Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029713 (immaturity)
 4,335 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The reactivity of endothelial cells to putative endothelial cell-specific markers varies with species, with vessel size and with the organ studied. To determine their value in studies of fetal rat lung, and whether organ immaturity would also influence reactivity, we studied endothelial cell immunoreactivity to antibodies against Factor VIII/von Willebrand factor (VIII/vWF), and binding reactivity to Bandeiraea (Griffonia) simplicifolia 1 lectin (BSL 1) during rat fetal lung development. Using an indirect immunofluorescent technique to detect Factor VIII/von Willebrand factor (VIII/vWF), endothelial cells lining the aortic arches were identified as early as day 11 of gestation (term = 22 days), prior to lung development. Immunoreactivity to VIII/vWF was subsequently localized to intrapulmonary endothelial cells and was not dependent on vessel size. In contrast, binding reactivity of FITC-conjugated BSL 1 was observed to both endothelial cells and to the basement membrane of developing airways, thus limiting its value as endothelial cell marker. During very early lung development solitary angioblasts could not be identified by reactivity to either VIII/vWF antibodies or to BSL 1, and neither marker appears to be of value for studies of early angiogenic events.
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PMID:Ontogeny of reactivity to endothelial cell markers during development of the embryonic and fetal rat lung. 145 80

Intraventricular hemorrhage (IVH) in premature infants may be related to the immaturity of the vascular bed in the germinal matrix. We measured six hemostatic parameters whose alterations may represent an additional risk factor for IVH in preterm infants. On postnatal day 1 there were differences between plasminogen activator inhibitor-1 (PAI-1) activity and antigen, of both full-term and preterm infants with and without IVH (P < 0.05). Preterms with IVH were different to both full-terms and preterms without IVH. No difference was observed in plasma concentrations of fibrinogen, plasminogen and von Willebrand factor. Plasma concentrations of antithrombin III were significantly higher in full-term infants than in preterm infants. The difference between the platelet counts of preterm infants with and without IVH was not significant (P > 0.05). Elevation of crosslinked fibrin degradation products (XDP), determined by the SimpliRED D-dimer test, correlated in four out of five premature infants with the diagnosis of IVH by ultrasonography. No elevation of D-dimer XDP was observed in premature infants without IVH (11/12) and full-term infants (6/6). In conclusion, a hypercoagulable state, indicated by a rise in D-dimer XDP, may be initiated by some types of trauma to fragile blood vessels of the preterm infants who develop IVH. This hypercoagulability is further exacerbated by the increased release of PAI-1 leading to suppressed fibrinolysis.
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PMID:Intraventricular haemorrhage in preterm infants: evidence of suppressed fibrinolysis. 873 35

Cell differentiation markers on placental villi from the first trimester of human pregnancy have been studied by indirect immunofluorescence. Fluorescence labelling with antibodies against CD34 and CD31 was conspicuous in the vascular cells. The vascular paracellular clefts were labelled by anti-cadherin-5. A few vascular cells exhibited a positive reaction for von Willebrand factor, high-molecular-weight melanoma-associated-antibody and alpha-sm-actin compared to term pregnancy, indicating changes in protein expression during vascular differentiation. The poor anti-collagen IV reaction and the absence of a sm-myosin fluorescent signal observed around the vessels confirned the immaturity of the vessels. In contrast, strong reactions have previously been obtained with the latter antibodies in similar locations using term placental villi. A labelling was observed for antibodies against alpha3 and alpha5 integrins in these immature placental vessels suggesting cell-matrix interactions with specific domains of laminin or fibronectin. The vascular cells were also stained by anti-CD26. Surprisingly, the fetal vascular cells exhibited immunostainings in common with the villous cytotrophoblast (CD26) or the syncytiotrophoblast (cadherin-5) and cell islands cytotrophoblast (CD31, cadherin-5, alpha3 and alpha5 integrin subunits). These observations suggested a two step process for fetal vasculogenesis in the villi: i/ the formation of peripheral vessels induced by growth factors or cytokines derived from the nearby trophoblast, ii/ the development of muscular vessels due to growth factors or cytokines production induced by circulatory changes.
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PMID:Characterization of first trimester human fetal placental vessels using immunocytochemical markers. 1193 78

Menorrhagia at the time of menarche is relatively common and historically attributed primarily to immaturity of the pituitary-ovarian-uterine axis. Intuitively, a proportion of these patients should have an underlying disorder of haemostasis, given the 5-20% prevalence of von Willebrand's disease and the > or =20% prevalence of platelet dysfunction in light of recent epidemiological studies in menorrhagia, although the average age of the patients in those studies has been approximately 35 years. However, there are a few comprehensive studies in the adolescent population determining whether widespread haemostasis evaluation should be carried out in adolescents presenting with menorrhagia. A retrospective chart review study of disorders of haemostasis was carried out in 61 consecutive adolescent patients, ages 11-19 at the time of evaluation referred to the Hemophilia Treatment Center (HTC)/Hematology unit. The mean and median ages were 15 +/- 2.2 and 14 years (11, 19), respectively. Standard evaluation included complete blood count, prothrombin time, partial thromboplastin time, von Willebrand factor (VWF) levels and platelet aggregation. The proportion of patients with VWF deficiency was 22/61 (36%) [95% confidence interval (CI), 24-49%]; the proportion of patients with platelet aggregation abnormalities was 4/61 (7%) (95% CI, 2-16%). There was no difference in the frequency of additional muco-cutaneous bleeding symptoms. A relatively high proportion of adolescents are identified with an underlying disorder of haemostasis when referred to an HTC for evaluation of menorrhagia. This involves in part a selective referral bias, but underscores the role of the HTC in evaluating adolescents referred with menorrhagia for an underlying bleeding disorder, given the relatively high yield of haemostatic disorders detected in this setting.
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PMID:The prevalence of disorders of haemostasis in adolescents with menorrhagia referred to a haemophilia treatment centre. 1788 Apr 54

Embryoid bodies (EBs) generated during differentiation of human embryonic stem cells (hESCs) contain vascular-like structures, suggesting that commitment of mesoderm progenitors into endothelial cells occurs spontaneously. We showed that bone morphogenetic protein 4 (BMP4), an inducer of mesoderm, accelerates the peak expression of CD133/kinase insert domain-containing receptor (KDR) and CD144/KDR. Because the CD133(+)KDR(+) population could represent endothelial progenitors, we sorted them at day 7 and cultured them in endothelial medium. These cells were, however, unable to differentiate into endothelial cells. Under standard conditions, the CD144(+)KDR(+) population represents up to 10% of the total cells at day 12. In culture, these cells, if sorted, give rise to a homogeneous population with a morphology typical of endothelial cells and express endothelial markers. These endothelial cells derived from the day 12 sorted population were functional, as assessed by different in vitro assays. When EBs were stimulated by BMP4, the CD144(+)KDR(+) peak was shifted to day 7. Most of these cells, however, were CD31(-), becoming CD31(+) in culture. They then expressed von Willebrand factor and were functional. This suggests that, initially, the BMP4-boosted day 7, CD144(+)KDR(+)CD31(-) population represents immature endothelial cells that differentiate into mature endothelial cells in culture. The expression of OCT3/4, a marker of immaturity for hESCs decreases during EB differentiation, decreasing faster following BMP4 induction. We also show that BMP4 inhibits the global expression of GATA2 and RUNX1, two transcription factors involved in hemangioblast formation, at day 7 and day 12.
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PMID:A boost of BMP4 accelerates the commitment of human embryonic stem cells to the endothelial lineage. 1954 43

Differentiation of human-induced pluripotent stem cells (hiPSCs) into vascular endothelium is of great importance to tissue engineering, disease modeling, and use in regenerative medicine. Although differentiation of hiPSCs into endothelial-like cells (hiPSC-derived endothelial cells [hiPSC-ECs]) has been demonstrated before, controversy exists as to what extent these cells faithfully reflect mature endothelium. To address this issue, we investigate hiPSC-ECs maturation by their ability to express von Willebrand factor (VWF) and formation of Weibel-Palade bodies (WPBs). Using multiple hiPSCs lines, hiPSC-ECs failed to form proper VWF and WPBs, essential for angiogenesis, primary and secondary homeostasis. Lowering the increased intracellular pH (pHi) of hiPSC-ECs with acetic acid did result in the formation of elongated WPBs. Nuclear magnetic resonance data showed that the higher pHi in hiPSC-ECs occurred in association with decreased intracellular lactate concentrations. This was explained by decreased glycolytic flux toward pyruvate and lactate in hiPSC-ECs. In addition, decreased expression of monocarboxylate transporter member 1, a member of the solute carrier family (SLC16A1), which regulates lactate and H+ uptake, contributed to the high pHi of hiPSC-EC. Mechanistically, pro-VWF dimers require the lower pH environment of the trans-Golgi network for maturation and tubulation. These data show that while hiPSC-ECs may share many features with mature EC, they are characterized by metabolic immaturity hampering proper EC function.
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PMID:Lowering the increased intracellular pH of human-induced pluripotent stem cell-derived endothelial cells induces formation of mature Weibel-Palade bodies. 3216 24