Biomedical subjects

B Christ

Publications and source records attributed to B Christ.

At least 37 records · Page 2Linked to original sources

PubMed2001

Endogenous origin of the lymphatics in the avian chorioallantoic membrane.

The lymphatics of the intestinal organs have important functions in transporting chyle toward the jugulosubclavian junction, but the lymphangiogenic potential of the splanchnic mesoderm has not yet been tested. Therefore, we studied the allantoic bud of chick and quail embryos. It is made up of endoderm and splanchnic mesoderm and fuses with the chorion to form the chorioallantoic membrane (CAM) containing both blood vessels and lymphatics. In day 3 embryos (stage 18 of Hamburger and Hamilton [HH]), the allantoic mesoderm consists of mesenchymal cells that form blood islands during stage 19 (HH). The endothelial network of the allantoic bud, some intraluminal and some mesenchymal cells express the hemangiopoietic marker QH1. The QH1-positive endothelial cells also express the vascular endothelial growth factor receptor-3 (VEGFR-3), whereas the integrating angioblasts and the round hematopoietic cells are QH1-positive/VEGFR-3-negative. The ligand, VEGF-C, is expressed ubiquitously in the allantoic bud, and later predominantly in the allantoic epithelium and the wall of larger blood vessels. Allantoic buds of stage 17-18 (HH) quail embryos were grafted homotopically into chick embryos and reincubated until day 13. In the chimeric CAMs, quail endothelial cells are present in blood vessels and lymphatics, the latter being QH1 and VEGFR-3 double-positive. QH1-positive hematopoietic cells are found at many extra- and intraembryonic sites, whereas endothelial cells are confined to the grafting site. Our results show that the early allantoic bud contains hemangioblasts and lymphangioblasts. The latter can be identified with Prox1 antibodies and mRNA probes in the allantoic mesoderm of day 4 embryos (stage 21 HH). Prox1 is a specific marker of the lymphatic endothelium throughout CAM development.

Animals↗

PubMed2001

Prox1 is a marker of ectodermal placodes, endodermal compartments, lymphatic endothelium and lymphangioblasts.

The lymphatic endothelium has mostly been thought to be derived by sprouting from specialized veins. Recently it has been shown that mice deficient for the homeobox transcription factor Prox1 are practically devoid of lymphatics. We have studied the expression of Prox1 mRNA and protein in chick embryos and human fetuses. In the chick, Prox1 is expressed in specific compartments of all germ layers. In the ectoderm, it is found in the neural tube, trigeminal, spinal and sympathetic ganglia and the retina, and also in placodal structures such as the lens, olfactory, otic, facial, glossopharyngeal and vagal placodes, and the apical ectodermal ridge. In the endoderm, Prox1 is a marker of hepatocytes, bile duct and pancreatic epithelium. In the mesoderm, weak expression is observed in cardiomyocytes, and strong expression in lymphatic endothelium. Identical expression domains are found in 19-week-old human fetuses. In day 6.5 chick embryos, there are several sites of contact of lymphatics with the jugular vein, which has a mixed endothelium of Prox1-positive and -negative cells. The only non-lymphatic endothelial cells expressing Prox1 are found on the concave side of the cardiac valves. To further analyse development of lymphatics, we studied early chick embryos and observed scattered Prox1-positive cells in the dermatome, giving rise to Prox1-positive lymphatic networks during subsequent development. Furthermore, the anlagen of the posterior lymph sacs and the paired thoracic duct can already be observed in day-4 chick embryos. Our studies show that lymphatics develop much earlier than previously described, and they mostly do not seem to be derived by sprouting from veins. In contrast, lymphangioblasts are present in the deep and superficial compartments of the early mesoderm, independently giving rise to the deep and superficial lymphatics.

Animals↗

PubMed2001

Molecular and cellular analysis of embryonic avian tongue development.

Signalling cascades first described in Drosophila have been found to regulate patterning and outgrowth in a number of structures in higher vertebrates. We sought to determine whether the evolutionarily conserved genes were important during the development of the tongue. In situ hybridisation was used to determine the temporo-spatial expression of a panel of conserved genes. Histological examination and incorporation of BrdU were used to determine the mechanism by which the tongue develops. We show that evolutionarily conserved genes were expressed in distinct dynamic patterns during tongue development. Sonic Hedgehog (Shh) and Patched (Ptc) were found only in the dorsal tongue epithelium. Shh expression was only observed in the suprabasal layers, whereas Ptc was observed in both basal and suprabasal layers. Cell division in the epithelium was concentrated in regions devoid of Shh. Expression of bone morphogenetic protein-7 (BMP) was identical to that of Shh. Shh and Ptc expression were never detected in the mesenchyme. Ectopic expression of Noggin (a potent antagonist of the BMPs) caused severe abnormalities in tongue morphology, including swelling of the mesenchymal component and a thickening of the epithelial layer. Data from this study suggests that the epithelium and mesenchyme express quite different genes during development. However BMP activity acts to inhibit growth in both tissues.

Activins↗

PubMed2001

Interactions of sildenafil and tacrolimus in men with erectile dysfunction after kidney transplantation.

OBJECTIVES: To study the pharmacokinetics of the combined use of sildenafil (which may provide an effective treatment for patients with erectile dysfunction after kidney transplantation) and tacrolimus, as interactions between them are expected because of a common elimination pathway. METHODS: Ten male patients (age 29 to 52 years) were included. Because of its importance in transplant recipients, medication remained unchanged. On day 1, tacrolimus was administered routinely, and blood samples for tacrolimus assays were drawn at predefined times. On day 2, sildenafil was added and blood was collected for assays of tacrolimus, sildenafil, and the sildenafil metabolite UK103,320 (UK) at the indicated times. Blood pressure was monitored on both study days. Sildenafil and UK were assessed by high-pressure liquid chromatography and tacrolimus was assessed by microparticle enzyme immunoassay. RESULTS: No effects of sildenafil on the tacrolimus pharmacokinetics were found. However, in the patients studied, the sildenafil and UK pharmacokinetics were altered compared with the results of previous studies. The mean peak concentration of sildenafil was higher by 44% and the area under the concentration-time data increased by 90%. The elimination half-life was prolonged (4.7 hours compared with 3 hours in healthy volunteers). The area under the concentration-time data for UK was about threefold larger than in healthy volunteers, and the half-life was prolonged from 3.8 hours to 11.4 hours. Pronounced blood pressure drops were observed. CONCLUSIONS: Tacrolimus or the concomitant medication or the disease itself might have altered the sildenafil and UK pharmacokinetics. Because of the drop in blood pressure, sildenafil therapy should start at the lowest dose and any antihypertensive medication should be adjusted.

Adult↗

PubMed2001

Patterning of fast and slow fibers within embryonic muscles is established independently of signals from the surrounding mesenchyme.

During embryonic development, and before functional innervation, a highly stereotypic pattern of slow- and fast-contracting primary muscle fibers is established within individual muscles of the limbs, from distinct populations of myoblasts. A difference between the fiber-type pattern found within chicken and quail pectoral muscles was exploited to investigate the contributions of somite-derived myogenic precursors and lateral plate-derived mesenchymal stroma to the establishment of muscle fiber-type patterns. Chimeric chicken/quail embryos were constructed by reciprocal transplantation of somites or lateral plate mesoderm at stages prior to muscle formation. Muscle fibers derived from quail myogenic precursors that had migrated into chicken stroma showed a quail pattern of mixed fast- and slow-contracting muscle fibers. Conversely, chicken myogenic precursors that had migrated into quail stroma showed a chicken pattern of nearly exclusive fast muscle fiber formation. These results demonstrate in vivo an intrinsic commitment to fiber-type on the part of the myoblast, independent of extrinsic signals it receives from the mesenchymal stroma in which it differentiates.

Animals↗

PubMed2000

Compartmentalization of the somite and myogenesis in chick embryos are influenced by wnt expression.

Muscles of the body and bones of the axial skeleton derive from specialized regions of somites. Somite development is influenced by adjacent structures. In particular, the dorsal neural tube and the overlying ectoderm have been shown to be necessary for the induction of myogenic precursor cells in the dermomyotome. Members of the Wnt family of signaling molecules, which are expressed in the dorsal neural tube and the ectoderm, are postulated to be responsible for this process. It is shown here that ectopically implanted Wnt-1-, -3a-, and -4-expressing cells alter the process of somite compartmentalization in vivo. An enlarged dorsal compartment results from the implantation of Wnt-expressing cells ventrally between the neural tube/notochord and epithelial somites, at the expense of the ventral compartment, the sclerotome. Thus, ectopic Wnt expression is able to override the influence of ventralizing signals arising from notochord and floor plate. This shift of the border between the two compartments was identified by an increase in the domain of Pax-3 expression and a complete loss of Pax-1 expression in somites close to the ectopic Wnt signal. The expanded expression of MyoD and desmin provides evidence that it is the myotome which increases as a result of Wnt signaling. Paraxis expression is also drastically amplified after implantation of Wnt-expressing cells indicating that Wnts are involved in the formation and maintenance of somite epithelium and suggesting that Paraxis is activated through Wnt signaling pathways. Taken together these results suggest that ectopic Wnts disturb the normal balance of signaling molecules within the somite, resulting in an enhanced recruitment of somitic cells into the myogenic lineage.

Animals↗

PubMed2000

Regulation by glucagon (cAMP) and insulin of the promoter of the human phosphoenolpyruvate carboxykinase gene (cytosolic) in cultured rat hepatocytes and in human hepatoblastoma cells.

A promoter fragment (-457 to +65) of the human cytosolic phosphoenolpyruvate carboxykinase gene, which by analogy to the rat promoter contains regulatory regions conferring glucagon (cAMP) and insulin responsiveness to the phosphoenolpyruvate carboxykinase gene, was cloned into a luciferase expression vector and transfected into cultured rat hepatocytes and human hepatoblastoma cells (HepG2) to study the regulation of the transgene by glucagon (cAMP) and insulin. A reporter gene that contained the rat promoter sequence from -493 to +33 was used for comparison. In cultured rat hepatocytes glucagon and its second messenger cAMP increased luciferase expression 4-6-fold over basal levels. Insulin reduced this effect by 40-70%. Luciferase expression was also stimulated by the combination of dexamethasone and cAMP in HepG2 cells and this effect was inhibited by insulin. The phosphoinositide 3-kinase (PI 3-kinase) inhibitor, wortmannin, abolished this action of insulin in cultured rat hepatocytes. The results show that the promoter of the human phosphoenolpyruvate carboxykinase gene mediates the stimulatory action of glucagon and its second messenger cAMP. The inhibitory action of insulin was exerted through the PI 3-kinase pathway in cultured rat hepatocytes.

Androstadienes↗

PubMed2000

The lymphatic endothelium of the avian wing is of somitic origin.

It has recently been shown that there are lymphangioblasts in the early avian wing bud, but fate map studies on the origin of these cells have not yet been performed. The lymphatics in the wings of 10-day-old chick and quail embryos are characterized by both the position along with all major blood vascular routes and by the Vascular Endothelial Growth Factor Receptor-3 (VEGFR-3) expression. In the quail, the endothelium of both blood vessels and lymphatics can be marked with the QH1 antibody. We have grafted the dorsal halves of epithelial somites of 2-day-old quail embryos homotopically into chick embryos. The grafting was performed at the wing level and the host embryos were reincubated until day 10. The chimeric wings were studied with the QH1 antibody alone and with double staining consisting of VEGFR-3 in situ hybridization and QH1 immunofluorescence. Our results show that in the wing the endothelium of both the blood vessels and the lymphatics is derived from the somites. QH1-positive endothelial cells form the vasculature of the chimeric wings. Chimeric lymphatics of the wing can be identified because of their typical position and their VEGFR-3 and QH1 double-positivity. This shows that not only the blood vascular cells but also the lymphatic endothelial cells of the avian wing are born in the paraxial/somitic mesoderm.

Animals↗

PubMed2000

Molecular and cellular biology of avian somite development.

Much of our understanding of early vertebrate embryogenesis derives from experimental work done with the chick embryo. Studies of the avian somite have played a key role in elucidating the developmental history of this important structure, the source of most muscle and bone in the organism. Here we review the development of the avian somite including morphological and molecular data on the origin of paraxial mesoderm, maturation of the segmental plate, specification and formation of somite compartments, and somite cell differentiation into cartilage and skeletal muscle.

Animals↗

PubMed2000

Phosphatidylinositol 3-kinase and protein kinase C contribute to the inhibition by interleukin 6 of phosphoenolpyruvate carboxykinase gene expression in cultured rat hepatocytes.

The participation of phosphatidylinositol 3-kinase (PI3-kinase), protein kinase C, and mitogen-activated protein kinase (MAP-kinase) in the inhibition by interleukin 6 (IL-6) and insulin of phosphoenolpyruvate carboxykinase (PCK) gene expression was investigated in cultured rat hepatocytes. IL-6 or insulin inhibited the glucagon-stimulated increase in PCK messenger RNA (mRNA) by about 70%. In the presence of either the PI3-kinase inhibitor, wortmannin, or the protein kinase C inhibitor, GF109203x, the inhibition by IL-6 was only about 40%, although it was abolished with both inhibitors in combination. Wortmannin alone but not GF109203x prevented the inhibition by insulin of glucagon-stimulated PCK gene expression. The MAP-kinase pathway inhibitor, PD98059, did not affect IL-6 or insulin inhibition of PCK mRNA increase. When chlorophenylthio-cyclic 3',5' adenosine monophosphate (CPT-cAMP) was used instead of glucagon, IL-6 or insulin inhibited the increase in PCK mRNA by 75% and 85%, respectively. The inhibition by IL-6 was only about 50% in the presence of either wortmannin or GF109203x alone but was abolished with the combination of both inhibitors. The inhibition by insulin was only about 50% in the presence of GF109203x and was abolished by wortmannin. The inhibitors did not affect the inhibition by IL-6 or insulin of the glucagon-stimulated increase in cAMP. It is concluded that the inhibition by IL-6 of PCK gene expression involved both PI3-kinase and protein kinase C, whereas the inhibition by insulin required only PI3-kinase. The inhibition occurred downstream from cAMP formation. Hence, IL-6 and insulin may share, in part, common signal transduction pathways in the inhibition of PCK gene expression.

Animals↗

PubMed2000

Active interaction of human A375 melanoma cells with the lymphatics in vivo.

We have used the avian chorioallantoic membrane (CAM) to study the interaction of tumor cells with the lymphatics in vivo. The vascular endothelial growth factor-C (VEGF-C) has been shown to be lymphangiogenic. We have therefore grown VEGF-C-expressing human A375 melanoma cells on the CAM. These tumors induced numerous lymphatics at the invasive front, and compressed or destroyed VEGF receptor (R)-3-positive lymphatics were observed within the solid tumors. The lymphatics in the CAM and in the A375 melanomas could also be demonstrated with an antibody against Prox 1, a highly specific marker of lymphatic endothelial cells. Proliferation studies revealed a BrdU labeling index of 11.6% of the lymphatic endothelial cells in the tumors and at their margins. A great number of melanoma cells invaded the lymphatics. Such interactions were not observed with VEGF-C-negative Malme 3 M melanoma cells. Lymphangiogenesis was inhibited to some extent when A375 melanoma cells were transfected with cDNA encoding soluble VEGFR-3 (sflt4), and the BrdU labeling index of the lymphatics in these tumors was 3.9%. Invasion of lymphatics and growth of blood vascular capillaries were not inhibited by the transfection. Therefore, tumor-induced lymphangiogenesis seems to be dependent to some extent on VEGF-C/flt4 interactions, but invasion of lymphatics seems to be a distinct mechanism.

Allantoin↗

PubMed2000

Induction of the blood-brain barrier marker neurothelin/HT7 in endothelial cells by a variety of tumors in chick embryos.

Neurothelin/HT7, a transmembrane glycoprotein of the immunoglobulin superfamily, is a marker of blood-brain barrier (BBB)-forming endothelial cells. We have studied the expression of neurothelin in tumors grown on the chorioallantoic membrane (CAM) of chick embryos. We inoculated each 3-5 x 10(6) rat C6 glioma, rat 10AS pancreatic carcinoma, human A375 melanoma, and human mammary duct adenoma cells on the CAM of 10-day-old chick embryos. The tumors were harvested on day 17. All four tumor cell lines formed solid tumors which were supplied by vessels of CAM origin. Foci of bleeding were regularly observed within the tumors. All four tumors induced the expression of neurothelin/HT7 (but not of glucose transporter-1) in tumor endothelial cells, whereas expression in adjacent endothelial cells of normal CAM did not occur. Confocal laser scanning microscopy revealed that the pattern of neurothelin expression in tumor endothelial cells was different from that in normal central nervous system (CNS) endothelium, but the relative molecular weight of neurothelin, studied by western blot analysis, was the same in brain and in tumors. It has been shown that, with increasing malignancy, vessels of CNS tumors lose their morphological characteristics, and BBB markers such as the glucose transporter-1 are downregulated. Our results show that, in contrast, the BBB marker, neurothelin, is expressed de novo in tumor endothelial cells. Potential common functions of neurothelin in endothelial cells of the CNS and tumors are discussed.

Allantois↗

PubMed2000

New experimental evidence for somite resegmentation.

According to the concept of resegmentation, the boundaries of vertebrae are shifted one half a segment compared with somite boundaries. This theory has been experimentally confirmed by interspecific transplantations of single somites. Due to the difficulty of exactly orientating individual somites in the host embryo, the outcome and interpretations of these experiments have occasionally been questioned. This is especially true for the formation of neural arches, their processes, and the ribs. We reinvestigated the formation of vertebrae in the avian embryo by grafting one and one half somites from quail to chick embryos. This method eliminates the possibility of a wrong somite orientation in the host embryo. Results show that the vertebral body, the neural arch and its processes are made up of material of two adjacent somites. This is also true for the rib, with the exception of the costal head, which is formed by only one somite. Whereas in the proximal part of the costal body the chick and quail cell regions border on each other in the middle of the rib, in its distal part quail cells gradually begin to mix with chick cells. The intersegmental muscles and their skeletal attachments sites are formed from the same somite. These results support and complete the data of previous studies and confirm the resegmentation concept.

Animals↗

PubMed2000

The development of the avian vertebral column.

Segmentation of the paraxial mesoderm leads to somite formation. The underlying molecular mechanisms involve the oscillation of "clock-genes" like c-hairy-1 and lunatic fringe indicative of an implication of the Notch signaling pathway. The cranio-caudal polarity of each segment is already established in the cranial part of the segmental plate and accompanied by the expression of genes like Delta1, Mesp1, Mesp2, Ulicx-1, and EphA4 which are restricted to one half of the prospective somite. Dorsoventral compartmentalization of somites leads to the development of the dermomyotome and the sclerotome, the latter forming as a consequence of an epithelio-to-mesenchymal transition of the ventral part of the somite. The sclerotome cells express Pax-1 and Pax-9, which are induced by notochordal signals mediated by sonic hedgehog (Shh) and noggin. The craniocaudal somite compartmentalization that becomes visible in the sclerotomes is the prerequisite for the segmental pattern of the peripheral nervous system and the formation of the vertebrae and ribs, whose boundaries are shifted half a segment compared to the sclerotome boundaries. Sclerotome development is characterized by the formation of three subcompartments giving rise to different parts of the axial skeleton and ribs. The lateral sclerotome gives rise to the laminae and pedicles of the neural arches and to the ribs. Its development depends on signals from the notochord and the myotome. The ventral sclerotome giving rise to the vertebral bodies and intervertebral discs is made up of Pax-1 expressing cells that have invaded the perinotochordal space. The dorsal sclerotome is formed by cells that migrate from the dorso-medial angle of the sclerotome into the space between the roof plate of the neural tube and the dermis. These cells express the genes Msx1 and Msx2, which are induced by BMP-4 secreted from the roof plate, and they later form the dorsal part of the neural arch and the spinous process. The formation of the ventral and dorsal sclerotome requires directed migration of sclerotome cells. The regionalization of the paraxial mesoderm occurs by a combination of functionally Hox genes, the Hox code, and determines the segment identity. The development of the vertebral column is a consequence of a segment-specific balance between proliferation, apoptosis and differentiation of cells.

Animals↗

PubMed2000

Origin of the epaxial and hypaxial myotome in avian embryos.

The myotome originates from the dermomyotome. Controversy surrounds the location of myotome precursor cells within the dermomyotome and their segregation from the dermomyotome. Here we addressed the problem of myotome formation by labeling dermomyotome cells using the quail-chick marking technique. We carried out five series of transplantation and replaced: (1) the medial third, (2) the intermediate third, (3) the lateral third, (4) the cranial half, (5) the caudal half of a thoracic dermomyotome. The grafting procedures were performed in HH-stages 15-17 of quail and chick embryos. The chimeras were reincubated for 2 days up to HH-stages 24-25. All of the grafted parts contributed to the myotome. The epaxial myotome is derived from the medial third of the dermomyotome, while the hypaxial myotome is formed by both the intermediate and lateral third of the dermomyotome. Ep- and hypaxial myotome domains meet in the thickest part of the myotome that is situated in the middle of its ventrolateral axis. Myotome growth in the epaxial domain begins earlier than in the hypaxial domain. Cranial and caudal edges of the dermomyotome contribute equally to both the epaxial and hypaxial myotomes. The first born myotome cells are located in the lateral part of the epaxial myotome and development then proceedes in medial and lateral directions.

Animals↗

PubMed2000

Contribution of single somites to the skeleton and muscles of the occipital and cervical regions in avian embryos.

Controversy has surrounded the process of resegmentation of cervico-occipital somites. We have reinvestigated this topic by grafting single somites of quail embryos homotopically into chick embryos. Somites one to five contribute to the skull. Somites one and two contribute to the parasphenoid, which develops by direct ossification in a non-segmental fashion. All cartilaginous derivatives of the somites are segmental. Somite two forms a stripe of cells in the basioccipital, exoccipital and supraoccipital. Somites three to five give rise to the subsequent caudal parts of the basioccipital and exoccipital. Somite five forms the first motion segment including the occipital condyle, the cranial part of the atlas and the tip of the dens axis. Therefore, the border between head and neck is in the centre of somite five, and corresponds to the expression boundary of Choxb-3. Somite six forms the caudal part of the atlas and the cranial part of the axis. Somites two to eight all contribute to the cranio-cervical muscles with the exception of the Mm. rectus capitis dorsalis and ventralis and the M. biventer cervicis, which do not receive contributions from somite two. In contrast, the M. cucullaris capitis is exclusively formed by myogenic cells from somite two, which parallels its exclusive innervation by the accessory nerve. Our data confirm the segmental nature of the occiput, and show that resegmentation is a very regular process involving all except the four cranialmost somites. Except for somites one and two, all of the somites contribute to the muscles located at the appropriate levels.

Animals↗

PubMed2000

Evolution and development of distinct cell lineages derived from somites.

In the vertebrate embryo, the somites arise from the paraxial mesoderm as paired mesodermal units in a craniocaudal sequence. Segmentation is also the underlying principle of the body plan in annelids and arthropods. Genes controlling segmentation have been identified that are highly conserved in organisms belonging to different phyla. Segmentation facilitates movement and regionalization of the vertebrate body. Its traces in humans are, for example, vertebral bodies, intervertebral disks, ribs, and spinal nerves. Somite research has a history of at least three centuries. Detailed morphological data have accumulated on the development of the avian somite. Especially in connection with the quailchick interspecific marker system, progress was made toward an understanding of underlying mechanisms. At first each somite consists of an outer epithelium and a mesenchymal core. Later, the ventral portion of the somite undergoes de-epithelialization and gives rise to the sclerotome, whereas the dorsal portion forms the dermomyotome. The dermomyotome is the source of myotomal muscle cells and the dermis of the back. It also yields the hypaxial muscle buds at flank level and the myogenic cells invading the limb buds. The dorsal and ventral somitic domains express different sets of developmental control genes, for example, those of the Pax family. During later stages of development, the sclerotomes undergo a new arrangement called "resegmentation" leading to the fusion of the caudal half of one sclerotome with the cranial half of the following sclerotome. Further somitic derivatives include fibroblasts, smooth muscle, and endothelial cells. While sclerotome formation is controlled by the notochord, signals from the dorsal neural tube and ectoderm support the development of the dermomyotome. Myogenic precursor cells for the limb bud are recruited from the dermomyotome by the interaction of c-met with its ligand scatter factor (SF/HGF). In the evolution of metamerism in vertebrates, the first skeletal elements were primitive parts of neural arches, while axial elements developed only later in teleosts as pleurocentra and hypocentra.

Animals↗

PubMed2000

Hyaluronan in the nuchal skin of chromosomally abnormal fetuses.

Nuchal skin oedema at 10-14 weeks gestation, observed by ultrasonography as increased nuchal translucency (NT), is found in approximately 70% of fetuses with trisomies 21, 18 and 13 as well as those with Turner's syndrome. This study investigates the possibility that one mechanism for increased translucency is an altered composition of the skin with a higher concentration of hyaluronan; large amounts of hyaluronan can lead to excessive hydration of the extracellular matrix. We isolated the hyaluronic acid binding region (HABR) from aggrecan in the extracellular matrix of hyaline cartilage and used it in a biotinylated form in combination with a fluorescent probe as a marker for hyaluronan. Immunohistochemistry was then used to examine the nuchal skin of chromosomally abnormal and normal fetuses, obtained after termination of pregnancy. In fetuses with trisomy 21 there was a substantial increase in hyaluronan, whereas in trisomies 18 and 13 and Turner's syndrome the amount was similar to that in chromosomally normal controls. This finding suggests that hyaluronan may be implicated in the pathogenesis of increased NT in fetuses with trisomy 21, but the common phenotypic expression of increased translucency in different chromosomal abnormalities may be the consequence of other mechanisms.

Chromosome Aberrations↗