PyMT-Maclow: A novel, inducible, murine model for determining the role of CD68 positive cells in breast tumor development

CD68+ tumor-associated macrophages (TAMs) are pro-tumorigenic, pro-angiogenic and are associated with decreased survival rates in patients with cancer, including breast cancer. Non-specific models of macrophage ablation reduce the number of TAMs and limit the development of mammary tumors. However, the lack of specificity and side effects associated with these models compromise their reliability. We hypothesized that specific and controlled macrophage depletion would provide precise data on the effects of reducing TAM numbers on tumor development. In this study, the MacLow mouse model of doxycycline-inducible and selective CD68+ macrophage depletion was crossed with the murine mammary tumor virus (MMTV)-Polyoma virus middle T antigen (PyMT) mouse model of spontaneous ductal breast adenocarcinoma to generate the PyMT-MacLow line. In doxycycline-treated PyMT-MacLow mice, macrophage numbers were decreased in areas surrounding tumors by 43%. Reducing the number of macrophages by this level delayed tumor progression, generated less proliferative tumors, decreased the vascularization of carcinomas and down-regulated the expression of many pro-angiogenic genes. These results demonstrate that depleting CD68+ macrophages in an inducible and selective manner delays the development of mammary tumors and that the PyMT-MacLow model is a useful and unique tool for studying the role of TAMs in breast cancer

Star Clusters in Virgo and Fornax Dwarf Irregular Galaxies

We present the results of a search for clusters in dwarf irregular galaxies in the Virgo and Fornax Cluster using HST WFPC2 snapshot data. The galaxy sample includes 28 galaxies, 11 of which are confirmed members of the Virgo and Fornax clusters. In the 11 confirmed members, we detect 237 cluster candidates and determine their V magnitudes, V-I colors and core radii. After statistical subtraction of background galaxies and foreground stars, most of the cluster candidates have V-I colors of -0.2 and 1.4, V magnitudes lying between 20 and 25th magnitude and core radii between 0 and 6 pc. Using H-alpha observations, we find that 26% of the blue cluster candidates are most likely HII regions. The rest of the cluster candidates are most likely massive (>10^4 Msol) young and old clusters. A comparison between the red cluster candidates in our sample and the Milky Way globular clusters shows that they have similar luminosity distributions, but that the red cluster candidates typically have larger core radii. Assuming that the red cluster candidates are in fact globular clusters, we derive specific frequencies (S_N) ranging from ~0-9 for the galaxies. Although the values are uncertain, seven of the galaxies appear to have specific frequencies greater than 2. These values are more typical of ellipticals and nucleated dwarf ellipticals than they are of spirals or Local Group dwarf irregulars.Comment: 46 pages, 14 figures, 3 tables, accepted by AJ. Higher quality PS version of entire paper available at http://www.astro.washington.edu/seth/dirr_gcs.htm

2,6-Disubstituted Piperidines as Modulators of Nicotinic Acetylcholine Receptor Mediated Neurotransmitter Release, Uptake and Storage

Compounds used for treating dependence on or withdrawal from a drug of abuse, for an eating disorder or for a CNS disease or pathology . . . To see the remainder of this abstract, please download this patent

Biomechanical, ultrastructural, and electrophysiological characterization of the non-human primate experimental glaucoma model.

Laser-induced experimental glaucoma (ExGl) in non-human primates (NHPs) is a common animal model for ocular drug development. While many features of human hypertensive glaucoma are replicated in this model, structural and functional changes in the unlasered portions of trabecular meshwork (TM) of laser-treated primate eyes are understudied. We studied NHPs with ExGl of several years duration. As expected, ExGl eyes exhibited selective reductions of the retinal nerve fiber layer that correlate with electrophysiologic measures documenting a link between morphologic and elctrophysiologic endpoints. Softening of unlasered TM in ExGl eyes compared to untreated controls was observed. The degree of TM softening was consistent, regardless of pre-mortem clinical findings including severity of IOP elevation, retinal nerve fiber layer thinning, or electrodiagnostic findings. Importantly, this softening is contrary to TM stiffening reported in glaucomatous human eyes. Furthermore, microscopic analysis of unlasered TM from eyes with ExGl demonstrated TM thinning with collapse of Schlemm's canal; and proteomic analysis confirmed downregulation of metabolic and structural proteins. These data demonstrate unexpected and compensatory changes involving the TM in the NHP model of ExGl. The data suggest that compensatory mechanisms exist in normal animals and respond to elevated IOP through softening of the meshwork to increase outflow

2,6-Disubstituted Piperidines and Piperazine Compounds

The preparation of novel microemulsions to be used as precursors for solid nanoparticles is described. The microemulsion precursors consist of either alcohol-in-fluorocarbon microemulsions, liquid hydrocarbon-in-fluorocarbon microemulsions, or liquid hydrocarbon-in-water microemulsions. The formed solid nanoparticles have diameters below 200 nanometers and can be made to entrap various materials including drugs, magnets, and sensors. The solid nanoparticles can be made to target different cells in the body by the inclusion of a cell-specific targeting ligand. Methods of preparing the novel microemulsion precursors and methods to cure solid nanoparticles are provided

Comparison of Oral Iron Supplement Formulations for Normalization of Iron Status Following Roux-EN-y Gastric Bypass Surgery: a Randomized Trial

Background The evidence behind recommendations for treatment of iron deficiency (ID) following roux-en-y gastric bypass surgery (RYGB) lacks high quality studies. Setting Academic, United States Objective The objective of the study is to compare the effectiveness of oral iron supplementation using non-heme versus heme iron for treatment of iron deficiency in RYGB patients. Methods In a randomized, single-blind study, women post-RYGB and iron deficient received non-heme iron (FeSO4, 195 mg/day) or heme iron (heme-iron-polypeptide, HIP, 31.5 to 94.5 mg/day) for 8 weeks. Measures of iron status, including blood concentrations of ferritin, soluble transferrin receptor (sTfR), and hemoglobin, were assessed. Results At baseline, the mean ± standard deviation for age, BMI, and years since surgery of the sample was 41.5 ± 6.8 years, 34.4 ± 5.9 kg/m2, and 6.9 ± 3.1 years, respectively; and there were no differences between FeSO4 (N = 6) or HIP (N = 8) groups. Compliance was greater than 94%. The study was stopped early due to statistical and clinical differences between groups. Values before and after FeSO4 supplementation, expressed as least square means (95% CI) were hemoglobin, 10.8 (9.8, 11.9) to 13.0 (11.9, 14.0) g/dL; sTfR, 2111 (1556, 2864) to 1270 (934, 1737) μg/L; ferritin, 4.9 (3.4, 7.2) to 15.5 (10.6, 22.6) μg/L; and sTfR:ferritin ratio, 542 (273, 1086) to 103 (51, 204); all p 0.05). Conclusions In accordance with recommendations, oral supplementation using FeSO4, but not HIP, was efficacious for treatment of iron deficiency after RYGB

H-alpha Survey of the Local Volume: Isolated Southern Galaxies

We present our H-alpha observations of 11 isolated southern galaxies: SDIG, PGC 51659, E 222-010, E 272-025, E 137-018, IC 4662, Sag DIG, IC 5052, IC 5152, UGCA 438, and E149-003, with distances from 1 to 7 Mpc. We have determined the total H-alpha fluxes from these galaxies. The star formation rates in these galaxies range from 10^{-1} (IC 4662) to 10^{-4}_{\odot}/yr (SDIG) and the gas depletion time at the observed star formation rates lies within the range from 1/6 to 24 Hubble times H_0^{-1} .Comment: 9 pages, 3 figure