its therapeutic actions. Many of the results obtained in nonclinical models with respect to the molecular mechanisms of diabetic organ damage have not yet been replicated in patients' tissues so their applicability to the human disease must be considered as inferential until the results of informative clinical studies become available. Based on evidence from the studies reviewed herein, trientine is now proceeding into the later stages of pharmaceutical development for the treatment of heart failure and other diabetic complications.
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PMID:Selective divalent copper chelation for the treatment of diabetes mellitus. 2245 87

The deficiency or excess intake of trace elements, including zinc, copper, selenium and iodine, has often been reported. Zinc deficiency is often observed in infants fed breast milk with low zinc concentration, individuals administered chelating medicines, athletes and patients with diabetes mellitus, hepatic cirrhosis or nephrosis syndrome. Menkes disease is associated with severe copper deficiency, and there is no effective treatment. Deficiencies of selenium and iodine are observed in patients who receive special formulas of milk and enteral formula with low selenium and iodine concentrations, respectively. In contrast, neonatal transient hypothyroidism due to excess intake of iodine in pregnant women has also reported in Japan. It is expected that collaborative studies by researchers and clinicians will contribute to clarify the detail mechanism, diagnosis and treatment of these abnormalities.
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PMID:[Recent Trends of Trace Element Studies in Clinical Medicine in Japan]. 2938 51