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

The Fas/Fas ligand (FasL) system plays an important role in the induction of lymphoid apoptosis and has been implicated in the suppression of immune responses. Recently, there has been renewed interest in immune privilege, as it was shown that two privileged sites (the eye and testes) constitutively express FasL, which kills lymphoid cells that invade these areas. We have established murine FasL-transgenic mice (B6) under the control of the cardiac alpha-myosin heavy chain promotor, and transplanted FasL-expressing F1(B6 x C3H/HeJ) heart grafts into syngeneic (F1) and allogeneic (C3H/HeJ) recipients. FasL-expressing F1 heart allografts placed in C3H/HeJ recipients as well as FasL-expressing F1 isografts placed in nontransgenic and FasL-transgenic F1 were more rapidly rejected, and their survival was much shorter than that of nontransgenic control F1 allografts placed in C3H/HeJ. Native control and FasL-expressing hearts looked normal in mice up to 8 wk of age on hematoxylin-eosin staining. Control heart allografts undergoing ordinally acute rejection showed moderate focal lymphocyte infiltrates, while FasL-expressing F1 allografts and isografts showed massive hemorrhage, edema, and massive neutrophil infiltration as early as 1 day after transplantation. In conclusion, FasL expression and surgical procedure (ischemia/reperfusion) were synergistic in the induction of accelerated heart graft rejection, while allogenicity was not necessary. It may be necessary to find ways of controlling neutrophilic reaction/apoptosis in infiltrating lymphocytes to use FasL in clinical organ transplantation.
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PMID:Accelerated rejection of Fas ligand-expressing heart grafts. 988 28

Hemorrhagic shock (HS) can cause whole body ischemia including the gastrointestinal tract. We investigated whether cells from small intestine Peyer's patches (PP) were capable of producing superoxide radical when animals underwent HS or HS followed by resuscitation (HS/RS). HS was initiated by removing 60% of the blood volume of surgically prepared guinea pigs. PP lymphoid cells were purified and stimulated with phorbol 12-myristate 13-acetate in the presence of spin trap 5-diethoxyphosphoryl-5-methyl-1-pyrroline-N-oxide (DEPMPO). Electron paramagnetic resonance spectra of PP lymphoid cells from sham-treated control, HS, and HS/RS animals produced DEPMPO radical adducts characterized as the adducts of superoxide (DEPMPO/*OOH) and hydroxyl (DEPMPO/*OH) radicals. The formation of both radical adducts was totally inhibited by superoxide dismutase or a nicotinamide adenine dinucleotide phosphate (reduced form) oxidase inhibitor, diphenyleneiodonium chloride. HS/RS increased radical adduct formation, expressed as a percentage control, by 160% and 225% for DEPMPO/*OOH, and DEPMPO/*OH, respectively. When animals were allowed to recover for 24 h post-HS/RS treatment, PP cells decreased the superoxide generation to the same level as controls. Thus, RS following HS may prime PP lymphoid cells for increased nicotinamide adenine dinucleotide phosphate (reduced form) oxidase-dependent superoxide generation, and this process may have cytotoxic and/or immunomodulatory effects on the host.
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PMID:Priming of Peyer's patch lymphoid cells by hemorrhagic shock and resuscitation to produce superoxide radical. 1003 Aug 1

A case of nasal NK/T cell lymphoma with central nervous system (CNS) involvement is reported. A 56-year-old man presented with eyelid edema and transverse myelopathy. Cerebrospinal fluid examination revealed atypical lymphoid cells with azurophilic granules, which were positive for CD2, CD8, and CD56, and negative for CD3 and CD5 by flow cytometry. Because a tumor mass was found involving the ethmoid and maxillary sinuses, CNS involvement was considered to have resulted from local invasion by the nasal lymphoma. In spite of intensive chemotherapy including intrathecal infusion, the patient died 6 months after the initial diagnosis. Autopsy revealed that lymphoma cells were positive for cytotoxic molecules, granzyme B and TIA-1, and EB virus-encoded RNA-1 (EBER-1), and they showed no rearrangement of TCR-beta, -gamma, or -delta genes, suggesting an NK-cell origin of the lymphoma cells. They showed an angiocentric and angiodestructive pattern in the subarachnoid space, focally extending to the cerebral cortex and cranial and spinal nerve roots. Marked demyelination was found in the lateral and posterior funiculi of the spinal cord. Thus, the pathogenesis of this spinal demyelination might be attributed to ischemia secondary to angiocentric and angiodestructive infiltration by lymphoma cells.
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PMID:Nasal NK/T cell lymphoma presenting as transverse myelopathy. 1083 45

Cathepsin D (CD) and cathepsin E are representative lysosomal and nonlysosomal aspartic proteinases, respectively, and play an important role in the degradation of proteins, the generation of bioactive proteins, antigen processing, etc. Recenty, several lines of evidence have suggested the involvement of these two enzymes in the execution of neuronal death pathways induced by aging, transient forebrain ischemia, and excessive stimulation of glutamate receptors with excitotoxins. CD has also been shown to mediate apoptosis induced by various stimuli and p53-dependent tumor suppression. To gain more insight into in vivo functions of CD, mice deficient in this enzyme were generated. The mutant animals showed a progressive atrophy of the intestinal mucosa, a massive destruction of lymphoid organs, and a profound accumulation of ceroid lipofuscin, and developed a phenotype resembling neuronal ceroid lipofucinosis, suggesting that CD is essential for proteolysis of proteins regulating cell growth and tissue homeostasis. It has also been shown that CD molecules secreted from human prostate carcinoma cells are responsible for the generation of angiostatin, a potent endogenous inhibitor of angiogenesis, suggesting its contribution to the prevention of tumor growth and angiogenesis-dependent growth of metastases. Interestingly, pro-CD from human breast carcinoma cells showed a significantly lower angiostatin-generating activity than that from prostate carcinoma cells. Since deglycosylated CD molecules from both carcinoma cells showed a low angiostatin-generating activity, this discrepancy appeared to be attributed to the difference in the carbohydrate structures of CD molecules between the two cell types and to contribute to their potency to prevent tumor growth and metastases.
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PMID:New functional aspects of cathepsin D and cathepsin E. 1121 63

Recently, it has been demonstrated that Secondary Lymphoid-tissue Chemokine (SLC) is constitutively expressed in secondary lymphoid organs and controls the homing of naive T-cells and mature dendritic cells. By screening cDNA isolated from ischemic mouse brain, we found expression of SLC mRNA 6 h up to 4 days after the onset of ischemia. In situ hybridization combined with immunohistochemistry showed neurons expressing SLC mRNA in the ischemic area of the cortex. SLC mRNA expression was also found in cultured neurones after various treatments known to induce neuronal death, but not in cultured glial cells. Stimulation with SLC induced intracellular calcium transients and chemotaxis in cultured microglia. Since mRNA encoding CXCR3, an alternative receptor for SLC, but no CCR7 mRNA was found in microglia, we suggest that the effects of SLC on microglia are mediated by CXCR3. This assumption was corroborated by cross-desensitization experiments using IP-10 as a ligand for CXCR3. The inducible expression of SLC in neurones acting on microglia suggests a new and important role of SLC in the neuroimmune system. We propose that SLC is part of a neurone-microglia signaling system which is related to pathological conditions of the brain like ischemia.
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PMID:Ischemia-induced neuronal expression of the microglia attracting chemokine Secondary Lymphoid-tissue Chemokine (SLC). 1130 61

We have recently described a novel population of CD8+ phagocytes that are strongly recruited to focal ischemic lesions of the rat brain but absent from axotomized central fiber tracts. To assess the relative contribution of infiltrating macrophages and resident microglia to the CD8+ phagocyte response, we selectively depleted peripheral macrophages by systemic administration of dichloromethylene diphosphonate-filled liposomes prior to the induction of permanent ischemia by photothrombosis of cortical microvessels. Macrophage depletion led to a dramatic reduction but not complete abolishment of CD8+ cells in the ensuing infarcts. Systemic administration of monoclonal antibody Ox-8 eliminated CD8+ cells from peripheral lymphoid organs but had no effect on CD8+ phagocytes in the ischemic brain lesions. To further characterize the lesion conditions inducing the recruitment of CD8+ phagocytes, we induced mild focal ischemia by transient occlusion of the middle cerebral artery that leads to a core infarction with ischemic pannecrosis surrounded by areas with selective neuronal cell death. Recruitment of CD8+ phagocytes was restricted to areas of ischemic pannecrosis. In areas undergoing selective neuronal loss microglia up-regulated complement receptor-3, exhibited ED1 immunoreactivity (indicating phagocytic activity), and to some extent expressed CD4, but not CD8 antigens. In conclusion our present study shows that CD8+ phagocytes in focal brain ischemia are predominantly derived from hematogenous macrophages and selectively target to areas of ischemic pannecrosis.
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PMID:CD8+ phagocytes in focal ischemia of the rat brain: predominant origin from hematogenous macrophages and targeting to areas of pannecrosis. 1148 15

An intact innate and acquired immune response are essential for defeating systemic microbial infections. Recognition molecules, inflammatory cells, and the cytokines they produce are the principal means for host tissues to recognize invading microbes and to initiate intercellular communication between the innate and acquired immune systems. However, activation of host innate immunity may also occur in the absence of microbial recognition, through expression of internal "danger" signals produced by tissue ischemia and necrosis. When activation of the innate immune system is severe enough, the host response itself can propel the patient into a systemic inflammatory response syndrome (SIRS), or even multiple system organ failure (MSOF) and shock. Although most patients survive the initial SIRS insult, these patients remain at increased risk of developing secondary or opportunistic infections because of the frequent onset of a compensatory anti-inflammatory response syndrome (CARS). The initial activation of the innate immune response often leads to macrophage deactivation, T-cell anergy, and the rapid apoptotic loss of lymphoid tissues, which all contribute to the development of this CARS syndrome and its associated morbidity and mortality. Initial efforts to treat the septic patient with anticytokine therapies directed at the SIRS response have been disappointing, and therapeutic efforts to modify the immune response during sepsis syndromes will require a more thorough understanding of the innate and acquired immune responses and the increased apoptosis in the lymphoid tissue.
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PMID:Sepsis syndromes: understanding the role of innate and acquired immunity. 1150 71

Pentostatin (2prime prime or minute-deoxycoformycin, dCF) is a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was speculated that pentostatin would be lymphocytotoxic, and this proved to be the case, promoting its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA---e.g., acute lymphocytic leukemia (ALL), particularly its T cell variety. Although pentostatin proved to be active in ALL, large doses were required and toxic effects outweighted therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T cell lymphomas, adult T cell lymphoma-leukemia, and low-grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppression, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppresive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia.
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PMID:Pentostatin (2prime prime or minute-Deoxycoformycin): Clinical Pharmacology, Role In Cancer Chemotherapy, and Future Prospects. 1184 52

Compared to the other organ transplantations, lung and heart-lung transplantations have the following peculiarities: (1) bacterial colonization of the bronchi or lung parenchyma is almost constant because of the contact of donor's and recipient's lungs to the air through the intubation tube; (2) the lung is a particularly fragile organ and sensitive to the hemodynamic modifications in the donor following brain death; (3) the lung is the only organ transplanted without systemic revascularization, which increases the risks of bronchial ischemia, bronchomalacia, and mucociliary dysfunction; and (4) the lung has a large amount of lymphoid tissue, rendering it particularly immunogenic.
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PMID:Human heart, lung and heart-lung transplantation. 1238 79

We studied 56 biopsy samples of conjunctiva and 50 corneal discs excised from 28 patients with acquired keratoconus cornea. The conjunctivas in all biopsy samples showed various stages of immune inflammation. Necrobiotic changes have been revealed in epithelium of the corneal discs going by the pathways of apoptosis--programmed cell death--and oncosis--initial edematic stage of necrobiosis. At the stage of acute inflammation they are due to cytotoxic effect of the lymphocytes, monocytes, and macrophages. Antibody-dependent cytotoxicity mediated by plasma and lymphoid cells predominates at this stage. At the reparative stage of inflammation ischemia, an inductor of apoptosis and oncosis, underlies necrobiotic changes in corneal epithelium.
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PMID:[The causes of necrobiosis and apoptosis of corneal epithelial cells during primary acquired keratoconus]. 1240 Mar 73


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