Disease relevance of DIC

• Highly immunogenic sublines of L1210 and LSTRA lymphomas were obtained from athymic (nude) mice treated with 4(5)-(3,3-dimethyl-1-triazeno)imidazole-5(4)carboxamide (DIC) in vivo [1].
• HSP induction by 3,4-dichloroisocoumarin is associated with antiviral activity during rhabdovirus infection [2].
• The cause appeared to be dilutional thrombocytopenia in five patients, and DIC in three [3].
• Necrotizing fascitis, shock, DIC, and admission to the intensive care unit were found only among patients infected with GAS [4].
• Furthermore, we found that the influenza C virus esterase was inhibited by isocoumarin derivatives, with 3,4-dichloroisocoumarin being the most potent inhibitor [5].

High impact information on DIC

• Letter: ICF instead of DIC [6]?
• Preincubation with the serine esterase inhibitor 3,4-dichloroisocoumarin blocked fragmentin-induced DNA damage, but had no effect on cytolysin [7].
• Immunologic alteration of the L5178Y lymphoma was obtained in vivo after treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC) [8].
• Adoptive transfer of lymphocytes from spleens of mice sensitized to the drug-altered tumor specifically protected immunosuppressed mice bearing the L5178Y/DIC tumor [8].
• Near simultaneous fluorescence and DIC light microscopy reveals that the amount of gamma-tubulin associated with the centrosome remains relatively constant throughout interphase, suddenly increases during prophase, and then decreases to interphase levels as the cell exits mitosis [9].

Chemical compound and disease context of DIC

• We have evaluated the effect of 1-Deamino-8D-arginine vasopressin (DDAVP) on an experimental model of intravascular coagulation (DIC) induced in rabbits by injection of 20 micrograms kg-1 h-1 during 6 h of E. coli lipopolysaccharide [10].
• In all four cases the syndrome developed in association with noradrenaline administration, sepsis and DIC, despite a high cardiac output and a low calculated systemic vascular resistance index [11].
• The biologic activity of Factor XIII was measured in four groups of patients: 20 with liver cirrhosis, ten with acute DIC, 30 with acute leukemia with DIC, and 20 with acute leukemia without DIC [12].
• It is concluded that additional administration of heparin does not improve the effect of AT III substitution in patients with DIC and that side effects such as thrombocytopenia and an increased blood loss are likely to develop when both substances are given simultaneously [13].
• Cephaloridine treatment of the DIC group was associated with increased BUN levels, proteinuria and diminished renal cortical slice accumulation of organic cations [14].

Biological context of DIC

• When extracellular Ca2+ was chelated by ethylene glycol-bis(beta-aminoethyl ether)-N,N,-tetraacetic acid (EGTA) during coincubation or when the pit cells were preincubated with the granzyme inhibitor 3,4-dichloroisocoumarin (DCI), the induction of apoptosis was abolished [15].
• 3,4-Dichloroisocoumarin, by reacting with the chymotrypsin-like, trypsin-like, and/or PGP-active sites, may promote a conformational change of MPC, rendering the caseinolytic active site accessible to the substrate [16].
• 3,4-Dichloroisocoumarin, the most effective compound, rapidly induces HSF1 DNA binding activity and phosphorylation, leading to transcription and translation of heat shock genes for a period of several hours [2].
• Immunologic cross-reactivity between two DIC-treated leukemic sublines has been demonstrated by cell-mediated immunity in vitro and by active or adoptive immunity in vivo [17].
• The Tctex-1 binding site on DIC was mapped to a 19-residue fragment immediately following the second alternative splicing site of DIC [18].

Anatomical context of DIC

• Anti-L5178Y/DIC lymphocytes did not cure mice challenged with the parent L5178Y tumor [8].
• We have used video-enhanced DIC microscopy to examine the effects of XMAP, a Mr 215,000 microtubule-associated protein from Xenopus eggs (Gard, D.L., and M. W. Kirschner. 1987. J. Cell Biol. 105:2203-2215), on the dynamic instability of microtubules nucleated from axoneme fragments in vitro [19].
• Simultaneous IRM and DIC imaging showed that cytoplasm invaded filopodia when only their tips were closely apposed to a substrate but not when they were closely apposed to a substrate along their entire lengths [20].
• In the other experiments, the ultraviolet output of a pulsed neodymium-YAG laser was focused to a microbeam through a quartz objective lens in epi-illumination mode and used to selectively kill individual unlabeled hair cells while the cells were simultaneously imaged by transmitted light DIC microscopy [21].
• For liver microsomes, the rate of reaction for BIC is greater than that for DIC, but apparently neither rate is fast enough to allow extensive metabolism of large doses of these agents [22].

Associations of DIC with other chemical compounds

• In addition, ERAD is limited in vitro in the presence of the proteasome inhibitors, 3,4-dichloroisocoumarin and lactacystin [23].
• The stimulation of annexin binding following osmotic shock is mimicked by addition of ceramide or purified sphingomyelinase and significantly blunted by genetic (aSM-deficient mice) or pharmacologic (50 microM 3,4-dichloroisocoumarin) knockout of sphingomyelinase [24].
• Likewise, the serine protease inhibitors, N-tosyl-L-phenyl chloromethyl ketone (TPCK) and 3,4-dichloroisocoumarin (DCI), prevented apoptosis, whereas N-tosyl-L-lysine chloromethyl ketone (TLCK), Ac-Leu-Leu-L-norleucinal, Ac-Leu-Leu-L-methional, and trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane were without effect [25].
• The antitumor agents 5-(3,3-dimethyl-1-triazenyl)imidazole-4-carboxamide (DIC) and 5-[3,3-bis(2-chloroethyl)-1-triazenyl]imidazole-4-carboxamide (BIC) are substrates for NADPH-requiring microsomal enzymes of mouse liver [22].
• Cbz-GPFL-CHO inhibited the BrAAP activity with the same Ki both before and after activation of this component by exposure of the MPC to 3,4-dichloroisocoumarin, suggesting that the peptidyl aldehyde is an effective inhibitor of both the overt and latent proteolytic activities of the MPC [26].

Gene context of DIC

• We further demonstrated that Tctex-1 binds directly to the intermediate chain (DIC) of dynein [18].
• Activation of tissue factor-dependent coagulation pathway not adequately balanced by TFPI has important roles in sustaining DIC and systemic inflammatory response syndrome, and it contributes to multiple organ dysfunction syndrome and death [27].
• These results suggest that interleukin-1 and TNF-alpha may play a pivotal role in the pathogenesis of DIC [28].
• Sf9 cells were infected with recombinant baculovirus expressing the cDNA of LSP1 truncates and mutants, and the morphology of infected Sf9 cells was documented by DIC optics [29].
• Generation and characterization of a murine model of a total PC gene inactivation has demonstrated that while an untreated total PC deficiency results in neonatal death through DIC-related abnormalities, a valuable resource is now available to study phenotypes of less severe deficiencies of this protein [30].

Analytical, diagnostic and therapeutic context of DIC

• It was concluded that antigeni( alterations of L5178Y cells occurred in (BALB/ctcr X DBA/2Cr)F1 mice after treatment with DIC in vivo [8].
• The DIC-treated sublines were not rejected by athymic mice, which indicated that the transplantation resistance to these tumors in conventional mice was thymus-cell dependent [1].
• In vitro assays (using biochemical methods, DIC microscopy and electron microscopy) demonstrate that Doublecortin binds microtubules directly, stabilizes them and causes bundling [31].
• Organelle movements were visualized by DIC optics and computer-enhanced video microscopy [32].
• On day 1 of the induction chemotherapy, TFR:AG in the 7 patients with DIC significantly increased to 288.9 +/- 153.1 ng/ml (p less than 0.01), whereas no increase in TFR:AG was recognized in the 3 patients without DIC [33].

References