In vivo expression of prostate-specific adenoviral vectors in a canine model

SummaryA non-stasis canine model of thrombogenicity has been used to evaluate batches of high purity factor IX concentrates from 4 manufacturers and a conventional prothrombin complex concentrate (PCC). Platelets, activated partial thromboplastin time (APTT), fibrinogen, fibrin(ogen) degradation products and fibrinopeptide A (FPA) were monitored before and after infusion of concentrate. Changes in FPA were found to be the most sensitive and reproducible indicator of thrombogenicity after infusion of batches of the PCC at doses of between 60 and 180 IU/kg, with a dose related delayed increase in FPA occurring. Total FPA generated after 100-120 IU/kg of 3 batches of PCC over the 3 h time course was 9-12 times that generated after albumin infusion. In contrast the amounts of FPA generated after 200 IU/kg of the 4 high purity factor IX products were in all cases similar to albumin infusion. It was noted that some batches of high purity concentrates had short NAPTTs indicating that current in vitro tests for potential thrombogenicity may be misleading in predicting the effects of these concentrates in vivo.

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The Development of Homologous (Canine/Anti-Canine) Antibodies in Dogs with Haemophilia A (Factor VIII Deficiency): A Ten-Year Longitudinal Study

Thrombosis and Haemostasis ◽

10.1055/s-0038-1651541 ◽

1993 ◽

Vol 69 (01) ◽

pp. 021-024 ◽

Cited By ~ 20

Author(s):

Shawn Tinlin ◽

Sandra Webster ◽

Alan R Giles

Keyword(s):

Factor Viii ◽

Canine Model ◽

Significant Inhibition ◽

Human Condition ◽

Haemophilia A ◽

Variable Expression ◽

The Family ◽

Over Time

SummaryThe development of inhibitors to factor VIII in patients with haemophilia A remains as a serious complication of replacement therapy. An apparently analogous condition has been described in a canine model of haemophilia A (Giles et al., Blood 1984; 63:451). These animals and their relatives have now been followed for 10 years. The observation that the propensity for inhibitor development was not related to the ancestral factor VIII gene has been confirmed by the demonstration of vertical transmission through three generations of the segment of the family related to a normal (non-carrier) female that was introduced for breeding purposes. Haemophilic animals unrelated to this animal have not developed functionally significant factor VIII inhibitors despite intensive factor VIII replacement. Two animals have shown occasional laboratory evidence of factor VIII inhibition but this has not been translated into clinical significant inhibition in vivo as assessed by clinical response and F.VIII recovery and survival characteristics. Substantial heterogeneity of inhibitor expression both in vitro and in vivo has been observed between animals and in individual animals over time. Spontaneous loss of inhibitors has been observed without any therapies designed to induce tolerance, etc., being instituted. There is also phenotypic evidence of polyclonality of the immune response with variable expression over time in a given animal. These observations may have relevance to the human condition both in determining the pathogenetic factors involved in this condition and in highlighting the heterogeneity of its expression which suggests the need for caution in the interpretation of the outcome of interventions designed to modulate inhibitor activity.

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Faculty Opinions recommendation of Apoglobin Stability Is the Major Factor Governing both Cell-free and in Vivo Expression of Holomyoglobin.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725670185.793526669 ◽

2016 ◽

Author(s):

Martin Gruebele ◽

Max Platkov

Keyword(s):

In Vivo Expression ◽

Factor Governing

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Appropriate In Vivo Expression of a Muscle-Specific Promoter by Using Avian Retroviral Vectors for Gene Transfer

Journal of Virology ◽

10.1128/jvi.66.8.5175-5175.1992 ◽

1992 ◽

Vol 66 (8) ◽

pp. 5175-5175

Keyword(s):

Gene Transfer ◽

Retroviral Vectors ◽

In Vivo Expression

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Leukocyte Adhesion to the Coronary Microvasculature During Ischemia and Reperfusion in an In Vivo Canine Model

Circulation ◽

10.1161/01.cir.93.10.1784 ◽

1996 ◽

Vol 93 (10) ◽

pp. 1784-1787 ◽

Cited By ~ 55

Author(s):

Frank M. Sheridan ◽

Paul G. Cole ◽

David Ramage

Keyword(s):

Leukocyte Adhesion ◽

Canine Model ◽

Ischemia And Reperfusion

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Identification of a natural soluble neuropilin-1 that binds vascular endothelial growth factor: In vivo expression and antitumor activity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.040337597 ◽

2000 ◽

Vol 97 (6) ◽

pp. 2573-2578 ◽

Cited By ~ 202

Author(s):

M. L. Gagnon ◽

D. R. Bielenberg ◽

Z.'e. Gechtman ◽

H.-Q. Miao ◽

S. Takashima ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Antitumor Activity ◽

Vascular Endothelial ◽

Neuropilin 1 ◽

In Vivo Expression ◽

Endothelial Growth Factor

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Electrospun PLGA and PLGA/gelatin scaffolds for tubularized urethral replacement: Studies in vitro and in vivo

Journal of Biomaterials Applications ◽

10.1177/08853282211030904 ◽

2021 ◽

pp. 088532822110309

Author(s):

Jinhua Hu ◽

Bin Ai ◽

Shibo Zhu ◽

Zhen Wang ◽

Huimin Xia ◽

...

Keyword(s):

Tensile Deformation ◽

Canine Model ◽

Urothelial Cells ◽

Acellular Matrix ◽

Urethral Strictures ◽

Acid Copolymer ◽

Hematoxylin Eosin ◽

Collagen Tissue

To investigate the biocompatibility of polylactic acid-glycolic acid copolymer (PLGA) and PLGA/gelatin scaffolds and their suitability for tubular urethral replacement in a canine model. PLGA and PLGA/gelatin scaffolds was constructed by electrospinning. Microstructural differences between the scaffolds was examined by Scanning electron microscopy (SEM) followed by mechanical properties testing. Biocompatibility of the material was evaluated using SEM 4, 8, 12 and 72 h after PLGA and PLGA/gelatin scaffolds co-culture with urothelial cells. And confocal analysis was also used to showed the cell adhesive and growth at 12 h. Approximately 2 cm of the anterior urethra of twelve dogs were removed and replaced with a scaffold. After the surgery for 1 month performed urethrography and for 3 month perform hematoxylin–eosin (H&E) and Masson. The results indicated that PLGA and PLGA/gelatin scaffolds had a void microfilament structure, similar to that of normal acellular matrix tissue. And the tensile strength was decreased whereas the tensile deformation and suture retention strength was increased in PLGA/gelatin scaffolds compared to that in PLGA scaffolds Urothelial cells grew well on both scaffolds. Postoperatively, animals recovered well and urinated spontaneously. However, urethrography showed varying degrees of urethral strictures in the reconstructed urethras. H&E and Masson showed that multilayer urothelial cells were formed in both the proximal and distal segments of the reconstructed urethras but without continuity. There was a small amount of smooth muscle and blood vessels under the epithelium, but regenerative urothelial cells at the midpoint of the reconstructed segment did not continue. Lots of lymphocyte infiltration was observed under the epithelium, some collagen tissue was deposited under the neo-urethral epithelium were observed. In conclusion, PLGA and PLGA/gelatin scaffolds are not suitable for tubularized urethral replacement in the canine model.

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In Vivo Expression of Reprogramming Factor OCT4 Ameliorates Myelination Deficits and Induces Striatal Neuroprotection in Huntington’s Disease

Genes ◽

10.3390/genes12050712 ◽

2021 ◽

Vol 12 (5) ◽

pp. 712

Author(s):

Ji-Hea Yu ◽

Bae-Geun Nam ◽

Min-Gi Kim ◽

Soonil Pyo ◽

Jung-Hwa Seo ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Cell Fate ◽

Gabaergic Neurons ◽

Oligodendrocyte Progenitor Cells ◽

Adeno Associated Virus ◽

In Vivo Expression ◽

Transcription Factor 4 ◽

Phosphate Buffered Saline

White matter atrophy has been shown to precede the massive loss of striatal GABAergic neurons in Huntington’s disease (HD). This study investigated the effects of in vivo expression of reprogramming factor octamer-binding transcription factor 4 (OCT4) on neural stem cell (NSC) niche activation in the subventricular zone (SVZ) and induction of cell fate specific to the microenvironment of HD. R6/2 mice randomly received adeno-associated virus 9 (AAV9)-OCT4, AAV9-Null, or phosphate-buffered saline into both lateral ventricles at 4 weeks of age. The AAV9-OCT4 group displayed significantly improved behavioral performance compared to the control groups. Following AAV9-OCT4 treatment, the number of newly generated NSCs and oligodendrocyte progenitor cells (OPCs) significantly increased in the SVZ, and the expression of OPC-related genes and glial cell-derived neurotrophic factor (GDNF) significantly increased. Further, amelioration of myelination deficits in the corpus callosum was observed through electron microscopy and magnetic resonance imaging, and striatal DARPP32+ GABAergic neurons significantly increased in the AAV9-OCT4 group. These results suggest that in situ expression of the reprogramming factor OCT4 in the SVZ induces OPC proliferation, thereby attenuating myelination deficits. Particularly, GDNF released by OPCs seems to induce striatal neuroprotection in HD, which explains the behavioral improvement in R6/2 mice overexpressing OCT4.

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