Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an attempt to obtain a biological marker for the enigmatic and fatal neurologic disorder, amyotrophic lateral sclerosis (ALS), several laboratories have explored alterations in various extracellular matrix components in both skeletal muscle and skin. We have studied the distribution of fibronectin, laminin, heparan sulfate proteoglycan (HSPG) and collagen types I, III and IV, along with the platelet alpha-granule glycoprotein, thrombospondin (TSP), by immunofluorescence in frozen sections of muscle from control denervating conditions and ALS patients. In ALS and control muscle, types I and III collagen were localized to the endomysium and the perimysium. Type IV collagen and laminin precisely delineated each muscle fiber (endomysium or basement membrane) but did not stain the perimysium. We found no marked quantitative or qualitative differences in the distribution of collagen types I, III and IV, laminin, fibronectin or HSPG in ALS patients compared to controls. However, when polyclonal antisera for TSP was used we found a marked increase in the deposition of this multi-domain glycoprotein in ALS patients' muscle compared to control muscle. Quantitative analysis of soluble extracts from control and ALS patients' muscle by ELISA also indicated that TSP was increased in ALS. TSP is released from platelet alpha-granules in response to thrombin stimulation. TSP elevation implies coagulation activity via the extravascular thrombolytic system in ALS and may correlate with regeneration. Other studies have indicated decreased circulating protease inhibitors and increased serine proteases in this disorder.
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PMID:Thrombospondin, a platelet alpha-granule and matrix glycoprotein, is increased in muscle basement membrane of patients with amyotrophic lateral sclerosis. 128 72

We measured the levels of amino acids in biopsied skin from eight patients with amyotrophic lateral sclerosis (ALS) and seven controls. The most conspicuous changes in ALS patients were as follows. First, the contents of the acidic amino acids glutamate and aspartate were significantly decreased in ALS, and were negatively and significantly associated with the duration of illness. Second, the levels of the collagen-associated amino acids hydroxyproline, proline, glycine, alanine, and hydroxylysine were significantly decreased in ALS, and correlated inversely with the duration of illness. These results suggest that there are abnormalities of acidic amino acids and collagen-associated amino acids in the skin of patients with ALS. These changes may underlie the pathogenesis of ALS.
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PMID:Glutamate and aspartate are decreased in the skin in amyotrophic lateral sclerosis. 821 62

Collagen cross-links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age-matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age-related, stable cross-link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride-reducible labile cross-links, dehydro-hydroxylysinonorleucine and dehydro-histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p less than 0.05 and r = 0.684, p less than 0.05, respectively). The results clearly indicate that during the course of ALS, the cross-linking pathway of skin collagen runs counter to its normal aging, resulting in a "rejuvenation" phenomenon of skin collagen. Thus, cross-linking of skin collagen is affected in ALS.
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PMID:Collagen cross-linking of skin in patients with amyotrophic lateral sclerosis. 163 38

We studied the solubility of skin collagen from six patients with amyotrophic lateral sclerosis (ALS) and six controls. The amount of collagen extracted with neutral salt solution was significantly greater in patients with ALS than in controls. In addition, there was a statistically significant increase in the proportion of collagen extracted from ALS patients with increased duration of illness. The collagen solubilized by pepsin and cyanogen bromide treatments was significantly higher in ALS patients than in controls, and its proportion was positively and significantly associated with duration of illness in ALS patients. These results indicate that the metabolism of skin collagen may be affected in the disease process of ALS, causing an increase in immature soluble collagen in the tissue, which is the opposite to that which occurs in the normal aging process.
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PMID:Amyotrophic lateral sclerosis: increased solubility of skin collagen. 164 Nov 49

There have been several reports concerning elevated glucose 6 phosphate dehydrogenase (G6PDH), the rate-limiting enzyme of pentose phosphate pathway (PPP), in experimental muscle disturbances. PPP produces ribose, a substrate of RNA, and NADPH which is a cofactor of fatty acid synthesis. PPP also has a role of by-path pathway of glycolysis. Then, we evaluated G6PDH activity and RNA content in biopsied quadriceps muscle. The subjects were muscles from 23 neurogenic amyotrophy, 54 myopathy including 19 progressive muscular dystrophy (PMD), and 10 controls whose muscle was obtained at orthopedic surgery. Neurogenic amyotrophy consisted of 12 amyotrophic lateral sclerosis (ALS), 4 spinal muscular atrophy and 7 peripheral nerve disorders. Myopathy were 3 Duchenne dystrophy, 2 congenital muscular dystrophy, 8 limb-girdle type dystrophy, 6 facio-scapular +-humeral muscular dystrophy, 6 myotonic dystrophy, 6 mitochondrial myopathy, 5 endocrinological myopathy, 3 hypokalemic myopathy, 8 polymyositis and 4 other inflammatory myopathy. The assays of G6PDH and RNA were performed after Glock's and Fleck's methods, respectively. The control values were 3.6 +/- 0.8 nmol formed NADPH/mg protein/min (M +/- SD) in G6PDH and 0.69 +/- 0.17 micrograms/mg non-collagen protein in RNA. Most cases of PMD, as well as some cases of ALS, hyperthyroidism, mitochondria hypokalemic myopathy, inflammatory myopathy showed increased values (beyond M + 2SD of control) both in G6PDH and RNA. There were significant positive correlations between G6PDH activity and RNA content in PMD and motor neuron disease. Myotonic dystrophy showed normal values in both G6PDH and RNA. Half number of cases of mitochondrial myopathy demonstrated increased G6PDH alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pentose phosphate pathway in neuromuscular diseases--evaluation of muscular glucose 6-phosphate dehydrogenase activity and RNA content]. 170 36

The skin tissues from patients with amyotrophic lateral sclerosis (ALS) and controls were studied by electron microscopy, and their amino acid compositions were examined. On electron microscopy, the most conspicuous findings in ALS were (1) a marked increase in amorphous material separating collagen bundles, and (2) the smaller diameter of collagen fibrils. These were more marked with longer duration of illness. Amino acid analysis showed that the levels of hydroxyproline, hydroxylysine, and glycine were significantly low (P less than 0.001, P less than 0.01, and P less than 0.001, respectively) in ALS patients as compared with those of controls, and there was a significant negative correlation between the level of hydroxyproline and duration of illness in ALS patients (r = -0.88, P less than 0.01). In addition, the collagen content per dry weight (mg) of the tissues in ALS was significantly smaller (P less than 0.001) than in controls. These results indicate that the metabolism of skin collagen might be affected in the disease process of ALS.
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PMID:Amyotrophic lateral sclerosis: unusually low content of collagen in skin. 208 37

Amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA) might be clinical variants caused by the same etiology, or different diseases altogether. We studied the skin in 12 patients with ALS and 7 patients with SMA. The "delayed return phenomenon" (DRP) was observed only in ALS patients. On light microscopy, collagen bundles in ALS dermis were seen to be less numerous, thinner and more loosely woven than in SMA. Electron microscopy revealed that in ALS (1) collagen fibers became thinner as the disease lasted longer, and (2) collagen bundles were separated by much more amorphous material. These findings were not observed in SMA. Our observations show that ALS may be distinguished from SMA by the presence of abnormal dermal collagen. Therefore, we suggest that comparable clinical and pathological skin analysis is the most important diagnostic tool in differentiating between ALS and SMA.
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PMID:Differential diagnosis between amyotrophic lateral sclerosis and spinal muscular atrophy by skin involvement. 276 98

When the skin of patients with amyotrophic lateral sclerosis (ALS) is stretched, it returns only sluggishly to its original position. We term this property of skin the "delayed return phenomenon" (DRP). The reticular dermis was examined in patients with ALS and controls with or without DRP, respectively. On light microscopy, ALS patients with DRP showed collagen bundles which were reduced in amount, more loosely woven, and separated by wide space, while controls with DRP revealed decrease of dermal thickness, without abnormalities of collagen bundles. Electron microscopy disclosed a markedly large amount of amorphous material positive for ruthenium red, separating collagen fibrils and bundles in ALS patients with DRP. These observations suggest that DRP in ALS is a specific feature not previously reported in cases of ALS.
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PMID:"Delayed return phenomenon" in amyotrophic lateral sclerosis. 214 22

Patients with amyotrophic lateral sclerosis are usually confined to bed within a few years from the onset of the disease; however, bedsores are not known to develop even at its terminal stages. In this study, skin from patients with amyotrophic lateral sclerosis, neuromuscular diseases other than amyotrophic lateral sclerosis, and nonneurologic disorders has been examined by light and electron microscopy for morphologic changes in the connective tissue. On physical examination of the skin in amyotrophic lateral sclerosis patients, the stretched fold showed a delayed relaxation phase. On light microscopy, collagen bundles in the dermis were disoriented, separated, and fragmented, especially in the papillary dermis. Ultrastructurally, extensive deposits of amorphous, fine granular material in the ground substance compartment of the dermis were observed. The preceding cutaneous changes became more apparent as the disease advanced. We speculate that the deposition of this amorphous material may play the role of pressure absorber, thus preventing the occlusion of blood vessels.
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PMID:Skin changes in patients with amyotrophic lateral sclerosis: light and electron microscopic observations. 296 35

In the current study we have measured collagenase activity released from skin explants and fibroblasts of patients with both Guam-type and sporadic amyotrophic lateral sclerosis and controls. The rationale for such a study derives from work reported more than 20 years ago demonstrating abnormalities in skin collagen metabolism in patients with the disease. We were not able to find significant differences in collagenase activity when fibroblasts were compared relative to the total protein secreted. This is explained, in part, by our finding of an increase in total protein released from fibroblasts of the amyotrophic lateral sclerosis patient group. Increased collagenase release did occur when activity was expressed per number of cells plated but was not statistically significant. In addition, increased release followed a 3-day lag period in skin organ culture. These results suggest that collagenase and other enzymes known to activate collagenase, such as plasminogen activator, capable of degrading extracellular matrix components might be responsible for the increased collagenolytic activity previously observed in amyotrophic lateral sclerosis patients' skin. Further evaluation of extracellular-acting degradative enzymes from skin, muscle, nerve and central nervous system may be important to follow-up such leads in understanding the pathogenesis of this enigmatic and fatal disorder.
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PMID:Collagenase activity in skin fibroblasts of patients with amyotrophic lateral sclerosis. 300 15


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