Gliomatosis Cerebri in the Brain of a Cat.

An eight-year-old, neutered, female, long-haired cat was presented with a three-week history of progressive lethargy, unlocalized pain in the cervical and lumbar spine, and unwillingness to move. An MRI (magnetic resonance imaging) of the brain revealed poorly circumscribed regions of non-contrast-enhancing heterogeneous T2 hyperintensity within the ventral forebrain and midbrain. A mass effect and evidence of increased intracranial pressure, including transtentorial herniation of the midbrain and herniation of the cerebellar vermis through the foramen magnum, were also observed.

Atrioventricular muscular dystrophy in a 5-month-old English springer spaniel.

Primary persistent atrial standstill due to atrioventricular muscle dystrophy is a rare familial disease in dogs. The diagnosis of this disorder in a 5-month-old English springer spaniel is the earliest in dogs that have been presented at the Ontario Veterinary College.

Attenuation of allergy to ovomucoid in pigs by neonatal treatment with heat-killed Escherichia coli or E. coli producing porcine IFN-gamma.

Food allergy is epidemic and prompts investigation to reduce allergic predisposition. It was hypothesized that heat-killed Escherichia coli injected intramuscularly (im) with or without interferon gamma (IFN-gamma), reduces neonatal susceptibility to experimental egg allergy. Two litters of Yorkshire pigs were assigned to three intramuscular treatment groups (four/group): control (PBS), heat-killed E.

RNA interference using a plasmid construct expressing short-hairpin RNA.

RNA interference (RNAi) is one of the most commonly used procedures for gene targeting in today's cutting edge technology and has great potential for use in clinical therapy. Using a plasmid construct that exogenously expresses short-hairpin RNAs (shRNAs) targeting a desired gene transcript not only helps to study the downstream effects of a gene product but also offers an alternative to viral vectors for gene therapy. Using a plasmid vector to knockdown a gene allows for long-term and permanent gene knockdown, without the need to generate knockout genotypes.

hTERT knockdown in human embryonic kidney cells using double-stranded RNA.

The method of RNA interference (RNAi) is an easy means of knocking down a gene without having to generate knockout mutants, which may prove to be difficult and time consuming. RNAi is a naturally occurring process that involves targeting the mRNA of a gene by introducing RNAs that are complementary to the target mRNA. The foreign RNAs activate an endogenous enzyme, DICER, which degrades the target mRNA.

Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop.

The human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the enzyme telomerase which is responsible for telomeric maintenance and extension. Using RNA interference to knock down hTERT mRNA expression, we provide evidence that hTERT exerts extra-telomeric effects on the cell cycle and on its own regulatory proteins, specifically: p53 and p21. We tested our hypothesis that hTERT regulates its own expression through effects on upstream regulatory genes using transformed human embryonic kidney (HEK 293) cells, p53 and p16(INK4a) null human ovarian cancer SKOV-3 cells, and p53-null MDA-MB-157 human mammary cancer cells.

Epigenetic control of telomerase and modes of telomere maintenance in aging and abnormal systems.

Epigenetic control provides a mechanism for the reversible silencing of telomerase expression that occurs as a natural consequence of differentiation. Significant overlap between indirect telomerase regulation pathways and cell cycle checkpoint pathways exist, suggesting that these discrete genetic elements (namely, p21, p53, and hTERT) synergistically cooperate to inhibit tumorigenesis. Mutations in these pathways have been known to contribute to cancer formation.

Genetic and epigenetic modulation of telomerase activity in development and disease.

Telomerase activity is one of the most important factors that have been linked to multiple developmental processes, including cell proliferation, differentiation, aging and senescence. Dysregulation of telomerase has often been found in developmental abnormalities, such as cancer, loss of function in the hematopoietic system, and low success rate of somatic cloning. A comprehensive network of transcription factors has been shown to be involved in the genetic control of telomerase expression and activity.