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S Jaworski

Publications and source records attributed to S Jaworski.

At least 19 recordsLinked to original sources

The activity of collagen-degrading enzymes of Wharton's jelly in EPH gestosis (pre-eclampsia).

Oedema/proteinuria/hypertension (EPH) gestosis is one of the more common complications observed during pregnancy. Our previous studies demonstrated some qualitative and quantitative changes in the extracellular matrix of Wharton's jelly in newborns delivered by mothers with EPH gestosis. For this reason it was decided to evaluate the effect of EPH gestosis on the activity of gelatinolytic and proteolytic enzymes which may be involved in collagen degradation in Wharton's jelly. Zymographic analysis of control and EPH gestosis samples of Wharton's jelly demonstrates different electrophoretic patterns of gelatinolytic enzymes. The control Wharton's jelly contains two latent forms of gelatinolytic enzymes: gelatinase A [metalloproteinase (MMP)-2, 72 kD] and gelatinase B (MMP-9, 92 kD). In contrast to control tissue, the main gelatinolytic enzyme of EPH gestosis Wharton's jelly is gelatinase A (MMP-2). It was found that the proteolytic activity in EPH gestosis Wharton's jelly differs from control. The decrease in gelatinase activity may be one of the factors which promote the accumulation of collagen in this tissue.

Adolescent↗

Pre-eclampsia-associated differential expression of proteoglycans in the umbilical cord arteries.

OBJECTIVE: The role of proteoglycans (PGs) of the umbilical cord arteries (UCAs) in the pathomechanism of pre-eclampsia is not known. Therefore we decided to compare the PGs of normal (control) UCAs and those of newborns delivered by mothers with pre-eclampsia. METHODS: PGs were extracted in dissociative conditions, purified by Q-Sepharose anion exchange chromatography and lyophilized. They were analyzed by gel filtration and SDS-PAGE before and after treatment with chondroitinase ABC. RESULTS: It was found that the PG preparation from pre-eclamptic UCAs had a higher amount of sulphated glycosaminoglycans (in relation to protein) than in the case of control UCAs. The predominant PG fraction included small PGs with core proteins of 45 and 47 kD, immunologically related to biglycan (45 kD) and decorin (45 and 47 kD). The expression of decorin core proteins was increased and that of biglycan slightly decreased in pre-eclamptic UCAs. Some other putative small PG core proteins (56, 53, 49, 42, 38 and 34 kD) were also found. They were present in higher amounts in pre-eclamptic UCAs. Larger PGs (core proteins of 99-110 and >150 kD), were detected in lower amounts, both in control and particularly in pre-eclamptic material. CONCLUSION: Pre-eclampsia is associated with alterations in PG composition of the UCAs. They may affect the mechanical properties of this organ and disturb fetal blood circulation.

Adult↗

Stimulation of collagen biosynthesis by the umbilical cord serum of newborns delivered by mothers with EPH-gestosis (preeclampsia).

Edema, proteinuria, hypertension (EPH)-gestosis, known also as preeclampsia, is the most common, pregnancy-associated pathological syndrome. It is accompanied by a significant increase in collagen content in the umbilical cord arteries and premature replacement of hyaluronic acid by sulfated glycosaminoglycans both in these arteries and in Wharton's jelly. This remodelling of the umbilical cord tissues is accompanied by a distinct increase in insulin-like growth factor-I (IGF-I) concentration in the umbilical cord serum. Such a serum introduced into the culture medium of fibroblasts growing in vitro strongly stimulated the incorporation of radioactive proline into collagen (hydroxyproline-containing and collagenase-sensitive protein). Biosynthesis of noncollagenous proteins was not stimulated. Since IGF-I is known as a stimulator of collagen and sulfated glycosaminoglycan biosynthesis, the high concentration of this growth factor in the umbilical cord plasma may be an agent responsible for preeclampsia-associated remodelling of the umbilical cord, which results in dysfunction in fetal circulation.

Adult↗

EPH-gestosis (pre-eclampsia)-induced decrease of gelatinase activity may promote an accumulation of collagen in the umbilical cord artery.

It was found in our previous paper that edema, proteinuria, hypertension (EPH)-gestosis-associated accumulation of collagen in the umbilical cord artery (UCA) is a result of increased biosynthesis and decreased degradation of this protein. It is known that the activity of collagenolytic enzymes is a main factor regulating collagen degradation rate in various tissues. For this reason it was decided to evaluate the effect of EPH-gestosis on the activity of proteolytic enzymes which may be involved in collagen degradation in the UCA wall. Proteolytic activity against bovine serum albumin, reconstituted collagen fibres and gelatin were evaluated. Latent forms of proteolytic enzymes were activated by the action of trypsin, p-chloromercuric benzoate (PCMB) and p-aminophenylmercuric acetate (APMA). A low activity of gelatinase (type IV collagenase) was detected in the extracts from the wall of the umbilical cord artery. This enzyme increased its activity several times after the action of trypsin, PCMB and APMA. EPH-gestosis results in a distinct reduction in gelatinase activity. Despite the action of activating agents the gelatinase from EPH-gestosis UCAs was considerably lower in comparison to control UCAs. It can be concluded that gelatinase of the umbilical cord artery forms an inactive complex with a tissue inhibitor of metalloproteinases. Such a complex dissociates under the action of trypsin, PCMB or APMA or sodium dodecyl sulphate. The decrease of gelatinolytic activity in the umbilical cord artery may be a factor that reduces the breakdown of collagen in the arterial wall and promotes an accumulation of this protein. The accumulation of collagen with simultaneous reduction in elastin content in the UCA may be the factors which reduce the elasticity of arterial wall and decrease the blood flow in the fetus of woman with EPH-gestosis.

Adult↗

An accumulation of IGF-I and IGF-binding proteins in human umbilical cord.

It is known that extracellular matrix components (ECM) may serve as a storage site to concentrate and stabilize growth factors in the vicinity of cells. IGF-I is expressed in most fetal tissues and it is involved in anabolic effects on protein and sulphated glycosaminoglycans biosynthesis, cell proliferation and differentiation. We demonstrated that human umbilical cord (UC) tissues contain large amounts of IGF-I and IGF-I-binding proteins (BP-3 and BP-1). Particularly Wharton's jelly appears to be an abundant reservoir of IGF-I and BPs. Relatively low amount of cells and large amounts of collagen and glycosaminoglycans in UC tissues (especially in Wharton's jelly) suggest that IGF-I may play a major role in stimulation of these cells to produce ECM components. The specific BPs in these tissues may be important modulators of IGF-I action during fetal development.

Chromatography, Gel↗

Pre-eclampsia-induced alterations in IGF-I of human umbilical cord.

BACKGROUND: Extracellular matrix (ECM)-components serve as a storage site to concentrate and stabilise growth factors in the vicinity of cells. Human umbilical cord (UC) tissues contain significant amounts of IGF-I and IGF-binding proteins (BPs). IGF-I is known as a stimulator of collagen and sulphated glycosaminoglycans (GAGs) biosynthesis. Pre-eclampsia, the most common pregnancy associated syndrome, is accompanied by an accumulation of collagen and sulphated glycosaminoglycans in the UC. One may expect that IGF-I and BPs play an important role in such a remodelling of the UC tissue. For this reason it was decided to evaluate the alterations in amounts of IGF-I and BPs in UC serum and in the UC arterial wall of newborns delivered by mothers with pre-eclampsia. MATERIALS AND METHODS: Studies were performed on the UCs of 12 control and 12 investigated newborns, delivered by mothers with pre-eclampsia (edema, proteinuria > 500 mg l-1, arterial pressure: systolic > 140 mmHg, diastolic > 100 mmHg). Radioimmunological techniques were employed to determine IGF-I and IGF-BPs (BP-1 and BP-3). RESULTS: It was found that pre-eclampsia is associated with an increase of IGF-I concentration in the UC serum and with simultaneous decrease of its content in the umbilical cord artery (UCA). The decrease of IGF-I content in the UCA wall was accompanied by an increase of BP-3 and BP-1 in this tissue. The increase in BPs content in the UCA wall was not associated with an enhancement of IGF binding by extracts from the homogenates of arterial wall. Heparin drastically decreased the binding of IGF-I by BP-3. CONCLUSIONS: Pre-eclampsia is associated with an increase of IGF-I-concentration in the umbilical cord blood and an elevation of BPs contents in the UCA wall. Despite a high concentration of binding proteins, IGF-I is not accumulated in this tissue. High amounts of sulphated GAGs in the UCA wall may be a factor that prevents the binding of IGF-I by BPs. Free IGF-I can easily bind to cell receptors and stimulate the cells to produce collagen and sulphated GAGs in the arterial wall.

Adult↗

Stimulation of glycosaminoglycan biosynthesis by umbilical cord serum of newborns delivered by mothers with EPH gestosis (preeclampsia).

OBJECTIVE: Edema, proteinuria, hypertension (EPH) gestosis, also known as preeclampsia, is the most common, pregnancy-associated pathological syndrome. It is accompanied by a significant increase in collagen content in the umbilical cord arteries and early replacement of hyaluronic acid by sulfated glycosaminoglycans (GAGs) both in these arteries and in Wharton's jelly. Such a remodelling of the umbilical cord tissues is accompanied by an increase in insulin-like growth factor-I (IGF-I) concentration in the umbilical cord serum. METHODS: Contact-inhibited human fibroblasts were incubated in Dulbecco culture medium containing control or EPH umbilical cord serum and supplemented with (14)C-glucosamine or (35)S-sulfate. Radioactive GAGs were isolated, submitted to electrophoretic fractionation and quantified. RESULTS: The presence of umbilical cord serum in culture medium strongly stimulated the incorporation of (14)C-glucosamine and (35)S-sulfate into GAGs synthesized by these cells. EPH serum was much more active in stimulation of sulfated GAGs biosynthesis than control serum, whereas the biosynthesis of hyaluronic acid was stimulated by both sera to a similar degree. CONCLUSION: Since IGF-I is known as a stimulator of collagen and sulfated GAG biosynthesis, the high concentration of this growth factor in the umbilical cord plasma may be responsible for preeclampsia-associated remodeling of the umbilical cord.

Adult↗

Preeclampsia is associated with alterations in insulin-like growth factor (IGF)-1 and IGF-binding proteins in Wharton's jelly of the umbilical cord.

Wharton's jelly is abundant in extracellular matrix, which is known as a storage site to concentrate and stabilise growth factors in the vicinity of cells. It was previously found that Wharton's jelly contains significant amounts of insulin-like growth factor (IGF)-1 and IGF-binding proteins (BPs). IGF-1 is a stimulator of biosynthetics of collagen and sulphated glycosaminoglycans. Preeclampsia (edema, proteinuria, hypertension (EPH)-gestosis) is accompanied by an accumulation of sulphated glycosaminoglycans in Wharton's jelly. IGF-1 and BPs may play an important role in such a remodelling of this tissue. It was decided to evaluate the alterations in amounts of IGF-1 and BPs in Wharton's jelly of newborns delivered by mothers with preeclampsia. Studies were performed on Wharton's jelly of 10 controls and 10 newborns delivered by mothers with preeclampsia (edema, proteinuria > 500 mg/l, arterial pressure: systolic > 140 mm Hg, diastolic > 90 mmHg). Radioimmunological techniques were employed to determine IGF-1 and IGF-BPs (BP-1 and BP-3). It was found that preeclampsia is associated with a decrease in IGF-1 and IGF-BP-1 in Wharton's jelly. A slight increase in IGF-BP-3 was found. Ligand blotting demonstrated that BP-3 (not BP-1) is a main component of Wharton's jelly, which binds IGF-1. Heparin drastically inhibited the binding of IGF-1 by BP-3. It is known from our previous studies that preeclampsia is associated with an increase in the amount of sulphated glycosaminoglycans (heparin, heparan sulphate, dermatan sulphate) in Wharton's jelly. This may be a factor, which prevents the binding of IGF-1 by BPs and facilitates the binding of IGF-1 to cells, stimulating them to produce sulphated glycosaminoglycans in Wharton's jelly.

Adult↗

[The phenotype characteristics of cord blood lymphocytes in premature neonates].

It has been observed high risk of infections in neonates as a result from lymphocytes immaturity. It is connected to phenotype differences of lymphocytes between neonates and adults. This high susceptibility to infections is especially high in premature neonates. With the use of flow cytometry we have evaluated the phenotype of cord blood lymphocytes in premature neonates. In comparison to results of healthy newborns we have observed significant decrease in CD7+, CD3+, CD4+, CD25+, CD57+ lymphocytes an increase in total number of CD8+ cells as well as alteration in CD4/CD8 ratio. Our results suggest deeply damage of cellular immunity in preterm infants.

Antibodies, Monoclonal↗

[Levels of alpha-2-macroglobulin in blood serum of women giving birth to hypotrophic and eutrophic newborns].

We tested the concentration of alpha-2-macroglobulin in sera of 33 women bearing eutrophic newborns, 36 women bearing hypotrophic newborns and 30 healthy not pregnant women in reproductive age. The concentration of this inhibitor was measured using radial immunodiffusion method according to Mancini et al. We found distinct decrease of alpha-2-macroglobulin concentration in sera of bearing women. In women bearing eutrophic newborns we found 154 mg/dl, in women bearing hypo-trophic newborns 171 mg/dl whereas in controls 250 mg/dl. We have noted statistically significant differences between tested groups to controls and between investigated groups. Taking under consideration the role of alpha-2-macroglobulin as the modulator of immune system as well as the activity of several cytokins, therefore one can suppose that alpha-2-M may affect on cellular growth developed foetus in intrauterine.

Adult↗

Proteoglycans of human umbilical cord arteries.

Proteoglycans (PGs) were dissociatively extracted from human umbilical cord arteries (UCAs) with 4 M guanidine hydrochloride containing Triton X-100 and protease inhibitors, purified by Q-Sepharose anion exchange chromatography and lyophilized. They were analysed by gel filtration, SDS/PAGE and agarose gel electrophoresis before and after treatment with chondroitinase ABC. It was found that the PG preparation was especially enriched in chondroitin/dermatan sulphate PGs. The predominant PG fraction included small PGs that emerged from Sepharose CL-2B with Kav = 0.74. Their molecular mass, estimated by SDS/PAGE, was 160-200 kDa and 90-150 kDa, i.e. it was typical for biglycan and decorin, respectively. Treatment with chondroitinase ABC yielded the core proteins of 45 and 47 kDa, characteristic for both small PGs. Remarkable amounts of the 45 kDa protein were detected in non-treated PG samples, suggesting the presence of free core proteins of biglycan and decorin. Large PGs were present in lower amounts. In intact form they were eluted from Sepharose CL-2B with Kav = 0.17 and 0.43. Digestion with chondroitinase ABC yielded the core proteins with a molecular mass within the range of 180-360 kDa but predominant were the bands of 200, 250 and 360 kDa. The large PGs probably represent various forms of versican or perlecan bearing chondroitin sulphate chains.

Chondroitin ABC Lyase↗

Elastin of the umbilical cord arteries and its alterations in EPH gestosis (preeclampsia).

Edema, proteinuria, hypertension (EPH) gestosis is accompanied by an increase of collagen content and premature replacement of hyaluronic acid by sulfated glycosaminoglycans both in the umbilical cord arteries and in Wharton's jelly. The effect of EPH gestosis on elastin content and metabolism in the umbilical cord arterial wall was the aim of this work. Studies were performed on normal umbilical cord arteries and those taken from newborns of mothers with EPH gestosis. Elastin was isolated from the arterial wall and quantified by a dye-binding method. Biosynthesis and degradation of this protein was evaluated by a pulse-chase experiment with the use of 14C-proline. It was found that EPH gestosis is associated with a significant reduction of elastin content in the umbilical cord arteries as a result of decrease in elastin biosynthesis rate and accelerated degradation of this protein. The replacement of elastin by collagen, and hyaluronate by sulfated glycosaminoglycans, may decrease the hydration of arterial wall and reduce its elasticity. Such rearrangement of extracellular matrix of the umbilical cord arteries may affect mechanical properties of these vessels and disturb fetal blood circulation.

Carbon Radioisotopes↗

Activities of some glycosaminoglycan- degrading enzymes in Wharton's jelly and their alteration in EPH-gestosis (Pre-eclampsia).

Oedema, proteinuria, hypertension (EPH)-gestosis (pre-eclampsia) is associated with a premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs), both in the umbilical cord arteries and in Wharton's jelly. It may be concluded from our previous report that such a phenomenon may be the result of reduction in degradation of these compounds. In order to support such a conclusion the activities of GAG-degrading enzymes in normal umbilical cord arteries and those taken from newborns delivered by mothers with EPH-gestosis were compared. It was found that EPH-gestosis results in a significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated GAGs (except keratan sulphate). In the case of acidic endoglycosidases, no characteristic alterations have been found. Only the activity of heparan sulphate-degrading endoglycosidase significantly decreased. In contrast to the above-mentioned endoglycosidases, the activities of arylsulphatase B and 6-sulphatase distinctly increased. The decrease in the activities of endoglycosidases are thought to be responsible for EPH-gestosis-associated accumulation of sulphated GAGs in extracellular matrix of Wharton's jelly. This leads to the suspicion that EPH-gestosis-induced changes in the GAGs composition may alter the fibrillogenesis conditions in Wharton's jelly. The sulphated GAGs accumulated in Wharton's jelly may interact with some growth factors which modify the myofibroblasts' proliferation, gene expression, protein biosynthesis and other processes. A significance of EPH-gestosis-induced alteration in Wharton's jelly is discussed.

Chondroitin Sulfates↗

The activities of some glycosaminoglycan-degrading enzymes in the wall of the umbilical cord artery and their alteration in edema, proteinuria, hypertension (EPH)-gestosis.

Edema, proteinuria, hypertension (EPH)-gestosis is associated with a premature replacement of hyaluronic acid by sulphated glycosaminoglycans (GAGs), both in the umbilical cord arteries (UCAs) and in Wharton's jelly. This phenomenon may be considered as a sign of premature ageing of the umbilical cord tissues. The decrease in hyaluronic acid content in the UCA was found to be the result of reduced biosynthesis of this substance, whereas an increase in sulphated GAGs-content is rather a result of slower degradation of newly synthesised GAGs. In this study the activities of GAGs-degrading enzymes in normal umbilical cord arteries and those taken from newborns delivered by mothers with EPH-gestosis were compared. It was found that EPH-gestosis results in a significant reduction in the activities of neutral endoglycosidases degrading most of the sulphated glycosaminoglycans (with the exception of heparan sulphate). The activities of exoglycosidases also decrease but to a lesser degree. These alterations are thought to be responsible for EPH-gestosis-associated accumulation of sulphated glycosaminoglycans in the extracellular matrix of the arterial wall. Such remodelling of the arterial wall may affect foetal blood circulation. The significance of these phenomena in the pathological mechanism of EPH-gestosis is discussed.

Endothelium, Vascular↗

[The concentration of alpha-2-antiplasmin in sera of women in post partum].

Alpha-2-antiplasmin is a main inhibitor of plasmin and play a crucial role in regulation of intravascular fibrinolysis. It is important to know, in pregnant women as well in the immediate post partum period the activation of hemostasis takes place and is observed thrombotic incidences. In our studies we have included 33 pregnant women whose delivered eutrophic newborns alpha-2-AP 7.79 mg/dl and 36 pregnant women whose delivered small-for-date newborns, alpha-2-AP 7.49 mg/dl. We found no significant statistically differences between tested groups and in comparison to control group 6.0 mg/dl. The presented results seems to indicate, the determination of concentration of alpha-2-AP in sera of women in immediate post partum period does not reflect the changes in the mechanisms of fibrinolytic system in the course of the partum.

Female↗

The concentration of alpha-1-antichymotrypsin in blood serum of women in labour.

Concentration of alpha-1-antichymotrypsin (A-1-ACT) in blood serum of parturient women was determined. The investigation was conducted in 33 women bearing eutrophic newborns and 36 women bearing hypotrophic newborns. The control group consisted of 30 healthy non-pregnant women in reproductive age. Concentrations of A-1-ACT were determined using the radial immunodiffusion method according to Mancini et al. Maximal concentration of A-1-ACT determined in group I was three times higher than minimal concentration. Maximal concentration of A-1-ACT determined in group II was two times higher than minimal concentration. In the control group, the difference between minimal and maximal concentrations of A-1-ACT was inconsiderable. The lack of statistically significant differences between these three groups suggests that labour stress does not influence serum concentrations of this inhibitor. The importance of A-1-ACT in the placental tissue may be connected with immunological mechanisms that assure development and maintenance of pregnancy.

Female↗

[The activities of some glycosaminoglycan degrading enzymes in the wall of the umbilical cord vein and their alteration in EPH-gestosis].

EPH-gestosis evokes great connective tissue rebuilding in the wall of umbilical cord arteries and Wharton's jelly. Not much is known about umbilical cord vein maintenance. For better understanding of processes proceeding in it we decided to determine activities of some glycosaminoglycan-degrading enzymes. It was found that specific activities of some neutral endoglycosidases and exoglycosidases decreased during EPH-gestosis. Acidic endoglycosidases and sulphatases specific activities did not change. Those results with no changes in content and proportional relationship of umbilical cord vein glycosaminoglycans suggest that EPH-gestosis disturbs markedly those connective tissue element metabolism.

Adult↗