Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report the first direct demonstration that the cytoplasmic transport of organelles and vesicles (collectively called particles) takes place along microtubules. Living keratocytes from the corneal stroma of the frog, Rana pipiens were observed with Allen video-enhanced contrast, differential interference contrast (AVEC-DIC) microscopy [Allen et al, 1981]. In sufficiently thin regions of these cells a network of linear elements was visible. When particles were observed in motion, they always moved along these linear elements. The linear elements remained intact and in focus on the microscope when lysed in a cell lysis solution that stabilized microtubules. Preparations were then fixed in formaldehyde, washed with phosphate-buffered saline (PBS), incubated with rabbit antitubulin, washed with PBS, stained with rhodamine-conjugated goat antirabbit, and washed with PBS. The extracted cells continued to remain in place and in focus on the microscope throughout these procedures. The same cells were then observed using epifluorescence optics and a silicon-intensified target (SIT) video camera. A network of fluorescent linear elements was seen to correspond in number, form, and position to the linear elements seen in the live AVEC-DIC image. Taken together, the AVEC-DIC and fluorescence microscopy observations prove that the linear elements along which particles move are microtubules (MTLEs). The observed particle speeds, pause times, and distances moved varied widely, even for the same particle on the same microtubule. Particles were also observed to switch from one microtubule to another as they were transported. The polarity of the microtubules did not seem to affect the particle direction, since particles were observed to move in both directions on the same MTLE. When not in motion these particles behaved as if anchored to the microtubules since they showed negligible Brownian motion. Finally, it was observed that an elongate particle could move onto two intersecting linear elements such that it was deformed into an inverted "Y" shape. This indicates that there may be more than a single site of attachment between the force generator and the particle.
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PMID:Cytoplasmic transport in keratocytes: direct visualization of particle translocation along microtubules. 660 92

Antithrombin III (AT-III) is the major inhibitor of thrombin, Factor Xa, and other coagulation enzymes. Congenital and acquired deficiencies of AT-III are thought to contribute to thrombosis and disseminated intravascular coagulation. Because a recent report suggested reduced AT III in stored blood, we evaluated blood bank storage effects. Serial samples were taken from 6 units of whole blood drawn into citrate-phosphate-dextrose-adenine over 42 days, and assays for AT-III functional activity were performed on the same day. The values (mean +/- SD) were as follows: day 0,91.8 +/- 10.7 percent; day 2, 101.9 +/- 10.7 percent; day 8, 107.3 +/- 7.4 percent; day 15, 118.9 +/- 11.1 percent; day 22, 105.4 +/- 9.8 percent; day 35, 93.4 +/- 8.8 percent; and day 42, 97.4 +/- 7.5 percent. The rise from day 0 to day 15 was significant but presumably secondary to interassay variation because analysis of frozen aliquots showed no significant change when all samples from each unit were assayed in one batch. Immunoassay of AT-III also showed no change with storage. The results indicate AT-III retains functional activity in whole blood stored at 2 to 6 degrees C for 42 days, and AT-III replacement does not require fresh blood or fresh-frozen plasma. Low values may reflect individual donor differences or dilution of plasma by anticoagulant.
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PMID:Preservation of antithrombin III activity in stored whole blood. 669 39

We found 5 cases of prostatic carcinoma with metastasis with alpha 2 macroglobulin (alpha 2 M) concentration below approximately 40 mg/dl in serum. All these patients had bone metastasis, and none of them had DIC. We found no other cases with such a low concentration of alpha 2 M. Their alpha 2 M level increased to normal level after treatment with transurethral resection of prostate or hormone agents, and the level was correlated with the clinical symptom. During the clinical course, their alpha 2 M level was negatively correlated with prostate-specific antigen (PSA) and prostatic acid phosphate (PAP). All these results suggest that alpha 2 M concentration in serum reflects the severity of prostatic carcinoma with metastasis and that alpha 2 M deficiency is an indicator of metastasis. The acute phase proteins of CRP and serum amyloid A did not increase in spite of the presence of metastasis in these patients with extremely low alpha 2 M level (< 20 mg/dl), suggesting that alpha 2 M is involved in the metabolism of these acute phase proteins. On immunohistochemical studies, their specimens of prostatic carcinoma gave positive stain for PSA and urokinase-type plasminogen activator (u-PA). Both PSA and u-PA formed a complex with alpha 2 M in vitro. The alpha 2 M deficiency in these patients might be due to the complex formation between alpha 2 M and these prostate-originated proteases and to the rapid disappearance of the complex.
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PMID:[Studies on alpha 2 macroglobulin deficiency in association with cancer metastasis]. 910 63

Acute promyelocytic leukaemia (APL) may be associated with disseminated intravascular coagulation, as a result of increased tissue factor (TF) expression and reduced thrombomodulin (TM) expression by APL blast cells. During retinoid acid (RA)- and dibutyryl cAMP (dbcAMP)-induced differentiation of the APL cells, there is a marked up-modulation of both the protein kinase A (PKA) and C (PKC) activities. In order to further assess whether these kinases are intimately associated with both the differentiation process and the regulation of TF and TM expression, we have correlated the modulation of their respective pathways with the extent of differentiation and modulation of these cellular receptors. NB4 cells were incubated with all-trans-RA (ATRA) or dbcAMP for up to 48 h. The contribution of phospholipase C (PLC), inositol phosphate (IP), PKC and PKA in the expression of CD11b, TF and TM was studied by the use of specific inhibitors. Myo-inositol uptake and PKC activity increased in cells induced to differentiate by ATRA but the retinoid did not affect cAMP levels or PKA activity. Under treatment with dbcAMP, PKA activity was increased while inositol uptake and PKC activity remained unchanged. Our results show that the effects of ATRA and dbcAMP on promyelocytic cells are closely related, respectively, to the PLC/IP/PKC and the cAMP/PKA pathways. In cells induced to differentiate by ATRA, CD11b expression seems more closely related to inositol uptake than to PKC activity while the expression of TF and TM show the opposite pattern, which suggests cellular events regulated at a different level within a common signal transduction pathway.
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PMID:Signal transduction pathways underlying the expression of tissue factor and thrombomodulin in promyelocytic cells induced to differentiate by retinoid acid and dibutyryl cAMP. 1143 80

We describe a case of cord blood harvest for autologous transfusion in a neonate weighing 3,992 g with a giant sacrococcygeal teratoma. The umbilical vein was pierced with an 18-gauge needle, and placental blood was withdrawn into two 50-ml syringes filled with 4 ml of citrate-phosphate-dextrose solution. Resection of the sacrococcygeal teratoma was performed on day one. During the operation the infant lost 46 ml of whole blood, more than 15% of the estimated total blood volume, and thus underwent autologous transfusion with 27.8 ml of packed red cells obtained from autologous cord blood. Consequently, she could avoid homologous blood transfusion during the hospital stay. This case highlights the safety of this procedure, with no evidence of consumption coagulopathy, hemolysis or bacterial infection.
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PMID:Autologous cord blood transfusion in an infant with a huge sacrococcygeal teratoma. 1508 99

Although most cellular glutathione (GSH) is in the cytoplasm, a distinctly regulated pool is present in mitochondria. Inasmuch as GSH synthesis is primarily restricted to the cytoplasm, the mitochondrial pool must derive from transport of cytoplasmic GSH across the mitochondrial inner membrane. Early studies in liver mitochondria primarily focused on the relationship between GSH status and membrane permeability and energetics. Because GSH is an anion at physiological pH, this suggested that some of the organic anion carriers present in the inner membrane could function in GSH transport. Indeed, studies by Lash and colleagues in isolated mitochondria from rat kidney showed that most of the transport (>80%) in that tissue could be accounted for by function of the dicarboxylate carrier (DIC, Slc25a10) and the oxoglutarate carrier (OGC, Slc25a11), which mediate electroneutral exchange of dicarboxylates for inorganic phosphate and 2-oxoglutarate for other dicarboxylates, respectively. The identity and function of specific carrier proteins in other tissues is less certain, although the OGC is expressed in heart, liver, and brain and the DIC is expressed in liver and kidney. An additional carrier that transports 2-oxoglutarate, the oxodicarboxylate or oxoadipate carrier (ODC; Slc25a21), has been described in rat and human liver and its expression has a wide tissue distribution, although its potential function in GSH transport has not been investigated. Overexpression of the cDNA for the DIC and OGC in a renal proximal tubule-derived cell line, NRK-52E cells, showed that enhanced carrier expression and activity protects against oxidative stress and chemically induced apoptosis. This has implications for development of novel therapeutic approaches for treatment of human diseases and pathological states. Several conditions, such as alcoholic liver disease, cirrhosis or other chronic biliary obstructive diseases, and diabetic nephropathy, are associated with depletion or oxidation of the mitochondrial GSH pool in liver or kidney.
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PMID:Mitochondrial glutathione transport: physiological, pathological and toxicological implications. 1660 Jan 97

We report a case of rapid progression of bilateral pyothorax exacerbated by viral influenza in an infant. The patient, an 11-month-old girl, was diagnosed with viral influenza, and oseltamivir phosphate was administered. However, after only 4 days the influenza was followed by rapid progression of methicillin-susceptible Staphylococcus aureus (MSSA) pneumonia and pyothorax, resulting in disseminated intravascular coagulation. Because thoracentesis and antibiotics could not control the pyothorax, a serious condition, we performed bilateral video-assisted thoracoscopic decortication on the eighth hospital day. She recovered with excellent lung expansion and was discharged on the 37th hospital day.
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PMID:Successful thoracoscopic treatment of severe bilateral empyema in an infant. 1744 12

Screening of the Arabidopsis thaliana genome revealed three potential homologues of mammalian and yeast mitochondrial DICs (dicarboxylate carriers) designated as DIC1, DIC2 and DIC3, each belonging to the mitochondrial carrier protein family. DIC1 and DIC2 are broadly expressed at comparable levels in all the tissues investigated. DIC1-DIC3 have been reported previously as uncoupling proteins, but direct transport assays with recombinant and reconstituted DIC proteins clearly demonstrate that their substrate specificity is unique to plants, showing the combined characteristics of the DIC and oxaloacetate carrier in yeast. Indeed, the Arabidopsis DICs transported a wide range of dicarboxylic acids including malate, oxaloacetate and succinate as well as phosphate, sulfate and thiosulfate at high rates, whereas 2-oxoglutarate was revealed to be a very poor substrate. The role of these plant mitochondrial DICs is discussed with respect to other known mitochondrial carrier family members including uncoupling proteins. It is proposed that plant DICs constitute the membrane component of several metabolic processes including the malate-oxaloacetate shuttle, the most important redox connection between the mitochondria and the cytosol.
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PMID:Molecular identification of three Arabidopsis thaliana mitochondrial dicarboxylate carrier isoforms: organ distribution, bacterial expression, reconstitution into liposomes and functional characterization. 1803 80

Hitherto, clinical fibrinogen methods were based on coagulation seconds, with assay conditions not similar to a plasma milieu. The fibrinogen functional turbidimetric assay included 50 microL citrated plasma + 100 microL 300 mIU/mL thrombin, 400 microg/mL polybrene, and 6% albumin-phosphate-buffered saline; an increase in absorbance at 405 nm/5 min at room temperature (or 2 minutes at 37 degrees C) was observed. In all, 6% albumin in the fibrinogen functional turbidimetric assay reagent abolishes falsely elevated fibrinogen to fibrin turbidity in hypoproteinemic plasma samples. This assay can detect fibrinogen activity of 250% to 300% of normal, the lower detection limit being 7% of normal (0.2 g/L). The normal range of this assay is 100% +/- 20% (mean value +/- 1 SD; coefficient of variations <4%). This assay imitates fibrinogen to fibrin conversion in clotting blood plasma; it is independent of plasmatic albumin or heparin and can be performed everywhere. This assay has a diagnostic value in pathology-disseminated intravascular coagulation and in assessing risk for atherothrombosis.
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PMID:The fibrinogen functional turbidimetric assay. 1816 May 94

Defining critical points of modulation across heterogeneous clinical syndromes may provide insight into new therapeutic approaches. Coagulation initiated by the cytokine-receptor family member known as tissue factor is a hallmark of systemic inflammatory response syndromes in bacterial sepsis and viral haemorrhagic fevers, and anticoagulants can be effective in severe sepsis with disseminated intravascular coagulation. The precise mechanism coupling coagulation and inflammation remains unresolved. Here we show that protease-activated receptor 1 (PAR1) signalling sustains a lethal inflammatory response that can be interrupted by inhibition of either thrombin or PAR1 signalling. The sphingosine 1-phosphate (S1P) axis is a downstream component of PAR1 signalling, and by combining chemical and genetic probes for S1P receptor 3 (S1P3) we show a critical role for dendritic cell PAR1-S1P3 cross-talk in regulating amplification of inflammation in sepsis syndrome. Conversely, dendritic cells sustain escalated systemic coagulation and are the primary hub at which coagulation and inflammation intersect within the lymphatic compartment. Loss of dendritic cell PAR1-S1P3 signalling sequesters dendritic cells and inflammation into draining lymph nodes, and attenuates dissemination of interleukin-1beta to the lungs. Thus, activation of dendritic cells by coagulation in the lymphatics emerges as a previously unknown mechanism that promotes systemic inflammation and lethality in decompensated innate immune responses.
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PMID:Dendritic cell PAR1-S1P3 signalling couples coagulation and inflammation. 1830 83


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