Dopamine-beta-hydroxylase in dog lymph--effect of sympathetic activation

In anesthetized dogs baroreceptor denervation and electrical stimulation of the left stellate ganglion caused marked arterial hypertension and tachycardia. These were associated with a 4-10-fold increase in the total output of dopamine-β-hydroxylase (DβH) in the thoracic duct lymph. Serum DβH activity was lower than that in man and changes during sympathetic activation were inconsistent. These results suggest that a major portion of DβH released from adrenergic nerve terminals is transported in the lymph before it enters the circulating blood.     

Partition of fatty acids

The partition ratios of radioactive fatty acids between n-heptane and a physiological buffer at 37 degrees C were measured. The fatty acids included the saturated acids with an even number of carbons from 10 to 18 and the unsaturated acids oleic, linoleic, and linolenic. In addition, the partition ratios of decanoate, myristate, and palmitate were determined over a wide pH range. Any single plot of partition ratio vs. aqueous concentration of an acid gave a nearly straight line, a finding consistent with very little association in the aqueous phase. In the case of the acids with 16 and 18 carbon atoms, however, comparison of the constants calculated from these plots with the assumption of no aqueous phase association revealed several inconsistencies. These inconsistencies cannot be resolved completely by assuming the existence of fatty acid association in the aqueous solution. We believe that at least some of the deviations are due to the presence of trace quantities of radioactive impurities in the labeled fatty acids. For example, purification of a sample of supposedly pure [1-(14)C]myristate by a series of solvent extractions increased the partition ratio by a factor of 1.5. Although all of the observations cannot be explained by this interpretation, we believe that our studies suggest that there is no appreciable association of fatty acids under the usual physiological conditions.     

Covalent enzyme-substrate intermediates in transferase reactions

Enzymatic transfer reactions are often depicted as occurring on the surface of the enzyme by direct transfer of a chemical group from a donor substrate molecule to an acceptor, in a single-displacement reaction without covalent participation of the enzyme. This picture of enzyme action is purely speculative, because no positive evidence in support of it exists. The kinetic argument, which formerly afforded the sole support for the single-displacement mechanism, is now known to be in error. Contrasting sharply with this dearth of proof is the substantial and growing body of evidence which upholds the double-displacement mechanism of enzymatic transfer. In this mechanism, a catalytic group (or atom) within the active site of the enzyme links covalently with one of the substrates, or some fragment of it, at some stage of the reaction. Through use of the covalent enzyme-substrate intermediate it may be that the enzyme is enabled to overcome certain entropic difficulties, thus accounting in part for the well-known speed of enzymatic reactions. Covalent participation by the enzyme also brings enzymatic catalysis into closer accord with homogenous and heterogeneous catalysis, in which the key reaction is the transient formation of a covalent bond between substrate and catalyst.     

Cytomegalovirus (CMV) DNA Load Is an Independent Predictor of CMV Disease and Survival in Advanced AIDS

The impact of cytomegalovirus (CMV) on human immunodeficiency virus type 1 (HIV-1) disease progression has been controversial. In this study, we sought to determine if CMV viral load is independent of HIV-1 viral load in predicting CMV disease and survival. Our findings indicate that in patients with advanced AIDS, CMV DNA load is an independent marker of CMV disease and survival and is more predictive than HIV-1 RNA load. Moreover, patients who respond to preemptive therapy with oral ganciclovir, with resulting undetectable levels of CMV DNA, in their plasma, have a significantly lower risk of developing CMV disease and higher rates of survival, despite stable or increasing HIV-1 RNA loads. These data provide support for CMV as an independent risk factor for mortality in persons with advanced AIDS and further suggest that effective preemptive therapy for CMV can improve patient survival rates.