Alterations in serum glycosaminoglycan profiles in Graves' patients.

BACKGROUND: Qualitative and quantitative analyses of glycosaminoglycans (GAGs) in serum obtained from Graves' disease (GD) patients without extrathyroidal complications were carried out to provide a clearer understanding of the role of these macromolecules in the disease pathogenesis. METHODS: GAGs were isolated from-SIMEL (Italian Society of Laboratory Medicine) Inter-associative Study Group on Diabetes Mellitus serum of 17 GD patients before treatment and after attainment of the euthyroid state, as well as from 20 healthy individuals. GAGs were quantified using the hexuronic acid assay and subjected to electrophoretic fractionation. RESULTS: Increased amounts of total GAGs were found in GD patients. Attainment of euthyroidism led to a decrease in, but not normalization of, total serum GAGs level. Electrophoretic analyses of GAGs before and after treatment identified the presence of chondroitin sulfate (CS), heparan sulfate/heparin (HS/H) and dermatan sulfate (DS) in serum from healthy subjects and GD patients. CS was the predominant serum GAG constituent in all subjects investigated. Enhanced CS levels in both GD patient groups were accompanied by increased structural heterogeneity of these compounds. Normalization of thyroid function did not change CS levels. DS levels in serum of untreated GD patients were elevated in comparison to healthy subjects. Anti-thyroid treatment led to a significant decrease in DS to levels below those in controls. DS in all serum samples investigated displayed a similar structure. HS/H levels in serum of untreated GD patients was seven-fold higher than in healthy subjects. In addition, HS/H in untreated GD patients were characterized by higher structural heterogeneity than those isolated from control subjects and euthyroid GD patients. Anti-thyroid therapy led to a decrease in HS/H concentrations towards normal values. CONCLUSIONS: Our results indicate that in the course of GD, the metabolism of particular types of GAGs is regulated by different mechanisms, including a hyperthyroid state and immunological abnormalities. Furthermore, qualitative and quantitative changes in serum GAGs seem to reflect GD-associated systemic changes in extracellular matrix properties.     

Hypoxia differentially enhances the effects of transforming growth factor-beta isoforms on the synthesis and secretion of glycosaminoglycans by human lung fibroblasts

Interstitial lung diseases associated with hypoxia, such as lung fibrosis, are characterized by enhanced production of transforming growth factor-beta (TGF-beta) and increased deposition of extracellular matrix (ECM) molecules, including glycosaminoglycans (GAGs). In this study, we investigated the effect of hypoxia (3% O(2)) on TGF-beta-induced GAG synthesis by primary human pulmonary fibroblasts, established from lung biopsies. Total GAG synthesis was assessed by the incorporation of [(3)H]glucosamine into GAGs associated with the cell layer (cells and ECM) or secreted in the medium. GAGs were isolated and purified by gel filtration, fractionated by electrophoresis on cellulose acetate membranes, and characterized using GAG-degrading enzymes. GAG molecules identified in the cell layer and the medium were: hyaluronic acid, and chondroitin, dermatan, and heparan sulfates. All TGF-beta isoforms time dependently induced [(3)H]glucosamine incorporation into GAGs of the cell layer or the medium. Characterization of individual GAG molecules indicated that this was attributed to dermatan and heparan sulfates in the cell layer and to hyaluronic acid and chondroitin and dermatan sulfates in the medium. Hypoxia enhanced the effect of all TGF-beta isoforms, particularly that of TGF-beta3, on the secretion of hyaluronic acid and chondroitin and dermatan sulfates. In the cell layer, hypoxia stimulated only the effect of TGF-beta2-induced [(3)H]glucosamine incorporation into GAGs. Our data indicate that hypoxia differentially enhances the effect of TGF-beta isoforms on the secretion and deposition of GAGs and may hasten ECM remodeling associated with the pathogenesis of lung fibrosis.     

Acidic glycosaminoglycans in human esophagus tissue.

The constitution of acidic glycosaminoglycans (AGAG) in the normal human esophagi which were obtained at autopsy from 13 female subjects, from 30 to 59 years old, was biochemically analyzed by the procedures such as resin chromatographic separation, electrophoretic characterization in 3 buffer systems and enzymic assay with chondroitinases and hyaluronidase. The main AGAG was hyaluronic acid which amounts to a half of total AGAG, followed by heparan sulfates and dermatan sulfate one fifth of total AGAG each, and small amounts of chondroitin-4- and -6-sulfates and oversulfated chondroitin sulfate. Heparin was not detected. A possible role of the esophageal AGAG was discussed.     

Fine characterization of mitral valve glycosaminoglycans and their modification with degenerative disease.

BACKGROUND: The levels and fine structure of complex polysaccharides, glycosaminoglycans (GAGs), were determined in segments of the posterior mitral valve leaflet (MVL) taken from 15 patients affected by mitral regurgitation and degenerative disease and were compared with segments from 15 multiorgan donors. METHODS: MVL GAGs were analyzed by agarose gel electrophoresis, and by HPLC and fluorophore-assisted carbohydrate electrophoresis to evaluate disaccharide patterns after treatment with chondroitinase ABC. RESULTS: GAGs from the control group were composed of approximately 37% hyaluronic acid and 63% chondroitin sulfate/dermatan sulfate with a charge density of approximately 0.61. Chondroitin sulfate/dermatan sulfate polymers contained approximately 23% of the disaccharide sulfated in position 6 on N-acetyl-galactosamine, approximately 38% of the 4-sulfated disaccharide and approximately 2% of the non-sulfated disaccharide (with a 4-sulfated/6-sulfated ratio of 1.7). The total amount of GAGs was 0.66 microg/mg tissue. The total amount of GAGs in patients suffering from mitral regurgitation and degenerative disease was approximately 51.5% higher (although the difference was not significant, probably because of the low number of subjects enrolled in the study). However, significantly higher hyaluronic acid content (approx. +38%, p<0.05) and lower sulfated GAG content (approx. -21%, p<0.005) were demonstrated. As a consequence, the total charge density decreased by approximately 23% (p<0.005). This macro-modification of GAG composition was also followed by a micro-alteration of the structure of the sulfated polysaccharides, in particular with a significant decrease in the 4-sulfated disaccharide (and a parallel increase in hyaluronic acid content) with no modification of the percentage of the 6-sulfated and non-sulfated disaccharides (with a significant decrease in the 4-/6-sulfated ratio). CONCLUSIONS: We assume that changes in the relative amount and distribution of GAGs in posterior MVL in subjects suffering from mitral regurgitation and degenerative disease are consistent with a decrease in the tension to which these tissues are subjected and with an abnormal matrix microstructure capable of influencing the hydration and of conditioning the mechanical weakness of these pathological tissues.     

Simple spectrophotometric quantification of urinary excretion of glycosaminoglycan sulfates

We describe a simple, rapid, precise, and sensitive spectrophotometric method for measuring urinary glycosaminoglycan (GAG) sulfate excretion. The GAG sulfates are precipitated with cetylpyridinium chloride, resuspended in water, and mixed with the basic dye 1,9-dimethylmethylene blue to produce a complex with the polyanionic molecule of sulfated GAGs. Absorbance is read at 535 nm. The standard curve for reaction was linear up to 12 micrograms of the different GAGs: dermatan sulfate, heparan sulfate, keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate. Within- and between-run precision (CV), measured at three different GAG concentrations (normal and pathological), varied from 1.6% to 2.5% and from 1.8% to 4.5%, respectively. Analytical recovery ranged from 71% to 107%. Urinary GAG excretion, measured by this procedure, correlates (r = 0.837; p less than 0.001) with the values obtained with the borate-carbazole reaction (Anal Biochem 1962;4:330-4).     

Urinary glycosaminoglycan (uGAG) excretion in healthy pediatric and adolescent population

ObjectivesThe influence of age and gender factor on the urinary excretion of total glycosaminoglycans (uGAGs) and their particular types: chondroitin/dermatan sulfates (CS/DSs), heparan sulfates (HSs) and hyaluronan (HA) was analyzed in healthy pediatric and adolescent population.Design and methodsUrine samples were collected from 95 healthy children. Sulfated GAGs excreted in the urine were quantitated using standardized dye-binding method, while the concentrations of HA were determined by immunoassay.ResultsAge-dependent decline in total uGAG excretion (r = − 0.686; p < 0.001), resulting from a decrease in particular GAG fractions i.e. CS/DS (r = − 0.757; p < 0.001), HS (r = − 0.401; p < 0.05) and HA (r = − 0.638; p < 0.001), was found in healthy subjects. The observed differences were not gender specific with the exception of HS, in which excretion declines with age in males (r = − 0.501; p < 0.05) and does not change in females. Changes in the distribution pattern of uGAG were also found. CS/DS were the predominant uGAG's fraction, representing from 55% to 76% of the total GAGs. Children up to 3 years excreted more GAGs than older subjects and with a higher proportion of CS/DS and less content of HS. Moreover, the relative contribution of HA was increased twofold in adolescents, aged 15–18, as compared to younger subjects. A negative correlation existed between uGAG excretion and body height, except for HS, for which this relationship was found only in males.ConclusionsChanges in urinary distribution pattern of particular GAG types during physiological human growth and development were found. Evaluation of urinary GAG screening procedures during pathological conditions should be based on the GAG/creatinine ratios with age and gender taken into account.     

Glycosaminoglycans of the hemodialysis-associated carpal synovial amyloid and of amyloid-rich tissues and fibrils of heart, liver, and spleen

Significant amounts of glycosaminoglycans (GAGs) were found in amyloid fibril preparations. Using two-dimensional electrophoresis to fractionate GAG mixtures, we quantified and identified for the first time the GAGs of the fibrils from carpal synovium of patients with amyloid associated with chronic hemodialysis. The total GAG content was small, but the GAG distribution (high relative content of chondroitin sulfate and hyaluronic acid and lack of the other GAGs) was unique, unlike that for the other amyloid fibril preparations. The amyloid-rich heart, liver, and spleen tissues, as well as the fibrils isolated from these tissues of patients with systemic forms (primary amyloid and secondary amyloid) of amyloid disease, were also analyzed for GAGs. Fibrils from heart tissue of a patient with primary amyloidosis, now examined for the first time, contained four major GAGs (chondroitin sulfate, dermatan sulfate, hyaluronic acid, and heparan sulfate).     

Influence of age, sex, and oral contraceptives on human blood cholinesterase activity.

We estimated cholinesterase (EC 3.1.1.8) activities in erthrocytes and plasma of 443 men, 188 women not taking oral contraceptives, and 70 women who were taking oral contraceptives. Men in the first six decades of life had higher plasma cholinesterase activity than did women who were not taking oral contraceptives, and these women had higher plasma cholinesterase activity than women taking oral contraceptives. After the age of 60 there was no intersex difference. Activity of erythrocytes from the oral contraceptive group was higher than in the other groups, men had the lowest activity, and there was an increased activity with age in both sexes until the age of 60. These findings suggest that there is no single "normal" value for cholinesterase activity for adults.     

Graves' disease-associated changes in the serum lysosomal glycosidases activity and the glycosaminoglycan content

BACKGROUND: This study was undertaken to elucidate the influence of Graves' hyperthyroidism upon the metabolism of proteoglycans (PGs), the extracellular matrix (ECM) components. We determined the serum activity of lysosomal hydrolases contributing to GAGs degradation (N-acetyl-beta-D-glucosaminidase, beta-D-glucuronidase, beta-D-galactosidase, alpha-D-mannosidase, beta-D-xylosidase and alpha-L-fucosidase). An effect of Graves' hyperthyroidism on total serum GAGs content was also analysed. METHODS: Blood samples were taken from 30 patients with newly diagnosed Graves' disease, prior to antithyroid treatment and after attainment of euthyroid state, as well as from 30 healthy individuals. RESULTS: The activity of all investigated enzymes involved in GAGs degradation was found markedly increased in blood serum of patients with hyperthyroidism, except for alpha-D-mannosidase, which was not significantly modified. Antithyroid treatment with thiamazole resulted in normalization of the lysosomal glycosidases activity, so they no longer differed from the healthy subjects. The total glycosaminoglycans content in blood serum of patients with newly diagnosed untreated Graves' disease significantly increased compared to control group. Following thiamazole therapy total serum amount of GAGs decreased significantly, but was still markedly increased as compared to serum of healthy individuals. CONCLUSIONS: The obtained results indicate that Graves' hyperthyroidism is associated with extracellular matrix components' alterations. Furthermore, we suggest that general increase of the serum lysosomal glycosidases activity and serum GAG concentration may both result from the same reason, i.e. excessive reactive oxygen species formation in the course of hyperthyroidism due to Graves' disease.     

Glycosaminoglycan composition of uninjured skin and of scar,tissue in fetal,newborn and adult sheep

Few details are available on the heterogeneity of glycosaminoglycans (GAGs) in healing fetal wound tissue. We used a sensitive assay for hexosamines to examine changes occurring in the development of normal sheep skin and of wound healing tissue in PVA sponges inserted subcutaneously at different stages of gestation. It was assumed that glucosamine was derived mainly from hyaluronan and galactosamine mainly from dermatan sulphate and chondroitin sulphate. Hexosamine-containing tissue infiltrating the sponges was deposited more repidly in the first week than in the second week. Three days after wounding, approximately 70% of the total GAGs in wound tissue was hyaluronan. The proportion of hyaluronan then fell progressively and by the 14th day contributed 57% to total GAGs. In uninjured skin the contribution of hyaluronan to the total GAGs fell progressively with increasing fetal maturity, the level being 70% at 75 days gestation, but only 35–40% in newborn or adult skin. At no stage of development was there a sudden change in GAG composition suggestive of a transition from regeneration to scar formation. It is concluded that hyaluronan may play an important role in the biochemical sequence leading to collagen fibrillogenesis and mature scar formation.     

Myocardial chondroitin sulfates D and E in a case of acute carbon monoxide poisoning

The glycosaminoglycans of the myocardium of an individual who died of acute carbon monoxide poisoning were quantified by two-dimensional electrophoresis on cellulose acetate membranes. The total glycosaminoglycan content was found to be approximately twice the normal value. In contrast to the content of each glycosaminoglycan of the normal heart, the level of the chondroitin sulfates of this patient's myocardium was found to be markedly increased whereas that of hyaluronic acid was decreased and dermatan sulfate could not be detected. Further, this tissue contained significant amounts of keratan sulfate and an oversulfated dermatan sulfate, glycosaminoglycans not found in normal myocardium. Of particular interest was the presence of two unusual oversulfated chondroitin sulfates (chondroitin sulfates D and E).     

Urinary glycosaminoglycans in patients with hypothyroidism and in healthy subjects

Although the changes in urinary glycosaminoglycans have been investigated in several endocrinopathies, no information was hitherto available on the content and composition of urinary glycosaminoglycans in hypothyroidism. Urinary glycosaminoglycans were therefore investigated in patients with hypothyroidism and in healthy subjects. The total daily excretion of urinary glycosaminoglycans was found to be significantly increased (by 41%) in hypothyroidism. Two electrophoretic bands were always detected in both examined groups: a major band of chondroitin sulphate and a minor band of heparan sulphate. Heparan sulphate and chondroitin sulphate levels were respectively 114% and 42% higher in patients with hypothyroidism than in controls. The respective increases in chondroitin-4-sulphate and chondroitin-6-sulphate were 31% and 41%. The relative quantities of chondroitin-4-sulphate, dermatan sulphate, chondroitin-6-sulphate and non-sulphated chondroitin sulphate were unchanged in the two examined groups. The changes observed in the levels of the excreted glycosaminoglycans may reflect the altered metabolism of connective tissue in hypothyroidism.     

Plasma tetranectin in healthy male and female individuals, measured by enzyme-linked immunosorbent assay

Tetranectin is a novel protein recently isolated from human plasma. It is a tetramer, composed of four identical, non-covalently bound, 181-amino-acid polypeptide chains (Mr = 20,100). We report here the quantification of plasma tetranectin in 457 healthy individuals, aged from birth to 85 years, using a newly developed sensitive and reproducible enzyme-linked immunosorbent assay (ELISA). Tetranectin was demonstrable in all subjects investigated, and within each sex and defined age group the concentration was well controlled within a relatively narrow range. The mean plasma tetranectin level in newborn infants (cord plasma) was about 8 mg/L. This was significantly less than in later life, during which mean plasma tetranectin level varied between 10 and 12 mg/L. After the age of 9 years, tetranectin level was continuously higher in males than in females, but the variations through the span of life were almost identical. Thus, a transitory increase in plasma tetranectin was observed in early puberty, reaching its climax about the age of 11 to 12 in girls and 14 to 15 in boys. A quantitatively similar, additional peak was observed during the period of 50 to 59 years of age in both sexes, whereupon the tetranectin concentration gradually decreased. The biologic function of tetranectin remains to be elucidated. Recently, we have reported that tetranectin is contained within hepatocytes and various endocrine cells, all known to process peptide hormones or glucoproteins. We propose that tetranectin may be involved in intracellular and extracellular serine protease-mediated proteolysis.     

Dermatan sulfate activates nuclear factor-kappab and induces endothelial and circulating intercellular adhesion molecule-1

Proteoglycans (PGs) can influence cell behaviors through binding events mediated by their glycosaminoglycan (GAG) chains. This report demonstrates that chondroitin sulfate B, also known as dermatan sulfate (DS), a major GAG released during the inflammatory phase of wound repair, directly activates cells at the physiologic concentrations of DS found in wounds. Cultured human dermal microvascular endothelial cells exposed to DS responded with rapid nuclear translocation of nuclear factor-kappaB (NF-kappaB), increased expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, and increased ICAM-1 cell surface protein. Heparan sulfate and chondroitin sulfates A and C had no effect on activation of NF-kappaB or induction of ICAM-1. Inhibition of NF-kappaB activation blocked the effect of DS. The increase in cell surface ICAM-1 did not involve TNF-alpha or IL-1 release by endothelial cells, but it was facilitated by autocrine factors whose release was initiated by DS. The ICAM-1-inductive activity of DS was confirmed in vivo. Injection of DS, but not heparin or other chondroitin sulfates, into mice greatly increased circulating levels of soluble ICAM. These data provide evidence that DS, but not other GAGs, initiates a previously unrecognized cell signaling event that can act during the response to injury.     

Glycosaminoglycans of porcine uteri

Glycosaminoglycan fractions were obtained from the pronase digests of the endometrium and myometrium of porcine uteri. Their glycosaminoglycan compositions were determined by the use of specific mucopolysaccharide-degrading enzymes and nitrous acid. It was found that the endometrium contained chondroitin sulfates, dermatan sulfate and heparan sulfate and a smaller amount of hyaluronic acid, whereas hyaluronic acid and dermatan sulfate were the major glycosaminoglycans in the myometrium.     

Influence of age and sex on five human plasma lysosomal enzymes assayed by automated procedures

Automated fluorimetric procedures for the assay of five lysosomal glycohydrolases—β-N-acetylglucosaminidase; β-galactosidase; β-glucuronidase; α-mannosidase; α-fucosidase—in human plasma were set up. A Carlo Erba autoanalyser CLA 1500, provided with a sampler refrigerating unit and connected with a recording Turner Mod 111 fluorimeter was employed. The automated procedures, under the established optimal conditions, proved to be highly accurate and reproducible.Using the automated assay procedures the effect of sex and age on the plasma levels of the same enzymes was studied. 1273 randomly selected healthy subjects were studied. No sex differences were observed for all the enzymes studied with the exception of β-glucuronidase which displayed higher values (about 30%) in males from 25 to 60 years. The developmental profiles of all enzymes in females and males were similar and characterised by: (a) absolute maximum level in the umbilical cord blood; (b) absolute minimum level at 10–14 years; (c) decrease to a second minimum occurring around 35 years (not displayed by β-galactosidase and by β-glucuronidase in males); (e) slow further increase up to the elderly level which was then maintained till the oldest age examined, 74 years.     

Ascidian dermatan sulfates attenuate metastasis,inflammation and thrombosis by inhibition of P‐selectin

See also Zacharski LR. Controlling cancer growth from within the blood coagulation mechanism. This issue, pp 1804–6. Summary. Background: Cancer‐associated thrombosis and enduring inflammation are strongly associated with cancer progression and metastasis. Heparin is the mostly clinically used anticoagulant/antithrombotic drug, and has recently been shown to exhibit antimetastatic and anti‐inflammatory activities that are linked to inhibition of P‐selectin and/or L‐selectin. P‐selectin‐mediated platelet–tumor cell and tumor cell–endothelium interactions facilitate the initial steps of metastasis. Objectives and Methods: The aim of the present study was to determine the capacity of dermatan sulfates to inhibit P‐selectin and to test their potential to affect thrombosis, inflammation and metastasis in respective experimental mouse models. Results: Two dermatan sulfates isolated from the ascidians Styela plicata and Phallusia nigra, composed of the same disaccharide core structure (IdoA2‐GalNAc)_n, but sulfated at carbon 4 or 6 of the GalNAc, respectively, have opposed heparin cofactor II (HCII) activities and are potent inhibitors of P‐selectin. The ascidian dermatan sulfates effectively attenuated metastasis of both MC‐38 colon carcinoma and B16‐BL6 melanoma cells and the infiltration of inflammatory cells in a thioglycollate peritonitis mouse model. Moreover, both glycosaminoglycans reduced thrombus size in an FeCl₃‐induced arterial thrombosis model, irrespective of their HCII activities. The analysis of arterial thrombi demonstrated markedly reduced platelet deposition after dermatan sulfate treatment, suggesting that the glycosaminoglycan inhibited P‐selectin and thereby the binding of activated platelets during thrombus formation. Conclusions: Collectively, these findings provide evidence that specific inhibition of P‐selectin represents a potential therapeutic target in thrombosis, inflammation and metastasis, and that ascidian dermatan sulfates may serve as antiselectin agents.     

Pharmacokinetics of nicotine in healthy elderly people

BACKGROUND: Mortality hazards of smoking extend well into later life; this suggests that smoking cessation will continue to improve life expectancy in older people. The pharmacology and pharmacokinetics of nicotine have not been studied in elderly subjects. Drug disposition and pharmacodynamic responsiveness to nicotine may change with age, and conclusions founded on data from studies of younger populations may not apply to elderly populations. Our aim was to assess the pharmacokinetics of nicotine in healthy elderly subjects compared with healthy adults. METHODS: Twenty healthy elderly subjects (age, 65-76 years) and 20 healthy adult subjects (age, 22-43 years) were given an intravenous infusion of 0.028 mg/kg of nicotine over 10 minutes. Nicotine and cotinine concentrations were measured in plasma and urine. Heart rate and blood pressure were monitored. RESULTS: For most adult and elderly subjects nicotine distributed according to a two-compartment system. Even though there was a large interindividual variation within and overlap between groups, nicotine total clearance (-23%), nonrenal clearance (-21%), renal clearance (-49%), volume of central compartment (-37%), volume of distribution at steady state (-17%), and cotinine renal clearance (-18%) were statistically significantly decreased in elderly subjects compared with adults. Maximal heart rate response to nicotine was decreased in the elderly subjects (-29%). CONCLUSION: Even though statistically significant differences were observed, the disposition of nicotine does not seem to be changed to a clinically important extent in elderly subjects compared with younger adults.     

The glycosaminoglycans of the human artery and their changes in atherosclerosis.

The changes in levels of glycosaminoglycans (GAGs) of the intima and media of the human artery in atherosclerosis were determined by a recently introduced two-dimensional electrophoresis technique that permits direct measurments of each of these macromolecules. To identify the arterial GAGs, they were fractionated by chromatography on a DEAE-Sephadex A-25 column, and the resulting three fractions (hyaluronic acid [HA], heparan sulfate [HS], and the partially separated chondroitin sulfates B [CSB] and C [CSC]) were analyzed for their electrophoretic mobilities by this electrophoretic method, for their digestability by highly specific hydrolases (leech hyaluronidase, heparinase, and chondroitinases ABC and AC) and for their iduronic acid content. From these studies we concluded that normal and atherosclerotic human aortas contain CSB, CSC, HA, and HS. Further, we demonstrated that CSB is a hybrid consisting of approximately 40% CSA and 60% CSB and that CSC appears to be a polymer consisting essentially of glucuronic acid and N-acetylgalactosamine-6-sulfate. Classical CSA as well as chondroitin (CH) were not present in detectable amounts. In the relatively normal intima, the mean concentrations of the GAGs were found to be 4.7, 20.9, 1.3, and 5.1 mg/g of dry, defatted, decalcified tissue for CSB, CSC, HA, and HS, respectively. With the progression of atherosclerosis, there was a pronounced decrease in the total GAG content (from 32 to 18 mg) associated with a decrease in the CSC and HS levels but without a change in the HA concentrations. Of particular interest, however, was the increase in the CSB level. In the media whose total GAG content averaged approximately 20 mg, no significant changes in these GAG levels were noted with the progression of the disease except for that of CSC. These findings may be important in explaining the increased lipoprotein and collagen deposition in the diseased aorta.     

Significance of adrenoceptor-mediated atrial natriuretic factor release in normal humans: Erratum

Abstract

The orosomucoid content of serum has been determined in healthy infants and children. Analyses of haptoglobin and of electrophoretic protein fractions have also been made.

The mean umbilical cord serum level of orosomucoid was significantly lower than the level in the maternal serum. Apart from a transient increase during the first week of life, low serum levels were found up to the age of three months.

The alpha₁, alpha₂ and beta globulins showed essentially the same changes with age as the orosomucoid.

The serum content of haptoglobin was very low at birth and rose slowly to the level found in adults.