Medulloblastoma growth inhibition by hedgehog pathway blockade

Constitutive Hedgehog (Hh) pathway activity is associated with initiation of neoplasia, but its role in the continued growth of established tumors is unclear. Here, we investigate the therapeutic efficacy of the Hh pathway antagonist cyclopamine in preclinical models of medulloblastoma, the most common malignant brain tumor in children. Cyclopamine treatment of murine medulloblastoma cells blocked proliferation in vitro and induced changes in gene expression consistent with initiation of neuronal differentiation and loss of neuronal stem cell-like character. This compound also caused regression of murine tumor allografts in vivo and induced rapid death of cells from freshly resected human medulloblastomas, but not from other brain tumors, thus establishing a specific role for Hh pathway activity in medulloblastoma growth.     

Genetic structure of human populations

We studied human population structure using genotypes at 377 autosomal microsatellite loci in 1056 individuals from 52 populations. Within-population differences among individuals account for 93 to 95% of genetic variation; differences among major groups constitute only 3 to 5%. Nevertheless, without using prior information about the origins of individuals, we identified six main genetic clusters, five of which correspond to major geographic regions, and subclusters that often correspond to individual populations. General agreement of genetic and predefined populations suggests that self-reported ancestry can facilitate assessments of epidemiological risks but does not obviate the need to use genetic information in genetic association studies.     

Cardiac disease in the geriatric horse.

Almost all equine cardiac diseases may affect the geriatric horse. This article focuses on those cardiac diseases that are most common in the older horse, including degenerative valve disease, aortocardiac fistula, and congestive heart failure. Other cardiac diseases, such as bacterial endocarditis, pericarditis, and arrhythmias, are seen in all age groups of horses and are beyond the scope of this article.     

Coagulase-positive staphylococcal mastitis in a herd with low somatic cell counts

An increase in clinical mastitis infections was observed in a high-producing 77-cow Holstein herd. Low bulk tank somatic cell counts and individual cow Dairy Herd Improvement Association somatic cell counts observed before, during, and after the epizootic were suggestive of herd environmental mastitis. However, bacteriologic culture survey of the total herd indicated that, in addition to infections possibly attributable to environmental pathogens, 22% (17/77) of the cows were infected with coagulase-positive Staphylococcus spp. Conceivably, investigative efforts and management changes, without bacteriologic culturing, might have resulted in reduction of the clinical infection rate in this herd. However, the continued high prevalence of a contagious pathogen with potential future implications would have gone unnoticed. Somatic cell count in milk from individual cows generally is a useful tool for monitoring the probability of intramammary infection, but must be complemented with bacteriologic culture of milk to determine whether contagious or environmental pathogens are responsible.     

Maedi-visna virus infection in commercial flocks of indigenous sheep in Britain

The recent identification of maedi-visna virus infection in three commercial flocks of indigenous sheep in Britain is described. In one flock the evidence suggested that overt clinical disease was present. The implications of the findings are discussed.     

Alternate day supplementation of corn stalk diets with soybean meal or corn gluten meal fed to ruminants.

Four experiments were conducted to determine the effect of adding corn gluten mean (CGM) or soybean meal (SBM) at 24- or 48-h intervals to diets based on corn stalks. In each experiment corn stalks was the primary diet ingredient fed to wethers or steers. Monensin was also fed to determine whether its effects on ruminal fermentation would improve the efficiency of N utilization under these conditions. Evaluation criteria included ruminal fermentation characteristics, DM intake and utilization, N balance in sheep, and steer feedlot performance. Ruminal ammonia nitrogen (NH3 N) concentrations measured over time were higher (P < .05) when diets contained SBM. Diet did not influence (P > .10) total VFA concentrations in ruminal fluid. Differences in diurnal shifts in ruminal NH3 N and total VFA due to protein source resulted in diet x hour interactions (P < .05). Dry matter intake response to protein source and frequency of supplement feeding was variable. Dry matter digestibility and nitrogen digestibility were not affected (P > .10) by protein source or feeding interval. The 48-h interval feeding of CGM was favorable compared with 24-h interval feeding (P < .05). The opposite response occurred with SBM, resulting in a diet x feeding interval interaction (P < .05). Nitrogen retention was greater (P < .05) when CGM was fed and with alternate day feeding. Diets that contained CGM supported higher (P < .05) ADG and gain/feed than diets that contained SBM when fed to steer calves. Alternate day feeding of supplements that contained monensin was detrimental to steer performance under the conditions of these experiments. Corn gluten meal is an effective substitute for SBM when alternate day protein supplementation is practiced.     

TRACHEITIS IN SHEEP AFTER ORAL ADMINISTRATION OF A MINERAL SUPPLEMENT

Outbreaks of illness and deaths in sheep after the concurrent administration of a cobalt, copper and zinc mineral supplement and laevamisole are described. Clinical illness was characterised by profound dyspnoea and inability to exercise. The consistent postmortem finding was severe, necrotising tracheitis with partial occlusion of the airway. This lesion was reproduced experimentally by intratracheal administration of the mineral supplement dissolved in one particular formulation of laevamisole but not in water or another preparation of laevamisole. Further experiments revealed that combined zinc sulphate and copper sulphate dissolved in the particular formulation of laevamisole would produce the tracheal lesions.     

Use of a particulate extracellular matrix bioscaffold for treatment of acquired urinary incontinence in dogs

OBJECTIVE: To evaluate use of a particulate bioscaffold consisting of the extracellular matrix (ECM) of the urinary bladder from pigs for treatment of acquired urinary incontinence in dogs resistant to medical treatment. DESIGN: Case series. ANIMALS: 9 female dogs with acquired urinary incontinence. PROCEDURE: In 6 dogs, 30 mg of particulate ECM in 1.0 mL of a carrier consisting of glycerin and saline 10.9% NaCI) solution was injected into each of 3 equally spaced sites around the circumference of the internal urethral sphincter via an endoscopic technique. In the remaining 3 dogs (control dogs), 1.0 mL of the carrier alone was injected in 3 equally spaced sites around the circumference of the internal urethral sphincter in a similar manner. RESULTS: For dogs treated with the ECM, median duration of urinary continence following treatment was 168 days (range, 84 to 616 days), whereas for the control dogs, median duration of urinary continence following the procedure was 14 days (range, 7 to 31 days). Two of the 3 control dogs were treated with the ECM at the end of the study and were continent for 119 and 252 days. No adverse effects were observed in any dog. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that endoscopically guided injection of particulate ECM into the internal urethral sphincter may be useful for the treatment of acquired urinary incontinence in female dogs.     

Age-related alterations to immune parameters in Labrador retriever dogs

In order to assess age-related changes in the immune status of Labrador retriever dogs, leukocyte phenotypes, lymphocyte proliferative capacity, and serum antibody levels were measured in four cohorts of dogs, ranging from 2 to 10 years of age. Absolute numbers of white blood cells, lymphocytes, monocytes, granulocytes, and CD3+, CD4+, CD8+ and CD21+ lymphocytes significantly decreased with increasing age. Relative percentages of lymphocytes and CD4 cells were significantly decreased, and relative percentages of granulocytes and CD8 cells significantly increased, with age. The CD4:CD8 ratio showed a significant age-related decrease. Proliferative responses of T-cells to mitogens in whole-blood cultures either increased (Concanavalin A) or remained the same (phytohemagglutinin) with age when data was normalised to allow for differences in responding cell number. Similarly, normalised data of proliferative response to anti-CD3 stimulation together with phorbol 12-myristate 13-acetate showed an age-related increase. Serum levels of total IgA significantly increased with age whereas total IgG levels remained unchanged. These observations illustrate a significant change to a number of immune parameters with age. However, further work is required to determine whether the differences reported here are sufficient to cause overt or functional immune senescence in Labrador retriever dogs.