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.     

Pregnancy-associated plasma protein-A in pregnant cynomolgus monkeys (Macaca fascicularis): radioimmunoassay, normal levels, effect of RU 486, and preliminary characterization

Pregnancy-associated plasma protein-A (PAPP-A) is a human macromolecular glycoprotein produced by the trophoblast and possibly by the decidua. Its biological function is unknown, but in vitro, PAPP-A has been reported to be an inhibitor of granulocyte elastase. The present study was undertaken to see if pregnant cynomolgus monkeys could be an animal model sufficiently close to the human situation to study the physiology of PAPP-A. An antiserum to pregnant cynomolgus plasma was raised in rabbits. After adsorption with normal monkey plasma, this antiserum was used together with radioiodinated human PAPP-A to develop an heterologous radioimmunoassay for measurements of monkey PAPP-A. On polyacrylamide gel electrophoresis, it was shown that this polyspecific-antiserum bound the same molecular species of radioiodinated human PAPP-A as the available anti-human PAPP-A antiserum. The concentrations of cynomolgus PAPP-A (cPAPP-A) throughout pregnancy follow the same pattern as human PAPP-A (hPAPP-A) with an almost exponential increase up to term. The doubling time of cPAPP-A was similar to that of hPAPP-A. After RU 486-induced abortion or after spontaneous abortion, the levels of cPAPP-A decreased, with an apparent half-life of 2-3 days. Preliminary characterization of cPAPP-A revealed that although cPAPP-A was only immunologically related to hPAPP-A, it was biochemically very similar: they had the same PI and the same molecular weight, and both PAPP-As bound heparin. It is concluded that pregnant cynomolgus monkeys are a good model to study the physiology of PAPP-A.     

Extracellular matrix influences hormone and protein production by human chorionic villi

Summary Increasing evidence confirms that the extracellular matrix greatly influences cell behaviour and function. Collagen and fibrin are in contact with trophoblast throughout pregnancy. To investigate whether these two matrices influence hormon production by the trophoblast, explants from first-trimester chorionic villi were cultured for up to 30 days either a) in medium with agitation, b) embedded in type-I collagen (three-dimensional gels), or c) embedded in fibrin (three-dimensional gels). The supernatant culture medium was changed every 48 h and tested by radioimmunoassay for hCG, progesterone and pregnancy-associated plasma protein A. In addition, after 3, 7, 15, and 30 days of culture villi were fixed and studied by light and electron microscopy. Embedding in the extracellular matrix showed higher and longer-lasting production rates of all measured products and superior structural preservation as compared to cultures with agitation. Collagen matrix proved to be superior to fibrin. As established by several tests, this difference was neither due to thrombin used to polymerize fibrinogen, nor to differences in the diffusion rates through the two different matrices used. We conclude that extracellular matrix, particularly collagen, influences the synthesis of trophoblastic products. Embedding of the villous explants in three-dimensional gels constitutes a new method for long-term cultures of chorionic villi.This study was presented at the workshop Placental-and decidual-specific protein synthesis and secretion: regulation, role and interaction, Zemun, Belgrade, Yugoslavia, 19–20 May, 1988 (Bischof and Castellucci 1988; see also J. Aplin 1989), and at the 11th Rochester Trophoblast Conference, Rochester, N.Y. USA, 9–12 October 1988 (Castellucci et al. 1988)     

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.     

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.     

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.     

Contributions of unstirred-layer effects to apparent electrokinetic phenomena in the gall-bladder

Summary Passage of electric current across rabbit gall-bladder, which is preferentially permeable to cations, causes water flow towards the negative electrode, as expected for electroosmosis in a cation-selective membrane. Current passage also causes development of a polarization potential difference, i.e. a transepithelial potential difference (p.d.) which transiently remains after cessation of current flow and decays back to zero with a half-time of 22 to 90 sec. The polarization p.d. is due to current-induced local changes of salt concentration in unstirred layers, mainly at the serosal face of the epithelium. These changes originate through the so-called transport-number effect. Calculation shows that much of the observed current-induced water flow represents an osmotic flow due to these local concentration changes, rather than representing true electroosmosis. By implication, a large component of streaming potentials in the gall-bladder is a boundary diffusion potential, owing to water flow producing local changes of salt concentration in unstirred layers.