Deficiency of reduced nicotinamide-adenine dinucleotide oxidase in chronic granulomatous disease

Reduced nicotinamide-adenine dinucleotide oxidase of normal human polymorphonuclear leukocytes has properties that would qualify it as the enzyme responsible for the respiratory burst during phagocytosis. The enzyme was deficient in leukocytes of five patients with chronic granulomatous disease. This lack of adequate reduced nicotinamide-adenine dinucleotide oxidase could be the basis for the metabolic abnormalities characteristic of these leukocytes and for their diminished bactericidal activity.     

Phospholipid-calcium phosphate complex: enhanced calcium migration in the presence of phosphate

In the presence of acidic phospholipids, inorganic phosphate greatly enhances the net migration of calcium ions from the aqueous phase to the organic phase, an effect that does not occur at less than the physiological pH. The calcium complex in the organic phase is shown by electron microscopy to consist of spherules, composed of stoichiometric amount of calcium, inorganic phosphate, and phospholipid. The demonstration of complex formation between calcium phosphate and acidic phospholipids adds Support to the concept that phospholipids are involved in biological mineralization.     

Lack of enhanced oxygen consumption by polymorphonuclear leukocytes on phagocytosis of virulent Salmonella typhi

Human polymorphonuclear leukocytes exhibit an enhanced rate of oxygen consumption during phagocytosis of relatively avirulent strains of Salmonella typhi or Staphylococcus aureus. However, phagocytosis of a virulent strain of Salmonella typhi is not associated with augmented oxygen consumption. The ability of a bacterial strain to alter the postphagocytic rate of oxygen consumption of polymorphonuclear leukocytes may be related to its in vivo virulence.     

Leukocyte oxidase: defective activity in chronic granulomatous disease

The intact leukocytes of two children with chronic granulomatous disease fail to reduce nitroblue tetrazolium during phagocytosis. This is due to defective operation of an oxidase of reduced nicotinamide adenine dinucleotide that is insensitive to cyanide and that indirectly stimulates the oxidation of glucose-6-phosphate in leukocytes. Such leukocytes undergo no increase in oxygen consumption or in activity of the hexose monophosphate shunt during phagocytosis, although lactate production is normal. The addition of nitroblue tetrazolium to a leukocyte suspension appears to provide a sensitive diagnostic screening test for this disease.     

Control of the activity of Escherichia coli carbamoyl phosphate synthetase by antagonistic allosteric effectors

The synthesis of carbamoyl phosphate required in both arginine and pyrimidine biosyntheses is carried out by a single enzyme in Escherichia coli. Opposed effects of pyrimidine nucleotides and of ornithine on the activity of the enzyme ensure a proper supply of carbamoyl phosphate according to the needs of the two biosynthetic sequences.     

Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity

Somatostatin and dopamine are two major neurotransmitter systems that share a number of structural and functional characteristics. Somatostatin receptors and dopamine receptors are colocalized in neuronal subgroups, and somatostatin is involved in modulating dopamine-mediated control of motor activity. However, the molecular basis for such interaction between the two systems is unclear. Here, we show that dopamine receptor D2R and somatostatin receptor SSTR5 interact physically through hetero-oligomerization to create a novel receptor with enhanced functional activity. Our results provide evidence that receptors from different G protein (heterotrimeric guanine nucleotide binding protein)-coupled receptor families interact through oligomerization. Such direct intramembrane association defines a new level of molecular crosstalk between related G protein-coupled receptor subfamilies.     

Glycerol metabolism in the human liver: inhibition by ethanol

Glycerol is metabolized predominantly in the liver, the first step presumably being phosphorylation to alpha-glycerophosphate. When ethanol is present in the blood the rate of glycerol uptake by the splanchnic organs is reduced to about one-third of the control value. At the same time glycerophosphate accumulates in the liver. Hepatic blood flow and oxygen consumption are not influenced by the combined infusion of glycerol and ethanol. The phenomenon may be connected with the increased concentration of the reduced form of diphosphopyridine nucleotide present in the liver during ethanol metabolism.     

Ethanol oxidation by hepatic microsomes: adaptive increase after ethanol feeding

Hepatic microsomes contain an ethanol-oxidizing system distinct from alcohol dehydrogenase. In vitro, it has characteristics comparable to those of microsomal drug-detoxifying enzymes and, in vivo, it is capable of adaptation to the administration of ethanol. The existence of this microsomal ethanol-oxidizing system may explain ultrastructural, pharmacological, and biochemical effects of ethanol.     

Dopamine-related tetrahydroisoquinolines: significant urinary excretion by alcoholics after alcohol consumption

Concentrations of dopamine-related tetrahydroisoquinolines (salsolinol and O-methylated salsolinol) were significantly higher in the daily urine samples of alcoholic subjects admitted for alcohol detoxification than in the daily urine samples of nonalcoholic control subjects. Salsolinol concentrations in alcoholic subjects appeared to drop to trace (control) values 2 to 3 days after admission, following the disappearance of ethanol and its reactive metabolite acetaldehyde from the blood. These results indicate that physiologically active tetrahydroisoquinolines increase in humans during long-term alcohol consumption, presumably because of acetaldehyde's direct condensation with catecholamines. The presence of these or similar condensation products in the urine could be useful as clinical indicators of prior blood acetaldehyde concentrations in chronic alcoholics.     

Olfaction: responses of a decapod crustacean are enhanced by flicking

Periodic movements of the olfactory organs, known as "flicking," temporally enhance the response of the olfactory receptors of the spiny lobster to changes in stimulus concentration. This reflex provides the lobster with a physiological mechanism to compensate for the indiscrete temporal nature of chemical stimuli.     

Serotonin-containing neurons in brain: depression of firing by monoamine oxidase inhibitors

Monoamine oxidase inhibitors were administered to rats while the activities of single, serotonin-containing neurons of the midbrain raphe nuclei were being monitored with microelectrodes. All the inhibitors tested (pargyline, tranylcypromine, phenelzine, iproniazid) caused depression of raphe unit firing rate. The ability of monoamine oxidase inhibitors to depress raphe units was impaired by prior treatment with p-chlorophenylalanine, an inhibitor of serotonin synthesis.     

Familial hypophosphatemic rickets: defective transport of inorganic phosphate by intestinal mucosa

Uptake of inorganic phosphate is impared in intestinal mucosa from hemizygous males and heterozygous females with X-linked familial hypophosphatemic rickets. Considerable intrafamilial and interfamilial variation in uptake of inorganic phosphate is observed in affected patients. Uptake by normal mucosa is concentrative and energy-dependent, and is mediated by at least two systems with widely different affinities. These results lend direct support to the thesis that the primary metabolic disturbance in this disease results from impaired transport of inorganic phosphate in kidney and gut.     

Tyrosine-alpha-ketoglutarate transaminase: induction by epinephrine and adenosine-3',5'-cyclic phosphate

Epinephrine and the N6-O2'-dibutyryl analog of adenosine-3', 5'-cyclic phosphate both are effective inducers of tyrosine-alpha-ketoglutarate transaminase in explants of fetal rat liver maintained in organ culture. Combinations of these inducers with each other and with hydrocortisone, another inducer, yielded results which suggest that cyclic adenylic acid is an intermediate in the induction by epinephrine and that the mechanism by which it induces is different from that by which hydrocortisone operates.     

Phytohemagglutinin: inhibition of the agglutinating activity by N-acetyl-D-galactosamine

The effect of simple sugars on the agglutinating activity of phytohemagglutinin was studied. N-Acetyl-d-galactosamine selectively inhibits the agglutination of leukocytes and erythro- cytes by phytohemagglutinin.     

Free-running activity rhythms in the rat: entrainment by melatonin

The pineal gland hormone melatonin may play a role in synchronization of rat circadian rhythms. Free-running activity rhythms of the rat were entrained by a daily melatonin injection, with entrainment occurring when the onset of activity coincided with the time of daily injections. When injections were stopped, activity rhythms became free-running again. Thus in pharmacological experiments, the time of day of melatonin administration is crucial.     

Divided by cytochrome oxidase: a map of the projections from V1 to V2 in macaques

Current models partition the primate visual system into dorsal (magno) and ventral (parvo, konio) streams. Perhaps the strongest evidence for this idea has come from the pattern of projections between the primary visual area (V1) and the second visual area (V2). Prior studies describe three distinct pathways: magno to thick stripes, parvo to pale stripes, and konio to thin stripes. We now demonstrate that V1 output arises from just two sources: patch columns and interpatch columns. Patch columns project to thin stripes and interpatch columns project to pale and thick stripes. Projection of interpatches to common V2 stripe types (pale and thick) merges parvo and magno inputs, making it likely that these functional channels are distributed strongly to both dorsal and ventral streams.     

Glycosphingolipids with Lewis blood group activity: uptake by human erythrocytes

The Lewis blood group antigens of the human erythrocyte are acquired from plasma and not synthesized in situ. Although assumed previously to be glycoproteins, tile Lewis antigens in plasma are glycosphingolipids Which are taken up by the the erythrocyte membrane from lipoproteins or from aqueous dispersions.     

Phosphorylase a activity in uterine muscle: stimulation by ethylenediaminetetraacetic acid

Injection of ethylenediaminetetraacetic acid into spayed rats or its use in phosphorylase extraction increases the activity of glycogen-phosphorylase a in uterine smooth muscle tissue. Since the total phosphorylase activity is not increased, the increase in phosphorylase a appears to result from a conversion of inactive phosphorylase b to the active form of the enzyme.