Imaging proliferation in vivo with [F-18]FLT and positron emission tomography

Positron emission tomography (PET) is now regularly used in the diagnosis and staging of cancer. These uses and its ability to monitor treatment response would be aided by the development of imaging agents that can be used to measure tissue and tumor proliferation. We have developed and tested [F-18]FLT (3'-deoxy-3'-fluorothymidine); it is resistant to degradation, is retained in proliferating tissues by the action of thymidine kinase 1 (TK), and produces high-contrast images of normal marrow and tumors in canine and human subjects.     

Decompression illness in sports divers detected with technetium-99m-HMPAO SPECT and texture analysis

Diving for sport and recreation has increased in recent years, resulting in more incidences of diving illness. Therefore, we studied potential use of regional cerebral blood flow SPECT imaging with 99mTc-HMPAO in the management of divers who have experienced decompression illness (DCI). METHODS: A group of ten sports divers who had no experience of DCI were compared with ten sports divers who had experienced at least one episode of DCI. Transaxial SPECT images were first compared objectively using a first-order texture measure and then subjectively using a receiver operator characteristic (ROC) experiment. Experienced observers were asked to rate images subjectively in terms of the images' textural appearance. RESULTS: Both these techniques showed that there is a statistically significant difference between the two groups and the images produced by the DCI divers were generally more coarsely patchy when compared to the non DCI divers. The quantitative texture technique proved significantly better in identifying divers with DCI than the visual analysis by observers using ROC curves. CONCLUSION: Differences between the cerebral blood flow patterns of sports divers who have experienced DCI and sports divers who have no experience of DCI can be detected using 99mTc-HMPAO SPECT and a texture analysis technique.     

Depression and self-medication with nicotine: The modifying influence of the dopamine D4 receptor gene.

This study evaluated whether there are genetic subgroups of depressed individuals who are more or less predisposed to engage in self-medication smoking practices. Smokers (N?=?231) completed self-report questionnaires of depression and smoking practices and were genotyped for the dopamine D4 (DRD4) gene. A significant interaction (DRD4 Genotype?×?Depression) was found for stimulation smoking and negative-affect reduction smoking. Specifically, these smoking practices were significantly heightened in depressed smokers homozygous for the short alleles of DRD4 but not in those heterozygous or homozygous for the long alleles of DRD4. These preliminary results suggest that the rewarding effects of smoking and the beneficial effects of nicotine replacement therapy for depressed smokers may depend, in part, on genetic factors involved in dopamine transmission. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Efficiency of use of metabolizable energy for body weight gain in pasture-based,nonlactating dairy cows

Four cohorts of nonlactating, pregnant dairy cows (n = 50, 47, 45, and 42) were individually fed indoors to determine the amount of feed required for body weight (BW) gain from autumn pasture and commonly used supplementary feeds. These results were used to estimate the apparent efficiency with which metabolizable energy (ME) is used for BW gain (app_k_g). Control cows were offered autumn pasture to estimated maintenance requirements (~0.55 MJ of ME/kg of BW^0.75), with an additional 20 MJ of ME/d allocated for pregnancy and activity. All other cows received the same allowance of autumn pasture and an additional allowance (2.5 or 5.0 kg of dry matter/d) of autumn pasture (Past), spring pasture silage (Psil), maize silage (Msil), cracked maize grain (Mgr), or palm kernel expeller (PKE), resulting in a total of 11 treatments. Individual cow dry matter intake was determined daily; BW was recorded once per week for cohorts 1 and 2, and 3 times per week for cohorts 3 and 4. The ME contents of feeds were estimated from feed quality assays. Regression analyses were used on each feed to determine the ME requirement for 1 kg of BW gain. The app_k_g of Past and Msil was 0.34 and 0.47, respectively; these estimates are in line with published literature. The app_k_g of Psil (0.50) was consistent with the published k_g for spring pasture, from which the silage was made. Palm kernel expeller had the greatest app_k_g (0.61). The reasons for this cannot be deduced from the current study but may reflect the relatively high fat content of the feed and the high k_g of fat. The app_k_g for Mgr was low (0.38) in comparison with the other supplementary feeds and, in particular, relative to its feed ME and published k_g estimates. Although the reason for the low app_k_g cannot be deduced from the current data, the most plausible reason is the preferential use of propionate-derived glucose for conceptus metabolism rather than BW gain, a factor not accounted for in previous experimental models that did not use late-gestation cows. In summary, the app_k_g for autumn pasture was low but consistent with historical growth rate trials in other ruminant species. In comparison, Msil, Psil, and PKE were used with a greater apparent efficiency (app_k_g = 0.47 to 0.61), but Mgr resulted in a relatively low rate of gain per MJ of ME (app_k_g = 0.38). These differences have implications for accurate feed budgeting on farm.     

Amino acid enrichment and compositional changes among mammalian milk proteins and the resulting nutritional consequences

Milk is a hallmark of mammalian evolution: a unique food that has evolved with mammals. Despite the importance of this food, it is not known if variation in AA composition between different species is important to milk proteins or how it might affect the nutritional value of milk. As milk is the only food source for newborn mammals, it has long been speculated that milk proteins should be enriched in essential AA. However, no systematic analysis supports this assumption. Although many factors influence the overall nutritional value of milk, including total protein concentration, we focused here on the AA composition of milk proteins and investigated the possibility that selection drives compositional changes. We identified 9 major milk proteins present in 13 mammalian species and compared them with a large group of nonmilk proteins. Our results indicate heterogeneity in the AA composition of milk proteins, showing significant enrichment and depletion of certain AA in milk-specific proteins. Although high levels of particular AA appear to be consistently maintained, orthologous milk proteins display significant differences in AA composition across species, most notably among the caseins. Interspecies variation of milk composition is thought to be indicative of nutritional optimization to the requirements of the species. In accordance with this, our observations indicate that milk proteins may have adapted to the species-specific nutritional needs of the neonate.     

The use of confocal microscopy in evaluating corneal wound healing after excimer laser keratectomy

Corneal wound healing following excimer laser keratectomy is the major cause of regression of treatment results. The amount of anterior strorhal haze that develops may be influenced by topical medications. Over a period of 6 months, we followed 15 New Zealand white rabbit eyes that underwent excimer laser keratectomy with the VISX 193-nm ArF laser at a fluence of 150 mJ/cm² for a depth of 130 μm. Eyes were randomized to treatment with prednisolone acetate, diclofenac sodium (Voltaren), a combination of both, and a control group. Drops were administered four times a day for 1 week, two times a day for 3 weeks, and the drops were then tapered. All eyes were reepithelialized by 5 to 7 days. The tandem scanning confocal microscope (TSCM) was used to evaluate the corneal wound in vivo weekly for a month and monthly for 6 months. During the early postoperative period, the TSCM revealed significant anterior stromal keratocyte activation with cell elongation and the spindle-shaped appearance of fibroblasts in all groups. Collagenous stromal scarring was evident initially, then slowly decreased in all treatment groups. This study shows that TSCM is clinically useful for successive in vivo examinations of corneal wounds after excimer laser keratectomy and for comparing the effects of various topical medications.     

Indoor hydrogen peroxide derived from ozone/d-limonene reactions

In this pilot study, performed in an office manipulated to resemble an environment with a strong indoor ozone source or a significant influx of outdoor air during a smog event, reactions between ozone and d-limonene produced hydroperoxides. Hydrogen peroxide (H202) presumably constituted the majority of the measured hydroperoxides, although a small amount of organic hydroperoxides (ROOH) may have contributed to the signal. Total hydroperoxides were 1.0-1.5 ppb at low air exchange rates (0.5-4 h(-1)) and 0.6-0.8 ppb at high air exchange rates (12-18 h-1). The net estimated yield ranged from 1.5 to 3.2%, consistent with values reported in the literature. Based on these yields and typical indoor scenarios, peak indoor concentrations of H202 are projected to be comparable with, but not significantly larger than, peak outdoor concentrations. Hygroscopic secondary organic aerosols (SOA; 10-100 microg m(-3)) were simultaneously generated by the ozone/d-limonene reactions; their co-occurrence with H202 provides a mechanism whereby H2O2 can be transported into the lower respiratory tract. The results demonstrate that reduced air exchange rates lead to increased concentrations of H2O2 and SOA as well as a shift in the size-distribution toward larger particles (0.3-0.7 microm diameter), potentially increasing the amount of H2O2 delivered to the lower respiratory region. This study increases our understanding of H2O2 exposures, including exposures to H2O2 associated with co-occurring hygroscopic aerosols. It also re-emphasizes the potential of ozone-driven chemistry to alter indoor environments, often producing products more irritating than their precursors.     

Regulation of T cell activation in vitro and in vivo by targeting the OX40-OX40 ligand interaction: amelioration of ongoing inflammatory bowel disease with an OX40-IgG fusion protein, but not with an OX40 ligand-IgG fusion protein

The role of GRP78/BiP in coordinating endoplasmic reticular (ER) protein processing with mRNA translation was examined in GH3 pituitary cells. ADP-ribosylation of GRP78 and eukaryotic initiation factor (eIF)-2alpha phosphorylation were assessed, respectively, as indices of chaperone inactivation and the inhibition of translational initiation. Inhibition of protein processing by ER stress (ionomycin and dithiothreitol) resulted in GRP78 deribosylation and eIF-2 phosphorylation. Suppression of translation relative to ER protein processing (cycloheximide) produced approximately 50% ADP-ribosylation of GRP78 within 90 min without eIF-2 phosphorylation. ADP-ribosylation was reversed in 90 min by cycloheximide removal in a manner accelerated by ER stressors. Cycloheximide sharply reduced eIF-2 phosphorylation in response to ER stressors for about 30 min; sensitivity returned as GRP78 became increasingly ADP-ribosylated. Reduced sensitivity of eIF-2 to phosphorylation appeared to derive from the accumulation of free, unmodified chaperone as proteins completed processing without replacements. Prolonged (24 h) incubations with cycloheximide resulted in the selective loss of the ADP-ribosylated form of GRP78 and increased sensitivity of eIF-2 phosphorylation in response to ER stressors. Brefeldin A decreased ADP-ribosylation of GRP78 in parallel with increased eIF-2 phosphorylation. The cytoplasmic stressor, arsenite, which inhibits translational initiation through eIF-2 phosphorylation without affecting the ER, also produced ADP-ribosylation of GRP78.     

Integrated diamond networks for quantum nanophotonics

We demonstrate an integrated nanophotonic network in diamond, consisting of a ring resonator coupled to an optical waveguide with grating in- and outcouplers. Using a nitrogen-vacancy color center embedded inside the ring resonator as a source of photons, single photon generation and routing at room temperature is observed. Furthermore, we observe a large overall photon extraction efficiency (10%) and high quality factors of ring resonators (3200 for waveguide-coupled system and 12,600 for a bare ring).     

Bubble-Based Microrobots with Rapid Circular Motions for Epithelial Pinning and Drug Delivery

Remotely powered microrobots are proposed as next-generation vehicles for drug delivery. However, most microrobots swim with linear trajectories and lack the capacity to robustly adhere to soft tissues. This limits their ability to navigate complex biological environments and sustainably release drugs at target sites. In this work, bubble-based microrobots with complex geometries are shown to efficiently swim with non-linear trajectories in a mouse bladder, robustly pin to the epithelium, and slowly release therapeutic drugs. The asymmetric fins on the exterior bodies of the microrobots induce a rapid rotational component to their swimming motions of up to ≈150 body lengths per second. Due to their fast speeds and sharp fins, the microrobots can mechanically pin themselves to the bladder epithelium and endure shear stresses commensurate with urination. Dexamethasone, a small molecule drug used for inflammatory diseases, is encapsulated within the polymeric bodies of the microrobots. The sustained release of the drug is shown to temper inflammation in a manner that surpasses the performance of free drug controls. This system provides a potential strategy to use microrobots to efficiently navigate large volumes, pin at soft tissue boundaries, and release drugs over several days for a range of diseases.