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Network medicine: a network-based approach to human disease
Advances in this direction are essential for identifying new disease genes, for uncovering the biological significance of disease-associated mutations identified by genome-wide association studies and full-genome sequencing, and for identifying drug targets and biomarkers for complex diseases. Expand
Endothelial cells in physiology and in the pathophysiology of vascular disorders.
THE ENDOTHELIUM has long been viewed as an inert cellophane-like membrane that lines the circulatory system with its primary essential function being the maintenance of vessel wall permeability.Expand
Biochemistry of nitric oxide and its redox-activated forms.
The integration of this chemistry with current perspectives of NO biology illuminates many aspects of NO biochemistry, including the enzymatic mechanism of synthesis, the mode of transport and targeting in biological systems, the means by which its toxicity is mitigated, and the function-regulating interaction with target proteins. Expand
A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds
It is reported that NO.-mediated neurotoxicity is engendered, at least in part, by reaction with superoxide anion (O.-2), apparently leading to formation of peroxynitrite (ONOO−), and not by NO. Expand
S-nitrosylation of proteins with nitric oxide: synthesis and characterization of biologically active compounds.
It is demonstrated that S-nitroso proteins form readily under physiologic conditions and possess EDRF-like effects of vasodilation and platelet inhibition, suggesting that S -nitrosothiol groups in proteins may serve as intermediates in the cellular metabolism of NO and raise the possibility of an additional type of cellular regulatory mechanism. Expand
Nitric oxide circulates in mammalian plasma primarily as an S-nitroso adduct of serum albumin.
It is found that naturally produced nitric oxide circulates in plasma primarily complexed in S-nitrosothiol species, principal among which is S-Nitroso-serum albumin, which likely serves as a reservoir with which plasma levels of highly reactive, short-lived free nitrics can be regulated for the maintenance of vascular tone. Expand
Pulmonary arterial hypertension
Pulmonary arterial hypertension is a disease of the small pulmonary arteries characterized by vascular narrowing and increased pulmonary vascular resistance, which eventually leads to rightExpand
Homocysteine and atherothrombosis.
In 1969, McCully reported autopsy evidence of extensive arterial thrombosis and atherosclerosis in two children with elevated plasma homocyst(e)ine concentrations and homocysteine thiolactone, and it has recently become clear that hyperhomocyst (e)inemia is an independent risk factor. Expand
The biology of nitrogen oxides in the airways.
Nitrogen oxides (NOx), regarded in the past primarily as toxic air pollutants, have recently been shown to be bioactive species formed endogenously in the human lung, and have opened a new horizon of therapeutic possibilities for pulmonary medicine. Expand
Uncovering disease-disease relationships through the incomplete interactome
A network-based framework to identify the location of disease modules within the interactome and use the overlap between the modules to predict disease-disease relationships is presented and it is found that disease pairs with overlapping disease modules display significant molecular similarity, elevated coexpression of their associated genes, and similar symptoms and high comorbidity. Expand