Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0392680 (shortness of breath)
 5,217 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this review is to enlighten the mechanisms of skeletal muscle dysfunction in heart failure. The muscle hypothesis suggests that chronic heart failure (CHF) symptoms, dyspnoea and fatigue are due to skeletal muscle alterations. Hyperventilation due to altered ergoreflex seems to be the cause of shortness of breath. Qualitative and quantitative changes occurring in the skeletal muscle, such as muscle wastage and shift from slow to fast fibers type, are likely to be responsible for fatigue. Mechanisms leading to muscle wastage in chronic heart failure, include cytokine-triggered skeletal muscle apoptosis, but also ubiquitin/proteasome and non-ubiquitin-dependent pathways. The regulation of fibre type involves the growth hormone/insulin-like growth factor 1/calcineurin/ transcriptional coactivator PGC1 cascade. The imbalance between protein synthesis and degradation plays an important role. Protein degradation can occur through ubiquitin-dependent and non-ubiquit-independent pathways. Systems controlling ubiquitin/ proteasome activation have been described. These are triggered by tumour necrosis factor and growth hormone/ insulin-like growth factor 1. However, an important role is played by apoptosis. In humans, and experimental models of heart failure, programmed cell death has been found in skeletal muscle and interstitial cells. Apoptosis is triggered by tumour necrosis factor and in vitro experiments have shown that it can be induced by its second messenger sphingosine. Apoptosis correlates with the severity of the heart failure syndrome. It involves activation of caspases 3 and 9 and mitochondrial cytochrome c release. Sarcomeric protein oxidation and its consequent contractile impairment can form another cause of skeletal muscle dysfunction in CHF.
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PMID:Physiological basis for contractile dysfunction in heart failure. 1899 74

An autopsy case of sporadic amyotrophic lateral sclerosis (ALS) associated with pleuroparenchymal fibroelastosis (PPFE), a rare form of idiopathic interstitial pneumonia, is reported. The patient, a 76-year-old man, presented with shortness of breath and dyspnea and died of progressive respiratory failure after a clinical course of 9 months. Muscle weakness and motor disturbance were mild, and the diagnosis of ALS was not established until one month prior to death. He had serum IgM-kappa monoclonal gammopathy (IgM: 1,232 mg/dL). Autopsy demonstrated ALS of the lower neuron-predominant type. The density of motor neurons in the spinal anterior horn showed a moderate decline, and many remaining neurons contained round inclusions that were immunoreactive for pTDP-43 (phosphorylated transactivation responsive DNA-binding protein of 43 kD) and ubiquitin. Betz cells and the pyramidal tracts were well preserved. The lung showed typical features of PPFE predominantly affecting the upper lobe: fibro-hyalinous thickening of the visceral pleura, a marked increase and aggregation of elastic fibers in the subpleural zone, and intra-alveolar collagenous fibrosis with an increase of elastic fibers in the alveolar septa. Although the complications from interstitial lung diseases including PPFE in ALS patients are usually regarded as incidental, PPFE is clinically important because of its markedly adverse influence on the clinical course. IgM-monoclonal gammopathy is another notable finding in the present case, which is occasionally seen in ALS patients, and the pathogenesis of PPFE is also considered to be associated with immunological derangements.
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PMID:Amyotrophic lateral sclerosis associated with pleuroparenchymal fibroelastosis. 3193 90