Antibody to native human immunodeficiency virus type 1 envelope glycoproteins induced by IIIB and MN recombinant gp120 vaccines. The NIAID AIDS Vaccine Evaluation Group.

The ability of antibody induced by MN and IIIB recombinant gp120 (rgp120) human immunodeficiency virus type 1 (HIV-1) vaccines the bind to oligomeric native and monomeric recombinant HIV-1 envelope glycoproteins (rgp 120) was measured in 25 uninfected, healthy adult volunteers. A major focus was to evaluate the effect of simultaneous and sequential immunization with vaccines representing different strains of HIV-1 on the ability to broaden cross-reactivity of antibodies against these and other HIV-1 strains. A flow cytometric indirect immunofluorescence assay (FIFA) to detect vaccine-induced antibody to envelope glycoprotein expressed by infected and rgp120-coated target cells was used, MN rgp120 HIV-1 vaccine given alone and coadministered with IIIB rgp120 HIV-1 vaccine elicited antibody which bound to cells infected with HIV-1MN, HIV-IIIB, HIV-1RF, and HIV-1-SF2. The presence of envelope glycoprotein-binding antibody detected by FIFA correlated to a moderate degree with functional antibody against HIV-1MN and HIV-IIIB. Priming immunization with IIIB rgp120 HIV-1 vaccine followed by booster injections of MN rgp120 HIV-1 vaccine resulted in increased cross-reactive antibody binding to these and heterologous clade B HIV-1 strains infecting cells. MN rgp120 HIV-1 vaccine given alone was better able to induce cross-reactive antibody to cells infected with heterologous HIV-1 laboratory strains than was IIIB rgp120 HIV-1 vaccine given alone. The vaccines induced binding antibody to rgp120 possessing the amino acid sequence of a clade E HIV-1 strain as measured by enzyme-linked immunosorbent assay. Levels of antibody binding to cells infected with clade B HIV-1 and cells coated with monomeric rgp120 were greater than that induced by HIV-1IIIB-based gp160 vaccines in previous studies.     

Inter-trial neuronal activity in inferior temporal cortex: a putative vehicle to generate long-term visual associations

When monkeys perform a delayed match-to-sample task, some neurons in the anterior inferotemporal cortex show sustained activity following the presentation of specific visual stimuli, typically only those that are shown repeatedly. When sample stimuli are shown in a fixed temporal order, the few images that evoke delay activity in a given neuron are often neighboring stimuli in the sequence, suggesting that this delay activity may be the neural correlate of associative long-term memory. Here we report that stimulus-selective sustained activity is also evident following the presentation of the test stimulus in the same task. We use a neural network model to demonstrate that persistent stimulus-selective activity across the intertrial interval can lead to similar mnemonic representations (distributions of delay activity across the neural population) for neighboring visual stimuli. Thus, inferotemporal cortex may contain neural machinery for generating long-term stimulus-stimulus associations.     

Reduced visuospatial performance in children with the D2 dopamine receptor A1 allele

Previous studies suggest a reduced dopaminergic function in subjects with the A1 (minor) allele of the D2 dopamine receptor (DRD2) gene. To explore influences on visuospatial ability as a function of the DRD2 gene, 182 alcohol- and other drug-naive sons (age 10–14) of active alcoholic, recovered alcoholic, and nonalcoholic fathers were administered a visuospatial task (Benton's Judgment of Line Orientation Test) which makes minimal motoric/verbal demands. Visuospatial scores were lower for boys with the A1 allele and for sons of active alcoholics. A1-allele boys made more errors than A2 boys on all 11 of the template lines, with the effect being largest for the rightmost presentations. In contrast, the effect of family history for alcoholism was strongest on both right and left midquadrant presentations. Moreover, separate analyses of the two types of errors produced allele but not family history of alcoholism effects when the two lines were misjudged as farther apart than they actually were and family history but not allele effects where the two lines were misjudged as closer together. These results suggest that polymorphism of the DRD2 gene and family history of alcoholism are dissociable determinants of visuospatial ability and that visuospatial defects previously observed in alcoholics may, in part, be antecedent to their drinking behavior.     

Preparation of Cell Wall Antigens of Staphylococcus aureus

Cell walls were prepared from Staphylococcus aureus strains Copenhagen and 263 by high-speed mixing in the presence of glass beads followed by differential centrifugation. Insoluble peptidoglycan complexes were derived from cell walls by extraction of teichoic acid with 10% trichloroacetic acid. Intact teichoic acid was prepared from each strain by digestion of cell walls with lysostaphin and isolated by column chromatography. Soluble glycopeptide (peptidoglycan in which only the glycan has been fragmented) and the stable complex of teichoic acid with glycopeptide were prepared by digestion of cell walls with Chalaropsis B endo-N-acetylmuramidase and were separated by column chromatography. Amino acid and amino sugar contents of walls and subunits of walls were comparable to those reported by others.     

MCP-1-dependent signaling in CCR2(-/-) aortic smooth muscle cells

Monocyte chemoattractant protein-1 (MCP-1, CCL2) is a mediator of inflammation that has been implicated in the pathogenesis of a wide variety of human diseases. CCR2, a heterotrimeric G-coupled receptor, is the only known receptor that functions at physiologic concentrations of MCP-1. Despite the importance of CCR2 in mediating MCP-1 responses, several recent studies have suggested that there may be another functional MCP-1 receptor. Using arterial smooth muscle cells (SMC) from CCR2(-/-) mice, we demonstrate that MCP-1 induces tissue-factor activity at physiologic concentrations. The induction of tissue factor by MCP-1 is blocked by pertussis toxin and 1,2-bis(O-aminophenyl-ethane-ethan)-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, suggesting that signal transduction through the alternative receptor is G(alphai)-coupled and dependent on mobilization of intracellular Ca(2+). MCP-1 induces a time- and concentration-dependent phosphorylation of the mitogen-activated protein kinases p42/44. The induction of tissue factor activity by MCP-1 is blocked by PD98059, an inhibitor of p42/44 activation, but not by SB203580, a selective p38 inhibitor. These data establish that SMC possess an alternative MCP-1 receptor that signals at concentrations of MCP-1 that are similar to those that activate CCR2. This alternative receptor may be important in mediating some of the effects of MCP-1 in atherosclerotic arteries and in other inflammatory processes.     

Effects of digoxin in infants with congested circulatory state due to a ventricular septal defect

Digoxin alone was used to treat a congested circulatory state in 21 infants (mean age, 2.7 months; mean weight, 3.8 kg) with a ventricular septal defect. The dose was adjusted on the basis of pharmacokinetics to achieve a mean steady-state concentration of 1.6 +/- 0.3 ng of digoxin per milliliter of serum. The mean red-cell level of sodium-potassium ATPase fell from 23.1 +/- 7.0 to 12.6 +/- 5.2 nmol per milligram per minute with treatment. Only 6 of the 21 patients had an inotropic response, as reflected by echocardiographic measurements, but the drug was of clinical benefit to 12 infants (including these 6). These results show that not all infants with a congested circulatory state due to a ventricular septal defect benefit from digoxin therapy. Furthermore, in some subjects clinical improvement occurs in the absence of a measurable inotropic response.     

Intracellular Ca++/Mg++ homeostasis during postnatal growth of experimental rats. Multiple time-point study

In most tissues, various cell membrane ion transporting systems are not fully developed and/or maximally active at the prenatal and early postnatal stage. Their progressive development and expression are a function of growth and maturity. We performed a multiple time-point study, in order to investigate the ability of a variety of tissues to maintain appropriate Ca++ and Mg++ homeostasis at different stages of postnatal development. Total intracellular Ca++ in one-week-old rat liver, brain and spinal cord tissues was significantly elevated, compared to mature animals. It increased further through the first three weeks of gestation. Intracellular Ca++ gradually and significantly declined in adult and mature animal groups. Alterations in total intracellular Mg++ of the same tissue samples, although not so profound, paralleled changes in total intracellular Ca++. We conclude that a developmental switch in intracellular Ca++ and Mg++ homeostasis occurs one to three weeks following birth. It might be related to the incomplete development of Ca++ and Mg++ transmembrane transporting systems, previously reported as being only partially expressed at the early postnatal stage. These developmental alterations in total intracellular Ca++ and Mg++ content might serve as a regulatory mechanism, adjusting cell activities to the physiological requirements of the growing and maturing animal.     

Intramural distribution of adrenergic and cholinergic nerve fibers innervating arterioles of the hamster cheek pouch

Electron microscopic, autoradiographic and histochemical techniques were used to determine the distribution of adrenergic and cholinergic nerve fibers within the walls of arterioles having a width of 35 to 60 μ in the hamster cheek pouch. Nerves were confined to the adventitia and their varicose regions were distributed so that 86% were located within 1 μ of the media. Arterioles exposed to ³H-norepinephrine and examined by light microscopic autoradiography exhibited several sites of silver grain accumulation, as a result of the uptake of ³H-norepinephrine by adrenergic nerve fibers. In electron autoradiographs, approximately 70% of all adventitial nerve fibers exhibited silver grains and are therefore considered to be noradrenergic. The majority of all nerve-associated silver grains were located near the adventitial-medial junction. Smooth muscle cells sometimes possessed concentrations of silver grains above background levels, perhaps reflecting the capacity of these cells to take up norepinephrine. Acetylcholinesterase activity was demonstrated in 16 to 44% of the adventitial nerve fibers and they are presumed to be cholinergic. Acetylcholinesterase-stained fibers were distributed throughout the adventitia with 43% being located closer than 1 μ to the media. The morphological identification of a dual adrenergic and cholinergic innervation of arterioles of the hamster cheek pouch indicates the probable presence of an active as opposed to a passive vasodilatory mechanism.