Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elastinolytic enzymes derived from alveolar macrophages (AM) are considered to play an important role in the development of emphysema associated with cigarette smoking. In this study, the enzyme activity and mRNA expression of cathepsin L were quantitated in AM and bronchoalveolar lavage (BAL) fluid obtained from current smokers and compared with those from nonsmokers. Activity was measured with the synthetic substrate Z-Phe-Arg-MCA combined with a novel cathepsin B inhibitor, CA-074. We found that the specific activity of cathepsin L was significantly elevated in BAL cells from smokers (7.1 +/- 0.7 mumol/mg protein/h, mean +/- SEM) compared with cells from nonsmokers (2.9 +/- 0.3) (p < 0.01). The expression of cathepsin L mRNA in BAL cells as determined by dot-blot analysis was also higher in BAL cells from smokers, which was comparable to the increase in the enzyme activity. About 5 to 6% of the specific activity of cathepsin L in BAL cell lysates was detected in unconcentrated BAL fluid; specific activity was also significantly higher in samples from smokers (0.38 +/- 0.04 mumol/mg protein/h) than from nonsmokers (0.14 +/- 0.02). In addition, procathepsin L (42 kD) and the mature form of cathepsin L (33 kD) were demonstrated in BAL fluid by immunoblot analyses. These data suggest that cigarette smoking induces mRNA expression and the synthesis of cathepsin L in AM and the release of procathepsin from AM into extracellular milieu. Furthermore, increased activity levels of cathepsin L in extracellular compartments may contribute to the proteolysis of elastin in the process of lung destruction associated with cigarette smoking.
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PMID:Cathepsin L activity is increased in alveolar macrophages and bronchoalveolar lavage fluid of smokers. 850 70

Heart valve substitutes of biological origin often fail by degenerative mechanisms. Many authors have hypothesized that mechanical fatigue and structural degradation are instrumental to in vivo failure. Since the properties of the structural matrix at implantation may predetermine failure, we have examined the ultrastructure, fracture, mechanics, and uniaxial high-strain-rate viscoelastic properties of: (1) fresh, (2) cryopreserved, and (3) cellular extracted porcine aortic valve leaflets. The cellular extraction process is being developed in order to reduce immunological attack and calcification. Cryopreservation causes cellular disruption and necrotic changes throughout the tissue, whereas extraction removes all cells and lipid membranes. Both processes leave an intact collagen and elastin structural matrix and preserve the high-strain-rate viscoelastic characteristics of the fresh leaflets. Extraction does cause a 20% reduction in the fracture tension and increases tissue extensibility, with the percent strain at fracture rising to 45.3 +/- 4 (mean +/- SEM) from 31.5 +/- 3 for fresh leaflets. However, extraction does preserve matrix structure and mechanics over the physiological loading range. Glutaraldehyde fixation produces increased extensibility, increased elastic behavior, and, when applied to extracted leaflets, it causes a marked drop in fracture tension, to 50% of that for fresh leaflets. The combination of extraction and fixation may lead to early degenerative failure. The cellular extraction technique alone may be a useful alternative to glutaraldehyde fixation in preparing bioprosthetic heart valves.
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PMID:Biomechanical and ultrastructural comparison of cryopreservation and a novel cellular extraction of porcine aortic valve leaflets. 860 Jan 41

Knowledge of the biomechanical behavior of abdominal aortic aneurysm (AAA) as compared to nonaneurysmal aorta may provide information on the natural history of this disease. We have performed uniaxial tensile testing of excised human aneurysmal and nonaneurysmal abdominal aortic specimens. A new mathematical model that conforms to the fibrous structure of the vascular tissue was used to quantify the measured elastic response. We determined for each specimen the yield (sigma y) and ultimate (sigma u) strengths, the separate contribution to total tissue stiffness by elastin (EE) and collagen (EC) fibers, and a collagen recruitment parameter (A), which is a measure of the tortuosity of the collagen fibers. There was no significant difference in any of these mechanical properties between longitudinal and circumferential AAA specimens, nor in EE and EC between longitudinally oriented aneurysmal and normal specimens. A, sigma y, and sigma u were all significantly higher for the normal than for the aneurysmal group: A = 0.223 +/- 0.046 versus A = 0.091 +/- 0.009 (mean +/- SEM; p < 0.0005), sigma y = 121.0 +/- 32.8 N/cm2 versus sigma y = 65.2 +/- 9.5 N/cm2 (p < 0.05), and sigma u = 201.4 +/- 39.4 N/cm2 versus sigma u = 86.4 +/- 10.2 N/cm2 (p < 0.0005), respectively. Our findings suggest that the AAA tissue is isotropic with respect to these mechanical properties. The observed difference in A between aneurysmal and normal aorta may be due to the complete recruitment and loading of collagen fibers at lower extensions in the former. Our data indicate that AAA rupture may be related to a reduction in tensile strength and that the biomechanical properties of AAA should be considered in assessing the severity of an individual aneurysm.
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PMID:Ex vivo biomechanical behavior of abdominal aortic aneurysm: assessment using a new mathematical model. 888 38

The aim of this study was to investigate the biochemical basis of biomechanical and morphological alterations of upper esophageal sphincter, which have been reported in patients with Zenker's diverticulum. 4-L-Hydroxyproline (4-Hyp) (collagen), isodesmosine (Ides), and desmosine (Des) (elastin) contents were measured in samples of cricopharyngeal muscle (CPM) and muscularis propria of the esophagus below the CPM. The specimens were collected from seven patients operated for Zenker's diverticulum and eight cadavers, without esophageal and connective tissue disease, 4-Hyp was assayed colorimetrically, Ides and Des by high-performance liquid chromatography. Mean (+/-SEM) values were compared by Mann-Whitney U test. In patients, collagen content was significantly increased, both in CPM and in the muscularis propria of the esophagus below the CPM (P < 0.05). In CPM, Ides to Des and collagen to elastin ratios were significantly higher in patients than in controls (P < 0.05). Both the CPM and the upper muscular cuff of the esophagus appear to be involved in the pathogenesis of Zenker's diverticulum. This finding supports the extension of the myotomy to the muscularis propria of the esophagus below the CPM. The alterated Ides to Des ratio suggests a primary disease of CPM as a cause of Zenker's diverticulum.
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PMID:Biochemical markers of upper esophageal sphincter compliance in patients with Zenker's diverticulum. 922 26

To investigate the functional role of interferon (IFN)-gamma in transplant arteriosclerosis, BALB/c hearts were transplanted in immunosuppressed C57BL/6J recipients with (n = 10) or without (n = 10) targeted IFN-gamma gene deletion. In 55-day heart allografts, IFN-gamma deficiency resulted in a significant decrease in vascular thickening. The severity of intimal thickening measured as the percentage of luminal occlusion (mean +/- SEM) in all elastin stained vessels (n = 410) decreased from 37+/-5% in wild-type recipients to 18+/-5% in IFN-gamma -/- recipients (P < 0.005). In the few diseased vessels in grafts from IFN-gamma -/- recipients, the neointima was more cellular with a 90% increase in the nuclear density. This finding correlated with a 50% reduction in fibrosis estimated by alpha-smooth muscle actin cell accumulation in the neointima. The reduction in severity and altered composition of vascular thickening in grafts from IFN-gamma -/- recipients shows that IFN-gamma contributes to arteriosclerotic development following transplantation.
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PMID:Reduced transplant arteriosclerosis in murine cardiac allografts placed in interferon-gamma knockout recipients. 946 61

Survival of the autograft and objective parameters for scar elasticity were evaluated after dermal substitution for acute burns and reconstructive surgery. The dermal substitute, which was based on bovine type I collagen and elastin-hydrolysate, was evaluated by intraindividual comparison in a clinical trial. The substitute was applied in a one-step procedure in combination with a split-thickness autograft. This treatment was compared with the conventional treatment, the split-thickness antograft. After 1 week, the percentage of autograft survival was assessed. The Cutometer SEM 474 was used to obtain objective measurements of skin elasticity parameters 3 to 4 months postoperatively. Forty-two pairs of wounds (31 patients, age 32.9 +/- 19.3 years; burned surface area, 19.8 +/- 14.5 percent) were treated because of acute burns. Reconstructive surgery was performed on 44 pairs of wounds (31 patients, age 33.9 +/- 17.5 years). Autograft survival was not altered by the substitute for reconstructive wounds, although a slight but significant reduction (p = 0.015) was established in the burn category for substituted compared with nonsubstituted wounds. However, the necessity for regrafting was not increased by substitution. Cutometer measurements of reconstructive wounds with a dermal substitute demonstrated a significant increase of pliability (50 percent, p < 0.001), elasticity (defined as immediate extension, 33 percent, p = 0.04), maximal extension (33 percent, p = 0.002), and immediate retraction (31 percent, p = 0.01), as compared with nonsubstituted wounds. After burn surgery, no improvement was found for the different elasticity parameters. Dermal substitution in a one-stage grafting model seems feasible with respect to graft survival. Skin elasticity was considerably improved by the collagen/elastin dermal substitute after reconstructive surgery.
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PMID:Graft survival and effectiveness of dermal substitution in burns and reconstructive surgery in a one-stage grafting model. 1098 68

We performed a systematic analysis of gene expression in arteries and veins by comparing message profiles of macaque aorta and vena cava media using a cDNA array containing 4048 known human genes, approximately 35% of currently named human genes (approximately 11,000). The data show extensive differences in RNA expression in artery versus vein media. Sixty-eight genes had consistent elevation in message expression by the aorta, but none were elevated in the vena cava. The most differentially expressed gene was regulator of G-protein signaling (RGS) 5, at an expression ratio of 46.5+/-12.6 (mean+/-SEM). The data set also contained 2 genes already known to be expressed in the aorta, elastin at 5.0+/-1.4, and the aortic preferentially expressed gene 1 (APEG-1) at 2.3+/-0.6. We chose to analyze RGS5 expression further because of its high level of differential expression in the aorta. Levels of RGS5 mRNA were confirmed by Northern analysis and in situ hybridization. A human tissue RNA dot blot showed that RGS5 message is highest in aorta, followed by small intestine, stomach, and then heart. Northern analysis confirmed that RGS5 expression in human aorta is higher than in any region of the heart. RGS5 is a G-protein signaling regulator of unknown specificity most homologous to RGS4, an inhibitory regulator of pressure-induced cardiac hypertrophy. The expression pattern of the 68 differential genes as a whole is a start toward identifying the molecular phenotypes of arteries and veins on a systematic basis.
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PMID:A comparison of aorta and vena cava medial message expression by cDNA array analysis identifies a set of 68 consistently differentially expressed genes, all in aortic media. 1100 69

We reexamined the morphological and functional properties of the hyoid, the tongue pad, and hyolingual musculature in chameleons. Dissections and histological sections indicated the presence of five distinctly individualized pairs of intrinsic tongue muscles. An analysis of the histochemical properties of the system revealed only two fiber types in the hyolingual muscles: fast glycolytic and fast oxidative glycolytic fibers. In accordance with this observation, motor-endplate staining showed that all endplates are of the en-plaque type. All muscles show relatively short fibers and large numbers of motor endplates, indicating a large potential for fine muscular control. The connective tissue sheet surrounding the entoglossal process contains elastin fibers at its periphery, allowing for elastic recoil of the hyolingual system after prey capture. The connective tissue sheets surrounding the m. accelerator and m. hyoglossus were examined under polarized light. The collagen fibers in the accelerator epimysium are configured in a crossed helical array that will facilitate limited muscle elongation. The microstructure of the tongue pad as revealed by SEM showed decreased adhesive properties, indicating a change in the prey prehension mechanics in chameleons compared to agamid or iguanid lizards. These findings provide the basis for further experimental analysis of the hyolingual system.
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PMID:Morphology and histochemistry of the hyolingual apparatus in chameleons. 1146 43

Tissue engineering and dermal substitution are currently prominent topics of wound-healing research. However, no extensive clinical trials with objective evaluation criteria have been published so far that support the clinical effectiveness of dermal equivalents in the long term. The dermal substitute that is discussed here is derived from bovine collagen and elastin-hydrolysate and has been shown to improve skin elasticity during a short-term clinical follow-up of scar reconstructions. In this study we will present the long-term outcome by means of objective and subjective scar assessment tools for dermal substitution in acute burn wounds and scar reconstructions. In a clinical trial, an intraindividual comparison was performed between the conventional split-thickness autograft and a combination of the collagen/elastin substitute with an autograft. After 1 year, scars were evaluated by the Cutometer SEM 474 for objective elasticity measurements and by planimetry to establish scar contraction. An independent observer subjected scars to a generally accepted clinical scar assessment tool: the Vancouver Scar Scale. In addition, patients gave their impression of the outcome. Forty-two paired burn wounds and 44 paired scar reconstructions were included and evaluated 1 year after surgery. Although substituted scar reconstructions demonstrated an elasticity improvement of approximately 20 percent compared with control wounds, no statistically significant differences were found for skin elasticity, scar contraction, Vancouver Scar Scale, and patient's impression in both categories after 1 year. An extensive long-term follow-up shows that the dermal substitute, which was proven effective in a clinical trial on a short-term basis, did not yield statistical evidence for a long-term clinical effectiveness of dermal substitution.
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PMID:Dermal substitution in acute burns and reconstructive surgery: a subjective and objective long-term follow-up. 1174 80

Microdeletion of chromosome 7q, encompassing the elastin locus, has been identified in patients with Williams syndrome (WS). This study tested the hypothesis that loss of medial elastin affects the discharge of baroreceptors and consequently the baroreflex sensitivity (BRS). Eight untreated patients with WS (14.8 +/- 2.4 y, m +/- SEM) were compared to 8 healthy subjects (15.1 +/- 2.3 y). Blood pressure (BP) was recorded using a Finapres monitor in the supine position. Systolic BP (SBP) levels were 117.8 +/- 4.4 mmHg in WS compared to 110.9 +/- 5.7 in controls (ns). Pulse rate (PR, taken as a surrogate for heart rate) was higher in the WS (89.6 +/- 1.0 vs 74.1 +/- 2.3 beats/min in controls, P < 0.01). The variance (total power) of PI variability was reduced in WS subjects. The amplitudes of the low frequency (LF, 0.1 Hz) and high frequency (HF, respiratory) PI component (modulus) were reduced in WS (210.5 +/- 4.3 vs 34.6 +/- 2.6 ms, P = 0.02 for LF, for HF). The gain of the SBP-PI transfer function was diminished in the low frequency (LF, 0.1 Hz) and the HF range as well (5.8 +/- 0.7 vs 12.1 +/- 1.8 ms/mmHg for LF, P < 0.01 and 6.2 +/- 1.0 vs 21.7 +/- 4.6 ms/mmHg for HF, P < 0.01). The BRS obtained with the sequence technique was also reduced in WS (8.2 +/- 0.9 vs 21.5 +/- 2.9 ms/mm Hg in controls, P < 0.001). The percent of beats involved in baroreflex sequences observed in WS was also diminished to 20% compared to 48% in controls (P < 0.001). In conclusion a BRS reduction associated with a PR elevation was observed in normotensive WS subjects. It is likely abnormal elastic fiber assembly at the arterial level alters baroreceptor discharges.
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PMID:Elastin mutation is associated with a reduced gain of the baroreceptor--heart rate reflex in patients with Williams syndrome. 1210 53


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