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)

The innate immune response to intraportally infused adenoviral vector was evaluated in rhesus monkeys. A first-generation adenovirus-expressing lacZ (Ad-lacZ) was administered at a dose just below that which causes severe morbidity. The response to vector was evaluated for the initial 24 h following infusion. Clinical findings during this time were primarily limited to petechiae, consistent with the development of thrombocytopenia and biochemical evidence of disseminated intravascular coagulation. Serum transaminases were elevated and a lymphopenia developed. Tracking of fluorescent-labeled vector demonstrated distribution to macrophages and dendritic cells of the spleen and Kupffer cells of the liver. A systemic release of the cytokine IL-6 occurred soon after vector infusion. Analysis of splenic cells revealed acute activation of macrophages and dendritic cells followed by massive apoptosis. Bone marrow cultures demonstrated normal erythroid and primitive progenitors with a significant decrease in myeloid progenitors. Similar findings, except the abnormality in bone marrow cultures, were observed in monkeys who received an identical dose of Ad-lacZ in which vector genes were inactivated with psoralen and UV irradiation. These data suggest that inadvertent targeting of antigen-presenting cells following intraportal infusion of vector leads to a systemic cytokine syndrome which may be triggered by the viral capsid proteins.
Mol Ther 2001 May
PMID:Activation of innate immunity in nonhuman primates following intraportal administration of adenoviral vectors. 1135 76

Complete nucleotide sequence of African swine fever (ASF) virus genome was determined in 1993-1999. Deletion mutants with low virulence for pigs were obtained. Genes of structural (p72, p54, p12, cleavage products pp220 and pp60, hemagglutinin) and nonstructural (p32) proteins were mapped. The significance of different proteins in virus adsorption and resistance to challenge was elucidated, their location in infected cell and virion was determined. Lipid composition of the virus was studied. A protocol of virion morphogenesis was suggested, which explains their morphology. Apoptosis, consumption coagulopathy, and development of delayed type hypersensitivity are regarded as the main pathogenetic mechanisms. Antigens acting as targets and inductors of immune cytological reactions and antibodies mediating suppression of virus reproduction were determined.
Mol Gen Mikrobiol Virusol 2001
PMID:[African swine fever virus: achievements over the last decade of the 20th century]. 1144 98

Currently, pyogenic liver abscess is not frequent, but it is a severe infectious disease. However a strategy for the effective treatment of liver abscess is not established. We analyzed 75 cases of liver abscess over an eight year period and evaluated their prognosis, any associated underlying disease, or the effect of percutaneous transhepatic abscess drainage (PTAD). For all 75 cases, laboratory data were analyzed and imaging studies were performed. Next, PTAD and antibiotic administration were started on these cases as first choice treatments. These treatments were continued until the laboratory data of the patient were restored to within the normal range. Those cases that were PTAD non-effective or required operation for underlying diseases, underwent operations. Of the total 75 cases, 63 survived after treatment and 12 cases died. Bacteria were detected in 50 cases and Klebsiella pneumoniae was detected in 31 of these 50 cases, but 25 out of 75 cases were negative. The biliary system was the main route of infection. PTAD was effective, especially in cases that were complicated with disseminated intravascular coagulation (DIC) or acute renal failure (ARF). PTAD is an effective treatment for liver abscess, it is especially useful in the restoration of severe general conditions as indicated by this study.
Int J Mol Med 2002 Nov
PMID:Clinicopathological analysis of liver abscess in Japan. 1237 5

In contrast to the complex, three-dimensional shape of myomeres in teleost fishes, the lateral hypaxial muscles of salamanders are nearly planar and their myosepta run in a roughly straight line from mid-lateral to mid-ventral. We used this relatively simple system as the basis for a mathematical model of segmented musculature. Model results highlight the importance of the mechanics of myosepta in determining the shortening characteristics of a muscle segment. We used sonomicrometry to measure the longitudinal deformation of myomeres and the dorsoventral deformation of myosepta in a swimming salamander (Siren lacertina). Sonomicrometry results show that the myosepta allow some dorsoventral lengthening, indicating an amplification of myomere shortening that is greater than that produced by muscle fiber angle alone (10% muscle fiber shortening produces 28.7% myomere shortening). Polarized light and DIC microscopy of isolated hypaxial myosepta revealed that the collagen fiber orientation in hypaxial myomeres is primarily mediolateral. The mediolateral collagen fiber orientation, combined with our finding that the hypaxial myosepta lengthen dorsoventrally during swimming, suggests that one possible function of hypaxial myosepta in S. lacertina is to increase the strain amplification of the muscle fibers by reducing the mediolateral bulging of the myomeres and redirecting the bulging toward the dorsoventral direction.
Comp Biochem Physiol A Mol Integr Physiol 2002 Dec
PMID:Morphology and mechanics of myosepta in a swimming salamander (Siren lacertina). 1248 86

FR167653 inhibits the production of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta, powerful inducers of CXC chemokines IL-8 and growth related oncogene (GRO)-alpha. The production of IL-8 and GRO-alpha was investigated and the effects of FR167653 were examined in a rabbit model of endotoxin shock. Male New Zealand rabbits were given endotoxin at a dose sufficient to induce DIC. Three groups of rabbits received FR167653 at different doses. TNF-alpha, IL-1beta, IL-8, and GRO-alpha levels were measured, several pathologic features were evaluated, and the results were compared with those obtained in control rabbits, which received only endotoxin. Endotoxin increased serum levels of IL-8 and GRO-alpha, which were associated with hypotension, renal dysfunction, and mortality, peaking at 4 h. FR167653 improved mortality, an event that was associated with decreased levels of not only TNF-alpha and IL-1beta but also IL-8 and GRO-alpha. TNF-alpha peaked at 2 h, at a time point before IL-8 and GRO-alpha reached their peak, and the TNF-alpha level was tightly correlated with that of IL-8 and GRO-alpha. Altogether, these data suggest the possible involvement of IL-8 and GRO-alpha in endotoxin shock, and FR167653 may foster a beneficial outcome in part by modulating the chemokines level by inhibiting TNF-alpha and IL-1beta.
Exp Mol Pathol 2002 Dec
PMID:Interleukin (IL)-8 and growth related oncogene-alpha in severe endotoxemia and the effects of a tumor necrosis factor-alpha/IL-1beta inhibitor on these chemokines. 1256 97

We report the death of an 18-year-old male with partial ornithine transcarbamylase (OTC) deficiency who participated in a pilot (safety) study of gene therapy. The vector used for this trial was based on human adenovirus type 5, deleted in E1 and E4, and contained human OTC cDNA. It was infused into the right hepatic artery at a dose of 6x10(11)particles/kg. Approximately 18 h. following gene transfer the subject was noted to have altered mental status and jaundice--clinical signs not seen in any of the first 17 subjects in this study. Subsequently, his clinical course was marked by systemic inflammatory response syndrome, biochemically detectable disseminated intravascular coagulation, and multiple organ system failure, leading to death 98 h following gene transfer. Post-mortem examination was consistent with the clinical course, and vector DNA sequences were readily detectable in most tissues. The subject had high serum levels of IL-6 and IL-10 but normal TNFalpha immediately after infusion of the vector. This experience points to the limitations of animal studies in predicting human responses, the steep toxicity curve for replication defective adenovirus vectors, substantial subject-to-subject variation in host responses to systemically administered vectors, and the need for further study of the immune response to these vectors.
Mol Genet Metab
PMID:Fatal systemic inflammatory response syndrome in a ornithine transcarbamylase deficient patient following adenoviral gene transfer. 1456 64

Lipopolysaccharide (LPS), a major component of the outer membrane of Gram-negative bacteria, can be beneficial to the host by activating the innate immune system, or harmful, by inducing inflammation, disseminated intravascular coagulation, multiple organ failure, shock and often death. On the bacteria, and in host biological fluids and cells, LPS is never free but constantly attached to cognate-binding proteins. Understanding how LPS is transported and further recognized by sensors able to deliver a signal, or by inactivating molecules able to neutralize its biological effects, is an important goal. This review describes the large panel of peptides and proteins reported to associate with LPS, and provides information on their origin, their structure and the location of amino acid residues involved in their interaction with LPS. A better understanding of the mode of recognition of LPS by cognate proteins prompted many laboratories to design on a rational basis synthetic molecules which can be used to detect low amounts of endotoxin, or to act as efficient blockers of in vitro and in vivo responses to LPS.
Cell Mol Life Sci 2004 Jul
PMID:Lipopolysaccharide-binding molecules: transporters, blockers and sensors. 1524 48

Urinary trypsin inhibitor (UTI), a serine protease inhibitor, has been widely used as a drug for patients with acute inflammatory disorders such as disseminated intravascular coagulation, shock, and pancreatitis in Japan. Recent studies have demonstrated that serine protease inhibitors may play an anti-inflammatory role beyond merely an inhibitory action on neutrophil elastase at the site of inflammation at least in vitro. To clarify the direct contributions of UTI to inflammatory condition in vivo, we analyzed its roles in experimental systemic inflammatory response induced by intraperitoneal administration of lipopolysaccharide (LPS) using UTI deficient (-/-) mice and corresponding wild-type (WT) mice. After LPS (1 mg/kg) challenge, UTI (-/-) mice revealed a significant elevation of plasma fibrinogen and fibrinogen/fibrin degradation products and a decrease in white blood cell counts compared with WT mice. LPS treatment induced more severe neutrophilic inflammation in the lung and the kidney obtained from UTI (-/-) mice than in those from WT mice, which was confirmed by histological examination. The protein levels of proinflammatory mediators, such as macrophage chemoattractant protein (MCP)-1 in the lungs, MCP-1 and keratinocyte chemoattractant (KC) in the kidneys, and interleukin-1beta, macrophage inflammatory protein-2, MCP-1, and KC in the liver, were significantly greater in UTI (-/-) mice than in WT mice after LPS challenge. Our results suggest that UTI protects against systemic inflammatory response and subsequent organ injury induced by bacterial endotoxin, at least partly through the inhibition of the enhanced expression of proinflammatory cytokines and chemokines.
Mol Pharmacol 2005 Mar
PMID:Urinary trypsin inhibitor protects against systemic inflammation induced by lipopolysaccharide. 1557 31

Intraflagellar transport (IFT) is a bidirectional process required for assembly and maintenance of cilia and flagella. Kinesin-2 is the anterograde IFT motor, and Dhc1b/Dhc2 drives retrograde IFT. To understand how either motor interacts with the IFT particle or how their activities might be coordinated, we characterized a ts mutation in the Chlamydomonas gene encoding KAP, the nonmotor subunit of Kinesin-2. The fla3-1 mutation is an amino acid substitution in a conserved C-terminal domain. fla3-1 strains assemble flagella at 21 degrees C, but cannot maintain them at 33 degrees C. Although the Kinesin-2 complex is present at both 21 and 33 degrees C, the fla3-1 Kinesin-2 complex is not efficiently targeted to or retained in the basal body region or flagella. Video-enhanced DIC microscopy of fla3-1 cells shows that the frequency of anterograde IFT particles is significantly reduced. Anterograde particles move at near wild-type velocities, but appear larger and pause more frequently in fla3-1. Transformation with an epitope-tagged KAP gene rescues all of the fla3-1 defects and results in preferential incorporation of tagged KAP complexes into flagella. KAP is therefore required for the localization of Kinesin-2 at the site of flagellar assembly and the efficient transport of anterograde IFT particles within flagella.
Mol Biol Cell 2005 Mar
PMID:The FLA3 KAP subunit is required for localization of kinesin-2 to the site of flagellar assembly and processive anterograde intraflagellar transport. 1561 87

Acute myelogenous leukemia (AML) is divided into 8 FAB subgroups based on differentiation and maturation properties of the neoplastic cells. Acute promyelocytic leukemia (APL), or M3 AML, is associated with disseminated intravascular coagulation (DIC). Flow cytometric immunophenotyping differentiates among the AML subtypes. Key markers in this classification include the myeloid antigens CD13 and CD33 and the hematopoietic precursor markers CD34 and HLA-DR. The present study analyzes and compares differences in the expression of these markers in 27 M0-M2 cases and 8 M3 cases. The M0-M2 cases generally expressed all four antigens. CD13 and CD33 were positively expressed in 23 (85.2%) and 21 (77.8%) of the 27 cases, respectively. CD34 and HLA-DR were present in 25 (92.6%) and 26 (96.3%) of the 27 cases, respectively. Analysis of the M3 cases revealed a different immunophenotype as CD13 and CD33 were each positive in all 8 (100%) M3 AML cases while CD34 and HLA-DR were negative in 6 (75%) and 8 (100%) of the 8 M3 cases, respectively. In contrast to expression of the early markers CD34 and HLA-DR in the M0-M2 group, these were negative in the M3 cases which were characterized by heterogeneous CD13 and generally homogeneous and bright CD33 expression.
Exp Mol Pathol 2007 Oct
PMID:Contrasting antigenic maturation patterns in M0-M2 versus M3 acute myeloid leukemias. 1760 36


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