Background-Endothelial progenitor cells (EPCs) circulate in adult peripheral blood (PB) and contribute to neovascularization. However, little is known regarding whether EPCs and their putative precursor, CD34-positive mononuclear cells (MNC CD34ϩ ), are mobilized into PB in acute ischemic events in humans. Methods and Results-Flow cytometry revealed that circulating MNC CD34ϩ counts significantly increased in patients with acute myocardial infarction (nϭ16), peaking on day 7 after onset, whereas they were unchanged in control subjects (nϭ8) who had no evidence of cardiac ischemia. During culture, PB-MNCs formed multiple cell clusters, and EPC-like attaching cells with endothelial cell lineage markers (CD31, vascular endothelial cadherin, and kinase insert domain receptor) sprouted from clusters. In patients with acute myocardial infarction, more cell clusters and EPCs developed from cultured PB-MNCs obtained on day 7 than those on day 1. Plasma levels of vascular endothelial growth factor significantly increased, peaking on day 7, and they positively correlated with circulating MNC CD34ϩ counts (rϭ0.35, Pϭ0.01). Conclusions-This is the first clinical demonstration showing that lineage-committed EPCs and MNCCD34ϩ , their putative precursors, are mobilized during an acute ischemic event in humans.
Serial changes in serum MMP-2 and plasma MMP-9 were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization.
Background-Endothelial progenitor cells (EPCs) have been identified in adult human peripheral blood. Because circulating EPCs should originate from bone marrow (BM), we examined whether BM mononuclear cells (BM-MNCs) can give rise to functional EPCs and whether transplantation of autologous BM-MNCs might augment angiogenesis and collateral vessel formation in a rabbit model of hindlimb ischemia. Methods and Results-Rabbit BM-MNCs were isolated by centrifugation through a Histopaque density gradient and cultured on fibronectin. EPCs developed from BM-MNCs in vitro, as assessed by acetylated LDL incorporation, nitric oxide (NO) release, and expression of von Willebrand factor and lectin binding. Unilateral hindlimb ischemia was surgically induced in rabbits (nϭ8), and fluorescence-labeled autologous BM-MNCs were transplanted into the ischemic tissues. Two weeks after transplantation, fluorescence microscopy revealed that transplanted cells were incorporated into the capillary network among preserved skeletal myocytes. In contrast, transplanted autologous BM-fibroblasts did not participate in EC capillary network formation (nϭ5). Then, in an additional 27 rabbits, saline (control; nϭ8), autologous BM-MNCs (nϭ13; 6.9Ϯ2.2ϫ10 6 cells/animal), or BM-fibroblasts (nϭ6; 6.5Ϯ1.5ϫ10
Cadherin-11 (cad-11) is a novel member of the cadherin family of cell adhesion molecules, having recently been identified by means of the polymerase chain reaction. To study the function and expression of this molecule, we cloned mouse, cad-11 cDNA. Transfection of L cells with cDNA led them to acquire a typical cadherin-dependent cell-cell adhesiveness, and the L cells expressing cad-11 did not coaggregate with L cells expressing E-, P-, N-, or R-cadherin when they were mixed, indicating that this novel cadherin has a homophilic binding specificity, as found for other cadherins. To determine the developmental expression pattern of this molecule, we performed in situ hybridization analysis on early mouse embryos. Cad-11 first appeared in mesodermal layers only in the head and tail regions at the mid-to-late primitive streak stages. In the head, this appearance was followed by strong expression in mesenchymal tissues including branchial arches. In the trunk, the paraxial mesoderm initially did not express cad-11. However, as the somites formed, they expressed cad-11, and this expression was strictly correlated with their initial condensation and segregation from the presomitic mesoderm. The cad-11 expression in the somites was eventually restricted to sclerotome cells. As the limb buds developed, cad-11 appeared in the distal portion of the limb mesenchyme, and, at later stages, its expression was most evident at the peripheral mesenchyme. Cad-11 was thus expressed by restricted populations of mesenchymal cells in early embryos, although it was also expressed in parts of the neural tube, such as the optic vesicle and dorsal midline, and in part of the otic vesicle. As a step to investigate the role of cad-11 in mesenchymal cell adhesion, we dissociated the limb bud mesenchyme into single cells, pelleted them, and cultured them as aggregates. In these cultures, cad-11-positive cells clearly sorted out of the negative cell population, suggesting that cad-11 might be involved in selective association of mesenchymal cells. For comparison, we studied the expression of N-cadherin and found that the expressions of these two cadherins were differential, and complementary in some tissues. These results suggest that cad-11 is involved in specific associations of subsets of mesenchymal cells and also of some neural cells during early embryogenesis.
Itx in children still is a high-risk procedure but has now become a viable option for children who otherwise have no hope for survival. Control of respiratory infection is of particular importance in the younger children.
. Dual effects of acupuncture on gastric motility in conscious rats. Am J Physiol Regul Integr Comp Physiol 285: R862-R872, 2003; 10.1152/ ajpregu.00715.2002The effects of manual acupuncture on gastric motility were investigated in 35 conscious rats implanted with a strain gauge transducer. Twenty (57.1%) rats showed no cyclic groupings of strong contractions (type A), whereas 15 (42.9%) rats showed the phase III-like contractions of the migrating motor complex (type B) in the fasting gastric motility. Acupuncture at the stomach (ST)-36 (Zusanli), but not on the back [Weishu, bladder (BL)-21], increased the peak amplitude of contractions to 172.4 Ϯ 25.6% of basal in the type A rats (n ϭ 20, P Ͻ 0.05). On the other hand, the motility index for 60 min after the acupuncture was not affected by the acupuncture in this group. On the contrary, acupuncture decreased the peak amplitude and motility index to 72.9 Ϯ 14.0% and 73.6 Ϯ 16.2% in the type B rats (n ϭ 15, P Ͻ 0.05), respectively. The stimulatory and inhibitory effects of acupuncture observed in each type were reproducible on the separate days. In 70% of type A rats, acupuncture induced strong phase III-like contractions lasting for over 3 h that were abolished by atropine, hexamethonium, atropine methyl bromide, and vagotomy. Naloxone significantly shortened the duration of the stimulatory effects from 3.52 Ϯ 0.21 to 1.02 Ϯ 0.15 h (n ϭ 3, P Ͻ 0.05). These results suggest that acupuncture at ST-36 induces dual effects, either stimulatory or inhibitory, on gastric motility. The stimulatory effects are mediated in part via vagal efferent and opioid pathways. vagal nerve; migrating motor complex; stomach-36; opioid ACUPUNCTURE HAS BEEN USED empirically in clinical practice in China for several millennia (59). In November 1997, the National Institutes of Health conducted a consensus conference regarding acupuncture and concluded that acupuncture is an effective treatment for several medical conditions. Although a large number of previous clinical studies support the efficacy of acupuncture for treating gastrointestinal (GI) symptoms and/or diseases (9, 16), little is known about the underlying mechanism(s).It has been demonstrated that the somatosensory inputs from the skin and/or muscle are involved in the control of various autonomic functions (22,26). A series of investigations regarding somato-autonomic reflexes has also been carried out focusing on GI function. In some of those investigations, there is good evidence indicating the importance of cutaneo-sensory inputs in the autonomic control of GI motility. In anesthetized rats, for instance, it has been shown that the cutaneogastric reflexes mediate the inhibition and the stimulation of gastric motility via sympathetic and parasympathetic efferents, respectively (24,28,47). It was shown that the cutaneo-sensory stimulation induced by pinching abdominal skin of rats inhibits gastric motility by increasing sympathetic activity. On the other hand, cutaneo-sensory stimulation induced by pinching the hindlimb enh...
Plasma P-selectin levels after angina increased significantly in patients with unstable angina but did not in patients with stable effort angina. These findings may contribute to understanding of the pathophysiology of the acute coronary syndrome of unstable angina.
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