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

Endocytosis of pigeon beta migrating very-low-density lipoprotein (beta VLDL) by monocyte-derived macrophages (monocyte/macrophages), cultured from Random Bred White Carneau (RBWC) pigeons, occurs by both coated and non-coated regions of the plasma membrane (Henson et al.: Exp. Mol. Pathol. 51:243-263, 1989). Secondary to binding, the beta VLDL is translocated to lysosomes for degradation. Ultimately these events lead to foam cell formation in vitro. Utilizing video-enhanced contrast light microscopy in conjunction with whole mount intermediate-voltage transmission electron microscopy (IVEM) and high-resolution scanning EM, the dynamics of beta VLDL binding have been correlated with ultrastructure. Beta VLDL conjugated to gold colloids was visualized at the surface of living cells by using Allen video-enhanced contrast-differential interference contrast microscopy (AVEC-DIC). Subsequent to AVEC-DIC, direct observation of the identical cells by IVEM and SEM was facilitated through the use of gold finder grids, and these EM observations confirmed identification of the video-observed beta VLDL particles. Upon addition of beta VLDL, pigeon monocyte/macrophages underwent gross morphological changes. These changes were recorded by video as movements at the cytoplasmic periphery, and the movements involved extension of microvilli, expression of retraction fibers, and elaboration of membrane ruffles. When secondarily observed by stereo (3-D) IVEM and SEM, the identification of microvilli, retraction fibers, and membrane ruffles was confirmed and the lipoprotein-gold conjugates were associated with these ligand-induced membrane structures. Beta VLDL-gold conjugates were also associated with pit-like regions at the base of microvilli, while at the base of ruffles, beta VLDL-gold conjugates were located in membrane invaginations and cytoplasmic vesicles.
 ...
PMID:Beta VLDL uptake by pigeon monocyte-derived macrophages: correlation of binding dynamics with three-dimensional ultrastructure. 187 84

Sequestration of activated polymorphonuclear leukocytes (PMN) within the lung microcirculation may contribute to pulmonary vascular injury following trauma, sepsis, or disseminated intravascular coagulation. In this study cultured rat endothelial cells were utilized to evaluate the effect of PMN activation on endothelial cell attachment. The concept that disruption of the extracellular fibronectin matrix is associated with altered endothelial cell adhesion was also tested. Rat endothelial cells were grown in culture and identified by morphological techniques as well as immunofluorescent staining of Factor VIII R:Ag. Endothelial cells were labeled with 51Cr in order to establish a cell injury assay based on release of free 51Cr or cell-associated 51Cr. PMN activation was verified microscopically and by chemiluminescence activity following phorbol myristate acetate (PMA) or opsonized zymosan exposure. Following incubation with PMA, the leukocytes aggregated, chemiluminesced vigorously, and caused endothelial cell injury and detachment as determined by release of 51Cr-labeled endothelial cells. PMNs exposed to serum-treated zymosan exhibited a more modest chemiluminescence burst which was consistent with their decreased activity to injure the endothelial monolayer. With PMA activation the degree of endothelial detachment from the monolayer increased as a function of time with a plateau observed by 3 hr. Microscopic immunofluorescent analysis of extracellular fibronectin in endothelial cell cultures revealed disruption of the fibrillar matrix fibronectin after incubation with PMA-activated neutrophils in association with endothelial cell disadhesion. Thus, exposure of activated rat PMN to rat endothelial cells in culture induces endothelial damage and an associated disruption of the fibronectin matrix which may contribute to endothelial cell detachment.
Exp Mol Pathol 1986 Aug
PMID:Matrix fibronectin disruption in association with altered endothelial cell adhesion induced by activated polymorphonuclear leukocytes. 309 67

The aim of this study is to qualify the application the new microscopic methods fluorescence and AVEC-DIC (Allen video-enhanced contrast differential interference contrast) microscopy for toxicity testing. The effects of 2-OH-ethyl methacrylate (HEMA), a toxic acrylic monomer, on human fibroblasts was tested. The HEMA concentrations used were 0.01-1% at incubation times of 1-24 h. The cells were observed with AVEC-DIC microscopy and fluorescent staining to evaluate the velocity of lysosomal movement, the number and morphology of the mitochondria, and the fine structure of the cell. In the samples treated with the toxic compound the lysosomal movement changed, as did the morphology of the mitochondria and of the whole cells. The results are compared and discussed with regard to the results of conventional cytotoxicity tests performed in parallel. The new methods proved to be more sensitive and yielded more specific information on the cellular changes caused by the compound.
Mol Toxicol
PMID:New methods for cytotoxicity testing: quantitative video microscopy of intracellular motion and mitochondria-specific fluorescence. 350 95

Patients with liver failure can present both thrombotic and hemorrhagic complications because of the deficiency in coagulation factors and inhibitors (protein C and S, antithrombin III) and impairment of fibrinolytic balance. Here we report the case of a 63-year-old man with liver cirrhosis, recurrent thrombosis, and features of low-grade consumption coagulopathy, showing severe antithrombin III deficiency (about 30% of normal values). Treatment with antithrombin III (2000 U/day) and low doses of heparin (5000 U b.i.d.) was successful in modulating the coagulation system toward an antithrombotic effect. After discharge from hospital the ambulatory treatment with antithrombin III concentrates (2000 U twice a week) allowed the attainment of antithrombin III activity of about 60% and prevented the patient from recurrence of venous thrombosis.
J Mol Med (Berl) 1995 Feb
PMID:Modulation of hemostatic balance with antithrombin III replacement therapy in a case of liver cirrhosis associated with recurrent venous thrombosis. 762 35

We evaluated the roles of plasma endothelin-1 and plasma thrombomodulin in the development of disseminated intravascular coagulation (DIC) in patients with sepsis. Plasma endothelin-1 was measured by radioimmunoassay (RIA). Plasma thrombomodulin and tumor necrosis factor-alpha (TNF-alpha) were measured by enzyme-linked immunosorbent assay (ELISA), and serum protein C (protein C) was measured by the synthetic substrate method. Endotoxin was measured by the Endospecy test, a synthetic substrate method. A new perchloric acid method was used for the pretreatment of plasma. Blood levels of endothelin-1 and thrombomodulin were significantly higher in patients with DIC than in those without DIC (p < 0.0001). Endothelin-1 and thrombomodulin levels were positively correlated (r = 0.8645, p = 0.0001), as were endothelin-1 and TNF-alpha levels (r = 0.5441, p = 0.0002). Thrombomodulin and protein C levels were negatively correlated (r = -0.5627, p = 0.0001). Endotoxin was elevated above the normal level 14.3% (6/42) for these patients. TNF-alpha is involved in the production of endothelin-1 and thrombomodulin, which play a role in the pathogenesis of DIC and whose blood levels reflect its severity.
Res Commun Mol Pathol Pharmacol 1995 Nov
PMID:Blood levels of endothelin-1 and thrombomodulin in patients with disseminated intravascular coagulation and sepsis. 874 95

We assessed the blood interleukin 11 (IL-11) levels in patients with disseminated intravascular coagulation (DIC). The IL-11 level exceeded the detection limit, i.e., IL-11 was positive, in 14 of the 21 patients in the group with DIC complicated by sepsis, with a mean value of 20.4 pg/ml. In the group with DIC uncomplicated by infection, IL-11 levels were above the detection limit in 8 of the 17 patients, and the average level was 10.6 pg/ml. The difference between the IL-11-positive rate in the two groups was not significant. Although IL-11 levels tended to be higher in the group with sepsis as a complication, the difference was not significant. The elevated IL-11 levels observed in patients with DIC, with or without complication by infection, seem quite appropriate as a biological response to increased platelets.
Res Commun Mol Pathol Pharmacol 1996 Feb
PMID:Interleukin 11 levels in patients with disseminated intravascular coagulation. 883 18

Thrombosis and disseminated intravascular coagulation (DIC) are common complications of infections. Abnormal activation of coagulation is due in part of expression of tissue factor on intravascular cells in response to cytokines, including interleukin-1 beta (IL1 beta ) and tumor necrosis factor (TNF). Both TNF and IL1 beta are thought to play significant roles in producing the pathologic manifestations of sepsis. Therefore, we examined the effects of thrombin on TNF and IL1 beta secretion of monocytes, and the ability of monocyte products to promote tissue factor expression by endothelial cells. Human monocytes were treated with thrombin or a thrombin receptor agonist peptide (SFLLRN), and/or bacterial lipopolysaccharide (LPS). The agonists were removed, and monocytes cultured 18 hours. The monocyte-conditioned supernatants were assayed for TNF and IL1 beta antigen, and for their ability to induce tissue factor expression on human umbilical vein endothelial cells and the Ea.hy endothelial cell line. Thrombin alone did not promote monocyte TNF or IL-1 beta secretion. However, thrombin enhanced LPS-induced TNF and IL1 secretion. Supernatants from monocytes exposed to LPS plus thrombin promoted greater tissue factor expression on endothelial cells than supernatants from those treated with LPS only. SFLLRN did not increase TNF secretion in response to LPS, but did enhance LPS-induced IL1 beta secretion and tissue factor-inducing activity. Neither SFLLRN nor active thrombin augmented the level of mRNA for TNF above that induced by LPS alone. However, both increased the LPS-induced level of IL1 beta message. Thus, thrombin enhanced LPS-induced TNF and IL1 beta secretion by monocytes. Unexpectedly, the effects on these two cytokines were mediated by different mechanisms. Enhancement of LPS-induced IL1 beta secretion was largely mediated via the tethered ligand type thrombin receptor and correlated with an increase in the steady state level of mRNA. By contrast, enhanced TNF required proteolytically active thrombin, but was not mediated by the tethered ligand receptor. These data demonstrate that physiologically relevant amounts of thrombin can synergize with endotoxin to stimulate monokine release. Thrombin could thereby play a role in the complex network of mediators involved in the pathophysiology of sepsis. We speculate that limiting thrombin activity during DIC could be a beneficial adjunct in the management of sepsis.
Blood Cells Mol Dis 1995
PMID:Thrombin enhances monocyte secretion of tumor necrosis factor and interleukin-1 beta by two distinct mechanisms. 884 45

A 44-year-old women was treated for hyperparathyroidism resulting from parathyroid hyperplasia. Several months later, following a flu-like episode, she developed fever, confusion, abdominal pain, and diffuse petechiae, with severe thrombocytopenia and hemolytic anemia. She died on the 11th day of hospitalization. At autopsy she had multiple endocrine neoplasia type I, with two islet cell tumors, adrenal adenoma, pituitary adenoma, and bronchial carcinoid with liver metastasis. Florid visceral microthrombi involved arterioles and capillaries of the heart, including the conduction system. Brain, kidney, pancreas, adrenal, and portal areas of the liver were also heavily involved, but thrombi were rare in the liver sinusoids and the lungs. PAS-positive subendothelial deposits were demonstrated. In spite of the disseminated malignancy, the morphologic and laboratory findings were inconsistent with disseminated intravascular coagulation (DIC), and supported the clinical diagnosis of TTP. To the best of our knowledge this is the first report association of TTP with MEN and raises the question of a genetic linkage and/or hormonal interaction.
Hematopathol Mol Hematol 1996
PMID:Fatal thrombotic thrombocytopenic purpura (TTP) presenting concurrently with metastatic multiple endocrine neoplasia (MEN) type I. 887 34

A 34-year-old male acutely presented with widely disseminated malignant melanoma, a microangiopathic hemolytic anemia, and disseminated intravascular coagulation. Although the patient had a history of intense childhood exposure to ultraviolet light and an occupational exposure to organic dyes, he had no history of a precursor skin lesion. The histopathology of the patient's bone marrow revealed sheets of malignant cells immunoreactive with S-100, HMB-45, and vimentin and also staining positively for melanin. A bone marrow aspirate revealed myeloid precursors filled with melanin-bearing vacuoles. Immunophenotypic analysis of the patient's bone marrow by flow cytometry revealed a paucity of hematopoietic cells. A karyotypic analysis of the patient's tumor cells demonstrated an abnormal hypertriploid composite clone characterized by multiple numerical and structural abnormalities. Although the patient was treated aggressively with transfusional support, heparin, and chemotherapy, he expired 3 weeks after diagnosis. This is the first recognized case of metastatic melanoma occurring in association with a microangiopathic hemolytic anemia.
Hematopathol Mol Hematol 1998
PMID:Fulminant metastatic melanoma complicated by a microangiopathic hemolytic anemia. 960 58

X-linked lissencephaly is a severe brain malformation affecting males. Recently it has been demonstrated that the doublecortin gene is implicated in this disorder. In order to study the function of Doublecortin, we analyzed the protein upon transfection of COS cells. Doublecortin was found to bind to the microtubule cytoskeleton. In vitro assays (using biochemical methods, DIC microscopy and electron microscopy) demonstrate that Doublecortin binds microtubules directly, stabilizes them and causes bundling. In vivo assays also show that Doublecortin stabilizes microtubules and causes bundling. Doublecortin is a basic protein with an iso-electric point of 10, typical of microtubule-binding proteins. However, its sequence contains no known microtubule-binding domain(s). The results obtained in this study with Doublecortin and our previous work on another lissencephaly gene ( LIS1 ) emphasize the central role of regulation of microtubule dynamics and stability during neuronal morphogenesis.
Hum Mol Genet 1999 Sep
PMID:Doublecortin, a stabilizer of microtubules. 1044 22


1 2 3 4 5 6 Next >>