Defining the resistance to oxygen transfer in tissue hypoxia

Studies of O2 supply in freshly isolated adult mammalian cells provide new insight into the factors that limit mitochondrial oxygenation in vivo. Of particular importance, mitochondria are present at high densities and often in apparent clusters, both of which contribute to local O2 gradients under hypoxic conditions. Current evidence indicates that the mitochondrial distribution is a component of the differentiated phenotype of adult mammalian cells and that specific motors and anchoring mechanisms are present to allow redistribution in response to developmental, physiological and pathological challenges. To compare the importance of resistance to O2 transfer under different conditions and at different sites along the supply path in vivo, a simple mathematical expression of relative resistance to O2 supply is introduced. Under various pathophysiological conditions, this resistance increases in specific regions of the pulmonary, circulatory or cellular supply path and results in O2 deficiency in the mitochondria. Regardless of cause, the relative resistance increases dramatically in the vicinity of mitochondrial clusters during hypoxia.     

Structure of tumour necrosis factor

Tumour necrosis factor is a trimeric molecule, each subunit of which consists of an antiparallel beta-sandwich. Individual subunits from the trimer by a novel edge-to-face packing of beta-sheets. A comparison of the subunit fold with that of other proteins reveals a remarkable similarity to the 'jelly-roll' structural motif characteristic of viral coat proteins.     

Dopamine-induced relaxation in human pulmonary arteries

Dose-dependent relaxations were induced by dopamine in human pulmonary arteries that had been contracted with prostaglandin F2 alpha without alpha-adrenergic blocking agents. The dopamine-induced relaxation was inhibited by haloperidol and fluphenazine, but not by domperidone, suggesting that this relaxation was mediated via DA1 receptors.     

Quantitative studies on in vitro transformation of hamster chondrocytes.

Hamster chondrocytes could be transformed in a quantitative assay system which used X-irradiated feeder layer cells. Morphological transformation occurred on addition of, 4NQO, but not in control cultures. Differentiation was classified into 3 types (good, poor and none); normal and transformed colonies contained similar proportions of the 3 types.     

A family of mammalian Na+-dependent L-ascorbic acid transporters.

Vitamin C (L-ascorbic acid) is essential for many enzymatic reactions, in which it serves to maintain prosthetic metal ions in their reduced forms (for example, Fe2+, Cu+), and for scavenging free radicals in order to protect tissues from oxidative damage. The facilitative sugar transporters of the GLUT type can transport the oxidized form of the vitamin, dehydroascorbic acid, but these transporters are unlikely to allow significant physiological amounts of vitamin C to be taken up in the presence of normal glucose concentrations, because the vitamin is present in plasma essentially only in its reduced form. Here we describe the isolation of two L-ascorbic acid transporters, SVCT1 and SVCT2, from rat complementary DNA libraries, as the first step in investigating the importance of L-ascorbic acid transport in regulating the supply and metabolism of vitamin C. We find that SVCT1 and SVCT2 each mediate concentrative, high-affinity L-ascorbic acid transport that is stereospecific and is driven by the Na+ electrochemical gradient. Despite their close sequence homology and similar functions, the two isoforms of the transporter are discretely distributed: SVCT1 is mainly confined to epithelial systems (intestine, kidney, liver), whereas SVCT2 serves a host of metabolically active cells and specialized tissues in the brain, eye and other organs.     

D-Amino acids in mouse tissues are not of microbial origin

Summary Neutral free D-amino acid contents in the serum, kidney, liver, brain, small intestine and urine in germ-free mice and those in specific pathogen-free mice were compared. No significant difference was found. This strongly suggests that the free D-amino acids which were shown to be present in mice in our previous work^{1, 2} did not originate from the enteric microbial flora.