Comparison of the capacity of two lipid A precursor molecules to express the local Shwartzman phenomenon.

SummaryThe local Sanarelli-Shwartzman phenomenon (SSP-L) in the skin of 30 rats was induced by an intr a cutaneous sensitizing injection of leukaemic leucocytes isolated from the peripheral blood of patients with chronic lymphocytic leukaemia (CLL), acute myeloblastic leukaemia (AL) and chronic granulocytic leukaemia (CGL) and challenged by an intravenous injection of 100(μ of E. coli endotoxin. SSP-L was observed in 7 rats after injection of CLL lymphocytes and in 6 and 2 rats after AL myeloblasts and the CGL granulocytes, respectively. The lesions in the skin after AL myeloblasts appeared in a shorter time and were of longer duration compared with those observed after CLL lymphocytes and CGL granulocytes. Histologically, the lesions consisted of areas of destruction in the superficial layers of the skin ; the demarcation line showed the presence of neutrophils, macrophages and erythrocytes. Haemorrhages and fibrin deposits near the demarcation line were larger after injection of CLL lymphocytes and AL myeloblasts than after CGL granulocytes. The possible role of leucocyte procoagulative substances in the differences observed have been discussed.

Download Full-text

A Re-Appraisal of the Role of Blood Coagulation and Platelets in the Generalized Shwartzman Phenomenon

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649455 ◽

1966 ◽

Vol 15 (03/04) ◽

pp. 519-538 ◽

Cited By ~ 10

Author(s):

J Levin ◽

E Beck

Keyword(s):

Blood Coagulation ◽

The State ◽

Coagulation System ◽

Renal Lesions ◽

Intravascular Coagulation ◽

Renal Glomeruli ◽

Coagulation Mechanism ◽

Shwartzman Phenomenon ◽

Do So

SummaryThe role of intravascular coagulation in the production of the generalized Shwartzman phenomenon has been evaluated. The administration of endotoxin to animals prepared with Thorotrast results in activation of the coagulation mechanism with the resultant deposition of fibrinoid material in the renal glomeruli. Anticoagulation prevents alterations in the state of the coagulation system and inhibits development of the renal lesions. Platelets are not primarily involved. Platelet antiserum produces similar lesions in animals prepared with Thorotrast, but appears to do so in a manner which does not significantly involve intravascular coagulation.The production of adrenal cortical hemorrhage, comparable to that seen in the Waterhouse-Friderichsen syndrome, following the administration of endotoxin to animals that had previously received ACTH does not require intravascular coagulation and may not be a manifestation of the generalized Shwartzman phenomenon.

Download Full-text

Induction of Endothelial Tissue Factor by Endotoxin and Its Precursors

Thrombosis and Haemostasis ◽

10.1055/s-0038-1649653 ◽

1993 ◽

Vol 70 (04) ◽

pp. 702-706 ◽

Cited By ~ 16

Author(s):

Charles F Moldow ◽

Ronald R Bach ◽

Katherine Staskus ◽

Paul D Rick

Keyword(s):

Tissue Factor ◽

Lipid A ◽

Umbilical Vein ◽

Structural Determinants ◽

Monophosphoryl Lipid A ◽

Maximal Induction ◽

Umbilical Vein Endothelial Cells ◽

Acyloxyacyl Hydrolase ◽

Endothelial Tissue ◽

Specific Mrna

SummaryThe structural determinants of lipopolysaccharide required for the induction of tissue factor in human umbilical vein endothelial cells were studied. Intact lipid A was essential for the induction of tissue factor whereas the incomplete lipid A precursors lipid IVA and lipid X, as well as monophosphoryl lipid A and acyloxyacyl hydrolase-treated lipopolysaccharide, were unable to induce tissue factor and tissue factor specific mRNA. However, the lipid A precursor, lipid IVA, was able to inhibit LPS-mediated induction of tissue factor; structural determinants distal to lipid A were found to be required for maximal induction of tissue factor activity and tissue factor mRNA. The presence of serum in the assay was found to amplify but was not obligate for tissue factor induction by LPS.

Download Full-text

Multi-Resolution Autoregressive Graph-to-Graph Translation for Molecules

10.26434/chemrxiv.8266745.v1 ◽

2019 ◽

Author(s):

Wengong Jin ◽

Regina Barzilay ◽

Tommi S Jaakkola

Keyword(s):

Drug Discovery ◽

State Of The Art ◽

Molecular Graph ◽

Biochemical Properties ◽

Large Margin ◽

Previous State ◽

Translation Methods ◽

Atom Level ◽

Precursor Molecules ◽

Prior State

The problem of accelerating drug discovery relies heavily on automatic tools to optimize precursor molecules to afford them with better biochemical properties. Our work in this paper substantially extends prior state-of-the-art on graph-to-graph translation methods for molecular optimization. In particular, we realize coherent multi-resolution representations by interweaving trees over substructures with the atom-level encoding of the original molecular graph. Moreover, our graph decoder is fully autoregressive, and interleaves each step of adding a new substructure with the process of resolving its connectivity to the emerging molecule. We evaluate our model on multiple molecular optimization tasks and show that our model outperforms previous state-of-the-art baselines by a large margin.

Download Full-text