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PubMed1998

Neural crest emigration from the neural tube depends on regulated cadherin expression.

During the emergence of neural crest cells from the neural tube, the expression of cadherins dynamically changes. In the chicken embryo, the early neural tube expresses two cadherins, N-cadherin and cadherin-6B (cad6B), in the dorsal-most region where neural crest cells are generated. The expression of these two cadherins is, however, downregulated in the neural crest cells migrating from the neural tube; they instead begin expressing cadherin-7 (cad7). As an attempt to investigate the role of these changes in cadherin expression, we overexpressed various cadherin constructs, including N-cadherin, cad7, and a dominant negative N-cadherin (cN390 ), in neural crest-generating cells. This was achieved by injecting adenoviral expression vectors encoding these molecules into the lumen of the closing neural tube of chicken embryos at stage 14. In neural tubes injected with the viruses, efficient infection was observed at the neural crest-forming area, resulting in the ectopic cadherin expression also in migrating neural crest cells. Notably, the distribution of neural crest cells with the ectopic cadherins changed depending on which constructs were expressed. Many crest cells failed to escape from the neural tube when N-cadherin or cad7 was overexpressed. Moreover, none of the cells with these ectopic cadherins migrated along the dorsolateral (melanocyte) pathway. When these samples were stained for Mitf, an early melanocyte marker, positive cells were found accumulated within the neural tube, suggesting that the failure of their migration was not due to differentiation defects. In contrast to these phenomena, cells expressing non-functional cadherins exhibited a normal migration pattern. Thus, the overexpression of a neuroepithelial cadherin (N-cadherin) and a crest cadherin (cad7) resulted in the same blocking effect on neural crest segregation from neuroepithelial cells, especially for melanocyte precursors. These findings suggest that the regulation of cadherin expression or its activity at the neural crest-forming area plays a critical role in neural crest emigration from the neural tube.

Adenoviridae↗

PubMed1999

Differential regulation of epaxial and hypaxial muscle development by paraxis.

In vertebrates, skeletal muscle is derived from progenitor cell populations located in the epithelial dermomyotome compartment of the each somite. These cells become committed to the myogenic lineage upon delamination from the dorsomedial and dorsolateral lips of the dermomyotome and entry into the myotome or dispersal into the periphery. Paraxis is a developmentally regulated transcription factor that is required to direct and maintain the epithelial characteristic of the dermomyotome. Therefore, we hypothesized that Paraxis acts as an important regulator of early events in myogenesis. Expression of the muscle-specific myogenin-lacZ transgene was used to examine the formation of the myotome in the paraxis-/- background. Two distinct types of defects were observed that mirrored the different origins of myoblasts in the myotome. In the medial myotome, where the expression of the myogenic factor Myf5 is required for commitment of myoblasts, the migration pattern of committed myoblasts was altered in the absence of Paraxis. In contrast, in the lateral myotome and migratory somitic cells, which require the expression of MyoD, expression of the myogenin-lacZ transgene was delayed by several days. This delay correlated with an absence of MyoD expression in these regions, indicating that Paraxis is required for commitment of cells from the dorsolateral dermomyotome to the myogenic lineage. In paraxis-/-/myf5-/- neonates, dramatic losses were observed in the epaxial and hypaxial trunk muscles that are proximal to the vertebrae in the compound mutant, but not those at the ventral midline or the non-segmented muscles of the limb and tongue. In this genetic background, myoblasts derived from the medial (epaxial) myotome are not present to compensate for deficiencies of the lateral (hypaxial) myotome. Our data demonstrate that Paraxis is an important regulator of a subset of the myogenic progenitor cells from the dorsolateral dermomyotome that are fated to form the non-migratory hypaxial muscles.

Animals↗

PubMed1980

Variations in the distribution and migration of centriole duplexes in mitotic PtK2 cells studied by immunofluorescence microscopy.

The localization and migration of centriole duplexes have been studied in PtK2 cells by indirect immunofluorescence microscopy using specific tubulin antibodies. The study demonstrated the usefulness of the immunofluorescence technique to quantitate studies of centriole migration and concomitant events such as cytoplasmic microtubule breakdown in large populations of cells. Centriole duplex locations in normal and Colcemid-treated interphase populations have been compared with duplex locations in prophase cells. A higher percentage of duplexes were found close to the nucleus in prophase than in interphase cells, but approximately 5% of the duplexes remained in the cytoplasm far removed from the nucleus in prophase and throughout the course of duplex separation. Duplex separation occurred along a wide variety of paths and duplexes did not have to be closely juxtaposed to the nuclear envelope for separation to occur. Some duplexes separated in the cytoplasm with no detectable nuclear attachment, with spindles forming far to the side of the condensing chromosomes. The timing of duplex separation did not always coincide either with chromosome condensation or with nuclear membrane breakdown, and in a small percentage of the cells separation occurred as late as prometaphase. These data suggest that normal spindle formation can occur despite the large variability in initial and final centriole duplex location, their migration patterns, and the timing of the different events. Breakdown of cytoplasmic microtubules began in prophase and progressed until prometaphase; the last cytoplasmic microtubules disappeared soon after the loss of the nuclear membrane.

Cell Line↗

PubMed1990

Identification and protein kinase C-dependent phosphorylation of alpha-adducin in human fibroblasts.

A protein of Mr approximately 120,000, related to the human erythrocyte membrane skeletal protein alpha-adducin, has been identified by immunological criteria in human fibroblasts. Using similar methods, beta-adducin (an Mr approximately 110,000 protein that forms a dimeric complex with alpha-adducin in the erythrocyte) is not present in fibroblasts. Subcellular distribution studies reveal that fibroblast alpha-adducin is largely associated with the particulate fraction and is most effectively solubilized from that fraction by a combination of nonionic detergent and high salt. Immunocytochemistry of quiescent fibroblasts shows that alpha-adducin is clustered in large perinuclear arrays that may correspond to vesicular structures; weak staining was also found in the sub-plasma membrane region. As in erythrocytes, the phosphorylation of fibroblast alpha-adducin is elevated on exposure of cells to phorbol esters that activate protein kinase C (PK-C). In addition, various mitogens such as serum, bradykinin and vasopressin also stimulate alpha-adducin phosphorylation by a PK-C-dependent pathway. The elevation in alpha-adducin phosphorylation is maintained for up to 30 min after mitogen addition. Peptide maps of phospho-alpha-adducin from both fibroblasts and erythrocytes after PK-C-mediated phosphorylation showed multiple phosphorylated peptides but with dissimilar migration patterns, suggesting divergence of structure around the phosphorylation sites. Adducin appears to play an important role in the regulation of spectrin-actin interactions in the red cell and may play a role in cytoskeletal function in the fibroblasts.

Calmodulin-Binding Proteins↗

PubMed1993

Three rhamnose-binding lectins from Osmerus eperlanus mordax (olive rainbow smelt) roe.

Three rhamnose-binding lectins were purified from the roe of Osmerus eperlanus mordax (olive rainbow smelt) by affinity chromatography and ion-exchange chromatography. The apparent molecular weights of Osmerus eperlanus mordax lectin (OML) -1, -2 and -3 were 25000, 32000 and 26000, respectively, on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) under reducing conditions. On native PAGE, these three lectins showed different migration patterns (Rm value; 0.37, 0.53 and 0.66, respectively). OMLs agglutinated rabbit and human type B erythrocytes and sarcoma 180 cells, but not human type A and O erythrocytes and AH109A cells. The most effective monosaccharide inhibitor was L-rhamnose. L-Mannose and D-galactose were also good inhibitors. Furthermore, OML-induced hemagglutination was inhibited more strongly by melibiose or raffinose rather than lactose or lactulose. Therefore, OMLs are L-rhamnose/alpha-D-galactosyl type lectins. OMLs did not require a detergent, when extracted from crude material, and Ca2+, Mg2+, EDTA and dithiothreitol were not necessary for the OML-induced hemagglutination activities. The OMLs had similar N-terminal amino acid sequences.

Amino Acid Sequence↗

PubMed1993

Capillary-zone electrophoretic analyses of the proteins and amino acid components in cerebrospinal fluid of central nervous system diseases.

Analysis systems for protein and amino acid components in cerebrospinal fluid (CSF) from patients with a variety of central nervous system (CNS) diseases were established employing capillary-zone electrophoresis (CZE). Under the conditions employed, the major proteins in CSF and the concurrent sera were separated into several respective fractions, and in the obtained electropherograms of serum proteins, the % values of areas of each major protein fraction (from gamma-globulin to albumin) were in close accord with those in the densitograms of stained protein bands after electrophoresis on cellulose-acetate strips which had been done as a routine laboratory test in the hospital. Some unusual migration patterns of major proteins were observed in various CNS diseases, and an increase of glutamine in hepatic encephalitis was also detected on the electropherograms. A peak responsible for a minor protein component with the molecular weight of 10000--30000, which was tentatively identified as beta-trace protein, was found to be contained in all the CSF samples examined, and its concentration levels were higher in some patients with cerebral infarction and multiple sclerosis. These results suggest that CZE can become a powerful aid in analyses of the protein and amino acid components in CSF for biochemical diagnosis of CNS diseases.

Amino Acids↗

PubMed2004

Orthovanadate stimulates cAMP phosphodiesterase 3 activity in isolated rat hepatocytes through mitogen-activated protein kinase activation dependent on cAMP-dependent protein kinase.

Orthovanadate (vanadate) as well as insulin stimulated phosphodiesterase 3 (PDE3) in the particulate fraction of rat hepatocytes. The vanadate-induced activations of PDE3 and mitogen-activated protein kinase (MAPK) were inhibited by H-89 and PD98059, suggesting that the MAPK activation via cAMP-dependent protein kinase (PKA) and MAPK kinase is involved in the vanadate action. On the other hand, the insulin-induced activations of PDE3 and Akt were inhibited by wortmannin, suggesting involvement of the Akt activation via phosphatidylinositol 3-kinase (PI3K) in the insulin action. The vanadate-induced activations of PKA and PDE3 were inhibited in part by propranolol or genistein, suggesting that vanadate may exert its actions via dual signaling pathways of beta-adrenergic receptors and receptor tyrosine kinases of growth factors. Vanadate, in contrast to insulin, did not promote the phosphorylation of insulin receptor substrate-1. The vanadate-induced increase in the phosphorylation of a main isoform of MAPKs, p44 protein, was detected by immunoblotting migration patterns of SDS-PAGE. A partially purified PDE3 activity was increased by addition of MAPK or Akt to the reaction mixture, suggesting that MAPK as well as Akt acts upstream of PDE3. The activation of PDE3 by insulin was independent of a transient increase in the MAPK activity, probably due to the dephosphorylated inactivation mediated by the induced activation of MAPK phosphatases (MKPs). Vanadate did not affect the MKP activity. These results indicate that vanadate stimulates the particulate PDE3 activity by activating mainly p44 MAPK via a PKA-dependent process, and that it differs from insulin with regard to a phosphorylation cascade of PDE3 activation.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2004

Migration of warble fly larvae in the yak and optimum timing of ivermectin treatment.

Sixty yaks were autopsied to determine the migration pattern of warble fly larvae. In August, first instars were observed in the body of yak for the first time. These larvae peaked in number in October. From November to February, second instars were detected and their number peaked in January. Third instars appeared in January and peaked in March. Forty-five yaks were administered with ivermectin: 15 animals in September, 15 in October and 15 in November. Between December and June, the number of warbles was checked by palpation. Although some warbles were observed in the September- and November-treated groups, no warbles were detected in the October-treated group. Treatment of yaks with ivermectin was most effective for warble fly in October.

Animals↗

PubMed1983

Biosynthesis of the common precursor to vasopressin and neurophysin in vitro in transplantable human oat cell carcinoma of the lung with ectopic vasopressin production.

Transplantable human oat cell carcinoma cells of the lung with ectopic vasopressin production were incubated with labeled amino acids and immunoreactive neurophysins in cell extracts were analyzed by isoelectric focusing. When the cells were incubated with L-(35S)-cysteine for 20 h, one major peak (isoelectric point; pI=5.3) and several minor peaks (pI=6.1, 5.7, 5.1, 4.9 and 4.7) of labeled proteins were observed. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the relative molecular mass (Mr) of the pI 5.7 protein was estimated to be 20,000 and that of the pI 6.1 species to be 19,000, while the remainder had a Mr of approximately 10,000. The result of the pulse-labeling experiment has clearly shown that the pI 5.7 and 6.1 proteins, which have affinity for concanavalin A, are biosynthetic precursors for the smaller form of neurophysin with a pI 5.3. When subjected to limited proteolysis with trypsin, the pI 5.7 protein generated a Mr 10,000 protein and a smaller peptide. The Mr 10,000 protein thus produced was identified as neurophysin on the basis of its pH-dependent affinity for vasopressin and the migration pattern on isoelectric focusing. The smaller peptide coeluted with synthetic arginine vasopressin and bound to neurophysin suggesting that it possesses a cysteine-tyrosyl sequence at its N-terminus. Similarly, the pI 6.1 protein liberated neurophysin and vasopressin-like peptide after incubation with trypsin. These results suggests that the glycosylated protein with a pI of 5.7 and a Mr of 20,000 is the common precursor to vasopressin and neurophysin in human oat cell carcinoma of the lung with ectopic vasopressin production. The pI 6.1 protein may be an intermediate in the conversion of the precursor to vasopressin and neurophysin.

Carcinoma, Small Cell↗

PubMed1993

Endogenous heterogeneity of relaxin and sequence of the major form in pregnant sow ovaries.

Using an extraction procedure that minimized proteolysis, followed by gel filtration, cation-exchange FPLC, and reverse-phase HPLC, the present study unambiguously showed the presence of multiple isoforms of relaxin in the ovaries of pregnant sows. Four relaxin isoforms were isolated (designated as R-I1, R-I2, R-II1 and R-III1). They had a similar migration pattern on SDS/urea PAGE, and showed no significant difference in biological activity. HPLC separation of the reduced and S-pyridylethylated relaxin variants indicated that R-I1, R-I2 and R-III1 each contained multiple relaxin molecules which showed variability of the B-chain, whereas R-II1 contained mostly a single relaxin molecule with only slight B-chain variability. R-II1 was thus considered likely to be the major form of relaxin stored in the ovary. Sequence analysis revealed that R-II1 contained 22 amino-acid residues in the A-chain and 29 residues in the B-chain, with a total molecular mass of 5814.8 Da. It was thus equivalent to CM-a' relaxin designated by Sherwood and O'Byrne (1974).

Amino Acid Sequence↗

PubMed1986

The isoelectric focusing of creatine kinase variants: I. The heterogeneity of creatine kinase in human heart cytosol and mitochondria.

Creatine kinase isoenzymes in cytosolic and mitochondrial fractions from human cardiac tissues were studied by analytical and preparative isoelectric focusing (IEF), electrophoresis and immunoinhibition. Analytical IEF on agarose gels revealed many creatine kinase variants in human cardiac cytosol prepared by extraction with a hypotonic medium. The bands located at approximately pH 5.5 were shown to contain creatine kinase-MB and minute creatine kinase-BB bands by electrophoresis. Two bands which focused closely together in IEF (pH 6.85-7.0) showed an electrophoretic migration pattern similar to creatine kinase-MM. One of them (IP 6.85) showed a complete inhibition by anti-creatine kinase-M antibodies, whereas the other showed only 50% inhibition. Increasing the salt concentration of tris-HCl (0.1 mol/l) in the extraction medium resulted in additional creatine kinase variants. They were characterized by high alkaline isoelectric points and were not inhibited by anti-creatine kinase-M antibodies. These variants corresponded to two cathodic bands in electrophoresis. The treatment of washed mitochondria with phosphate buffer resulted in a release of mitochondrial variants with different isoelectric points, as shown by analytical IEF in agarose gels. The same pattern was obtained by using preparative IEF. Variants with high alkaline isoelectric points gave rise to two cathodic bands upon electrophoresis. These two bands resembled those present in cytosol after extraction with high salt concentration. No complete inhibition with anti-creatine kinase-M was observed in any of the eluates. The mitochondrial variants exhibited different affinities towards creatine phosphate and ADP. Variants with higher alkaline isoelectric points showed lower Km-values for these substrates than those with less alkaline isoelectric points.

Creatine Kinase↗

PubMed2003

Endocrine gland abnormalities in thalassemia major: a brief review.

Thalassemia major (beta-thalassemia) affects a significant segment of the population in certain areas of the world. Alterations in migration patterns have changed the geographic distribution of this disease and made it a worldwide health problem. Over the course of the past 2-3 decades hypertransfusion therapy has significantly increased the life expectancy, and improved the quality of life of these patients. At the same time there has been an increase in the frequency of complications of this therapy caused by iron overload. Endocrine gland abnormalities contributed little to the morbidity or mortality of beta-thalassemia in the past. As a result of hypertransfusion therapy and increased longevity, however, endocrinopathies have become more common and contribute significantly to morbidity in these patients. In this article we briefly review the current understanding of endocrine gland abnormalities, primarily caused by iron overload, in patients with thalassemia major.

Adrenal Insufficiency↗

PubMed1978

Different behaviour of 19S thyroglobulin extracted from normal thyroid, simple goitre and toxic goitre in polyacrylamide slab gel isoelectric focusing.

19S thyroglobulin (19S TG) was isolated from normal thyroids, simple goitres and one case of toxic goitre (Graves' disease). With isoelectric focusing on polyacrylamide gel slabs (pH 4--6) several bands for each specimen were detected. The migration patterns of the toxic goitre 19S TG were clearly different from the patterns of normal 19S TG and simple goitre 19S TG.

Electrophoresis, Polyacrylamide Gel↗

PubMed1995

Oncogenic mutations of alpha-Gi2 protein are not determinant for human adrenocortical tumourigenesis.

Activating mutations of G proteins, which are membrane signal transducers, have been associated recently with the development of various endocrine neoplasms. Mutations of two highly conserved codons, Arg201 and Gln227, in the alpha-subunit of the Gs protein, the adenylyl cyclase-stimulating protein, were first described in growth hormone-producing pituitary tumours. They resulted in constitutive activation of the alpha s-subunit by decreasing intrinsic GTPase activity. A similar mutation, affecting codon Arg179 (exon 5) in the alpha-subunit of the Gi2 protein, the adenylyl cyclase-inhibiting protein, has been described by a single group in ovarian and adrenocortical tumours. We evaluated the frequency of activating mutations in the alpha-subunit of the Gi2 protein in 18 human adrenocortical tumours. We screened exons 5 (codon Arg179) and 6 (codon gln205) for mutations by denaturing gradient gel electrophoresis analysis of leucocyte and tumoural DNA. No abnormal migration pattern was found in either exon. The absence of mutation in exon 5, which includes the Arg179 codon, was confirmed in all tumoural DNA by direct sequencing. In conclusion, we did not find any oncogenic mutations in the GTPase domain of the alpha-subunit of the Gi2 protein in adrenocortical tumours. Thus, the previously oncogenic gip2 mutations do not appear to be determinant for adrenocortical tumourigenesis.

Adolescent↗

PubMed2001

Novel mutations of the thyroid peroxidase gene in patients with permanent congenital hypothyroidism.

OBJECTIVE: It is suggested that iodide organification defects account for 10% of all cases with congenital hypothyroidism (CH). One candidate gene for these defects is the thyroid peroxidase (TPO) gene. DESIGN: Exons 2, 8-10 and 14 of the TPO gene were examined in 30 patients with permanent CH without a family history of CH. This group was characterized by the presence of an orthotopic thyroid gland and elevated TSH levels. METHODS: The mutational screening was performed by single-strand conformational polymorphism followed by sequence analysis of fragments with abnormal migration patterns and by restriction enzyme analysis. RESULTS: In four patients we were able to identify mutations on both alleles which have not been described so far. One patient was a carrier of a new homozygous point mutation in exon 9 resulting in an exchange from Leu to Pro at codon 458. Another patient was found to be compound heterozygous for two mutations, a 20 bp duplication in exon 2 and a new mutation in exon 9 (Arg491His). Two brothers of consanguineous parents showed a homozygous T deletion in exon 14 at position 2512. CONCLUSIONS: Our findings confirm the genetic heterogeneity of TPO defects and support the suggested prevalence of organification defects.

Congenital Hypothyroidism↗

PubMed2002

Homozygous mutation within the conserved Ala-Phe-Asn-Glu-Thr motif of exon 7 of the LH receptor causes male pseudohermaphroditism.

BACKGROUND: Human chorionic gonadotropin/luteinizing hormone (hCG/LH) function in the male is mediated by the LH receptor (LHR) and is crucial for the normal development of internal and external genitalia. We report a 46, XY patient who presented at the age of 16 with a female phenotype and delayed puberty. Gonads were located bilaterally in the inguinal canal, removed surgically and showed hypoplastic Leydig cells. Immunostaining for the LHR revealed that some Leydig cell progenitors were positive, while others were negative, reflecting different developmental stages of Leydig cell maturation. METHODS AND RESULTS: Molecular analysis of the LHR was performed on DNA extracted from blood samples of the patient, her parents and sister. The 11 exons of the LHR gene were amplified by PCR and subjected to further single stranded conformation polymorphism (SSCP) analysis. Aberrant migration patterns were observed in exon 7. Upon sequencing, a homozygous T to G transversion was identified, resulting in a F194V substitution located in the extracellular domain. The parents and sister were heterozygous carriers of this mutation. Functional studies in transiently transfected COS-7 cells with the F194V LHR mutation showed the lack of cAMP production upon hCG stimulation, indicating complete inactivation of the receptor due to impaired trafficking of the receptor to the membrane. The mutation is located within a stretch of five amino acids Ala (A)-Phe (F)-Asn (N)-Gly (G)-Thr (T), highly conserved in glycoprotein hormone receptors. For the follicle-stimulating hormone (FSH) receptor (FSHR) loss-of-function mutations have been allocated to this region, a homozygous A189V mutation resulting in a resistant ovary syndrome and impaired spermatogenesis and a heterozygous N191I mutation with no apparent phenotype. Further mutational and functional analysis of the AFN region in the LHR and FSHR revealed that the integrity of this amino acid sequence is crucial for receptor function.

Adolescent↗

PubMed2005

Mutation screening of the thyroid peroxidase gene in a cohort of 55 Portuguese patients with congenital hypothyroidism.

OBJECTIVE: Defects in the human thyroid peroxidase (TPO) gene are reported to be one of the causes of congenital hypothyroidism (CH) due to a total iodide organification defect. The aim of the present study was to determine the nature and frequency of TPO gene mutations in patients with CH, characterised by elevated TSH levels and orthotopic thyroid gland, identified in the Portuguese National Neonatal Screening Programme. SUBJECTS AND METHODS: The sample comprised 55 patients, from 53 unrelated families, with follow-up in the endocrinology clinics of the treatment centres of Porto and Lisbon. Mutation screening in the TPO gene (exons 1-17) was performed by single-strand conformational analysis followed by sequencing of fragments with abnormal migration patterns. RESULTS: Eight different mutations were detected in 13 patients (seven homozygotes and six compound heterozygotes). Novel mutations included three missense mutations, namely 391T > C (S131P), 1274A > G (N425S) and 2512T > A (C838S), as well as the predictable splice mutation 2748G > A (Q916Q/spl?). The undocumented polymorphism 180-47A > C was also detected. CONCLUSION: The results are in accordance with previous observations confirming the genetic heterogeneity of TPO defects. The proportion of patients in which the aetiology was determined justifies the implementation of this molecular testing in our CH patients with dyshormonogenesis.

Adolescent↗

PubMed2004

Role of platelet activation in catheter-induced vascular wall injury.

PURPOSE: To investigate the role of smooth muscle cell (SMC) response and platelet activation in peripheral venous catheterization using a model of catheter injury associated with thrombocytopenic treatment. METHODS: Silicon elastic catheters were inserted into New Zealand White rabbit external jugular veins from 24 hours to 60 days. Immunocytochemical procedures with antibodies to differentiation markers specific for SMCs, myofibroblasts, and endothelial cells were used to ascertain the phenotypic features of injured venous SMCs and the tissue sleeve formed around the catheter. Thrombocytopenia was induced in rabbits by busulfan treatment and the effect on catheter injury development examined after 15 days. The putative direct effect of this drug on the venous SMC proliferation, migration, and differentiation was assayed in vitro for 48 hours. RESULTS: Catheter injury is characterized by the progressive formation of (1) a neointima, containing differentiating SMCs, which are derived from the media and adventitial layer, and (2) by the organizing thrombus formed around the catheter, which contains myofibroblasts. In busulfan-treated thrombocytopenic animals, there was no evidence for either neointimal development or thrombus formation. A direct role of this drug in the unresponsiveness of vascular wall can be excluded by the unchanged proliferation and migration pattern of cultured venous SMCs treated with busulfan compared to control cultures. CONCLUSIONS: In our model, accumulation of differentiated SMCs in the neointima and myofibroblast appearance in the thrombus are linked, although distinct, events regulated by platelet activation, which is able to furnish the appropriate microenvironment for vascular SMC recruitment from the media/adventitial layer.

Animals↗