Possible adhesion molecule with a role in early hematopoiesis by mediating the attachment of stem cells to the bone marrow extracellular matrix or directly to stromal cells. Could act as a scaffold for the attachment of lineage specific glycans, allowing stem cells to bind to lectins expressed by stromal cells or other marrow components. Presents carbohydrate ligands to selectins.
Interacting selectively and non-covalently with any carbohydrate, which includes monosaccharides, oligosaccharides and polysaccharides as well as substances derived from monosaccharides by reduction of the carbonyl group (alditols), by oxidation of one or more hydroxy groups to afford the corresponding aldehydes, ketones, or carboxylic acids, or by replacement of one or more hydroxy group(s) by a hydrogen atom. Cyclitols are generally not regarded as carbohydrates.
Lymphocyte homing to lymph nodes is regulated by transient but specific interactions between lymphocytes and high endothelial venules (HEVs), the initial phase of which is mainly governed by the leukocyte adhesion molecule L-selectin, which recognizes sulfated and sialylated O-linked oligosaccharides displayed on sialomucin core proteins. One of the sialomucin proteins, endomucin, is predominantly expressed in vascular endothelial cells of a variety of tissues including the HEVs of lymph nodes; however, whether it functions as a ligand for L-selectin remains to be formally proven. Here we show that the endomucin splice isoform a is predominantly expressed in PNAd+ HEVs and MAdCAM-1+ HEVs, as seen in non-HEV-type vascular endothelial cells. Using affinity purification with soluble L-selectin, we found that HEV endomucin is specifically modified with L-selectin-reactive oligosaccharides and can bind L-selectin as well as an HEV-specific mAb, MECA-79. Our results also indicated that a 90-100 kDa endomucin species is preferentially decorated with L-selectin-reactive sugar chains, whereas an 80 kDa species represents conventional forms expressed in non-HEV-type vascular endothelial cells in lymph nodes. Furthermore, a CHO cell line expressing endomucin together with a specific combination of carbohydrate-modifying enzymes [core-2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT), alpha-1,3-fucosyltransferase VII (FucTVII) and L-selectin ligand sulfotransferase (LSST)] showed L-selectin-dependent rolling under flow conditions in vitro. These results suggest that when endomucin is appropriately modified by a specific set of glycosyltransferases and a sulfotransferase, it can function as a ligand for L-selectin, and that the endomucin expressed in HEVs may represent another sialomucin ligand for L-selectin.
The transcription factor RUNX1 is essential to establish the haematopoietic gene expression programme; however, the mechanism of how it activates transcription of haematopoietic stem cell (HSC) genes is still elusive. Here, we obtained novel insights into RUNX1 function by studying regulation of the human CD34 gene, which is expressed in HSCs. Using transgenic mice carrying human CD34 PAC constructs, we identified a novel downstream regulatory element (DRE), which is bound by RUNX1 and is necessary for human CD34 expression in long-term (LT)-HSCs. Conditional deletion of Runx1 in mice harbouring human CD34 promoter-DRE constructs abrogates human CD34 expression. We demonstrate by chromosome conformation capture assays in LT-HSCs that the DRE physically interacts with the human CD34 promoter. Targeted mutagenesis of RUNX binding sites leads to perturbation of this interaction and decreased human CD34 expression in LT-HSCs. Overall, our in vivo data provide novel evidence about the role of RUNX1 in mediating interactions between distal and proximal elements of the HSC gene CD34.
Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
Lymphocyte homing to lymph nodes is regulated by transient but specific interactions between lymphocytes and high endothelial venules (HEVs), the initial phase of which is mainly governed by the leukocyte adhesion molecule L-selectin, which recognizes sulfated and sialylated O-linked oligosaccharides displayed on sialomucin core proteins. One of the sialomucin proteins, endomucin, is predominantly expressed in vascular endothelial cells of a variety of tissues including the HEVs of lymph nodes; however, whether it functions as a ligand for L-selectin remains to be formally proven. Here we show that the endomucin splice isoform a is predominantly expressed in PNAd+ HEVs and MAdCAM-1+ HEVs, as seen in non-HEV-type vascular endothelial cells. Using affinity purification with soluble L-selectin, we found that HEV endomucin is specifically modified with L-selectin-reactive oligosaccharides and can bind L-selectin as well as an HEV-specific mAb, MECA-79. Our results also indicated that a 90-100 kDa endomucin species is preferentially decorated with L-selectin-reactive sugar chains, whereas an 80 kDa species represents conventional forms expressed in non-HEV-type vascular endothelial cells in lymph nodes. Furthermore, a CHO cell line expressing endomucin together with a specific combination of carbohydrate-modifying enzymes [core-2 beta-1,6-N-acetylglucosaminyltransferase (C2GnT), alpha-1,3-fucosyltransferase VII (FucTVII) and L-selectin ligand sulfotransferase (LSST)] showed L-selectin-dependent rolling under flow conditions in vitro. These results suggest that when endomucin is appropriately modified by a specific set of glycosyltransferases and a sulfotransferase, it can function as a ligand for L-selectin, and that the endomucin expressed in HEVs may represent another sialomucin ligand for L-selectin.
The multiplication or reproduction of endothelial cells, resulting in the expansion of a cell population. Endothelial cells are thin flattened cells which line the inside surfaces of body cavities, blood vessels, and lymph vessels, making up the endothelium.
Transplantation of human CD34(+) stem cells to ischemic tissues has been associated with reduced angina, improved exercise time, and reduced amputation rates in phase 2 clinical trials and has been shown to induce neovascularization in preclinical models. Previous studies have suggested that paracrine factors secreted by these proangiogenic cells are responsible, at least in part, for the angiogenic effects induced by CD34(+) cell transplantation.
The process whose specific outcome is the progression of an endothelium over time, from its formation to the mature structure. Endothelium refers to the layer of cells lining blood vessels, lymphatics, the heart, and serous cavities,and is derived from bone marrow or mesoderm. Corneal endothelium is a special case, derived from neural crest cells.
Evidence
1:
Inferred from Expression PatternUniProtKB
Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
The aggregation, arrangement and bonding together of a set of components to form an extracellular vesicular exosome, a membrane-bounded vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane.
Transplantation of human CD34(+) stem cells to ischemic tissues has been associated with reduced angina, improved exercise time, and reduced amputation rates in phase 2 clinical trials and has been shown to induce neovascularization in preclinical models. Previous studies have suggested that paracrine factors secreted by these proangiogenic cells are responsible, at least in part, for the angiogenic effects induced by CD34(+) cell transplantation.
The process whose specific outcome is the progression of the glomerular endothelium over time, from its formation to the mature structure. The glomerular endothelium is an epithelial tissue that covers the internal surfaces of the glomerulus.
Evidence
1:
Inferred from Expression PatternUniProtKB
Tohoku J. Exp. Med. 212, 81-90 (2007)[PubMed:17464107]
The process of glomerular development consists of four developmental stages: vesicle (V) stage, S-shaped body (S) stage, capillary loop (C) stage and maturation (M) stage. However, the development of glomerular endothelial, mesangial and epithelial cells in fetal and infant kidneys remains unclear. In order to determine the characteristics of human glomerular development, we investigated the process of glomerular development by staining fetal and infant kidneys for CD31, CD34 and FB21, markers for endothelial cells, alpha-smooth muscle actin (alpha-SMA), a marker for mesangial cells, and nephrin, a marker for podocytes. These series of studies were carried out on kidneys obtained at autopsy from 27 fetuses and 5 infants. The fetuses were divided into the following 5 groups according to gestational age; 13-19, 20-24, 25-29, 30-34 and 35-39 weeks. In each group, glomerular development was classified according to the developmental stage and the staining patterns for CD31, CD34, FB21, alpha-SMA and nephrin. The proportion of V-stage development in 100 glomeruli examined was highest at 13-19 weeks. After 20 weeks, the V-stage proportion decreased gradually, and the proportion of S stage became highest at 20-24 weeks. The C-stage proportion was highest at 25-29 weeks, while the M-stage proportion was highest in infants aged 1-6 months. The staining patterns for CD31, CD34 and FB21 were similar in endothelial cells after 25 weeks of gestation. Staining of alpha-SMA and nephrin was first observed in the S stage. In conclusion, maturation of endothelial cells starts at 25 weeks and is completed by 35 weeks of gestation. Epithelial cells and mesangial cells first appear during the S stage.
The process in which plasma is filtered through the glomerular membrane which consists of capillary endothelial cells, the basement membrane, and epithelial cells. The glomerular filtrate is the same as plasma except it has no significant amount of protein.
Evidence
1:
Inferred from Expression PatternUniProtKB
In ischemic acute kidney injury, renal blood flow is decreased. We have previously shown that reperfused, transplanted kidneys exhibited ischemic injury to vascular endothelium and that preservation of peritubular capillary endothelial integrity may be critical to recovery from ischemic injury. We hypothesized that bone marrow-derived (BMD) endothelial progenitor cells (EPCs) might play an important role in renal functional recovery after ischemia. We tested this hypothesis in recipients of cadaveric renal allografts before and for 2 weeks after transplantation. We found that the numbers of circulating CD34-positive EPCs and CD146-positive endothelial cells (ECs) decreased immediately after ischemia-reperfusion. In renal allograft tissues obtained 1 hr after reperfusion, CD34-positive cells were more frequently observed along the endothelial lining of peritubular capillaries compared with non-ischemic controls. Moreover, 0-17.5% of peritubular capillary ECs were of recipient origin. In contrast, only 0.1-0.7% of tubule cells were of recipient origin. Repeat graft biopsy samples obtained 35 and 73 days after transplant did not contain capillary ECs of recipient origin, whereas 1.4% and 12.1% of tubule cells, respectively, were of recipient origin. These findings suggest that BMD EPCs and ECs may contribute to endothelial repair immediately after ischemia-reperfusion.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
The expansion of a hematopoietic stem cell population by cell division. A hematopoietic stem cell is a stem cell from which all cells of the lymphoid and myeloid lineages develop.
Evidence
1:
Inferred from Mutant PhenotypeUniProtKB
The transcription factor RUNX1 is essential to establish the haematopoietic gene expression programme; however, the mechanism of how it activates transcription of haematopoietic stem cell (HSC) genes is still elusive. Here, we obtained novel insights into RUNX1 function by studying regulation of the human CD34 gene, which is expressed in HSCs. Using transgenic mice carrying human CD34 PAC constructs, we identified a novel downstream regulatory element (DRE), which is bound by RUNX1 and is necessary for human CD34 expression in long-term (LT)-HSCs. Conditional deletion of Runx1 in mice harbouring human CD34 promoter-DRE constructs abrogates human CD34 expression. We demonstrate by chromosome conformation capture assays in LT-HSCs that the DRE physically interacts with the human CD34 promoter. Targeted mutagenesis of RUNX binding sites leads to perturbation of this interaction and decreased human CD34 expression in LT-HSCs. Overall, our in vivo data provide novel evidence about the role of RUNX1 in mediating interactions between distal and proximal elements of the HSC gene CD34.
The process whose specific outcome is the progression of the myeloid and lymphoid derived organ/tissue systems of the blood and other parts of the body over time, from formation to the mature structure. The site of hemopoiesis is variable during development, but occurs primarily in bone marrow or kidney in many adult vertebrates.
Evidence
1:
Inferred from Mutant PhenotypeUniProtKB
The homing and tissue-specific recruitment of bone marrow-derived progenitor cells is a major issue in stem cell research and therapy. Chemokine biology plays a central role in the homing and trafficking of leukocytes. Here we show functional expression of the chemokine receptors CCR1, CCR4, CCR7, CCR10, and CXCR5 on primary isolates of CD34- mesenchymal progenitor cells as well as immortalized mesenchymal stem cell (MSC) lines. Although mRNA expression of CXCR4 was detected in both primary cells and immortalized clones, the receptor was not expressed on the cell surface. On the basis of this expression profile, the MSC could potentially home to secondary lymphatic organs (CCR7, CXCR5), skin (CCR4, CCR10), small intestine (CCR10), and salivary glands (CCR10). To study tissue-specific homing, murine CD34- MSC lines showing concordant chemokine receptor expression were either transiently labeled with CMFDA, or were stably transfected with green fluorescent protein (GFP) expression plasmids. The MSC were then injected into syngeneic healthy mice, and the distribution of the cells determined. The injected cells efficiently homed to spleen, thymus, and lymph nodes. In addition, cells were found in the mucosa of the small intestine, skin, and salivary gland. No significant recruitment to bone marrow, liver, or kidney was seen. Chemokine biology may play an important role in the homeostasis and potentially tissue recruitment of early adult progenitor cells.
The binding of a mesangial cell to the extracellular matrix via adhesion molecules. A mesangial cell is a cell that encapsulates the capillaries and venules in the kidney.
The process in which relatively unspecialized cells acquire specialized structural and/or functional features that characterize the glomerular mesangial cells of the metanephros as it progresses from its formation to the mature state.
Evidence
1:
Inferred from Expression PatternUniProtKB
The paper reports the results of recordings and maps of event-related potentials (ERPs) obtained in normal subjects. ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In normal subjects, topographical distribution of all ERP components is described in detail. Our findings in normals suggest that the early modulation of stimulus-related potentials could be located in primary associative areas, and that N2, P3a, P3b, and SW have different distributions.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA (for protein-coding genes) and the translation of that mRNA into protein. Some protein processing events may be included when they are required to form an active form of a product from an inactive precursor form.
Evidence
1:
Inferred from Mutant PhenotypeUniProtKB
The homing and tissue-specific recruitment of bone marrow-derived progenitor cells is a major issue in stem cell research and therapy. Chemokine biology plays a central role in the homing and trafficking of leukocytes. Here we show functional expression of the chemokine receptors CCR1, CCR4, CCR7, CCR10, and CXCR5 on primary isolates of CD34- mesenchymal progenitor cells as well as immortalized mesenchymal stem cell (MSC) lines. Although mRNA expression of CXCR4 was detected in both primary cells and immortalized clones, the receptor was not expressed on the cell surface. On the basis of this expression profile, the MSC could potentially home to secondary lymphatic organs (CCR7, CXCR5), skin (CCR4, CCR10), small intestine (CCR10), and salivary glands (CCR10). To study tissue-specific homing, murine CD34- MSC lines showing concordant chemokine receptor expression were either transiently labeled with CMFDA, or were stably transfected with green fluorescent protein (GFP) expression plasmids. The MSC were then injected into syngeneic healthy mice, and the distribution of the cells determined. The injected cells efficiently homed to spleen, thymus, and lymph nodes. In addition, cells were found in the mucosa of the small intestine, skin, and salivary gland. No significant recruitment to bone marrow, liver, or kidney was seen. Chemokine biology may play an important role in the homeostasis and potentially tissue recruitment of early adult progenitor cells.
Clin. Cancer Res. 1, 95-9103 (1995)[PubMed:9815891]
Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine tumors has been shown to induce immune suppressive cells having homology with GM progenitor cells. The purpose of this study was to determine if human head and neck cancers secrete GM-CSF, if this is associated with an intratumoral presence of similar cells expressing the hematopoietic progenitor cell antigen CD34, and if such CD34(+) cells suppress functions of intratumoral T cells. This was evaluated with fresh head and neck cancers, and in some instances regional lymph nodes and control tissue. Ten of the 14 squamous cell carcinomas (SCCs) studied secreted greater than 5 ng GM-CSF/g tissue. GM-CSF was not secreted in significant levels by either the other cancer types or by control normal muscle. Each of the high GM-CSF-secreting SCCs, but none of the cancers that did not secrete GM-CSF, contained cells expressing the hematopoietic progenitor cell antigen CD34 that had the capacity to grow into colonies in soft agar. Available regional lymph nodes from patients with high GM-CSF-producing cancers also contained CD34(+) cells. Depletion of CD34(+) cells from dissociated cancers increased interleukin 2 secretion by the intratumoral lymphocytes while addition of the CD34(+) cells to dissociated cancers reduced interleukin 2 production, indicating that the presence of CD34(+) cells within GM-CSF-producing head and neck SCCs results in suppressed functional competence of lymphocytes within the SCCs. These results show that GM-CSF-secreting SCCs contain cells expressing the hematopoietic antigen CD34 which are inhibitory to the capacity of lymphocytes within the SCCs to secrete interleukin 2.
Any process that decreases the rate, frequency or extent of necrotic cell death. Necrotic cell death is a cell death process that is morphologically characterized by a gain in cell volume (oncosis), swelling of organelles, plasma membrane rupture and subsequent loss of intracellular contents.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Any process that stops, prevents, or reduces the frequency, rate or extent of the chemical reactions and pathways resulting in the formation of nitric oxide.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
The transfer of information from one cell to another, where the signal travels from the signal-producing cell to the receiving cell by passive diffusion or bulk flow in intercellular fluid. The signaling cell and the receiving cell are usually in the vicinity of each other.
Transplantation of human CD34(+) stem cells to ischemic tissues has been associated with reduced angina, improved exercise time, and reduced amputation rates in phase 2 clinical trials and has been shown to induce neovascularization in preclinical models. Previous studies have suggested that paracrine factors secreted by these proangiogenic cells are responsible, at least in part, for the angiogenic effects induced by CD34(+) cell transplantation.
Vasculogenesis describes the process by which endothelial precursor cells form new blood vessels. To characterize the topography and the cellular processes underlying vascularization of human dental pulp, we examiend the expression of the human hematopoietic progenitor cell antigen CD34. Dental pulps, obtained from deciduous and permanent teeth, were morphologically examined at light- and electron-microscope levels and by expression of CD34. The findings indicate that vasculogenesis of dental pulp is a complicated process starting from single CD34(+) cells. These subsequently coalesce to form solid vascular cords inside the developing connective tissue, which later hollows. Pericytes were embedded within the fully formed microvessels' basement membrane. The presence of CD34(+) endothelial cells in permanent teeth reveals that the process of vasculogenesis persists into adult life, where it contributes to continuous adjustment of vessel and network structures in response to functional needs and dental tissue homeostasis.
Transplantation of human CD34(+) stem cells to ischemic tissues has been associated with reduced angina, improved exercise time, and reduced amputation rates in phase 2 clinical trials and has been shown to induce neovascularization in preclinical models. Previous studies have suggested that paracrine factors secreted by these proangiogenic cells are responsible, at least in part, for the angiogenic effects induced by CD34(+) cell transplantation.
Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product or products (proteins or RNA). This includes the production of an RNA transcript as well as any processing to produce a mature RNA product or an mRNA (for protein-coding genes) and the translation of that mRNA into protein. Some protein processing events may be included when they are required to form an active form of a product from an inactive precursor form.
Evidence
1:
Inferred from Expression PatternUniProtKB
Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Clin. Cancer Res. 1, 95-9103 (1995)[PubMed:9815891]
Production of granulocyte-macrophage colony-stimulating factor (GM-CSF) by murine tumors has been shown to induce immune suppressive cells having homology with GM progenitor cells. The purpose of this study was to determine if human head and neck cancers secrete GM-CSF, if this is associated with an intratumoral presence of similar cells expressing the hematopoietic progenitor cell antigen CD34, and if such CD34(+) cells suppress functions of intratumoral T cells. This was evaluated with fresh head and neck cancers, and in some instances regional lymph nodes and control tissue. Ten of the 14 squamous cell carcinomas (SCCs) studied secreted greater than 5 ng GM-CSF/g tissue. GM-CSF was not secreted in significant levels by either the other cancer types or by control normal muscle. Each of the high GM-CSF-secreting SCCs, but none of the cancers that did not secrete GM-CSF, contained cells expressing the hematopoietic progenitor cell antigen CD34 that had the capacity to grow into colonies in soft agar. Available regional lymph nodes from patients with high GM-CSF-producing cancers also contained CD34(+) cells. Depletion of CD34(+) cells from dissociated cancers increased interleukin 2 secretion by the intratumoral lymphocytes while addition of the CD34(+) cells to dissociated cancers reduced interleukin 2 production, indicating that the presence of CD34(+) cells within GM-CSF-producing head and neck SCCs results in suppressed functional competence of lymphocytes within the SCCs. These results show that GM-CSF-secreting SCCs contain cells expressing the hematopoietic antigen CD34 which are inhibitory to the capacity of lymphocytes within the SCCs to secrete interleukin 2.
Evidence
2:
Inferred from Expression PatternUniProtKB
Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Vasculogenesis describes the process by which endothelial precursor cells form new blood vessels. To characterize the topography and the cellular processes underlying vascularization of human dental pulp, we examiend the expression of the human hematopoietic progenitor cell antigen CD34. Dental pulps, obtained from deciduous and permanent teeth, were morphologically examined at light- and electron-microscope levels and by expression of CD34. The findings indicate that vasculogenesis of dental pulp is a complicated process starting from single CD34(+) cells. These subsequently coalesce to form solid vascular cords inside the developing connective tissue, which later hollows. Pericytes were embedded within the fully formed microvessels' basement membrane. The presence of CD34(+) endothelial cells in permanent teeth reveals that the process of vasculogenesis persists into adult life, where it contributes to continuous adjustment of vessel and network structures in response to functional needs and dental tissue homeostasis.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
Vasculogenesis describes the process by which endothelial precursor cells form new blood vessels. To characterize the topography and the cellular processes underlying vascularization of human dental pulp, we examiend the expression of the human hematopoietic progenitor cell antigen CD34. Dental pulps, obtained from deciduous and permanent teeth, were morphologically examined at light- and electron-microscope levels and by expression of CD34. The findings indicate that vasculogenesis of dental pulp is a complicated process starting from single CD34(+) cells. These subsequently coalesce to form solid vascular cords inside the developing connective tissue, which later hollows. Pericytes were embedded within the fully formed microvessels' basement membrane. The presence of CD34(+) endothelial cells in permanent teeth reveals that the process of vasculogenesis persists into adult life, where it contributes to continuous adjustment of vessel and network structures in response to functional needs and dental tissue homeostasis.
Any process that modulates the force with which blood travels through the circulatory system. The process is controlled by a balance of processes that increase pressure and decrease pressure.
Multiorgan dysfunction ensuing from severe heatstroke includes hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. We attempted to assess whether human umbilical cord blood-derived CD34+ cell therapy improves survival during experimental heatstroke by attenuating multiorgan dysfunction. Anesthetized rats, immediately after the onset of heatstroke, were divided into 2 major groups and given CD34- or CD34+ cells (1 x 10(5)-5 x 10(5)/mL/kg body weight) i.v. They were exposed to ambient temperature of 43 degrees C to induce heatstroke. Another group of rats were exposed to room temperature (26 degrees C) and used as normothermic controls. Hypotension, hepatic and renal failure (evidenced by increased serum urea nitrogen, creatinine, aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase levels in plasma), hypercoagulable state (evidenced by increased prothrombin time, activated partial thromboplastin time, and D-dimer, and decreased platelet count and protein C in plasma), activated inflammation (evidence by increased TNF-alpha levels in serum), and cerebral dysfunction (evidenced by intracranial hypertension, cerebral hypoperfusion and hypoxia, and cerebral ischemia and injury) were monitored. When the CD34- cell-treated or untreated rats underwent heat stress, their survival time values were found to be 19 to 23 min. Resuscitation with CD34+ cells significantly improved survival time (duration, 63-291 min). As compared with normothermic controls, all CD34- cell-treated heatstroke animals displayed hypotension, hepatic and renal failure, hypercoagulable state, activated inflammation, and cerebral ischemia and injury. However, CD34+ cell therapy significantly caused attenuation of all the above-mentioned heatstroke reactions. In addition, the levels of IL-10 in plasma and glial cell line-derived neurotrophic factors in brain were all significantly increased after CD34+ cell therapy during heatstroke. Our data indicate that CD34+ cell therapy may resuscitate persons who had a heatstroke by reducing multiorgan dysfunction or failure.
The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
Evidence
1:
Inferred from Expression PatternUniProtKB
Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
The multiplication or reproduction of stem cells, resulting in the expansion of a stem cell population. A stem cell is a cell that retains the ability to divide and proliferate throughout life to provide progenitor cells that can differentiate into specialized cells.
Evidence
1:
Inferred from Expression PatternUniProtKB
Recently, accumulating evidence has indicated that bone marrow-derived stem cells are capable of differentiating into vascular cells. It has been hypothesized that the inflammatory response after vascular injury triggers the mobilization of endothelial and smooth muscle progenitor cells from bone marrow.
A homeostatic process involved in the maintenance of an internal steady state within a defined tissue of an organism, including control of cellular proliferation and death and control of metabolic function.
Vasculogenesis describes the process by which endothelial precursor cells form new blood vessels. To characterize the topography and the cellular processes underlying vascularization of human dental pulp, we examiend the expression of the human hematopoietic progenitor cell antigen CD34. Dental pulps, obtained from deciduous and permanent teeth, were morphologically examined at light- and electron-microscope levels and by expression of CD34. The findings indicate that vasculogenesis of dental pulp is a complicated process starting from single CD34(+) cells. These subsequently coalesce to form solid vascular cords inside the developing connective tissue, which later hollows. Pericytes were embedded within the fully formed microvessels' basement membrane. The presence of CD34(+) endothelial cells in permanent teeth reveals that the process of vasculogenesis persists into adult life, where it contributes to continuous adjustment of vessel and network structures in response to functional needs and dental tissue homeostasis.
The conversion of a differentiated cell of one fate into a differentiated cell of another fate without first undergoing cell division or reversion to a more primitive or stem cell-like fate.
Evidence
1:
Inferred from Expression PatternUniProtKB
The paper reports the results of recordings and maps of event-related potentials (ERPs) obtained in normal subjects. ERPs were recorded from 19 scalp electrode derivations using both visual and acoustic paradigms. In normal subjects, topographical distribution of all ERP components is described in detail. Our findings in normals suggest that the early modulation of stimulus-related potentials could be located in primary associative areas, and that N2, P3a, P3b, and SW have different distributions.
Blood vessel formation when new vessels emerge from the proliferation of pre-existing blood vessels and contribute to the series of events that restore integrity to damaged vasculature.
Evidence
1:
Inferred from Expression PatternUniProtKB
In ischemic acute kidney injury, renal blood flow is decreased. We have previously shown that reperfused, transplanted kidneys exhibited ischemic injury to vascular endothelium and that preservation of peritubular capillary endothelial integrity may be critical to recovery from ischemic injury. We hypothesized that bone marrow-derived (BMD) endothelial progenitor cells (EPCs) might play an important role in renal functional recovery after ischemia. We tested this hypothesis in recipients of cadaveric renal allografts before and for 2 weeks after transplantation. We found that the numbers of circulating CD34-positive EPCs and CD146-positive endothelial cells (ECs) decreased immediately after ischemia-reperfusion. In renal allograft tissues obtained 1 hr after reperfusion, CD34-positive cells were more frequently observed along the endothelial lining of peritubular capillaries compared with non-ischemic controls. Moreover, 0-17.5% of peritubular capillary ECs were of recipient origin. In contrast, only 0.1-0.7% of tubule cells were of recipient origin. Repeat graft biopsy samples obtained 35 and 73 days after transplant did not contain capillary ECs of recipient origin, whereas 1.4% and 12.1% of tubule cells, respectively, were of recipient origin. These findings suggest that BMD EPCs and ECs may contribute to endothelial repair immediately after ischemia-reperfusion.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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