Six-month outcome of critically ill patients given glutamine-supplemented parenteral nutrition

Tetrahydrobiopterin is an essential cofactor required for activity of nitric oxide synthases. Existing evidence suggests that, during activation of constitutive and inducible isoforms of nitric oxide synthase, tetrahydrobiopterin is needed for allosteric and redox activation of enzymatic activity. However, precise mechanisms underlying the role of tetrahydrobiopterin in regulation of nitric oxide formation is not fully understood. In cerebral and peripheral arteries, increased availability of tetrahydrobiopterin can augment production of nitric oxide. In contrast, in arteries depleted of tetrahydrobiopterin, production of nitric oxide is impaired. Proinflammatory cytokines enhance mRNA expression of the rate-limiting enzyme of tetrahydrobiopterin biosynthesis, GTP cyclohydrolase I and stimulate production of tetrahydrobiopterin. The ability of vascular tissues to synthesize tetrahydrobiopterin plays an important role in regulation of nitric oxide synthase under physiological conditions as well as during inflammation and sepsis. More recent studies concerning expression and function of recombinant nitric oxide synthases suggest that availability of tetrahydrobiopterin is important for production of nitric oxide in genetically engineered blood vessels. In this review, mechanisms regulating availability of intracellular tetrahydrobiopterin and its role in control of vascular tone under physiological and pathological conditions will be discussed.     

Suspected skeletal dysplasias: femur length to abdominal circumference ratio can be used in ultrasonographic prediction of fetal outcome

OBJECTIVES: Skeletal dysplasias are a group of bone growth disorders, some of which can be recognized prenatally. Certain types of skeletal dysplasias result in a lethal fetal outcome. The ability to predict this outcome prenatally would be important in counseling parents. This study evaluated the ratio of femur length to abdominal circumference as a predictor of fetal outcome in cases of suspected skeletal dysplasia. STUDY DESIGN: This 3-year retrospective study identified 18 cases of prenatally suspected skeletal dysplasia from a population of approximately 35,000 fetuses undergoing prenatal ultrasonography. The femur length/abdominal circumference ratio was calculated and compared with fetal-neonatal outcomes and diagnoses. RESULTS: Eighteen cases of suspected skeletal dysplasia were identified, and the femur length/abdominal circumference ratio was found to be a good predictor of fetal outcome independent of gestational age. A ratio < 0.16 resulted in a lethal outcome in nine of nine cases. Conversely, a ratio > or = 0.16 resulted in a diagnosis of a nonlethal form of skeletal dysplasia or a diagnosis that ruled out any form of skeletal dysplasia in nine of nine cases. CONCLUSIONS: The femur length/abdominal circumference ratio may be useful to predict a lethal fetal outcome when ultrasonography indicates a possible skeletal dysplasia.     

Structural polymorphism of the RecA protein from the thermophilic bacterium Thermus aquaticus

The Escherichia coli RecA protein has served as a model for understanding protein-catalyzed homologous recombination, both in vitro and in vivo. Although RecA proteins have now been sequenced from over 60 different bacteria, almost all of our structural knowledge about RecA has come from studies of the E. coli protein. We have used electron microscopy and image analysis to examine three different structures formed by the RecA protein from the thermophilic bacterium Thermus aquaticus. This protein has previously been shown to catalyze an in vitro strand exchange reaction at an optimal temperature of about 60 degrees C. We show that the active filament formed by the T. aquaticus RecA on DNA in the presence of a nucleotide cofactor is extremely similar to the filament formed by the E. coli protein, including the extension of DNA to a 5.1-A rise per base pair within this filament. This parameter appears highly conserved through evolution, as it has been observed for the eukaryotic RecA analogs as well. We have also characterized bundles of filaments formed by the T. aquaticus RecA in the absence of both DNA and nucleotide cofactor, as well as hexameric rings of the protein formed under all conditions examined. The bundles display a very large plasticity of mass within the RecA filament, as well as showing a polymorphism in filament-filament contacts that may be important to understanding mutations that affect surface residues on the RecA filament.