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A Linkage Map Of The Canine Genome, Cathryn Mellersh, Amelia Langston, Gregory Acland, Melissa Fleming, Kunal Ray, Neil Weigand, Leigh Francisco, Mark Gibbs, Gustavo Aguirre, Elaine Ostrander Dec 1997

A Linkage Map Of The Canine Genome, Cathryn Mellersh, Amelia Langston, Gregory Acland, Melissa Fleming, Kunal Ray, Neil Weigand, Leigh Francisco, Mark Gibbs, Gustavo Aguirre, Elaine Ostrander

Gustavo D. Aguirre, VMD, PhD

A genetic linkage map of the canine genome has been developed by typing 150 microsatellite markers using 17 three-generation pedigrees, composed of 163 F2individuals. One hundred and thirty-nine markers were linked to at least one other marker with a lod score ≥ 3.0, identifying 30 linkage groups. The largest chromosome had 9 markers spanning 106.1 cM. The average distance between markers was 14.03 cM, and the map covers an estimated 2073 cM. Eleven markers were informative on the mapping panel, but were unlinked to any other marker. These likely represent single markers located on small, distinct canine chromosomes. This map …


Construction Of A Panel Of Canine–Rodent Hybrid Cell Lines For Use In Partitioning Of The Canine Genome, Amelia A. Langston, Cathryn S. Mellersh, Cassandra L. Neal, Kunal Ray, Gregory M. Acland, Mark Gibbs, Gustavo D. Aguirre, R.E. K. Fournier, Elaine A. Ostrander Dec 1997

Construction Of A Panel Of Canine–Rodent Hybrid Cell Lines For Use In Partitioning Of The Canine Genome, Amelia A. Langston, Cathryn S. Mellersh, Cassandra L. Neal, Kunal Ray, Gregory M. Acland, Mark Gibbs, Gustavo D. Aguirre, R.E. K. Fournier, Elaine A. Ostrander

Gustavo D. Aguirre, VMD, PhD

We have constructed a collection of canine–rodent microcell hybrid cell lines by fusion of canine fibroblast microcell donors with immortalized rodent recipient cells. Characterization of the hybrid cell lines using a combination of fluorescencein situhybridization and PCR analysis of canine microsatellite repeat sequences allowed selection of a panel of hybrids in which most canine chromosomes are represented. Approximately 90% of genetic markers and genes that were tested could be assigned to 1 of 31 anonymous canine chromosome groups, based on common patterns of retention in the hybrid set. Many of these putative chromosome groups have now been validated …


The Placebo Effect, Charles Weijer Oct 1997

The Placebo Effect, Charles Weijer

Charles Weijer

No abstract provided.


Canine Rod Photoreceptor Cgmp-Gated Channel Protein Α-Subunit: Studies On The Expression Of The Gene And Characterization Of The Cdna, Qi Zhang, Sue Pearce-Kelling, Gregory Acland, Gustavo Aguirre, Kunal Ray Jul 1997

Canine Rod Photoreceptor Cgmp-Gated Channel Protein Α-Subunit: Studies On The Expression Of The Gene And Characterization Of The Cdna, Qi Zhang, Sue Pearce-Kelling, Gregory Acland, Gustavo Aguirre, Kunal Ray

Gustavo D. Aguirre, VMD, PhD

Rod photoreceptor cyclic GMP gated-channel protein is a key component of the visual transduction cascade in the vertebrate retina. The protein is composed of at least two subunits (α and β). Mutations in the α-subunit (CNGC1) have been shown to cause retinitis pigmentosa (RP) in humans. Several heterogeneous canine retinal diseases, which are clinically similar to RP, are known collectively as progressive retinal atrophy (PRA) and occur in dogs in a breed-specific manner. For the purpose of examining CNGC1 gene as a candidate for PRA, we report here the characterization of canine CNGC1 cDNA, and examine the expression of the …


Duty And Healing: The Lifework Of Benjamin Freedman, Charles Weijer May 1997

Duty And Healing: The Lifework Of Benjamin Freedman, Charles Weijer

Charles Weijer

BENJAMIN FREEDMAN, un des plus grands bioéthiciens du Canada et universitaire re- connu sur la scène internationale, est mort le 20 mars 1997. Professeur de médecine à l’Université McGill de Montréal, Freedman a beaucoup contribué au domaine de la bioéthique, où il a fait notamment des travaux fondamentaux sur le consentement éclairé et la compétence. Dans le domaine de l’éthique de la recherche, Freedman est l’auteur du concept de l’équivalence clinique comme condition préalable à l’exécution éthique de recherches cliniques. Des travaux subséquents ont clarifié l’analyse éthique du risque et les limites du risque permis- sible en recherche sur les …


Differential Expression Of Photoreceptor-Specific Proteins During Disease And Degeneration In The Progressive Rod-Cone Degeneration (Prcd) Retina, Kathryn Gropp, Jun Huang, Gustavo Aguirre May 1997

Differential Expression Of Photoreceptor-Specific Proteins During Disease And Degeneration In The Progressive Rod-Cone Degeneration (Prcd) Retina, Kathryn Gropp, Jun Huang, Gustavo Aguirre

Gustavo D. Aguirre, VMD, PhD

Progressive rod-cone degeneration (prcd) is a late-onset hereditary retinal degeneration characterized by normal development of photoreceptors prior to degeneration and death of visual cells. We reported previously that expression of opsin mRNA and protein decreases prior to visual cell degeneration. To examine the specificity of this reduction, we have used immunocytochemistry to correlate photoreceptor-specific protein expression with visual cell disease progression. Eyes from light-adapted age-matched control andprcd-affected dogs were fixed in paraformaldehyde, embedded in diethylene glycol distearate (DGD) wax, and reacted with antibodies specific to interphotoreceptor retinoid-binding protein (IRBP), S-antigen, opsin, phosducin, γ-phosphodiesterase (γ-PDE), and β1-transducin. While IRBP expression did …


Superior Vena Cava Obstruction In Small-Cell Lung Cancer, Roscoe Chan, A. Dar, Edward Yu, Larry Stitt, Francis Whiston, Pauline Truong, Mark Vincent, Walter Kocha May 1997

Superior Vena Cava Obstruction In Small-Cell Lung Cancer, Roscoe Chan, A. Dar, Edward Yu, Larry Stitt, Francis Whiston, Pauline Truong, Mark Vincent, Walter Kocha

Edward Yu

PURPOSE: To identify prognostic or treatment factors influencing the response of superior vena cava obstruction (SVCO), time to SVCO recurrence, and overall survival of SCLC patients with SVCO at presentation; and to assess the role of retreatment in patients with SVCO at recurrent or persistent disease. METHODS AND MATERIALS: Between January 1983 and November 1993, 76 consecutive patients who had small-cell lung cancer (SCLC) with SVCO were treated in our institution. Analysis was done according to the disease status at diagnosis of SVCO. The first analysis concerned a group of 50 patients who had SVCO at initial presentation. The second …


Spilker's Guide To Clinical Trials On Cd-Rom, Charles Weijer May 1997

Spilker's Guide To Clinical Trials On Cd-Rom, Charles Weijer

Charles Weijer

No abstract provided.


Remembering Benjamin Freedman (1951-1997), Françoise Baylis, Charles Weijer Apr 1997

Remembering Benjamin Freedman (1951-1997), Françoise Baylis, Charles Weijer

Charles Weijer

No abstract provided.


Selecting Subjects For Participation In Clinical Research: An Empirical Inquiry And Ethical Analysis, Charles Weijer Apr 1997

Selecting Subjects For Participation In Clinical Research: An Empirical Inquiry And Ethical Analysis, Charles Weijer

Charles Weijer

Procedures for the selection of subjects for participation in randomized clinical trials--usually formalized as eligibility criteria in the study protocol--have both scientific and ethical implications. In this thesis, I undertake an examination of eligibility criteria at three stages in the genesis and dissemination of medical knowledge: clinical trial protocol, interpretation by investigators, and reporting of study results.

In the first chapter, ethical issues in subject selection are reviewed and the main study questions are presented. In the second chapter, the results of an examination of eligibility criteria in two sets of clinical trials, one sponsored by the NSABP, the other …


The Human Radiation Experiments: Final Report Of The Advisory Committee On Human Radiation Experiments, Charles Weijer Apr 1997

The Human Radiation Experiments: Final Report Of The Advisory Committee On Human Radiation Experiments, Charles Weijer

Charles Weijer

No abstract provided.


Bioethics For Clinicians: 10. Research Ethics, Charles Weijer, Bernard Dickens, Eric Meslin Apr 1997

Bioethics For Clinicians: 10. Research Ethics, Charles Weijer, Bernard Dickens, Eric Meslin

Charles Weijer

Medical research involving human subjects raises complex ethical, legal and social issues. Investigators sometimes find that their obligations with respect to a research project come into conflict with their obligations to individual patients. The ethical conduct of research rests on 3 guiding principles: respect for persons, beneficience, and justice. Respect for persons underlies the duty to obtain informed consent from study participants. Beneficence demands a favourable balance between the potential benefits and harms of participation. Justice requires that vulnerable people not be exploited and that eligible candidates who may benefit from participation not be excluded without good cause. Studies must …


Full House: The Spread Of Excellence From Plato To Darwin, Charles Weijer Mar 1997

Full House: The Spread Of Excellence From Plato To Darwin, Charles Weijer

Charles Weijer

No abstract provided.


Impact Of Radiation Therapy Fraction Size On Local Control Of Early Glottic Carcinoma, Edward Yu, George Shenouda, Marie Beaudet, Martin Black Jan 1997

Impact Of Radiation Therapy Fraction Size On Local Control Of Early Glottic Carcinoma, Edward Yu, George Shenouda, Marie Beaudet, Martin Black

Edward Yu

Purpose: Different radiotherapy fractionation schedules were used over a 10-year period to treat patients with early squamous cell carcinoma of the vocal cords at McGill University. A retrospective analysis was performed to study the effect of fraction size on local control in this group of patients. Methods and materials: A total of 126 previously untreated patients with T1 invasive squamous cell carcinoma of the true vocal cords were irradiated between January 1978 and December 1988 in the Department of Radiation Oncology at McGill University. All patients received megavoltage irradiation, 94 patients received daily fractions > 2 Gy (64 patients received 50 …


Differential Expression Of Gap Junctions In Neurons And Astrocytes Dervied From P19 Embryonal Carcinoma Cells, Daniel Belliveau, J. Bechberger, K. Rodgers, C. Naus Dec 1996

Differential Expression Of Gap Junctions In Neurons And Astrocytes Dervied From P19 Embryonal Carcinoma Cells, Daniel Belliveau, J. Bechberger, K. Rodgers, C. Naus

Daniel J. Belliveau

The P19 embryonal carcinoma cell line represents a pluripotential stem cell that can differentiate along the neural or muscle cell lineage when exposed to different environments. Exposure to retinoic acid induces P19 cells to differentiate into neurons and astrocytes that express similar developmental markers as their embryonic counterparts. We examined the expression of gap junction genes during differentiation of these stem cells into neurons and astrocytes. Untreated P19 cells express at least two gap junction proteins, connexins 26 and 43. Connexin32 could not be detected in these cells. Treatment for 96 hr with 0.3 mM retinoic acid induced the P19 …


Blocking Nerve Growth Factor Binding To The P75 Neurotrophin Receptor On Sympathetic Neurons Transiently Reduces Trka Activation But Does Not Affect Neuronal Survival, C. Lachance, Daniel Belliveau, P. Barker Dec 1996

Blocking Nerve Growth Factor Binding To The P75 Neurotrophin Receptor On Sympathetic Neurons Transiently Reduces Trka Activation But Does Not Affect Neuronal Survival, C. Lachance, Daniel Belliveau, P. Barker

Daniel J. Belliveau

Nerve growth factor interacts with the trkA tyrosine kinase receptor and with the p75 neurotrophin receptor. It is clear that trkA mediates most, if not all, of the stereotypical responses of sympathetic neurons to nerve growth factor but the role of the p75 neurotrophin receptor is unclear. In this study, we have asked whether a functional interaction between p75 neurotrophin receptor and trkA exists in primary sympathetic neurons by disrupting nerve growth factor binding to p75 neurotrophin receptor. Acute assays reveal that blocking antibodies directed against p75 neurotrophin receptor reduce nerve growth factor-mediated trkA tyrosine phosphorylation and reduce the amount …


Transgenic Mice Expressing The Intracellular Domain Of The P75 Neurotrophin Receptor Undergo Neuronal Apoptosis, M. Majdan, C. Lachance, A. Gloster, R. Aloyz, C. Zeindler, S. Bamji, A. Bhakar, Daniel Belliveau, J. Fawcett, F. Miller, P. Barker Dec 1996

Transgenic Mice Expressing The Intracellular Domain Of The P75 Neurotrophin Receptor Undergo Neuronal Apoptosis, M. Majdan, C. Lachance, A. Gloster, R. Aloyz, C. Zeindler, S. Bamji, A. Bhakar, Daniel Belliveau, J. Fawcett, F. Miller, P. Barker

Daniel J. Belliveau

We have asked whether p75NTR may play a role in neuronal apoptosis by producing transgenic mice that express the p75NTR intracellular domain within peripheral and central neurons. These animals showed profound reductions in numbers of sympathetic and peripheral sensory neurons as well as cell loss in the neocortex, where there is normally little or no p75NTR expression. Developmental loss of facial motor neurons was not observed, but induced expression of the p75NTR intracellular domain within adult animals led to increased motor neuron death after axotomy. Biochemical analyses suggest that these effects were not attributable to a p75NTR-dependent reduction in trk …


Ngf And Neurotrophin-3 Both Activate Trka On Sympathetic Neurons But Differentially Regulate Survival And Neuritogenesis, Daniel Belliveau, I. Krivko, C. Lachance, J. Kohn, D. Rusakov, D. Kaplan, F. Miller Dec 1996

Ngf And Neurotrophin-3 Both Activate Trka On Sympathetic Neurons But Differentially Regulate Survival And Neuritogenesis, Daniel Belliveau, I. Krivko, C. Lachance, J. Kohn, D. Rusakov, D. Kaplan, F. Miller

Daniel J. Belliveau

In this report we examine the biological and molecular basis of the control of sympathetic neuron differentiation and survival by NGF and neurotrophin-3 (NT-3). NT-3 is as efficient as NGF in mediating neuritogenesis and expression of growth-associated genes in NGF-dependent sympathetic neurons, but it is 20-40-fold less efficient in supporting their survival. Both NT-3 and NGF induce similar sustained, long-term activation of TrkA, while NGF is 10-fold more efficient than NT-3 in mediating acute, short-term TrkA activity. At similar acute levels of TrkA activation, NT-3 still mediates neuronal survival two- to threefold less well than NGF. However, a mutant NT-3 …


Canine Rod Transducin A-1: Cloning Of The Cdna And Evaluation Of The Gene As A Candidate For Progressive Retinal Atrophy, Kunal Ray, Victoria J. Baldwin, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre Dec 1996

Canine Rod Transducin A-1: Cloning Of The Cdna And Evaluation Of The Gene As A Candidate For Progressive Retinal Atrophy, Kunal Ray, Victoria J. Baldwin, Caroline Zeiss, Gregory M. Acland, Gustavo D. Aguirre

Gustavo D. Aguirre, VMD, PhD

Purpose: Progressive retinal atrophy (PRA) represents a heterogeneous group of retinal dystrophies, distinct forms of which occur in different canine breeds. The present study was undertaken to evaluate the gene for the a-1 subunit of the rod specific G-protein transducin (GNAT1), a member of the phototransduction pathway, as a candidate for progressive rod cone degeneration (prcd) in poodles, early retinal degeneration (erd) in elkhounds, and rod cone dysplasia 2 (rcd 2) in collies. 
Methods: Oligonucleotide primers were designed from the consensus region of known cDNA sequences for GNAT1 from other species. Canine GNAT1 cDNA was cloned and sequenced after reverse …