Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apoptotic cells were histochemically demonstrated by the TdT-mediated biotinylated dUTP nick end-labeling (TUNEL) method in formalin-fixed and paraffin-embedded sections of the human endometrium and placental villi. In 53 endometrial biopsy specimens, labeled nuclei were identified in 16 samples showing a desquamating change, associated with menstruation, functional bleeding or adenocarcinoma. Cells in the normal proliferative and secretory phases were unlabeled. The labeled nuclei in the gland and stroma corresponded well to the so-called apoptotic bodies. Placental tissues at various stages of gestation were obtained by spontaneous abortion, intrauterine fetal death or normal delivery. Syncytiotrophoblastic cells in an early gestational stage (7-12 weeks) and in the term placenta were focally labeled, and the labeled cells possessed pyknotic nuclei and densely eosinophilic cytoplasm. In the early gestational chorionic villi with marked hydropic degeneration or in hydatidiform mole, the stromal cells were frequently labeled. Villous cells in coagulation necrosis (infarction) also revealed strong signals. The apoptotic bodies were not recognizable histologically in these labeled villi. The placenta at the 20th to 33rd week of gestation lacked labeling. From a technical point of view, it should be noted that cells in the foci showing ischemia or coagulation necrosis were labeled positively.
 ...
PMID:Apoptotic cells in the human endometrium and placental villi: pitfalls in applying the TUNEL method. 757 70

The CA1 pyramidal neurons in the hippocampus are selectively vulnerable to transient ischemic damage. In experimental animals, the CA1 pyramidal neurons undergo cell death several days after brief forebrain ischemia. It remains, however, unknown whether this delayed neuronal death is necrosis or apoptosis. To investigate the degenerating processes of the CA1 pyramidal neurons in gerbil hippocampus after brief ischemia, lysosomal and nuclear alterations in the cells were examined using immunocytochemistry, in situ nick-end labeling, and Southern blotting. By light and electron microscopy, immunoreactivity for cathepsins B, H, and L, representative lysosomal cysteine proteinases, increased in the CA1 pyramidal neurons 3 d after ischemic insult, which showed cell shrinkage. By morphometric analysis, the volume density of cathepsin B-positive lysosomes markedly increased 3 d after ischemic insult, while that of autophagic vacuole-like structures also increased at this stage, suggesting that cathepsin B-immunopositive lysosomes increasing in the neurons after ischemic insult are mostly autolysosomes. Nuclei of the CA1 neurons were nick-end labeled by biotinylated dUTP mediated by terminal deoxytransferase 3 and 4 d after ischemic insult, but not in the prior stages. Simultaneously, dense chromatin masses appeared in nuclei of the neurons. By Southern blotting, laddering of DNA occurred only in CA1 hippocampal tissues obtained 4 d after ischemic insult. Confocal laser scanning microscopy demonstrated that the fragmented DNA in the CA1 pyramidal layer was phagocytosed by microglial cells. The results suggest that delayed death of the CA1 pyramidal neurons after brief ischemia is not necrotic but apoptotic.
 ...
PMID:Delayed neuronal death in the CA1 pyramidal cell layer of the gerbil hippocampus following transient ischemia is apoptosis. 786 78

The expression of the immediate early genes (IEGs) c-fos and e-jun have been hypothesized to potentially play key roles in mediating cellular responses following injury to the liver. In this study, we sought to evaluate the potential involvement of c-jun and c-fos as determinants either of cellular regeneration or programmed cell death following ischemia/reperfusion (I/R) in mouse liver. To this end, we have analyzed the in situ messenger RNA (mRNA) expression patterns of c-jun and c-fos following lobar I/R in mouse liver. The expression patterns of c-jun and c-fos were correlated with four criteria for tissue repair and injury, including: 1) morphological determinations of regeneration using immunocytochemical detection of proliferating cell nuclear antigen (PCNA), 2) programmed cell death (apoptosis) using the in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method, 3) histopathologic assessment of hepatocellular necrosis, and 4) serum glutamic pyruvic transaminase (GPT) levels. Increasing lengths of lobar ischemia for 3, 60, and 90 minutes followed by reperfusion directly correlated with the extent of liver injury as determined by serum transaminases and hepatocellular necrosis. PCNA expression in the liver was elevated at 1 to 6 hours following liver reperfusion and returned to baseline levels by 20 hours in both ischemic and nonischemic lobes. In contrast, apoptotic responses peaked only in ischemic lobes at 6 hours' postreperfusion and remained elevated out to 20 hours. Two distinct patterns of c-jun and c-fos expression were observed during the acute (1-3 hours) and subacute (6-20 hours) phases of liver responses to I/R including: 1) coexpression of c-jun and c-fos mRNA within damaged regions of the liver at 1 to 3 hours' postreperfusion, and 2) a decline in c-fos expression with sustained high levels of c-jun expression within a subset of cells bordering necrotic/apoptotic regions of the liver at 6 to 20 hours' postreperfusion. These findings suggest that coexpression of both c-jun and c-fos may be involved in mediating early tissue repair processes in liver remodeling following I/R. In contrast, the onset of hepatocellular apoptosis correlated with sustained c-jun expression, in the absence of c-fos, and suggests that these changes in the molecular profile of immediate early gene expression may regulate cellular responses that signal hepatocytes for programmed cell death.
 ...
PMID:Expression of c-fos and c-jun during hepatocellular remodeling following ischemia/reperfusion in mouse liver. 867 76

Focal cerebral ischemia in rats subjected to middle cerebral artery (MCA) occlusion results in apoptotic DNA fragmentation and activation of putative cell death effector genes in neurons and functional impairment of the plexus choroideus. In the present study we investigated whether cerebral ischemia may induce apoptotic cell death in the choroid plexus. Using in situ end-labeling by terminal transferase and fluorescein-dUTP, nuclear DNA breaks were detected in the choroid plexus of the lateral ventricle of the ischemic hemisphere after 6 h but not after 1.5 h of MCA occlusion. Intense cytoplasmic immunostaining for pro-apoptotic Bax protein and moderate immunolabeling for Bcl-X was observed in the epithelium of the choroid plexus of the lateral and third ventricles. However, constitutive expression of Bax and Bcl-X proteins in the plexus choroideus did not change significantly following focal ischemia. Thus, cells of the choroid plexus may die by apoptosis after several hours of cerebral ischemia. Modulation of cell death effector genes of the bcl-2 family however, may not be required for apoptotic cell death to occur.
 ...
PMID:Evidence for apoptotic cell death in the choroid plexus following focal cerebral ischemia. 873 34

In this study we examined the time course of apoptotic cell death after photochemically induced focal ischemia of the rat cerebral cortex. For unequivocal differentiation between apoptosis and necrosis two criteria of programmed cell death were used: terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and morphological evidence of fragmentation and marginalization of nuclei. After photothrombosis, many TUNEL-positive cells were found within the infarct region from 12 h to 3 days. By day 6 they were preferentially located in the boundary zone of the infarct, and by day 14 they had disappeared. A high proportion of TUNEL-positive cells displayed fragmentation or marginalization of their nuclei, indicating apoptosis. Neurons, but not T cells and macrophages, were apoptotic. Inflammatory infiltrates were in close contact to apoptotic neurons throughout the infarct areas at day 1 and in the boundary zone between days 2 and 6 after photothrombosis. In summary, our study shows that neuronal apoptosis after cerebral ischemia is a prolonged process to which leukocyte-derived cytokines may contribute. In contrast to autoimmune diseases of the nervous system, termination of the local inflammatory response after cerebral ischemia does not involve apoptosis.
 ...
PMID:Spatiotemporal relationship of apoptotic cell death to lymphomonocytic infiltration in photochemically induced focal ischemia of the rat cerebral cortex. 887 Aug 27

During cerebral ischemia, nitric oxide (NO) production via stimulation of NO synthase, is likely one of the major events leading to neuronal death. Recently, we have demonstrated that after reversible focal ischemia, apoptosis was implicated in the penumbra whereas necrosis was prominent in the ischemic core. We have now examined the effect of a non-specific inhibitor of NO synthase, NG-nitro-L-arginine methyl ester (L-NAME, 3 ing kg-1 i.p., 5 min and 3 h after the onset of ischemia), on the progress of apoptotic and necrotic nuclei following transient focal cerebral ischemia, using DNA electrophoresis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end labeling (TUNEL assay). Our results indicated that L-NAME prevented the loss of necrotic, but not apoptotic cells.
 ...
PMID:NG-nitro-L-arginine methyl ester reduces necrotic but not apoptotic cell death induced by reversible focal ischemia in rat. 888 9

To clarify the development of tubular necrosis and its healing process in ischemic renal failure observing degeneration, necrosis, cell proliferation and the involvement of apoptosis in the renal tubular epithelial cells before and after renal ischemia in rats through morphological examination. Eight week-old male rats were used for this study. The model for acute renal failure was by obstruction of bilateral renal arteries and veins for 45 minutes in several intervals (0 hr, 1 hr, 3 hr, 6 hr, 12 hr, 24hr, 48 hr, 96 hr, 1 week, 2 weeks and 4 weeks) each following reperfusion. Urinary beta 2-microglobulin (BMG) levels were measured to evaluate renal tubular function. In evaluating tubular necrosis and cell proliferation, observations of renal tubular tissue were made serially by use of light microscopy and immunological staining of proliferating cell nuclear antigen (PCNA) and bromodeoxyuridine (BrdU), respectively. The number of nuclei in the proximal tubular epithelium/circumference of the basement membrane (n/BM index) was calculated using a tissue measuring device. Transmission electron microscopy and the TdT-mediated dUTP-biotin nick end labeling (TUNEL) methods were used as indices of apoptosis. Maximal BMG values were obtained 24 hours after ischemia when injury in the proximal tubular epithelium was most prominent. The maximal number of PCNA and BrdU-positive cells were obtained 24 hours after ischemia and thereafter gradually decreased. The n/BM index in the disorder group was significantly increased 96 hours and 1 week after ischemia (p < 0.001). Electron microscopy revealed nuclear fragmentation and apoptosis in the tubular area indicating that there were significant differences. The number of positive cells for in situ nick end labelling increased 24 hours and 2 weeks after ischemia, exhibiting a two peak curve. However, the number of positive cells significantly decreased 4 weeks after ischemia. In the proximal kidney tubules damaged by reperfusion after ischemia, epithelial hyperplasia developed 3 to 6 days after the most active period of S-phase cells was noted. Thereafter, a decreasing number of epithelial cells was observed. It seemed that the decreasing number of these cells had been produced by apoptosis detected 2 weeks after ischemia.
 ...
PMID:[A pathomorphological study on damage and repair process of tubuli after renal ischemia]. 895 3

We tested the hypothesis that treatment of transient focal cerebral ischemia in rat with antibodies directed against adhesion molecules reduces apoptosis. Rats (n = 31) were subjected to 2 h of middle cerebral artery (MCA) occlusion induced by intraluminal insertion of a nylon monofilament into the internal carotid artery. Upon reperfusion, animals were treated with monoclonal antibodies directed against intercellular adhesion molecule (ICAM)-1) (n = 8) or integrin CD11b/CD18 (n = 10), or administered IgG1 as a control (n = 13). At 48 h after ischemia, animals were killed and the brains analyzed for ischemic cell damage, using hematoxylin and eosin (H/E); apoptosis, using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling (TUNEL) method; and inflammatory cells, using immunohistochemistry with an anti-myeloperoxidase (MPO) antibody. Data revealed a significant reduction in the volume of infarction (p < 0.01) and a decline in the absolute (p < 0.001), and normalized (to the ischemic areas, p < 0.05) numbers of apoptotic cells in both animals treated with anti-ICAM-1 and anti-CD11b antibodies compared to control animals. The numbers of immunoreactive MPO cells were also reduced in the treatment groups compared to those in the control group (p < 0.05). These data suggest that treatment with anti-adhesion molecule antibodies selectively reduce apoptosis, and that a contributing factor to the beneficial effect of antibody treatment for reducing ischemic cell damage may be a reduction in numbers of apoptotic cells.
 ...
PMID:Antibodies against adhesion molecules reduce apoptosis after transient middle cerebral artery occlusion in rat brain. 896 96

Permanent focal cortical ischemia was induced in mice by electrocoagulation of the middle cerebral artery. At different time intervals after the injury, the volume of infarction was assessed together with an analysis of neuronal death. Morphological studies of ischemic brains and detection of nucleosomal DNA ladder within ipsilateral cortices might implicate a component of this neuronal loss to apoptosis as well as necrosis. Furthermore, we used the TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling) procedure to detect in situ DNA fragmentation. The localization and the proportion of apoptotic cells in the ischemic mouse brain would indicate that apoptosis contributes largely to the cellular loss induced by cerebral ischemia.
 ...
PMID:Apoptotic death in cortical neurons of mice subjected to focal ischemia. 897 68

Impaired energy metabolism may play an important role in neuronal cell death after brain ischemia and in late-onset neurodegenerative diseases. Both excitotoxic necrosis and apoptosis have been implicated in cell death induced by metabolic impairment. However, the factors that determine whether cells undergo apoptosis or necrosis are not known. In the present study, metabolic impairment was induced by 3-nitropropionic acid (3-NP), a suicide inhibitor of succinate dehydrogenase. Treatment of cultured rat hippocampal neurons with 3-NP resulted in two types of cell death with distinct morphological, pharmacological, and biochemical features. A rapid necrotic cell death, characterized by cell swelling and nuclear shrinkage, could be completely prevented by the NMDA receptor antagonist MK-801 (10 microM) and dose-dependently potentiated by low micromolar levels of extracellular glutamate. A slowly evolving apoptotic death, characterized by nuclear fragmentation, was not attenuated by MK-801 but was prevented by cycloheximide (1 microg/ml). The combination of MK-801 and cycloheximide resulted in an almost complete protection against 3-NP-induced cell death. DNA fragmentation, detected by the terminal deoxynucleotidyl transferase-mediated dUTP-X 3' nick end-labeling technique, was a late event in apoptosis and also occurred after necrotic cell death. ATP depletion was an early event in the 3-NP-induced neuronal degeneration, and the decline in ATP was exacerbated by glutamate. We conclude that 3-NP triggers two separate cell death pathways: an excitotoxic necrosis as a result of NMDA receptor activation and a delayed apoptosis that is NMDA receptor-independent. Mildly elevated levels of extracellular glutamate shift the cell death mechanism from apoptosis to necrosis.
 ...
PMID:Mechanisms of cell death induced by the mitochondrial toxin 3-nitropropionic acid: acute excitotoxic necrosis and delayed apoptosis. 909 41


1 2 3 4 5 6 7 8 9 10 Next >>