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At least 19 recordsLinked to original sources
PubMed1989

Polyclonal anti-desmosine antiserum is specific to desmosine molecule: no cross-reaction to pyridinoline.

Inhibition ELISA assay was used to examine the cross-reaction of the polyclonal anti-desmosine antiserum produced in rabbit against molecules possessing a "pyridinium ring" as their core structure i.e. isodesmosine, pentasine, pyridinoline and 2'-deoxypyridinoline, highly purified with column chromatography, and structurally unrelated substances, i.e. cysteic acid, taurine and 2-aminopyridine (core structure of desmosine). No cross-reaction was observed to the pyridinoline, 2'-deoxypyridinoline possessing "pyridinium ring" and derived from collagen cross-links, structurally unrelated cysteic acid and taurine, nor core structure of 2-aminopyridine. The antiserum specifically recognized the molecules derived from the elastin cross-links. Using the ELISA assay system with antisera and amino acids analysis, 10 micrograms of desmosine were extracted from 1.0 mg of the hydrolysate of commercial elastin.

Amino Acids↗
PubMed1991

Measurement of urinary desmosine by isotope dilution and high performance liquid chromatography. Correlation between elastase-induced air-space enlargement in the hamster and elevation of urinary desmosine.

The accuracy of methods employed to measure the elastin-specific crosslinks, desmosine (DES) and isodesmosine (IDES), has been called into question because contaminants in the urine may cause elevated values. In the present study urine samples were spiked with a known amount of [14C]DES and refluxed in 6 N HCl. Sephadex G-15 chromatography of the hydrolyzed urine employed to remove contaminants. DES and IDES were quantified by high performance liquid chromatography (HPLC) as well as by amino acid analysis. The amount of isotope recovered was used to determine losses during the overall procedure and the isotope dilution to calculate the amounts of endogenous DES and IDES originally present in the urine. Because similar values were obtained by both methods, the more rapid HPLC method was used for all succeeding analyses. In one experiment, the DES amounts in urine collected from hamsters for 3 days after intratracheal treatment with human neutrophil elastase (300 micrograms) or porcine pancreatic elastase (300 micrograms) were 0.212 +/- 0.012 (mean +/- SEM, two measurements on a single pool) and 0.816 +/- 0.005 (two measurements) microgram per hamster per day, respectively. Urine from control hamsters had a mean value of 0.074 +/- 0.008 (eight measurements) microgram per hamster per day. The HNE- and PPE-treated hamsters had mean linear intercept values of 119 and 159% of control values, respectively, giving a positive correlation between increase in airspace size and elevation of urinary DES.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Quantitation of elastin in human urine and rat pleural mesothelial cell matrix by a sensitive avidin-biotin ELISA for desmosine.

A specific enzyme-linked immunosorbent assay (ELISA) was developed for the determination of desmosine, a cross-linked amino acid specific to fibrous elastin. Competition between solid phase-bound desmosine-protein conjugate and free desmosine for binding to monospecific anti-desmosine antiserum constituted the underlying principle of the assay. The conjugation of desmosine to different protein carriers was carried out with the 1-ethyl-3-(dimethylamino-propyl)carbodiimide (ECDI); rabbits were immunized with desmosine-bovine serum albumin and micro-titer plates were coated with desmosine-egg albumin. An avidin-biotin peroxidase system was used to reveal anti-desmosine antibodies bound to the desmosine-protein conjugate. As both conjugates revealed new non-specific common epitopes on the carrier proteins, prior absorption of the anti-desmosine antiserum on rabbit albumin polymerized with ECDI was required to remove the antibodies directed against these neo-antigens. The absorption procedure resulted in an increased specificity and sensitivity. Values ranging from 0.07 to 4 ng of desmosine/well could be detected and this sensitivity was greater than that obtained in previous immunoassays for desmosine. In order to assess the specificity of the test, samples containing aminoacids and urine hydrolysates were included in an assay. Some cross-reactivity was observed with the desmosine precursor lysinonorleucine and the desmosine isomer isodesmosine but, in contrast the very low cross-reactivity observed with collagen hydrolysate was similar to that exhibited by albumin hydrolysate. Analysis of urine samples from 118 normal male volunteers showed, firstly, that urinary creatinine measurement was a good indicator of the amount of urine which could be safely introduced in the assay without risk of non-specific interference by other organic compounds and, secondly, that the desmosine/creatinine ratio was a reliable index for an in vivo assessment of degraded elastin excretion. The assay also allowed quantitation of elastin fiber biosynthesis in the connective tissue matrix of cultured rat pleural mesothelial cells. This ELISA for demosine is a simple technique which should be useful for further in vivo or in vitro investigations of fibrous elastin tissue metabolism.

Amino Acids↗
PubMedDate not supplied

Urinary desmosine as a biomarker in acute lung injury.

Acute lung injury (ALI) is a complex disorder associated with an acute inflammatory response thought to contribute to tissue injury. Desmosine, a cross-linking amino acid present in elastin, is released during matrix degradation and cleared by the kidney. Results from animal models and human disease studies have suggested that ALI is associated with the release of desmosine, resulting in increased urinary desmosine. A radioimmunoassay was used to monitor urinary desmosine levels over 10 days in ten patients with ALI. The concentration of desmosine was measured with and without acid hydrolysis. Baseline urinary desmosine was increased in two of ten patients. The concentration of desmosine at baseline did not appear to be related to age, gender, neutrophil elastase (NE)/alpha(1)-antiprotease complex concentration or P(a)O(2)/F(i)O(2) ratio. No meaningful changes in desmosine levels were noted after removal from mechanical ventilation. Baseline desmosine concentrations did not appear to correlate with the risk of death. The limited sensitivity, predictive correlations and dynamic modulation would suggest that urine desmosine has a limited role as a biomarker for ALI. Hydrolysis of urine samples appears necessary for optimal measurement of urine desmosine.

Aged↗
PubMed1979

Studies on the absorption of desmosine and isodesmosine.

Intestinal absorption of desmosine and isodesmosine was investigated in several animal species. Hamsters given desmosine injections intraperitoneally excreted 70% of the injected dose in the urine. When desmosines or elastin were given via gastric intubation, desmosines failed to appear in the urine, indicating a lack of desmosine absorption. Additional studies with everted hamster intestine in vitro showed that norleucine was actively transported from the mucosal to the serosal side but that desmosines and lysinonorleucine were not transported. Intestinal slice experiments with hamster, rabbit, and dog intestine indicated desmosines only in the extracellular space and not absorbed by the mucosal cells. These studies strongly suggest that desmosines are not absorbed via the gastrointestinal tract. The importance of this study rests with the conclusion that desmosines recovered in the urine must represent the degradation products of elastin destruction in the tissue. Newly synthesized elastin cannot interfre, since elastin precursor molecules do not contain desmosines. Thus quantitation of urinary desmosines may be of clinical value as a method of evaluating elastin catabolism.

Amino Acids↗
PubMed1980

Desmosine radioimmunoassay for measuring elastin degradation in vivo.

Desmosine is a cross-link amino acid unique to elastin. Previous work has shown that during turnover in the body, desmosine is not reused, and that desmosine is not absorbed from the intestine. Instead, all desmosine released in the course of elastin metabolism is excreted in the urine attached to low molecular weight peptides. Therefore, measurement of desmosine in acid-hydrolysates of urine might be used to monitor elastin breakdown in several pathologic states, including pulmonary emphysema. In the present report, we have described a sensitive, highly specific radioimmunoassay capable of detecting as little as 200 pg of desmosine in acid-hydrolysates of urine. The assay was specific for desmosine; cross-reactivity with merodesmosine, isodesmosine, lysine, and mixed amino acids was 0.25%, 0.1%, less than 0.0003%, and 0%, respectively. Twenty-three normal, nonsmoking subjects had a mean 24-hr desmosine excretion of 47 +/- 15 microgram. In a group of smokers with evidence of chronic obstructive disease and/or lung infection, the values for desmosine excretion ranged from 40 to 400 microgram/24 h. Desmosine radioimmunoassay may find application in the study of diseases involving increased destruction of elastin in the body.

Adolescent↗
PubMed1989

An enzyme-linked immunosorbent assay (ELISA) for the quantitation of urinary desmosine.

An enzyme-linked immunosorbent assay (ELISA) method has been developed for the quantitation of the elastin cross-link desmosine in urine. The system employs Rabbit antisera directed to the conjugate of desmosine and bovine serum albumin which was conjugated using carbodiimide reagent. The ELISA was done in microtiter plates which were coated with a desmosine-gelatin conjugate. And the assay system is based on an inhibition immunoassay. With this assay system, desmosine could be detected in a range between 0.4-400 ng/ml. Recovery of desmosine (DES) added to urine was 90.6-117.0% as measured by this method. Anti-DES antisera obtained from rabbits, showed no cross-reaction to 19 standard amino acids, two elastines nor mouse acetone liver power (which contained degradated elastin). But iso-desmosine cross-reacted with the antisera 13-45% at the isodesmosine concentration range of 40-400 ng/ml. Column purification of the urinary desmosine with CF-1 cellulose will not be necessary for desmosine measurement in ELISA assay. This paper described the detail procedures for sample preparation and the desmosine measurement in urine. Desmosine measurement can be an effective marker for screening the lung elastin degradation caused by cigarette smoking and environmental pollution to human lung.

Air Pollutants↗
PubMed1989

[An enzyme-linked immunosorbent assay for measuring desmosine in vivo].

Pulmonary emphysema may be a disease in which some elastin in lung is lost. In order to evaluate lung elastin degradation, we developed an enzyme-linked immunosorbent assay for desmosine and measured urinary desmosine excretion and serum desmosine levels in healthy individuals and patients with pulmonary emphysema and other chronic pulmonary disorders. The measurement was performed by the inhibition technique of ELISA so that the samples had to be applied to CF11 cellulose mini-column for partial purification of desmosine. Total urinary excretion of desmosine was uniformly low in healthy individuals and patients with lung cancer, but urinary desmosine was elevated in some cases of pulmonary emphysema and diffuse panbronchiolitis. Using this ELISA method, more than 0.06 micrograms/ml serum desmosine concentration could be measured in 3 out of 25 healthy subjects who had never smoked (13.6%), 4/9 healthy current smokers (44.4%) and 19/26 patients with pulmonary emphysema (73.1%). Mean serum desmosine levels of meseared 19 cases of empysema were 0.182 micrograms/ml. It has been reported that approximately 15% of smokers develop pulmonary emphysema. The most important problem now is whether smokers with elevated urinary desmosine or with high serum desmosine will eventuality develop pulmonary emphysema.

Amino Acids↗
PubMed2006

Higher urine desmosine levels are associated with mortality in patients with acute lung injury.

Desmosine is a stable breakdown product of elastin that can be reliably measured in urine samples. We tested the hypothesis that higher baseline urine desmosine would be associated with higher mortality in 579 of 861 patients included in the recent Acute Respiratory Distress Syndrome Network trial of lower tidal volume ventilation (1). We also correlated urine desmosine levels with indexes of disease severity. Finally, we assessed whether urine desmosine was lower in patients who received lower tidal volumes. Desmosine was measured by radioimmunoassay in urine samples from days 0, 1, and 3 of the study. The data were expressed as a ratio of urine desmosine to urine creatinine to control for renal dilution. The results show that higher baseline (day 0) urine desmosine-to-creatinine concentration was associated with a higher risk of death on adjusted analysis (odds ratio 1.36, 95% confidence interval 1.02-1.82, P=0.03). Urine desmosine increased in both ventilator groups from day 0 to day 3, but the average rise was higher in the 12-ml/kg predicted body weight group compared with the 6-ml/kg predicted body weight group (P=0.053, repeated-measures model). In conclusion, patients with acute lung injury ventilated with lower tidal volumes have lower urine desmosine levels, a finding that may reflect reduced extracellular matrix breakdown. These results illustrate the value of evaluating urinary biological markers that may have prognostic and pathogenetic significance in acute lung injury.

Adult↗
PubMed1991

Urinary desmosine excretion as a marker of lung injury in the adult respiratory distress syndrome.

Desmosine, the intermolecular and intramolecular cross link between the chains of elastin polypeptide, may be useful as a marker of a lung injury in adult respiratory distress syndrome (ARDS). A radioimmunoassay for rabbit antibody developed against desmosine, conjugated to bovine serum albumin, can detect as little as 100 pg of desmosine in plasma or urine. Desmosine is not metabolically absorbed, reused, or catabolized by the body, but rather eliminated unchanged in the urine as low molecular weight peptides. The lung is relatively rich in elastin, and we reasoned that a timed collection could be used as an index of elastin degradation in vivo. A 2-h collection of urine for desmosine assay was obtained at the time of Swan-Ganz catheter insertion in 41 consecutive patients. On the basis of clinical and initial Swan-Ganz catheter data, the patients were assigned to one of three groups: an ARDS group (n = 12); a cardiogenic pulmonary edema (CPE) group (n = 12); and a critically ill, nonpulmonary edema group (NPE, n = 17). The mean urine desmosine concentration (mg/L) for the ARDS group (0.728 +/- 0.22 SE) differed from the CPE group (0.149 +/- 0.07; p less than 0.001). The total excretion (microgram/2 h) was 64.95 +/- 24.7 in the ARDS group and 24.71 +/- 11.7 in the CPE group (p less than 0.05). Urine desmosine concentration/serum creatinine index for the ARDS group (0.78 +/- 0.28) was greater than in the CPE group (0.07 +/- 0.04; p = 0.019). Desmosine excretion was increased in the NPE group compared with CPE and ARDS groups, possibly reflecting heterogeneity in this group. In the differentiation of ARDS from CPE, we conclude that substantial increases in urinary desmosine excretion favor a diagnosis of ARDS.

Adult↗
PubMed1985

An enzyme-linked immunosorbent assay to quantitate the elastin crosslink desmosine in tissue and urine samples.

An enzyme-linked immunosorbent assay method has been developed for the determination of desmosine. The method is based on an inhibition immunoassay (under nonequilibrium conditions) and uses rabbit antisera directed against a desmosine-bovine serum albumin conjugate and microtiter plates coated with desmosine-gelatin conjugate. The assay quantitates desmosine in the range 2.5-50 pmol in tissue and urine samples. Important applications of this rapid and sensitive assay are in studying elastin metabolism and in screening for monoclonal antibodies against desmosine. Methods are described for obtaining a constant level of substitution of desmosine per molecule of bovine serum albumin and for preparing a desmosine-gelatin coating antigen. Five different antibody preparations directed against desmosine exhibit 15-20% cross-reactivity toward pyridinoline (3-hydroxypyridinium), a nonreducible collagen crosslinking compound also present in urine and many tissue samples.

Amino Acids↗
PubMed2002

Urinary desmosine excretion is inversely correlated with the extent of emphysema in patients with chronic obstructive pulmonary disease.

An enhanced proteolysis of lung interstitium is key event in the pathogenesis of emphysema, a major constituent of chronic obstructive pulmonary disease. To assess whether urinary desmosine and/or hydroxyproline may be used as a marker of lung destruction we studied urinary excretions of these products in 20 patients with chronic obstructive pulmonary disease and in 19 appropriate controls in 24h urine collection samples. For desmosine measurements, we developed a new indirect competitive enzyme-linked immunosorbent assay. The extent of emphysema was measured in high resolution computed tomography (CT) scans, by considering lung area with CT numbers <-950 Hounsfield units (HU). Urinary desmosine excretion was significantly higher in patients with chronic obstructive pulmonary disease than in controls (294+/-121 microg versus 183+/-93 microg, P=0.003), and was unrelated with both age and smoking habits. In patients with no evidence or only mild emphysema, desmosine excretion values were significantly higher (P=0.006) than those of patients with moderate to severe emphysema. In patients with chronic obstructive pulmonary disease, urinary hydroxyproline excretion was positively correlated with urinary desmosine excretion but on the average, it was not different from that of controls. These data indicate that urinary desmosine is a sensitive biological marker of lung elastin catabolism. The relatively low levels of urinary desmosine observed in patients with severe emphysema may be accounted for a decrease in elastin catabolism due to reduced lung elastin mass. Urinary desmosine may be used to identify subjects at risk of developing emphysema and to assess the efficacy of therapeutic interventions.

Adult↗
PubMed2004

High levels of desmosines in urine and plasma of patients with pseudoxanthoma elasticum.

BACKGROUND: Pseudoxanthoma elasticum (PXE), a rare heritable disorder caused by mutations of the ABCC6 gene, is characterized by fragmentation and mineralization of elastic fibres. We determined the extent of degradation of elastin by measuring and comparing the amount of desmosines in plasma and urine of PXE patients, healthy carriers and normal subjects. METHODS: Using capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) we measured the amount of desmosines in the urine of 46 individuals (14 PXE patients, 17 healthy carriers and 15 controls) and in the plasma of 56 subjects (18 PXE patients, 23 healthy carriers and 15 controls). Pseudoxanthoma elasticum patients and carriers were identified by clinical, structural and molecular biology analyses. RESULTS: The urinary excretion of desmosines was two-fold higher in PXE patients than in controls (P < 0.01); the values for healthy carriers were intermediate between those of PXE patients and controls. A very similar trend between patients and their relatives was observed for plasma desmosines. There was a significant correlation between the amount of the desmosines in plasma and urine. Moreover, a positive correlation was observed between urinary desmosine content and age of the patients as well as between urinary desmosine content and severity of clinical manifestations. CONCLUSIONS: Both the urinary and plasma desmosine concentrations indicate that elastin degradation is higher in PXE patients and, to a lesser extent, in healthy carriers than in normal subjects. Data seem to indicate that the amount of elastin breakdown products correlates with the age of patients as well as with the severity of the disease.

Adult↗
PubMed1978

Urinary excretion of elastin peptides containing desmosin after intratracheal injection of elastase in hamsters.

The intratracheal injection of pancreatic elastase results in an acute loss of elastin from the lungs of hamsters and the development of emphysema. We used measurements of the unique covalent cross linking amino acids of elastin, desmosine and isodesmosine, to quantitate elastin. Direct measurements on the lungs estimated an average loss of elastin of 57% after elastase injection. Elastin breakdown products were also quantitated in the urine and feces after injection. An average of 8.8 nmol of desmosines was recovered from the urine of each hamster. This amount represented the desmosines from 61% of the elastin lost from the lungs. Desmosine and isodesmosine existed in the urine in peptide fractions that ranged from 9 to 27,000 daltons with an average of 13,000. Only trace quantities of desmosines could be detected in feces. Desmosines injected intraperitoneally were completely recovered in the urine, and radioactive tracer studies failed to reveal in vivo catabolism of injected desmosines. These results suggest that measurement of urinary desmosines holds promise for the study of elastin turnover.

Animals↗
PubMed1989

Bronchoalveolar lavage desmosine in bleomycin-induced lung injury in marmosets and patients with adult respiratory distress syndrome.

Measurement of urinary desmosine in experimental models of emphysema has been used to demonstrate elastin catabolism. In order to evaluate the hypothesis that accelerated elastin degradation also occurs in association with acute lung injury characterized by fibrotic repair, we prepared acid hydrolysates of lung lavage (LL) and used a radioimmunoassay for desmosine to measure concentrations of this elastic-specific cross-link in LL. Lavage desmosine (pmol/100 microliter LL) was measured following bleomycin-induced lung injury in marmosets and was shown to be elevated at 1 week (median 6.0, range 5.1-7.8), 2 weeks (8.4, 6.2-8.7), and 4 weeks (7.6, 4.8-7.8) compared to control levels (1.8, 1.4-3.7). Elevations of lavage desmosine after bleomycin were temporarily associated with remodeling of the lung as indicated by increased total lung collagen, reduced diffusing capacity and lung compliance, and histologic evidence of pulmonary fibrosis. Bronchoalveolar lavage (BAL) desmosine was measured in patients with the Adult Respiratory Distress Syndrome (ARDS) and compared with patients at risk, patients with other interstitial lung diseases, and normal healthy controls. BAL desmosine (pmol/100 microliters) was not significantly different in patients with ARDS (3.2, 2.1-3.0), patients at risk for ARDS (2.8, 2.5-4.4), and those with interstitial lung disease (3.0, 1.7-5.3) compared to normal controls (2.9, 1.9-4.7). There were poor correlations of BAL desmosine with physiologic indices of severity of disease in patients with ARDS and those at risk. Accelerated elastolysis occurred in the lower respiratory tract during the evaluation of bleomycin-induced pulmonary fibrosis in marmosets but was undetectable in BAL of patients studied within the first 3 days of ARDS.

Amino Acids↗
PubMed1980

Radioimmunoassay for desmosine.

A radioimmunoassay was developed for the determination of desmosine. Desmosine conjugated to albumin was injected into rabbits which developed useful titers of serum antibodies after six months. A radioactive probe was prepared with desmosine using [125I]-Bolton-Hunter reagent. Bound desmosine was separated from free desmosine by cellulose acetate filter binding. The sensitivity of the assay is 1-50 picomoles of desmosine. The antibody is highly selective for desmosine, reacting less than 1% with other known crosslinks. Some prepurification may be necessary with complex samples which contain trace amounts of elastin peptides.

Albumins↗
PubMed1985

Photolysis and ozonolysis of desmosine and elastolytic peptides.

This paper describes the combined effects of photolysis and ozonolysis upon the main interchain crosslinks of elastin, desmosine and isodesmosine. Photolysis of purified (iso)desmosines in solution leads to the cleavage of the pyridinium rings to give lysine and an analogue of glutaconic aldehyde which is deformylated to a stable compound absorbing at 242 nm. This photoproduct is subsequently fragmented by ozone into glutamic, alpha-aminoadipic and possibly alpha-amino-delta-oxocaproic acids. However the yields of these different compounds are very low because we observed that numerous competing side reactions (polymerisation, recyclisation) accompany the photoozonolytic decomposition of the pyridinium rings of free (iso)desmosines. The results are clearer when reticulated elastolytic peptides are photoozonolysed. The (iso)desmosines, covalently linked in these peptides, are cleaved into lysine, glutamic and alpha-aminoadipic acids (in a ratio 2:1) with yields corresponding to 80-90% of those expected from the decomposition of the (iso)desmosines originally present in the peptide fraction. We have also observed that ozonolysis alone degraded another crosslink present in these peptides, the aldol condensation product, resulting in the production again of glutamic and alpha-aminoadipic acids in amounts consistent with the known concentrations of this particular crosslink in elastin. Finally we noted that the complete photoozonolytic degradation of the (iso)desmosines present in a semi purified reticulated elastolytic fraction resulted in a shift of the size distribution of these peptides toward lower values. It is not certain however that this shift, indicative of a freeing of the polypeptide chains from their original three dimensional network, is due uniquely to the cleavage of the (iso)desmosines. Indeed we have observed that tyrosine and phenylalanine were also degraded during photoozonolysis. Not knowing the mechanism of this degradation it is impossible to rule out the possibility that concomitant cleavages of peptide bonds did occur.

Amino Acids↗