Gene/Protein Disease Symptom Drug Enzyme Compound
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 37,932 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 42-year-old black woman presented with dermatosis papulosa nigra lesions of 15 years' duration. Coincident with the diagnosis of symptomatic iron-deficiency anemia about 1 year ago, she reported an "explosion" in number and size of the lesions progressing from her face to her trunk and arms. Physical examination revealed numerous 1-5-mm, black, smooth, verrucous papules predominantly on the forehead, malar region of the face, neck, and upper trunk (Figs 1 and 2). The lesions on the back were situated in a "Christmas tree" pattern and included two 1-cm papules. She had multiple 1-mm papules on the upper arms. A biopsy confirmed the diagnosis of dermatosis papulosa nigra, showing parakeratosis, acanthosis, hyperpigmentation, thick interwoven tracts of epithelial cells, and horn cysts. Given the eruptive nature of her disease, the possibility of an underlying malignancy was entertained. Six weeks later, she went to the emergency room for severe weakness; a colonoscopy revealed an ascending colon adenocarcinoma with a negative metastatic work-up.
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PMID:Eruptive dermatosis papulosa nigra as a possible sign of internal malignancy. 1726 73

We describe a 52-year-old man with body weight loss and bulbar palsy, who exhibited muscle atrophy and weakness with fasciculation especially in the respiratory muscles 4 years prior to death, necessitating respiratory support for 4 years, but who was able to walk until the end-stage. He had no significant family history. Neuropathological examination revealed severe loss of motor neurons in the spinal cord and brainstem, and ubiquitin-positive skein-like inclusions and Bunina bodies in the remaining neurons. In addition, prominent degeneration of the anterolateral funiculus and severe loss of neurons in the intermediate zone of the spinal cord were evident, without marked alteration of the corticospinal tracts. Degeneration of the subthalamic nucleus, increased iron deposition in the substantia nigra, and axonal swelling, residual nodules and acidophilic granules in the spinal ganglia were found. The patient's condition was considered to have been a forme fruste or incipient form of widespread-type amyotrophic lateral sclerosis (ALS) or motor neuron disease (MND) with pallido-nigro-luysian atrophy (PNLA). The neuropathological features of the present case appear to be important for understanding the nature of widespread-type ALS and MND with PNLA.
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PMID:Forme fruste or incipient form of widespread-type amyotrophic lateral sclerosis, or motor neuron disease with pallido-nigro-luysian atrophy? An autopsy case report. 1817 5

The recognition and treatment of stroke in children is challenging as there are fundamental developmental differences in children compared to adults. A young boy presented with sudden weakness of right side of body followed by unconsciousness and convulsion that was not preceded by any history of fever or trauma. Neurological examination revealed upper motor neuron lesion in the right extremities. CT scan showed diffuse hypodense area in fronto-parietal regions. Complete blood count and iron profile evaluated iron deficiency anemia with thrombocytosis. Thrombosis resulting from thrombocytosis secondary to iron deficiency anemia was considered as etiological explanation of stroke in this young child.
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PMID:Stroke in the young: relationship with iron deficiency anemia and thrombocytosis. 1828 38

The Authors, after having defined the phenomenon and the biological characteristics of natural magnets, evaluate their ability in accelerating the formation of bone callus in hand and wrist fractures compared to treatment with immobilization in a plaster cast. Forty patients (4 females and 37 males) between 20 and 86 years of age were treated. A small natural magnet was inserted in each of the plaster casts (diameter: 2cm, height: 0.5cm) made of 4 blocks in Neodymium-Iron-Boron, capable of generating 4 magnetic poles (2 positive and 2 negative) of diagonal alternate polarity that produced a symmetric, quadruple static magnetic field. The created magnetic flow was wavelike, concentrated in one direction, and developed a force up to 12,500 gauss. From this study it has emerged that inserting a quadruple magnet in a plaster cast in hand and wrist fractures results in the formation of bone callus in an average time that is 35% inferior to the "standard" time. Accelerating the healing of the fracture is important since it reduces immobilization time for the joints involved, avoiding subsequent weakness and stiffness and allowing the patient to begin rehabilitative physiotherapy sooner, which permits a faster functional recovery.
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PMID:Treatment of wrist and hand fractures with natural magnets: preliminary report. 1833 79

Renal osteodystrophy (ROD), the abnormal bone histology that occurs in the context of kidney disease, is a disease spectrum and not a uniform progressive bone disease. It is an important component of the broad disturbances of bone and mineral metabolism associated with chronic kidney disease (CKD). There are multiple pathogenetic factors which contribute to the histological abnormalities seen on bone biopsy. The patients with ROD are rarely symp-tomatic in the early stages of CKD. It is also noteworthy that the clinical manifestations are usually preceded by biochemical changes that are insidious and subtle. This makes it difficult for the clinician to suspect the presence of bone and mineral metabolism abnormalities without direct testing. The serum calcium, phosphorus, and alkaline phosphatase levels are usually normal until late in the course of CKD. The main screening test for abnormal bone and mineral metabolism is the measurement of parathyroid hormone which is also somewhat delayed. The clinical signs and symptoms are also challenging to interpret because of their slow and non-specific nature which may include vague, ill-defined, bone aches and pains, and muscle weakness. The gold standard for diagnosis of ROD is bone biopsy with mineralized bone histology after double tetracycline labeling, iron staining and aluminum staining. The currently used histomorphometric descriptions of bone histology are not well integrated clinically and a new nomenclature that is clinically more relevant and useful has been proposed. Additional studies are required to define the spectrum of ROD in the current therapeutic era, and to find clinically useful non-invasive biomarkers to improve the treatment and monitoring of the abnormal bone in the setting of CKD.
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PMID:Role of bone biopsy in renal osteodystrophy. 1911 14

Iron accelerates the production of reactive oxygen species (ROS). Excessive levels of ROS are thought to accelerate skeletal muscle fatigue and contribute to the loss of skeletal muscle mass and function with age. Patients with an iron overload disease frequently report symptoms of weakness and fatigue, which is attributed to reduced cardiac function. The contribution of skeletal muscle to these symptoms is unknown. Using a mouse model of iron overload, we determined the extent of iron accumulation in skeletal muscle and the concentrations of the iron storage protein ferritin. The level of oxidative stress, changes in antioxidant enzymes and exercise performance were also assessed. Compared with control mice, the iron overloaded mice had elevated levels of iron in the tibialis anterior muscle and a fourfold increase in ferritin light chain. The oxidative stress product malondialdehyde was increased in the iron group compared with the control group, as was the antioxidant enzyme activity of glutathione reductase and glutathione peroxidase. The iron group performed less work on an endurance test and produced less force in a strength test. Body weight and skeletal muscle weight were lower in the iron group following the intervention. Iron loading reduced the weight of the fast-twitch extensor digitorum longus muscle more than the slow-twitch soleus muscle. In summary, iron accumulation in skeletal muscle may play a significant role in the reduced exercise capacity seen in iron overload disorders and in ageing, and may play an underlying role in skeletal muscle atrophy.
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PMID:Iron injections in mice increase skeletal muscle iron content, induce oxidative stress and reduce exercise performance. 1920 85

Friedreich ataxia is the most frequent hereditary ataxia, with an estimated prevalence of 3-4 cases per 100,000 individuals. This autosomal-recessive neurodegenerative disease is characterized by progressive gait and limb ataxia, dysarthria, lower-limb areflexia, decreased vibration sense, muscular weakness in the legs, and a positive extensor plantar response. Non-neurological signs include hypertrophic cardiomyopathy and diabetes mellitus. Symptom onset typically occurs around puberty, and life expectancy is 40-50 years. Friedreich ataxia is usually caused by a large GAA-triplet-repeat expansion within the first intron of the frataxin (FXN) gene. FXN mutations cause deficiencies of the iron-sulfur cluster-containing subunits of the mitochondrial electron transport complexes I, II, and III, and of the iron-sulfur protein aconitase. Mitochondrial dysfunction has been addressed in several open-label, non-placebo-controlled trials, which indicated that treatment with idebenone might ameliorate hypertrophic cardiomyopathy; a well-designed phase II trial suggested concentration-dependent functional improvements in non-wheelchair-bound children and adolescents. Other current experimental approaches address iron-mediated toxicity, or aim to increase FXN expression through the use of erythropoietin and histone deacetylase inhibitors. This Review provides guidelines, from a European perspective, for the diagnosis of Friedreich ataxia, differential diagnosis of ataxias and genetic counseling, and treatment of neurological and non-neurological symptoms.
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PMID:Diagnosis and treatment of Friedreich ataxia: a European perspective. 1934 27

Between 1996 and 1999, five mining subsidence events occurred in the iron-ore field in Lorraine, France, and damaged several hundred buildings. Because of the thousand hectares of undermined areas, an assessment of the vulnerability of buildings and land is necessary for risk management. Risk assessment methods changed from initial risk management decisions that took place immediately after the mining subsidence to the risk assessment studies that are currently under consideration. These changes reveal much about the complexity of the vulnerability concept and about difficulties in developing simple and relevant methods for its assessment. The objective of this article is to present this process, suggest improvements on the basis of theoretical definitions of the vulnerability, and give an operational example of vulnerability assessment in the seismic field. The vulnerability is divided into three components: weakness, stakes value, and resilience. Final improvements take into account these three components and constitute an original method of assessing the vulnerability of a city to subsidence.
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PMID:Vulnerability assessment of mining subsidence hazards. 1947 13

Myopathy with deficiency of succinate dehydrogenase and aconitase is a recessively inherited disorder characterized by childhood-onset early fatigue, dyspnoea and palpitations on trivial exercise. The disease is non-progressive, but life-threatening episodes of widespread weakness, severe metabolic acidosis and rhabdomyolysis may occur. The disease has so far only been identified in northern Sweden. The clinical, histochemical and biochemical phenotype is very homogenous and the patients are homozygous for a deep intronic IVS5 + 382G>C splicing affecting mutation in ISCU, which encodes the differently spliced cytosolic and mitochondrial iron-sulphur cluster assembly protein IscU. Iron-sulphur cluster containing proteins are essential for iron homeostasis and respiratory chain function, with IscU being among the most conserved proteins in evolution. We identified a shared homozygous segment of only 405,000 base pair with the deep intronic mutation in eight patients with a phenotype consistent with the original description of the disease. Two other patients, two brothers, had an identical biochemical and histochemical phenotype which is probably pathognomonic for muscle iron-sulphur cluster deficiency, but they presented with a disease where the clinical phenotype was characterized by early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy. The brothers were compound heterozygous for the deep intronic mutation and had a c.149 G>A missense mutation in exon 3 changing a completely conserved glycine residue to a glutamate. The missense mutation was inherited from their mother who was of Finnish descent. The intronic mutation affects mRNA splicing and results in inclusion of pseudoexons in most transcripts in muscle. The pseudoexon inclusion results in a change in the reading frame and appearance of a premature stop codon. In western blot analysis of protein extracts from fibroblasts, there was no pronounced reduction of IscU in any of the patients, but the analysis revealed that the species corresponding to mitochondrial IscU migrates slower than a species present only in whole cells. In protein extracted from isolated skeletal muscle mitochondria the western blot analysis revealed a severe deficiency of IscU in the homozygous patients and appearance of a faint new fraction that could represent a truncated protein. There was only a slight reduction of mitochondrial IscU in the compound heterozygotes, despite their severe phenotype, indicating that the IscU expressed in these patients is non-functional.
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PMID:Clinical manifestation and a new ISCU mutation in iron-sulphur cluster deficiency myopathy. 1956 99

Iron-sulphur cluster deficiency myopathy is caused by a deep intronic mutation in ISCU resulting in inclusion of a cryptic exon in the mature mRNA. ISCU encodes the iron-sulphur cluster assembly protein IscU. Iron-sulphur clusters are essential for most basic redox transformations including the respiratory-chain function. Most patients are homozygous for the mutation with a phenotype characterized by a non-progressive myopathy with childhood onset of early fatigue, dyspnoea and palpitation on trivial exercise. A more severe phenotype with early onset of a slowly progressive severe muscle weakness, severe exercise intolerance and cardiomyopathy is caused by a missense mutation in compound with the intronic mutation. Treatment of cultured fibroblasts derived from three homozygous patients with an antisense phosphorodiamidate morpholino oligonucleotide for 48 h resulted in 100% restoration of the normal splicing pattern. The restoration was stable and after 21 days the correctly spliced mRNA still was the dominating RNA species.
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PMID:Antisense oligonucleotide therapeutics for iron-sulphur cluster deficiency myopathy. 1984 8


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