Rapid Antiretroviral Therapy Initiation for Women in an HIV-1 Prevention Clinical Trial Experiencing Primary HIV-1 Infection during Pregnancy or Breastfeeding

During an HIV-1 prevention clinical trial in East Africa, we observed 16 cases of primary HIV-1 infection in women coincident with pregnancy or breastfeeding. Nine of eleven pregnant women initiated rapid combination antiretroviral therapy (ART), despite having CD4 counts exceeding national criteria for ART initiation; breastfeeding women initiated ART or replacement feeding. Rapid ART initiation during primary HIV-1 infection during pregnancy and breastfeeding is feasible in this setting.     

Assessing Greater Sage-Grouse Selection of Brood-Rearing Habitat Using Remotely-Sensed Imagery: Can Readily Available High-Resolution Imagery Be Used to Identify Brood-Rearing Habitat Across a Broad Landscape?

Greater sage-grouse populations have decreased steadily since European settlement in western North America. Reduced availability of brood-rearing habitat has been identified as a limiting factor for many populations. We used radio-telemetry to acquire locations of sage-grouse broods from 1998 to 2012 in Strawberry Valley, Utah. Using these locations and remotely-sensed NAIP (National Agricultural Imagery Program) imagery, we 1) determined which characteristics of brood-rearing habitat could be used in widely available, high resolution imagery 2) assessed the spatial extent at which sage-grouse selected brood-rearing habitat, and 3) created a predictive habitat model to identify areas of preferred brood-rearing habitat. We used AIC model selection to evaluate support for a list of variables derived from remotely-sensed imagery. We examined the relationship of these explanatory variables at three spatial extents (45, 200, and 795 meter radii). Our top model included 10 variables (percent shrub, percent grass, percent tree, percent paved road, percent riparian, meters of sage/tree edge, meters of riparian/tree edge, distance to tree, distance to transmission lines, and distance to permanent structures). Variables from each spatial extent were represented in our top model with the majority being associated with the larger (795 meter) spatial extent. When applied to our study area, our top model predicted 75% of naïve brood locations suggesting reasonable success using this method and widely available NAIP imagery. We encourage application of our methodology to other sage-grouse populations and species of conservation concern.     

Compartmentalization of proline pools and apparent rates of collagen and non-collagen protein synthesis in arterial smooth muscle cells in culture.

Rates of collagen and non-collagen protein synthesis in rabbit arterial smooth muscle cells (SMC) were determined by using the specific (radio)activity of [3H]proline in the extracellular, intracellular, and prolyl-tRNA pools. The intracellular free proline specific activity was only 25% of the extracellular value in cultures incubated for 12 h in 0.25 mM-proline. The specific activity of prolyl-tRNA was less than 10% of the extracellular specific activity. Increasing the extracellular proline concentration 10-fold (to 2.5 mM), while keeping the extracellular specific activity of proline constant, resulted in equilibration of the specific activities of intracellular and extracellular free proline, but the specific activity of prolyl-tRNA remained at less than 10% of the extracellular specific activity. Therefore, calculated rates of collagen and non-collagen protein synthesis were greatly underestimated using the intracellular or extracellular specific activity of proline. SMC were also incubated with 0.1 mM-[14C]ornithine in 0.25 nM or 2.5 mM non-labelled proline to examine synthesis de novo of proline and prolyl-tRNA from ornithine. In SMC cultures containing 0.25 mM unlabelled proline, the specific activity of intracellular ornithine was approx. 45% of the extracellular specific activity, due to the production of unlabelled ornithine. The specific activity of ornithine-derived intracellular free proline in SMC incubated with 2.5 mM-proline was significantly lower than in SMC incubated in 0.25 mM-proline, due to the influx of unlabelled proline. However, a corresponding difference in the specific activity of [14C]prolyl-tRNA between SMC in 0.25 mM- or 2.5 mM-proline was not observed. Ornithine-derived [14C]proline was incorporated into proteins in a manner different from that of exogenously added radiolabelled proline. A much higher proportion of the proline synthesized de novo was channelled into collagen synthesis relative to total protein synthesis. Together, these results show that intracellular proline pools are highly compartmentalized in arterial SMC. They also suggest that proline synthesized from ornithine may enter a prolyl-tRNA pool separate from that of proline entering from the extracellular medium.     

Thermoregulatory adjustments during continuous heat exposure

Body temperature regulation was studied in 6 male subjects during an acclimation procedure involving uninterrupted heat exposure for 5 successive days and nights in a hot dry environment (ambient temperature = 35 degrees C, dew-point temperature = 7 degrees C; air velocity = 0.2 m.s-1). Data were obtained at rest and during exercise (relative mechanical workload = 35% VO2max). At rest, hourly measurements were made of oesophageal and 4 local skin temperatures, to allow the calculation of mean skin temperature, and of body motility and heart rate. During the working periods these measurements were made at 5 min intervals. Hourly whole-body weight loss was measured at rest on a sensitive platform scale while in the working condition just before starting and immediately after completing the bicycle exercise. The results show that, in both exercise and at rest, the successive heat exposures increased the sweat gland output during the first 3 days. Afterwards, sweat rate decreased without any corresponding change in body temperature. For the fixed workload, the sweat rate decline was associated with a decrease in circulatory strain. Adjustments in both sweating and circulatory mechanisms occur in the first 3 days of continuous heat exposure. The overall sweat rate decline could involve a redistribution of the regional sweating rates which enhances the sweat gland activities of skin areas with maximal evaporative efficiencies.     

pH Dependence of Histidine Affinity for Blood-Brain Barrier Carrier Transport Systems for Neutral and Cationic Amino Acids

The effects of pH (3.5-7.5) on the brain uptake of histidine by the blood-brain barrier (BBB) carriers for neutral and cationic amino acids were tested, in competition with unlabeled histidine, arginine, or phenylalanine, with the single-pass carotid injection technique. Cationic amino acid ( [14C]arginine) uptake was increasingly inhibited by unlabeled histidine as the pH of the injection solution decreased. In contrast, the inhibitory effect of unlabeled histidine on neutral amino acid ( [14C]phenylalanine) uptake decreased with decreasing pH. Brain uptake indices with varying histidine concentrations indicated that the neutral form of histidine inhibited phenylalanine uptake whereas the cationic form competed with arginine uptake. Since phenylalanine decreased [14C]histidine uptake at all pH values whereas arginine did not, it was concluded that the cationic form of histidine had an affinity for the cationic carrier, but was not transported by it. We propose that the saturable entry of histidine into brain is, under normal physiological circumstances, mediated solely by the carrier for neutral amino acids.     

Venous occlusion pressure and vascular permeability in the dog lung after air embolization

Pulmonary edema has frequently been associated with air embolization of the lung. In the present study the hemodynamic effects of air emboli (AE) were studied in the isolated mechanically ventilated canine right lower lung lobe (RLL), pump perfused at a constant blood flow. Air was infused via the pulmonary artery (n = 7) at 0.6 ml/min until pulmonary arterial pressure (Pa) rose 250%. While Pa rose from 12.4 +/- 0.6 to 44.6 +/- 2.0 (SE) cmH2O (P less than 0.05), venous occlusion pressure remained constant (7.0 +/- 0.5 to 6.8 +/- 0.6 cmH2O; P greater than 0.05). Lobar vascular resistance (RT) increased from 2.8 +/- 0.3 to 12.1 +/- 0.2 Torr.ml-1.min.10(-2) (P less than 0.05), whereas the venous occlusion technique used to determine the segmental distribution of vascular resistance indicated the increase in RT was confined to vessels upstream to the veins. Control lobes (n = 7) administered saline at a similar rate showed no significant hemodynamic changes. As an index of microvascular injury the pulmonary filtration coefficient (Kf) was obtained by sequential elevations of lobar vascular pressures. The Kf was 0.11 +/- 0.01 and 0.07 +/- 0.01 ml.min-1.Torr-1.100 g RLL-1 in AE and control lobes, respectively (P less than 0.05). Despite a higher Kf in AE lobes, total lobe weight gains did not differ and airway fluid was not seen in the AE group. Although air embolization caused an increase in upstream resistance and vascular permeability, venous occlusion pressure did not increase, and marked edema did not occur.     

Intranuclear distribution of SV40 large T-antigen and transformation-related protein p53 in abortively infected cells

The intranuclear localization of SV40 T-antigen (T-Ag) and the cellular protein p53 was studied in SV40 abortively infected baby mouse kidney cells using two complementary methods of ultrastructural immunocytochemistry in combination with preferential staining of nuclear RNP components and electron microscope autoradiography. Both proteins were revealed in association with peri- and interchromatin RNP fibrils containing the newly synthesized hnRNA. In addition, T-Ag and p53 remained bound, at least in part, to the residual internal nuclear matrix following nuclease and salt extractions of infected cells. The localization of T-Ag was different in SV40 lytically infected monkey kidney cells since, in addition to hnRNP fibrils, the viral protein was also associated with cellular chromatin. However, when lytic infection was performed in conditions of blocked viral DNA replication, T-Ag was no longer associated with the cellular chromatin but remained bound to the hnRNP fibrils. We conclude that the transforming and lytic functions of T-Ag can be distinguished by different subnuclear distributions. The significance of the association of T-Ag and p53 with hnRNP fibrils and the internal nuclear matrix is discussed in relation to the role of these structures in the control of cellular mRNA biogenesis.     

Use of phlorizin binding to demonstrate induction of intestinal glucose transporters

Summary We used specific binding of phlorizin to the intact intestinal mucosa in order to measure glucose transport site density in intestines of mice fed a high-carbohydrate or no-carbohydrate diet. Nonspecific binding varied with intestinal position but showed only modest dependence on diet. Specific binding to glucose transporters was 1.9 times greater in jejunum of high-carbohydrate mice than of no-carbohydrate mice; this ratio was the same as the ratio for V_max values of actived-glucose uptake between the two diet groups. The gradient in specific binding of phlorizin along the intestine paralleled the gradient in V_max of glucose transport. These results directly demonstrate that the increase in intestinal glucose transport caused by a high-carbohydrate diet is due to induction of glucose transporter. They also indicate that the normal positional graident in glucose transport along the intestine arises from a gradient in transporters, induced by the normal gradient in luminal glucose concentration.     

Prostanoid inhibition potentiates vasoconstrictor response to acetylcholine in dog lung

We determined whether cyclooxygenase or phosphodiesterase inhibition would alter the vasomotor response to acetylcholine in the dog lung. Lower left lobes were removed and then cannulated, ventilated, and pump perfused with autogenous blood at constant flow [6.0 +/- 0.1 ml X min-1 X g-1 lower left lobe (LLL)]. LLLs were challenged with graded doses of acetylcholine (ACh) (100-1,000 nmol) into the arterial cannula before and after administration of either 40 microM indomethacin (n = 5), 1 mM aspirin (n = 4), or 1 mM theophylline (n = 5). ACh produced a dose-dependent increase in pulmonary arterial pressure (Pa) and a decrease in the upstream-to-down-stream resistance ratio (Rus/Rds). Pretreatment with either indomethacin or aspirin potentiated the Pa response to ACh while eliminating the ACh-associated decrease in Rus/Rds. Pretreatment with the phosphodiesterase inhibitor theophylline significantly antagonized the ACh pressor response and decrease in the Rus/Rds. The present study suggests that the pulmonary pressor response to ACh is enhanced with cyclooxygenase inhibition. Our results indicate that ACh stimulates pulmonary vascular muscarinic cholinoceptors to cause vasoconstriction. Additionally or as sequelae to this response, predominantly vasodilatory prostanoids appear to be released.     

How do food passage rate and assimilation differ between herbivorous lizards and nonruminant mammals?

Summary What digestive adaptations permit herbivorous nonruminant mammals to sustain much higher metabolic rates than herbivorous lizards, despite gross similarity in digestive anatomy and physiology? We approached this question by comparing four herbivorous species eating the same diet of alfalfa pellets: two lizards (chuckwalla and desert iugana) and two mammals (desert woodrat and laboratory mouse). The mammals had longer small and large intestines, greater intestinal surface area, much higher (by an order of magnitude) food intake normalized to metabolic live mass, and much faster food passage times (a few hours instead of a few days). Among both reptiles and mammals, passage times increase with body size and are longer for herbivores than for carnivores. The herbivorous lizards, despite these much slower passage times, had slightly lower apparent digestive efficiencies than the mammals. At least for chuckwallas, this difference from mammals was not due to differences in body temperature regime. Comparisons of chuckwallas and woodrats in their assimilation of various dietary components showed that the woodrat's main advantage lay in greater assimilation of the dietary fiber fraction. Woodrats achieved greater fiber digestion despite shorter residence time, but possibly because of a larger fermentation chamber, coprophagy, and/or different conditions for microbial fermentation. We conclude with a comparative overview of digestive function in herbivorous lizards and mammals, and with a list of four major unsolved questions.