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)

Hepatocyte growth factor (HGF) is the most potent mitogen for mature hepatocytes and seems to act as a hepatotropic factor that has not been purified over the past 30 years. HGF was first purified from rat platelets in 1986. HGF is a hetrodimer molecule composed of 69-kDa alpha-subunit and 34-beta-subunit. In 1989, cDNAs of both human and rat HGF were cloned and primary structure of HGF was determined. HGF is derived from preproprecursor of of 728 amino acids, which is proteolytically processed to form mature HGF. The alpha-chain contains four kringle domains and it has 38% homology with plasmin. HGF mRNA and HGF activity increase markedly in the liver of rats after various liver injuries such as hepatitis, ischemia, physical crush, and partial hepatectomy. Production of HGF in the liver occurs in Kupffer cells and sinusoidal endothelial cells, but not in parenchymal hepatocytes. HGF mRNA is also markedly increased even in the intact lung, kidney, and spleen after injuries of the liver. Therefore, HGF may act as a trigger for liver regeneration through two mechanisms: a paracrine mechanism and an endocrine mechanism. Moreover, HGF mRNA increases markedly in the kidney after various renal injuries, thus it suggests that HGF may act not only as a hepatotropic factor but also as a renotropic factor. HGF receptor with a Kd of 20 to 30 pM is widely distributed in various epithelial cells including hepatocytes. HGF receptor was recently identified as the product of c-met protooncogene, which encodes a 190-kDa transmembrane protein possessing tyrosine kinase domain. HGF has recently been shown to be a pleiotropic factor. HGF stimulates growth of various epithelial cells, including renal tubular cells (Mitogen). It is worth noting that HGF strongly enhances motility of epithelial cells (Motogen) and induces epithelial tubule formation (Morphogen), while it strongly inhibits growth of several tumor cells. All these findings indicate that HGF may have important roles in organogenesis, morphogenesis, carcinogenesis, as well as in organ regeneration.
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PMID:Hepatocyte growth factor: molecular structure, roles in liver regeneration, and other biological functions. 131 69

The following species; superoxide (O2-.), hydrogen peroxide (H2O2), hydroxyl radical (.OH) and singlet oxygen (1O2), are generally called as reactive oxygen species (ROS). These species have been suggested to play important roles in various diseases caused by oxygen toxicity such as ischemia, carcinogenesis, inflammation, diabetes and aging. During the past two decades, considerable interests have been focused on chemical and biological research of ROS. We have also reported about the research results on ROS, which can be classified as following below; 1) chemical reactivities of O2-., 2) formation and toxicity of 1O2, 3) chemical reactivities of .OH, 4) enzyme mechanism of xanthine oxidase, 5) development of the compounds which induce the formation of O2-. and H2O2 in living cells and 6) development of superoxide dismutase mimics. These studies are reviewed from the standpoint of both chemical and biological interests.
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PMID:[Chemical and biochemical studies on reactivities, formations and toxicities of reactive oxygen species]. 164 54

Oxygen in absolutely necessary to life but it is also a toxic gas. 1 to 2% of molecular oxygen undergoes an univalent reduction which produces very reactive and very cytotoxic species. Against them there are different protector antioxidant systems, called scavengers. Pathologically four points are fundamental: Free radicals have a main role in inflammation and fight against bacteria. In carcinogenesis, they have a key role in promotion. The cellular ageing appears to be imputable to a defect of the scavengers. Reflow following ischemia involves toxic free radicals. To prevent the tissue injury due to reperfusion pre treatment by SOD, catalase, allopurinol are at their beginning but the first results are hopeful for skin, kidney, heart and pancreas.
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PMID:[Free radicals]. 301 11

In the normal digestive tract, interaction of the mucosa with a large and varied microbial flora is inevitable. In fact, the "normal" state of the digestive tract reflects the impact of the resident flora to a significant degree. The pathogenesis of various infectious conditions encountered by the surgical pathologist in the gut is understood more readily when the gastrointestinal tract is viewed as a complex ecosystem. Significant disease may result from perturbation of the normal flora, as well as from exogenous infection, and susceptibility of the host may vary with disturbances of the digestive ecosystem. An ecologic perspective is essential in the consideration not only of the "infected" gut, but of conditions as diverse as ischemia or even carcinogenesis in the gastrointestinal mucosa.
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PMID:Surgical pathology of the infected gut. 302 89

Toxic oxygen free radicals have been implicated as important pathologic mediators in many clinical disorders. We discuss the chemistry of oxygen radical production and the roles of iron and of various antioxidants as well as the diseases that have received active attention in oxy-radical research. Particular attention is focused on cigarette smoke oxidants, ischemia-reperfusion-induced radical production, carcinogenesis, and aging. Such research may well provide a firm foundation for therapeutic breakthroughs.
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PMID:Oxygen radicals and human disease. 330 85

Oxidative modification of proteins has been implicated in aging, ischemia reperfusion, carcinogenesis, and other phenomena. Oxidation of the C-2 position of the imidazole ring of histidine converts the residue to 2-oxohistidine, a novel amino acid which may serve as a marker of oxidative modification of proteins (K. Uchida and S. Kawakishi, J. Biol. Chem. 269, 2405-2410, 1994). It has been identified in oxidatively modified proteins by electrochemical detection during reverse-phase high-pressure liquid chromatography, by mass spectrometry, and as the phenylthiohydantoin after Edman degradation, but not by amino acid analysis of protein hydrolysates. We now describe procedures for stabilizing 2-oxohistidine which allow its quantification by routine methods of amino acid analysis. These include classical ion exchange chromatography with postcolumn derivatization by o-phthaldialdehyde, reverse-phase chromatography with precolumn derivatization by o-phthaldialdehyde, and reverse-phase chromatography with precolumn derivatization by 6-aminoquinolyl-N-hydroxysuccinimidyl carbamate. Using these techniques, a previously unidentified amino acid which appears during the oxidative inactivation of glutamine synthetase was shown to be 2-oxohistidine. One picomole of 2-oxohistidine was readily detected in a protein hydrolysate containing 1700 pmol total amino acids.
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PMID:Determination of 2-oxohistidine by amino acid analysis. 859 98

Chemical carcinogens are of two distinct types, DNA-reactive and epigenetic. Testing methodology can be directed toward detecting effects of both types of carcinogen. Carcinogens of the DNA-reactive type are defined by the formation of covalently bound DNA adducts. These chemicals have structures that yield electrophilic reactants either directly or after bioactivation. These agents cause genomic alteration in the structure or function of DNA in the target cell. In addition, these compounds can exert other cellular and tissue epigenetic effects, such as cell proliferation and growth promotion. Carcinogens of the epigenetic (paragenetic) type, in contrast, do not react with DNA, but rather display cellular effects such as neoplasm growth promotion, cytotoxicity, inhibition of tissue growth regulation, peroxisome proliferation, endocrine modification, immunosuppression and/or sustained tissue ischemia that can be the basis for increases in neoplasia. Their chemical structure is such that they do not give rise to a reactive electrophile. The testing methodologies to identify either type follow a Decision Point Approach designed to identify potential carcinogenicity and yield mechanistic information on the production of effects that underlie carcinogenicity. It has 5 stages focusing on the chemical structure, DNA-reactivity, epigenetic effects, limited bioassays and finally the application of the accelerated bioassay (ABA). ABA requires 40 weeks and applies the use of sensitive markers for induction of neoplasia in comparison to positive control compounds for important organs in human carcinogenesis. It enables data acquisition of the entire carcinogenic process directed toward developing mechanistic information. The ABA has the potential to replace the chronic bioassay in rodents in some circumstances and can serve as an alternative to a chronic bioassay in a second species.
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PMID:Chemical carcinogen mechanisms of action and implications for testing methodology. 867 63

Oxidative injury caused by free radicals is an important cause of tissue injury now recognized to occur in inflammation, ischemia and by the action of xenobiotics. It is also recognized to induce gene mutation and promote carcinogenesis. In this review the general concept of nett free radical injury counterbalanced by antioxidants is discussed as oxidative stress. The role of oxidative stress in intestinal ischemia, radiation enteritis, inflammatory bowel disease and the promotion of gastric and colorectal cancer is discussed. The data for the role of oxidative stress in the pathogenesis of ischemic, inflammatory and radiation induced disease are strong, but interventional studies with antioxidants have shown only weak beneficial effects in the above diseases. Therefore the role of antioxidants in the therapy of gastrointestinal diseases remains controversial and should be the subject of controlled trials.
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PMID:Oxidative stress and antioxidants in intestinal disease. 961 34

Evidence continues to accumulate on the importance of neutrophils (PMNs) and phagocytes in the causation of tissue and endothelial injury that frequently accompanies the inflammatory response. Increased production of superoxide anions in combination with decreased endothelial antioxidant activity may contribute to the development of vascular disease including atherosclerosis, vasospasm, diabetic vascular complications, tissue damage in ischemia-reperfusion, and hypotension. Free radicals generated in the vascular wall may act directly on smooth muscle or interact with each other thus producing biologically active endogenous mediators. Derangement of macrophage function may occur in conditions characterized by protein malnutrition, thus leading to failure to develop a specific immunoresponse and to an increase in the production of oxygen intermediate radicals, which may cause tissue damage. A local inflammatory response followed by endothelial cell activation could also facilitate migration of immunocompetent cells into the parenchyma of grafted organs and stimulate dendritic cells in the graft. There is now convincing evidence that excessive and prolonged production of NO contributes to tissue damage in septicemia, ischemia/reperfusion injury, and other inflammatory conditions. There is also increasing evidence that the complement system plays an important role in tissue damage in association with phagocytes, e.g., in ischemia/reperfusion injury, carcinogenesis, and aging. It can therefore be surmised that phagocytic cells may act both as "friends" and as "foes" and that they are important mediators of tissue damage in a variety of conditions.
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PMID:Host tissue damage by phagocytes. 970 69

The formation of reactive oxygen species (ROS), although a normal cellular activity, is considerably enhanced under chronic inflammatory conditions and ischemia. These species have been implicated in various disorders, mutagenesis, carcinogenesis and aging. Of many macromolecules, DNA is the most susceptible to hydroxyl radical, the most reactive of the ROS. The present study is designed to detect oxidative DNA damage in cancer patients and healthy aged humans using an anti-ROS-DNA monoclonal antibody (mAb). Purified calf thymus DNA fragments (approximate size 400 bp) were modified with OH, generated by UV-irradiation (254 nm) of hydrogen peroxide. ROS-modified DNA was characterized by UV-spectroscopy, melting temperature, alkaline sucrose density gradient ultracentrifugation and ion-exchange chromatography. ROS-DNA showed single strand breaks, decrease in Tm, modification of thymine (58.3%) and guanine (20%). The mAb generated against ROS-DNA was characterized for antigen binding specificity by competition ELISA. Monoclonal antibody showed strong binding to ROS-modified DNA, its modified fragments, polynucleotides and bases. With the exception of native DNA, binding of unmodified polynucleotides and bases was much lower. The mAb distinctly recognized DNA samples from lymphocytes of healthy aged humans and gave maximum inhibitions of 49, 53, 64 and 70%, while not reacting with DNA from young population. Similarly, oxidative lesions in DNA from cancer patients were also efficiently recognized by the mAb. DNA from healthy controls served as negative control. The studies demonstrate that the mAb, although cross-reactive, preferentially binds ROS-modified epitopes on DNA. High reactivity of mAb to DNA samples from cancer patients and healthy aged humans indicates increased oxidative stress leading to DNA damage.
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PMID:Immunochemical detection of oxidative DNA damage in cancer and aging using anti-reactive oxygen species modified DNA monoclonal antibody. 992 6


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