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 296,593 document(s) hit in 31,850,051 MEDLINE articles (0.02 seconds)

Frequent coitus with several partners or at a very young age carries the greatest risk of cancer of the uterine cervix. Lowest risk is among celibate women and those who live in communities where marriage is stable and where premarital and extramarital coitus is infrequent. All evidence points to the venereal hypothesis of cervical cancer. Herpes simplex virus Type 2 (HSV-2) has been implicated. Immunological defenses, oxygen tension, pH, and hormonal changes in the cervical tissues may also be factors. It has been reported that 15% of women whose cervical smears indicated recent herpes infection had either epithelial dysplasia or carcinoma in situ. In 350 women with squamous cancer of the cervix, antibodies to HSV-2 have been reported to be higher than in controls. As shown by serological evidence to have had HSV-2 infection, among 1500 women studied, dysplasia, carcinoma in situ, or invasive cervical cancer has been reported to have been 5-6 times more frequent than in controls. A diagnosis of HSV-2 infection warrants a fluorescent antibody test of even a virus culture. Patients with a positive test should be checked frequently as they seem to be at considerable risk of developing carcinoma of the uterine cervix.
Br Med J 1976 Mar 20
PMID:Editorial: Herpesvirus and cancer of uterine cervix. 17 80

Extent of O-2-release and chemiluminescence, attributed to singlet oxygen, has been compared in human monocytes and neutrophils during phagocytosis, stimulation by the surface-active agent phorbol myristate acetate, or contact with aggregated IgG in a model of immune complex disease. Monocytes generated O-2-and chemiluminescence with each of the three stimuli, although values were significantly less than those of neutrophils from the same individuals. Lymphocytes had no significant activity in either assay with any stimulus. Oxygen metabolites released from mononuclear phagocytes are highly reactive and could play a part in both the beneficial and detrimental aspects of chronic inflammation.
J Exp Med 1976 Jun 01
PMID:Generation of superoxide anion and chemiluminescence by human monocytes during phagocytosis and on contact with surface-bound immunoglobulin G. 17 24

Isopropylnoradrenaline (ISO), 3',5'-AMP and dibutyryl-3',5'-AMP decreased the oxygen tension (pO2) in the liver and the spleen and increased the body oxygen consumption (VO2). Time dynamics of these two effects was closely correlated for ISO and 3',5'-AMP. An increase of heat output was not accompanied by any significant changes in the respiration coefficient. Pempidine and dihydroergotamine failed to prevent 3',5'-AMP effects; inderal somewhat decreased these effects. Apparently, the catecholamine influence upon pO2 was a result of the VO2 increase through 3'5'-AMP effects are largely direct, but they include the in vivo and beta-receptor component; 2',3'-AMP decreased pO2 and VO2.
Biull Eksp Biol Med 1977 Feb
PMID:[Effect of cyclic nucleotides and isopropylnoradrenaline on oxygen tension and absorption]. 19 82

It has been established that granulocytes generate superoxide (O-2) as well as hydrogen peroxide (H2O2) during phagocytosis. The chemiluminescence (CL) generated by phagocytes appears dependent on these oxygen radicals (or). however, recent studies suggest that oxygen molecules, including singlet oxygen (1O2) or hydroxyl radicals (OH-), may also be generated during phagocytosis and contribute to CL. We have tested this possibility by studying human granulocyte CL in the presence of 0.1 mM sodium azide, a known inhibitor of myeloperoxidase and catalase and a scavenger of 1O2. The effects of azide on CL were correlated with the effects of this compound on hexose monophosphate shunt (hmps) activity, nitroblue tetrazolium (NBT) dye reduction, formate oxidation, and cytochrome c reduction. CL generated by granulocytes during the phagocytosis of zymosan particles was markedly impaired by azide (24% to 47% of control values). On the other hand, phenomena dependent in part on the presence of O2 radicals, i.e., reduction of NBT dye and cytochrome c, were not impaired by the presence of azide. As would be expected, inhibition of catalase by azide virtually abolished the oxidation of formate, but the burst in HMPS activity associated with phagocytosis was augmented further. The latter observation indicated that azide did not impair generation of H2O2 but increased the relative amount detoxified via the HMPS. The experiment provides evidence that radicals other than O-2 and H2O2 are generated during phagocytosis and that these radicals are major contributors to the CL phenomenon.
J Lab Clin Med 1977 Jun
PMID:The effect of sodium azide on the chemiluminescence of granulocytes--evidence for the generation of multiple oxygen radicals. 19 5

We studied the capacity of cultured mouse peritoneal macrophages to generate superoxide anion (O(2-)), the initial product of conversion of oxygen to microbicidal species, during phagocytosis of opsonized zymosan or upon contact with the membrane-active agent phorbel myristate acetate (PMA). Macrophages from mice infected with Bacille Calmette-Guerin (BCG) or injected intraperitoneally with thioglycollate broth or endotoxin, released up to 12 times more O(2-) than did resident peritoneal macrophages, depending upon the cell type and whether the stimulus was zymosan or PMA. There was little if any O(2-) release from resting (unstimulated) macrophages. The density of cells on culture dishes was an important variable since crowding of the dish markedly reduced the efficiency of O(2-) production. The enhanced O(2-) release of chemically elicited and infection-activated macrophages was noted after stimulation with a wide range of concentrations of PMA and zymosan, at all time points studied (up to 120 min), and with cells maintained for 140 rain to 16 days in culture. The O(2-) response of resident cells improved twofold to zymosan and ninefold to PMA during the first 3 days in culture. The capacity to release O~ appears to be limited to actively phagocytic cell types: murine macrophage-like tumor lines and cultured human monocytes released O(2-) when stimulated by PMA or zymosan, fibroblast and endothelial lines and embryo-derived cells did not. Activity of superoxide dismutase, which removes O(2-), was not detectable in culture supernates of any cell type, and thus, differences in detectable O(2-) could not be attributed to variations in the release of this enzyme. We conclude that the phagocytosis- associated respiratory burst is significantly enhanced in mononuclear phagocytes obtained ai~r chemical inflammation or BCG infection. Increased capacity to generate O(2-) and other oxygen radicals during phagocytosis could contribute to the improved microbicidal and tumoricidal activity of activated macrophages.
J Exp Med 1978 Jul 01
PMID:Increased superoxide anion production by immunologically activated and chemically elicited macrophages. 20 22

A mercapto analogue of histidine (1), (RS)-2-mercapto-3-(5-imidazolyl)propionic acid (2), was prepared by treatment of (RS)-2-bromo-3-(5-imidazolyl)propionic acid with trithiocarbonate. Decomposition of the resulting intermediate with hydrochloric acid followed by Sephadex G-15 chromatography permitted isolation of 2 as a hydrobromide complex having unusual stability and properties as evidenced by IR and 1H NMR data. The potency of this complex in inhibiting tissue (Rana catesbiana) collagenase was estimated by radial diffusion assay. The amount of 2 required to produce 50% inhibition was 3.8 +/- 1.5 mM compared to 8.7 +/- 2.5 mM for cysteine. Preliminary tests of oxygen susceptibility, mutagenicity, and toxicity suggest that this substance may warrant study as a therapeutic agent for control of collagenase-linked corneal ulcerations.
J Med Chem 1978 Jul
PMID:Mercaptoimidazolylpropionic acid hydrobromide. Inhibition of tadpole collagenase and related properties. 20 89

The decrease in tyrosinase activity following incubation of melanosomes isolated from mouse melanoma with dopa appeared to be related to the degree of in vitro melanization of melanosomes caused by incubation with dopa. The inactivation similarly occurred in the dopa-tyrosinase reaction system containing ascorbic aicd, although in the presence of ascorbic acid the dopa-quinone is immediately converted back to dopa and therefore melanin formation does not take place. The mode of inactivation of tyrosinase in melanosomes appeared to be similar to the reaction inactivation which is known to occur in the reaction of plant plant tyrosinase. Superoxide anion (O-2) and singlet oxygen (1O2) were estimated but undetectable during the dopa-tyrosinase reaction. Thus the inactivation of tyrosinase is not caused by the reaction products or the oxygen radicals.
Tohoku J Exp Med 1978 Jul
PMID:Nature of tyrosinase inactivation in melanosomes. 21 76

Ethylene formation from the thioethers, beta-methylthiopropionaldehyde (methional) and 2-keto-4-thiomethylbutyric acid by phagocytosing polymorphonuclear leukocytes (PMNs) was found to be largely dependent on myeloperoxidase (MPO). Conversion was less than 10% of normal when MPO-deficient PMNs were employed; formation by normal PMNs was inhibited by the peroxidase inhibitors, azide, and cyanide, and a model system consisting of MPO, H2O2, chloride (or bromide) and EDTA was found which shared many of the properties of the predominant PMN system. MPO-independent mechanisms of ethylene formation were also identified. Ethylene formation from methional by phagocytosing eosinophils and by H2O2 in the presence or absence of catalase was stimulated by azide. The presence of MPO-independent, azide-stimulable systems in the PMN preparations was suggested by the azide stimulation of ethylene formation from methional when MPO-deficient leukocytes were employed. Ethylene formation by dye-sensitized photooxidation was also demonstrated and evidence obtained for the involvement of singlet oxygen (1O2). These findings are discussed in relation to the participation of H2O2, hydroxyl radicals, the superoxide anion and 1O2 in the formation of ethylene by PMNs and by the MPO model system.
J Exp Med 1978 Aug 01
PMID:Ethylene formation by polymorphonuclear leukocytes. Role of myeloperoxidase. 21 2

The acetaldehyde-xanthine oxidase system in the presence and absence of myeloperoxidase (MPO) and chloride has been employed as a model of the oxygen-dependent antimicrobial systems of the PMN. The unsupplemented xanthine oxidase system was bactericidal at relatively high acetaldehyde concentrations. The bactericidal activity was inhibited by superoxide dismutase (SOD), catalase, the hydroxyl radical (OH.) scavengers, mannitol and benzoate, the singlet oxygen (1O2) quenchers, azide, histidine, and 1,4-diazabicyclo[2,2,2]octane (DABCO) and by the purines, xanthine, hypoxanthine, and uric acid. The latter effect may account for the relatively weak bactericidal activity of the xanthine oxidase system when purines are employed as substrate. A white, carotenoid-negative mutant strain of Sarcina lutea was more susceptible to the acetaldehyde-xanthine oxidase system than was the yellow, carotenoid-positive parent strain. Carotenoid pigments are potent 1O2 quenchers. The xanthine oxidase system catalyzes the conversion of 2,5-diphenylfuran to cis-dibenzoylethylene, a reaction which can occur by a 1O2 mechanism. This conversion is inhibited by SOD, catalase, azide, histidine, DABCO, xanthine, hypoxanthine, and uric acid but is only slightly inhibited by mannitol and benzoate. The addition of MPO and chloride to the acetaldehyde-xanthine oxidase system greatly increases bactericidal activity; the minimal effective acetaldehyde concentration is decreased 100-fold and the rate and extent of bacterial killing is increased. The bactericidal activity of the MPO-supplemented system is inhibited by catalase, benzoate, azide, DABCO, and histidine but not by SOD or mannitol. Thus, the acetaldehyde-xanthine oxidase system which like phagocytosing PMNs generates superoxide (O.2-) and hydrogen peroxide, is bactericidal both in the presence and absence of MPO and chloride. The MPO-supplemented system is considerably more potent; however, when MPO is absent, bactericidal activity is observed which may be mediated by the interaction of H2O2 and O.2- to form OH. and 1O2.
J Exp Med 1979 Jan 01
PMID:Bactericidal activity of a superoxide anion-generating system. A model for the polymorphonuclear leukocyte. 21 66

While the previously used displacement reaction of sodim 1-adamantyl oxide on 4-fluoronitrobenzene was applicable to the preparation of 4-(1-adamantyloxy)aniline and several related compounds, certain derivatives were not easily accessible by this route. Thus the recently reported ortho alkylation of anilines and the dicyclohexylcarbodiimide-promoted coupling of 1-adamantanol with phenols were useful in the preparation of aromatic-substituted derivatives. Furthermore, addition of phenylmagnesium bromide to 1-cyanoadamantane provided entry to the 4-(1-adamantylmethyl)aniline series. 4-(1-Adamantyloxy)aniline (3) is herein reported to be a more potent hypobetalipoproteinemic agent than the previously reported bicyclooctyloxy analogue. Replacement of the oxygen atom of 3 with sulfur (74) or methylene (62), but not nitrogen (71), results in active compounds. In the oxygen series derived from 3, the widest scope of substitution on nitrogen resulting in activity is found. The N-ethoxycarbonyl (5), acetyl (6), methyl (12), ethyl (13), N-methyl-N-(2-hydroxyethyl) (19), N-methyl-N-formyl (22), N,N-dimethyl (26), pyrrolidine (14), and piperidine (15) derivatives are active. Aromatic ring substitution also provided the active 3-chloro (44b), 2-fluoro (41b, 42, and 43), and 2-methylthiomethyl (48) compounds. Thus these active compounds are identified for further development as hypobetalipoproteinemic agents.
J Med Chem 1979 Jan
PMID:Hypobetalipoproteinemic agents. 2. Compounds related to 4-(1-adamantyloxy)aniline. 21 7


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