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Mechanisms of morphogen movement.

Morphogens are defined as signaling molecules that are produced locally, yet act directly at a distance to pattern the surrounding field of cells in a concentration-dependent manner. In recent years many laboratories have devoted their attention to how morphogens actually reach distant cells. Several models have been proposed, including diffusion in the extracellular space and planar transcytosis. A combination of genetic, developmental, and cell-biological approaches have been taken to tackle this issue. I will present the models and discuss the types of experiments that have been designed to test them. It stands out that most of the work has been carried out in Drosophila. Morphogens contribute to patterning of the vertebrate nervous system, and the same signaling molecules have recently been shown to play important, possibly instructive, roles in axon guidance. Little, if anything, is known about the movement of morphogens in the context of nervous system development. The long-standing tradition of biophysical studies on diffusion in the brain extracellular space, along with the sophisticated in vitro culture systems developed in neurobiology laboratories, may provide new tools and ideas to test these models in a new context.

Animals↗

Metabolism of uridine in expanded extracellular volume states.

1. Uridine and uridine monophosphate (UMP) are natriuretic and a vasopressor in intact rats. In deoxycorticosterone acetate (DOCA)-salt hypertensive rats metabolic clearance rate (MCR) of uridine is raised and basal plasma uridine diminished, suggesting that metabolism of uridine is linked to changes in extracellular space. 2. Plasma uridine concentration was raised in 38 patients with chronic renal failure compared with age- and sex-matched healthy controls (8.49 mumol/L, 4.37-13.74 mumol/L median, interquartile range, and 2.64 mumol/L 2.51-2.74 mumol/L, respectively, P < 0.001). Plasma uridine was significantly diminished after isotonic fluid removal by ultrafiltration (UF) from 7.25 mumol/L (3.7-11.08) to 5.07 mumol/L (3.3-8.3), P < 0.001, whereas concentration of marker solutes urea and creatinine remained unchanged. During haemodialysis (HD), plasma uridine fell significantly from its pre-HD level. 3. In an animal model of expanded extracellular space the one-kidney, one-clip rat, plasma uridine was significantly higher (20.56 +/- 1.19 mumol/L, P < 0.01) and MCR diminished (34.93 +/- 3.44 mL/kg per min, P < 0.01) compared with sham-operated animals (plasma uridine 12.14 +/- 1.07 and MCR 53.59 +/- 4.11 mL/kg per min). Uridine or UMP did not inhibit Na+, K(+)-ATPase in either of the two assay systems. 4. It was concluded that catabolism of uridine is reduced by extracellular expansion and probably increased by volume reduction by UF.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

Effect of ovulation on the ionic and water content of rabbit oviduct.

The water content, extracellular space, intracellular water, potassium, sodium and chloride content of oviduct and uterus removed from rabbits in estrus and 24 and 72 h following hCG injection have been determined. Following ovulation, there was an increase in water content of the region of the oviduct corresponding to the ampullary -isthmic junction which, at 24 h, is probably due to increased intracellular water. In the ampullary-isthmic junction, ovulation decreases the potassium content and, at 24 h in the isthmic region of the oviduct, chloride is reduced. The water and ionic content of mucosa and smooth muscle cells has been calculated and mucosa cells have greater intracellular water and chloride and sodium content and less potassium and extracellular space than the smooth muscle cells of the oviduct. The significance of the changes in ionic and water content is discussed.

Animals↗

Computational properties of peri-dendritic calcium fluctuations.

Using a model of the extracellular space, we show how external calcium fluctuations, engendered during normal neural activity, can act as a rapid information-bearing signal in nervous systems. We demonstrate that action potentials propagating along a dendrite can induce large peri-dendritic calcium fluctuations, lowering significantly the external calcium available to overlying presynaptic terminals. The geometrical distribution of active calcium sinks critically influences the time and spatial extent of fluctuations in external calcium. In particular, clusters of coactive dendrites can prolong and amplify an external calcium fluctuation. This latter effect provides a natural substrate for a computational mechanism that locates specific volumes of neural tissue on rapid time scales. Such an interpretation suggests that the detailed structure of the extracellular space, in combination with the three-dimensional distribution of active calcium sinks, may play a role in neural information processing.

Action Potentials↗

Role of connexin-based gap junction channels and hemichannels in ischemia-induced cell death in nervous tissue.

Gap junction channels and hemichannels formed of connexin subunits are found in most cell types in vertebrates. Gap junctions connect cells via channels not open to the extracellular space and permit the passage of ions and molecules of approximately 1 kDa. Single connexin hemichannels, which are connexin hexamers, are present in the surface membrane before docking with a hemichannel in an apposed membrane. Because of their high conductance and permeability in cell-cell channels, it had been thought that connexin hemichannels remained closed until docking to form a cell-cell channel. Now it is clear that at least some hemichannels can open to allow passage of molecules between the cytoplasm and extracellular space. Here we review evidence that gap junction channels may allow intercellular diffusion of necrotic or apoptotic signals, but may also allow diffusion of ions and substances from healthy to injured cells, thereby contributing to cell survival. Moreover, opening of gap junction hemichannels may exacerbate cell injury or mediate paracrine or autocrine signaling. In addition to the cell specific features of an ischemic insult, propagation of cell damage and death within affected tissues may be affected by expression and regulation of gap junction channels and hemichannels formed by connexins.

Animals↗

Kinetics of sodium in rabbit arterial wall: inability of aldosterone to alter extra to intracellular distribution.

Transport rate constants (kij) describing the kinetics of Na exchanges in isolated rabbit aorta wall were determined by a previously established method involving the use of 22Na as a tracer and digital computer simulation without recourse to ancillary chemical measurements of extracellular space. A three compartment model consisting of (i) extracellular, (ii) intracellular and (iii) subcellular spaces (compartments) was found to describe adequately the kinetics of 22Na. Normative values for intercompartmental kij and extra to intracellular Na ratio were established. It appears that the Na extracellular space in rabbit arterial wall is larger than that in dog or rat arterial wall. Surprisingly, at variance with several tissues of different species (dog, rat, mouse and human tissues), aldosterone did not influence the extra to intracellular distribution of Na. The findings are interpreted in the light of results obtained previously by other workers using entirely unrelated methodologies and suggest that species difference is an important factor to consider when studying effects of aldosterone on tissue electrolyte distribution in the rabbit.

Aldosterone↗

Hyponatraemia and intracellular water in sepsis: an experimental comparison of the effect of fluid replacement with either 0.9% saline or 5% dextrose.

Hyponatraemia associated with sepsis is known to have an increased morbidity and mortality. The cause of this phenomenon is unknown, but may be related to dilution of the extracellular space with retained exogenous fluid. Fluid and ion redistribution across the cell membrane of striated muscle was investigated in an animal sepsis model and compared with sham controls. The objective was to study the effect of different volumes of fluid replacement with either 0.9% saline or 5% dextrose. Significant shifts of sodium, chloride, and water occurred into the cell in all septic animals but not in controls. This trend was exacerbated by the use of dextrose for intravenous replacement even when the estimated normal fluid requirements had not been exceeded. Hyponatraemia and plasma hypoosmolality were induced only in septic animals, which received 100% of their fluid requirements as dextrose. These animals at the same time had significantly reduced extracellular and increased intracellular volumes compared with controls and the septic animals that received saline replacement. It is concluded that the hyponatraemia and plasma hypoosmolality that occurs in these animals is caused by a combination of intracellular shift of sodium and water, and dilution of the extracellular space, probably on the basis of physiological antidiuretic hormone (ADH) secretion. Dextrose (and by implication 4% dextrose/0.18% saline) is inappropriate, potentially dangerous, and should be avoided in these circumstances.

Analysis of Variance↗

Differences in ischaemic myocardial potassium leakage after treatment with the calcium antagonist anipamil or the beta-blocker atenolol.

The abilities of the new calcium antagonist anipamil as well as the beta-blocker atenolol to reduce the amount of K+ released into the extracellular space during the first minutes of acute coronary artery occlusion were investigated in anaesthetized pigs. [K+]e was continuously measured epicardially with ion selective electrodes. Immediately after starting an occlusion [K+]e rose steeply from normal plasma levels of 3.5 mmol/l to values about three times as high at the end of the 6-min occlusion. This was reproducible in a second and third occlusion in the untreated control group. In the treatment groups either anipamil (0.5; 1.0 mg/kg) or atenolol (0.3 mg/kg) were injected intravenously 10 min before the second occlusion. Anipamil inhibited K+ loss into the extracellular space dose relatedly and significantly throughout the 6-min occlusion period, whereas atenolol showed no protection. The cardioprotective effect of anipamil was also demonstrated in a third occlusion 60 min post application. This different profile cannot be explained by differences in the ability of the two drugs to lower myocardial oxygen consumption; indeed this was only achieved after atenolol. It is concluded that anipamil exerted a direct protective effect on the cardiac myocyte level during ischaemia.

Animals↗

Protective effect of transfection with secretable superoxide dismutase (SOD) (a signal sequence-SOD fusion protein coding cDNA) expression vector on superoxide anion-induced cytotoxicity in vitro.

For ex vivo gene therapy, superoxide dismutase (SOD) must be secreted into the extracellular space and delivered to damaged cells. Recombinant DNA technique can be used to produce a secretory protein that is fused to a non-secretory protein and a signal peptide of another secretory protein gene. We constructed a secretable SOD eukaryotic expression vector which expresses human SOD cDNA by fusing it to the signal peptide DNA sequence of the human interleukin-2 (IL-2) gene. The ILSOD cDNA constructed by PCR-based gene expression was ligated into the multicloning site of the pRc/CMV plasmid (pRc/CMV-ILSOD). Rat lung epithelial like cells (L2 cells) were transfected with pRc/CMV-ILSOD by lipofection. The extracellular SOD activity of ILSOD-L2 cells (transfected cells with pRc/CMV-ILSOD) was 3 times as high as that of host cells. We used the xanthin (X)/xanthin oxidase (XO) system to produce superoxide anions at the extracellular space. We initially investigated the direct cytotoxicity of superoxide anions upon cells. Host and ILSOD-L2 cells were killed by using X/XO, although the sensitivity of the ILSOD-L2 cells to X/XO induced cytotoxicity was significantly decreased compared with that of host cells. The production of lipid peroxidated substances in the host in the presence of X/XO increased to about twice the control (absence of X/XO) level. However, that of ILSOD-L2 cells did not change in the presence of X/XO. Therefore, ILSOD-L2 cells were resistant to X/XO induced lipid peroxidation. These findings indicated that ILSOD gene transfection protected against direct oxidant stress by X/XO. We then investigated the effect of extracellular SOD secreted from ILSOD-L2 cells on extracellular superoxide anion induced cytotoxicity in normal cells. The conditioned media of host cells had no significant effect upon X/XO induced cytotoxicity. However, the conditioned media of ILSOD-L2 cells protected against X/XO induced cytotoxicity. Furthermore, the conditioned medium of ILSOD-L2 cells was more effective than that of host cells against the production of lipid peroxidated substances by normal cells under conditions of oxidative stress. These results indicated that non-secretable protein could be delivered to target cells by means of DNA engineering. This strategy could thus provide an ex vivo means of applying gene therapy using non-secretable proteins.

Animals↗

Modulation of excitatory synaptic transmission by adenosine released from single hippocampal pyramidal neurons.

Adenosine is a potent neuromodulator in the CNS, but the mechanisms that regulate adenosine concentrations in the extracellular space remain unclear. The present study demonstrates that increasing the intracellular concentration of adenosine in a single hippocampal CA1 pyramidal neuron selectively inhibits the excitatory postsynaptic potentials in that cell. Loading neurons with high concentrations of adenosine via the whole-cell patch-clamp technique did not affect the GABAA-mediated inhibitory postsynaptic potentials, the membrane resistance, or the holding current, whereas it significantly increased the adenosine receptor-mediated depression of excitatory postsynaptic currents. The effects of adenosine could not be mimicked by an agonist at the intracellular adenosine P-site, but the effects could be antagonized by a charged adenosine receptor antagonist and by adenosine deaminase, demonstrating that the effect was mediated via adenosine acting at extracellular adenosine receptors. The effect of adenosine loading was not blocked by BaCl2 and therefore was not caused by an adenosine-activated postsynaptic potassium conductance. Adenosine loading increased the paired-pulse facilitation ratio, demonstrating that the effect was mediated by presynaptic adenosine receptors. Finally, simultaneous extracellular field recordings demonstrated that the increase in extracellular adenosine was confined to excitatory synaptic inputs to the loaded cell. These data demonstrate that elevating the intracellular concentration of adenosine in a single CA1 pyramidal neuron induces the release of adenosine into the extracellular space in such a way that it selectively inhibits the excitatory inputs to that cell, and the data support the general conclusion that adenosine is a retrograde messenger used by pyramidal neurons to regulate their excitatory input.

Adenosine↗

Na-KATPase activity and intracellular ion concentrations in the lactating guinea pig mammary gland. Studies on Na-K activated adenosine triphosphatase, XXXVI.

The intracellular sodium, potassium and chloride concentrations in slices of lactating guinea pig mammary gland have been determined by chemical analysis and the use of appropriate values for extracellular space. These ion concentrations after 1 hr incubation at 37 degrees C in a Krebs-Ringer bicarbonate solution are 45mM Na+, 138 mM K+ and 44 mM Cl-, which values are in agreement with those found in fresh mammary gland slices. Inhibition of the NaK activated ATPase cation pump system of the tissue by 10(-4)M ouabain, anoxia or cooling to 0 degrees C Causes a gain of Na+ and an equimolar loss of K+ without a significant change in chloride concentration. The effect of cooling (0 degrees C) is reversible by reincubation at 37 degrees C. Water content of the tissue (76.5% of wet weight) and extracellular space (40.5%) do not change under these conditions. The results permit the conclusion that the NaK activated ATPase system is responsible for the maintenance of the intracellular Na+ and K+ concentrations, but do not support the presence of a chloride pump.

Adenosine Triphosphatases↗

The ultrastructural organization of the visual system of the wax moth, Galleria mellonella: the optic tract.

The ultrastructural organization of the axons of retinula cells of the eye of the wax moth Galleria mellonella are described. The axons traverse an appreciable distance between the basement membrane of the retina and the lamina ganglionaris of the optic lobe of the brain. The optic tract was reconstructed from serial thin sections. Axons emanating from a single ommatidium are closely associated together in the optic tract. Adjacent cartridges fuse together to form large clusters of axons (8 to 10 cartridges). There is further coalescence between these large clusters. Extracellular space within the optic tract is severely limited and axons are sheathed by glial lamellae. Extracellular space between the axons and glia has been measured between 50 and 120 A. Calculations are presented that suggest that the glial interstices between the axons could increase the space constants of the axons significantly. Potentials could be transmitted along the length of the axons with between 59 to 37% decremental decrease, depending upon the number of glial interstices.

Animals↗

The N-terminal hydrophobic sequence of autotaxin (ENPP2) functions as a signal peptide.

Autotaxin, also known as ENPP2, was originally isolated from the culture medium of melanoma cells as a cell-motility promoting protein. It regulates cell growth, motility, and angiogenesis through the production of lysophosphatidic acid and sphingosine 1-phosphate. Because autotaxin shows overall structural similarity to the well-characterized PC-1, it has been assumed to be a type II transmembrane protein that is expressed on the cell surface and is released into the extracellular space after proteolytic cleavage. We found, however, that while autotaxin was efficiently secreted into the extracellular space both in vitro and in vivo, it was expressed neither on the surfaces of autotaxin-transfected cells nor on those of the autotaxin-expressing choroid plexus epithelium cells. N-terminal sequencing of the secreted autotaxin revealed that it was cleaved at two N-terminal sites that match the consensus sequences for cleavage by a signal peptidase and furin. In addition, when translated in vitro, autotaxin was co-translationally translocated into microsome membranes, and its N-terminal 3-kDa fragment corresponding to a signal sequence was cleaved. These data demonstrate that the N-terminal hydrophobic sequence of autotaxin functions as a signal peptide, not as a transmembrane segment, and thus autotaxin is synthesized as a secreted protein.

Amino Acid Sequence↗

UL20 protein functions precede and are required for the UL11 functions of herpes simplex virus type 1 cytoplasmic virion envelopment.

Egress of herpes simplex virus type 1 (HSV-1) from the nucleus of the infected cell to extracellular spaces involves a number of distinct steps, including primary envelopment by budding into the perinuclear space, de-envelopment into the cytoplasm, cytoplasmic reenvelopment, and translocation of enveloped virions to extracellular spaces. UL20/gK-null viruses are blocked in cytoplasmic virion envelopment and egress, as indicated by an accumulation of unenveloped or partially enveloped capsids in the cytoplasm. Similarly, UL11-null mutants accumulate unenveloped capsids in the cytoplasm. To assess whether UL11 and UL20/gK function independently or synergistically in cytoplasmic envelopment, recombinant viruses having either the UL20 or UL11 gene deleted were generated. In addition, a recombinant virus containing a deletion of both UL20 and UL11 genes was constructed using the HSV-1(F) genome cloned into a bacterial artificial chromosome. Ultrastructural examination of virus-infected cells showed that both UL20- and UL11-null viruses accumulated unenveloped capsids in the cytoplasm. However, the morphology and distribution of the accumulated capsids appeared to be distinct, with the UL11-null virions forming aggregates of capsids having diffuse tegument-derived material and the UL20-null virus producing individual capsids in close juxtaposition to cytoplasmic membranes. The UL20/UL11 double-null virions appeared morphologically similar to the UL20-null viruses. Experiments on the kinetics of viral replication revealed that the UL20/UL11 double-null virus replicated in a manner similar to the UL20-null virus. Additional experiments revealed that transiently expressed UL11 localized to the trans-Golgi network (TGN) independently of either gK or UL20. Furthermore, virus infection with the UL11/UL20 double-null virus did not alter the TGN localization of transiently expressed UL11 or UL20 proteins, indicating that these proteins did not interact. Taken together, these results show that the intracellular transport and TGN localization of UL11 is independent of UL20/gK functions, and that UL20/gK are required and function prior to UL11 protein in virion cytoplasmic envelopment.

Animals↗

Mature eosinophils stimulated to develop in human cord blood mononuclear cell cultures supplemented with recombinant human interleukin-5. Part I. Piecemeal degranulation of specific granules and distribution of Charcot-Leyden crystal protein.

Human cord blood mononuclear cells were cultured for 35 days in media containing recombinant human interleukin 5 (rhIL-5) supplemented with a fraction of the culture supernatant of phytohemagglutinin (PHA)-stimulated human T lymphocytes from which interleukin 2 (IL-2) was eliminated. Cultured cells were studied by electron microscopy and an immunogold procedure to detect subcellular site(s) of Charcot-Leyden crystal (CLC) protein. The majority of cells (greater than 70%) developing in this system were mature eosinophils, with descending frequency of other cells, including macrophages, mature basophils, eosinophilic myelocytes, and mature neutrophils. Mature eosinophils were characterized by increased numbers of primary granules, small granules, tubulovesicular structures, and decreased secondary granules. These eosinophils showed extensive piecemeal degranulation (PMD) characterized by partially empty and empty secondary granule chambers in the cytoplasm. Small, smooth vesicles were evident within empty granule chambers as well as adjacent to them. Eosinophils formed close associations with phagocytic macrophages that contained both standard-shaped and irregularly shaped CLC within phagolysosomes. Subcellular sites of CLC protein were demonstrated by immunogold in eosinophils and macrophages arising in these cultures. Charcot-Leyden crystal protein was present in the nuclear matrix and extraorganellar cytoplasm of eosinophils. Primary granules and some cytoplasmic vesicles were labeled for CLC protein, but full and empty secondary granules and the extensive network of tubulovesicles were not. Charcot-Leyden crystals were absent from eosinophils, nor were they present in the extracellular space. Charcot-Leyden crystals were absent from eosinophils, nor were they present in the extracellular space. Charcot-Leyden crystals within phagosomes of macrophages were labeled by the immunogold procedure for CLC protein. These results demonstrate that rhIL-5-supplemented, PHA-stimulated, T-cell-conditioned media induced the development of mature human eosinophils from cord blood cells. These eosinophils underwent PMD of secondary granule contents. Immunogold analysis showed eosinophil CLC protein in the cytoplasm, nucleus, and primary granules of eosinophils. Macrophages also were present in these cultures. They contained CLC protein-containing crystals in their phagosomes, suggesting active sequestration of eosinophil CLC protein by macrophages in vitro.

Cell Degranulation↗

Role of extracellular proteins in the dynamics of vasogenic brain edema.

The relationship between extravasation of proteins into extracellular spaces of brain parenchyma and the water content of such regions were evaluated in an experimental model. In this model, a temporary opening of the blood-brain barrier (BBB) to proteins was produced without significant injury to the cellular elements of brain tissue. Rabbits were subjected to bolus injection of their own blood under 360-400 mm Hg pressure via the internal carotid artery. The opening of the barrier and its duration were evaluated with Evans blue (EB), horseradish peroxidase (HRP), and sodium fluorescein (NaFl) tracers. The water content of brain tissue was assessed by specific gravity (SG) measurements in 1-mm-diameter tissue samples. Quantitative evaluation of protein penetration into brain tissue was carried out using 125I bovine serum albumin (BSA). The opening of the BBB to proteins persisted up to 9 h, whereas the barrier remained permeable to small molecular NaFl for 24 h. The SG measurements indicated in the areas of EB extravasation a progressive increment in water content up to 9 h, i.e., the duration of BBB opening to proteins. Following this, there was a progressive clearance of edema in spite of the BBB remaining open for NaFl for 24 h. Quantitative evaluations of 125I-BSA and SG in the same tissue samples, supported by statistical analysis, indicated approximately linear relationship analysis, indicated approximately linear relationship between albumin and water, implying a strong correlation between the development of vasogenic edema and extravasation of proteins into extracellular spaces.

Animals↗

Cerebellar capillary hemangioblastoma: its histogenesis studied by organ culture and electron microscopy.

A capillary hemangioblastoma from the vermis of a 21-year-old man with von Hippel-Lindau's disease was successfully maintained in organ culture systems on Millipore filter platforms and gelatin sponge foam matrices up to 48 days. Three cell types--endothelial cells, pericytes, and stromal cells--identified by their fine structural features and their architectural relationships to vascular lumens and to the extracellular space were recognized in the original tumor. By light microscopy the explants showed, in the late stages, increased lipid droplets in the stromal cells and perivascular hyaline thickening. By electron microscopy, endothelial cells, pericytes, and stromal cells remained distinguishable as cell types. However, the stromal cells demonstrated, in addition to an increase of their normal complement of microfilaments and lipid droplets, features that were more characteristic of the two other cell types, i.e. micropinocytotic vesicles and the formation of zonula occludens junctions and hemidesmosomes. Basement membranes also became more apparent around the stromal cells. With increasing time in vitro, there was a striking increase in mature collagen fibers in the extracellular space. The roles of the different cell types in capillary hemangioblastoma and the histogenesis of the stromal cells are discussed in light of these observations. It is concluded that the capillary hemangioblastoma consists of multiple cell lines--endothelial cells, pericytes, stromal cells and, occasionally, hematopoietic cells--all of which are neoplastic and replicate in parallel with one another. Stromal cells may be regarded as an aberrant monopotential cell type which shares with the endothelial cell and pericyte a common mesenchymal, presumably angiogenic, ancestry, and may, on occasion, display morphological features, such as increased basement membrane formation and the formation of zonula occludens junctions, which recall its angiogenic lineage. However, interconvertibility between endothelial cells and stromal cells does not appear to occur in vivo or in vitro.

Adult↗

Serum xylosyltransferase: a new biochemical marker of the sclerotic process in systemic sclerosis.

UDP-D-xylose:proteoglycan core protein beta-D-xylosyltransferase (EC2.4.2.26) is the initial enzyme in the biosynthesis of chondroitin sulfate and dermatan sulfate proteoglycans in fibroblasts and chondrocytes. Secretion of xylosyltransferase into the extracellular space was determined in cultured human dermal fibroblasts. A more than 6-fold accumulation of xylosyltransferase activity in cell culture supernatant was observed (day 1, 0.6 microU per 106 cells; day 9, 4.1 microU per 106 cells); however, intracellular xylosyltransferase activity remained at a constant level (0.4 microU per 106 cells). Exposure of human chondrocytes to colchicine led to a 3-fold decreased level of xylosyltransferase and chondroitin-6-sulfate concentration in cell culture. Specific xylosyltransferase activity and chondroitin-6-sulfate concentration decreased in a concentration-dependent manner and in parallel in culture medium and accumulated 5-fold in cell lysates indicating that xylosyltransferase is secreted simultaneously into the extracellular space with chondroitin sulfate proteoglycans. Xylosyltransferase activities were determined in serum samples of 30 patients with systemic sclerosis. Xylosyltransferase activities in female (mean value 1.28 mU per liter, 90% range 1.10-1.55 mU per liter) and male patients (mean 1.39 mU per liter, 90% range 1.16-1. 57 mU per liter) with systemic sclerosis were significantly increased in comparison with blood donors of a corresponding age. Furthermore, xylosyltransferase activity was correlated with the clinical classification of systemic sclerosis. Female patients with diffuse cutaneous systemic sclerosis showed higher serum xylosyltransferase activities than patients with limited systemic sclerosis. These results confirm that the increase of proteoglycan biosynthesis in sclerotic processes of scleroderma is closely related to an elevated xylosyltransferase activity in blood and demonstrate the validity of xylosyltransferase as an additional diagnostic marker for determination of sclerotic activity in systemic sclerosis.

Adult↗