Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0235394 (wasting)
 8,040 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exercise-induced oxidative stress has been reported in patients with chronic obstructive pulmonary disease (COPD) and may play a role in muscle fatigue. It is speculated that oxidative stress during exercise originates from the contracting muscles but this has not been documented. The accumulation of lipofuscin, a marker of cellular oxidative damage, was evaluated in the vastus lateralis muscle in 17 patients with COPD and 10 healthy subjects of similar age. Each subject performed a stepwise exercise test up to maximal capacity during which oxygen uptake (VO(2)) was measured. Resting and peak exercise blood gases were also obtained. Two indices of lipofuscin accumulation were used: lipofuscin inclusions/fiber ratio (LI/F) and lipofuscin inclusions/fiber cross-sectional area ratio (LI/CSA). These ratios were also determined for each specific fiber-type. LI/F (P < 0.01) and LI/CSA (P < 0.01) were greater in COPD compared to healthy subjects. LI/F and LI/CSA for all fiber types were also greater in COPD (P < 0.001). In both groups, LI/F (P < 0.001) and LI/CSA (P < 0.01) were higher in type I than in type II fibers. LI/F and LI/CSA did not correlate significantly with resting PaO(2) and SaO(2), peak VO(2), and DeltaPaO(2) and DeltaSaO(2) during exercise (P > 0.05). Increased lipofuscin accumulation, a marker of oxidative damage, was found in the vastus lateralis muscle in patients with COPD compared to healthy subjects. Oxidative damage of muscle tissue may thus be involved in skeletal muscle dysfunction and wasting in COPD.
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PMID:Lipofuscin accumulation in the vastus lateralis muscle in patients with chronic obstructive pulmonary disease. 1187 Jul 15

Quadriceps weakness is an important complication of advanced chronic obstructive pulmonary disease (COPD) but few data exist concerning muscle bulk in early disease. We hypothesised that quadriceps bulk, measured by ultrasound rectus femoris cross-sectional area (USRF(CSA)), would be reduced in mild, as well as advanced, COPD compared with controls, and would correlate with physical activity. 161 patients with stable COPD and 40 healthy subjects had a measurement of USRF(CSA) and wore a multisensor armband to record physical activity. USRF(CSA) was reduced in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I patients compared with healthy subjects (p=0.0002). Stage II-IV patients had reduced USRF(CSA) (p<0.0001) compared with controls but were not significantly different from those with stage I disease. Physical activity level was reduced in stage I (p=0.002) and stage II-IV disease compared with controls. Using regression analysis, physical activity level was independently associated with USRF(CSA) in stage I (p=0.01) but not stage II-IV disease, where residual volume to total lung capacity ratio was the only independent predictor of physical activity level. Quadriceps wasting exists in patients with mild, as well as advanced, COPD, and is independently associated with physical inactivity in GOLD stage I disease. The identification of these patients may guide early lifestyle and therapeutic interventions.
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PMID:Quadriceps wasting and physical inactivity in patients with COPD. 2236 54

Cockayne syndrome (CS) is a rare autosomal recessive neurodegenerative disease that is associated with mutations in either of two transcription-coupled DNA repair genes, CSA or CSB. Mice with a targeted mutation in the Csb gene (Cs-b(m/m)) exhibit a milder phenotype compared with human patients with mutations in the orthologous CSB gene. Mice mutated in Csb were crossed with mice lacking Xpc (Xp-c(-/-)), the global genome repair gene, to enhance the pathological symptoms. These Cs-b(m/m).Xp-c(-/-) mice were normal at birth but exhibited progressive failure to thrive, whole-body wasting, and ataxia and died at approximately postnatal day 21. Characterization of Cs-b(m/m).Xp-c(-/-) brains at postnatal stages demonstrated widespread reduction of myelin basic protein (MBP) and myelin in the sensorimotor cortex, the stratum radiatum, the corpus callosum, and the anterior commissure. Quantification of individual axons by electron microscopy showed a reduction in both the number of myelinated axons and the average diameter of myelin surrounding the axons. There were no significant differences in proliferation or oligodendrocyte differentiation between Cs-b(m/m).Xp-c(-/-) and Cs-b(m/+).Xp-c(-/-) mice. Rather, Cs-b(m/m).Xp-c(-/-) oligodendrocytes were unable to generate sufficient MBP or to maintain the proper myelination during early development. Csb is a multifunctional protein regulating both repair and the transcriptional response to reactive oxygen through its interaction with histone acetylase p300 and the hypoxia-inducible factor (HIF)1 pathway. On the basis of our results, combined with that of others, we suggest that in Csb the transcriptional response predominates during early development, whereas a neurodegenerative response associated with repair deficits predominates in later life.
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PMID:Dysmyelination not demyelination causes neurological symptoms in preweaned mice in a murine model of Cockayne syndrome. 2239 14