Refinement of an orthotopic lung cancer model in the nude rat

Over 85% of people with lung cancer eventually succumb to this disease, largely because current chemotherapies are ineffective. The testing and validation of promising new approaches generally rely on achieving responses with cell lines in vitro or in tumor xenografts in nude mice. However, quite often the results seen with these models are not recapitulated in the clinic, thus necessitating the need for better animal models of lung cancer for preclinical testing of new therapies. One promising model is that of orthotopic lung cancer, where xenografts of human lung cancer are established in lungs of immunodeficient rodents. The problems associated with this model include poor rates of engraftment, limited tumor multiplicity, and a heightened risk for surgical trauma. The purpose of our study was to develop an efficient approach to engraftment of orthotopic tumors throughout the lungs of the Rowett nude rat. Initially, we augmented immunosuppression in the rats with whole-body X-irradiation and then used orotracheal cannulas to intratracheally instill human cancer cells from the Calu-6 cell line. This protocol produced a low rate of engraftment and low tumor multiplicity. The hypothesis that slight disruption of the pulmonary epithelium or the surfactant layer would allow better tumor engraftment was tested by coadministration of either pancreatic elastase or ethylenediaminetetraacetic acid (EDTA) along with the cell instillations. Lung tumor engraftment was evaluated 8 weeks after instillation. The inclusion of elastase or EDTA with the Calu-6 cells resulted in an 80-100% engraftment rate, respectively. Coadministration of EDTA resulted in significantly larger and greater numbers of tumors/lung than those in elastase-treated animals. Temporal studies demonstrated that small nodules were scattered throughout the lung parenchyma 5 weeks after instilling Calu-6 cells and EDTA. These nodules grew to coalesce and form large masses that effaced >75% of the parenchyma at 9 weeks postinstillation. The refinements made through our studies have led to the development of an orthotopic lung cancer model that should facilitate the evaluation of novel therapies designed to treat or impede lung cancer development.     

Changes in volatile terpene and diterpene resin acid composition of resistant and susceptible white spruce leaders exposed to simulated white pine weevil damage

Induced (traumatic) resin in white spruce (Picea glauca (Moench) Voss) leaders resistant or susceptible to the white pine weevil (Pissodes strobi Peck) was analyzed for volatile terpenes and diterpene resin acids after simulated white pine weevil damage. Leaders from 331 trees were wounded just below the apical bud with a 1-mm diameter drill, coinciding with the natural time of weevil oviposition in the spring. Leaders were removed in the fall, and the bark and xylem from the upper and lower regions of the leader extracted and analyzed by gas chromatography. Unwounded trees had low amounts of resin in xylem compared with bark. In response to wounding, volatile terpenes and diterpene resin acids increased in the upper xylem (area of wounding), with resistant trees showing a greater increase than susceptible trees. Wounding caused monoterpenes in particular to decrease in the lower region of the leader (away from the drilled area) in greater amounts in susceptible trees than in resistant trees. In response to wounding, the proportion of monoterpene to resin acid increased in the upper and lower xylem of resistant trees, and slightly increased in the upper xylem of susceptible trees. Monoterpene-enriched resin is more fluid than constitutive resin, and probably flows more readily into oviposition cavities and larval mines, where it may kill immature weevils. Loss of resin components in the lower xylem suggested catabolism and transport of these materials to the site of wounding; however, energetic and regulatory data are necessary to confirm this hypothesis. This study provides a basis for measuring the ability of a tree to undergo traumatic resinosis that could be used to screen for resistance to white pine weevil.     

Small-scale jetlike features in penumbral chromospheres

We observed fine-scale jetlike features, referred to as penumbral microjets, in chromospheres of sunspot penumbrae. The microjets were identified in image sequences of a sunspot taken through a Ca II H-line filter on the Solar Optical Telescope on board the Japanese solar physics satellite Hinode. The microjets' small width of 400 kilometers and short duration of less than 1 minute make them difficult to identify in existing observations. The microjets are possibly caused by magnetic reconnection in the complex magnetic configuration in penumbrae and have the potential to heat the corona above a sunspot.     

Serologic correlation of suspected Leptospira interrogans serovar pomona-induced uveitis in a group of horses

After the observation of 2 horses with uveitis on a horse farm in the Minnesota River valley, 100 horses from this geographic area were given ophthalmologic examinations and were evaluated serologically for leptospirosis. A statistically significant (P less than 0.001) association was observed between the finding of antibodies against Leptospira interrogans serovar pomona and uveitis.     

Recording of the reticular motility in cattle with experimental and spontaneous traumatic reticuloperitonitis

Using the method described in a previous publication for recording the reticulum action in normal cows the authors have investigated three cows with experimentally produced reticuloperitonitis as well as a group of cows with spontaneous peritonitis under treatment at the stationary clinic. The experimental animals were provided with permanent rumen fistulas.In the three cows with experimentally produced peritonitis the pointed object worked loose spontaneously during the first 24 hrs. The symptoms were mild after the first perforation and became aggravated after further perforations.An abnormally prolonged reticulum interval was recorded immediately after the perforation and continued to be clearly distinguishable for two to three days. In the cows with spontaneous peritonitis, this change was observed only in the acute stage.Prolongation of the second phase of the reticulum was the most pronounced finding from the recordings of the reticular movements, both in the cows with experimental peritonitis and in those in the spontaneous group. The change was at its height after two to seven days, and then subsided gradually in the experimental animals in which repeated recordings had been made.The pressure elevation in reticulum during the contractions was lower both in the animals with experimental peritonitis and in the spontaneous group than in the healthy animals.The cows with reticuloperitonitis also displayed impaired ability to pass the recording catheter from the atrium ruminis to the reticulum.