Vancouver Hospital and Health Sciences Centre

About: Vancouver Hospital and Health Sciences Centre is a healthcare organization based out in Vancouver, British Columbia, Canada. It is known for research contribution in the topics: Population & Transplantation. The organization has 1082 authors who have published 904 publications receiving 48935 citations.

In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease.

Abstract: Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD.

STAT5 as a molecular regulator of proliferation, differentiation and apoptosis in hematopoietic cells

Abstract: Signal transducers and activators of transcription (STATs) play key roles in growth factor‐mediated intracellular signal transduction. In the present study using a constitutively active STAT5 mutant, we show that STAT5 has pleiotropic functions regulating cell proliferation, differentiation and apoptosis in an IL‐3‐dependent Ba/F3 cell line. The mutant STAT5 possessed constitutive tyrosine phosphorylation and DNA binding activity, induced expression of bcl‐xL and pim‐1 in the absence of IL‐3 in Ba/F3 cells, and rendered Ba/F3 cells factor‐independent. Unexpectedly, IL‐3 treatment of the factor‐independent Ba/F3 cells expressing the constitutively active STAT5 resulted in apoptosis within 24 h, or differentiation followed by cell death. In these cells, mRNA expression of growth inhibitory genes downstream of STAT5 such as CIS, JAB/SOCS‐1/SSI‐1, and p21 WAF1/Cip1 was highly induced, correlating with prolonged hyper‐phosphorylation of the mutant STAT5 after IL‐3 stimulation. Of the STAT5‐regulated genes, we found that constitutive expression of JAB/SOCS‐1/SSI‐1 was sufficient to induce apoptosis of Ba/F3 cells, while p21 WAF1/Cip1 could induce differentiation of these cells. In contrast, constitutive expression of pim‐1 was sufficient to induce IL‐3‐independent growth of Ba/F3 cells. These findings suggest that a single transcription factor regulates cell fate by varying the intensity and duration of the expression of a set of target genes.