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Biomedical subjects

A Gagnon

Publications and source records attributed to A Gagnon.

At least 73 records · Page 4Linked to original sources

A case of viral neonatal calf diarrhea in a Quebec dairy herd.

This report is concerned with a consistent problem of neonatal calf diarrhea (NCD) in a dairy herd in which, for nearly two years, the morbidity had approached 100% and the mortality had varied from 20% to 45%. Generally, diarrhea appeared at three days of age. By the fluorescent antibody tissue section technique the two Nebraska NCD viruses (reo-like and corona-like) were detected in the cytoplasm of many absorptive cells of the small intestine from a calf submitted for necropsy. Reo-like virus antigen was not detected in the absorptive and crypt cells of the colon but coronavirus-like antigen was. An adenovirus was also isolated from the small intestine of this calf. The disease was reproduced experimentally in a two day old colostrum deprived calf with a bacteria free intestinal homogenate obtained from the naturally infected calf. Both Nebraska NCD viruses were demonstrated in this experimental animal. However, the adenovirus was not re-isolated. Histological lesions observed in the small and large intestines of the naturally and experimentally infected calves were similar and because of their good correlation with the immunofluorescent findings, a combination of the two Nebraska NCD viruses was thought to be a major cause of the neonatal calf diarrhea problem afflicting this dairy herd.

Adenoviridae↗

Intergenerational correlation of effective family size in early Québec (Canada).

The use of a comprehensive demographic database of the early French Canadian population (1608-1800) reveals an almost null impact of parents' fertility on children's fertility (r approximately 0.01-0.05), which contradicts the commonly held view that family size has a tendency to run in families. However, in this population, there is a clear transmission from one generation to the next of the effective family size within a given geographical area (EFS, defined as the number of children that settle per settled individual). Three types of correlations between EFS of parents and children are presented in order to account for the impact of socio-demographic differentials. Individuals who belong to a large sibship and who settled in a given subdivision tend to encourage the settlement of a high number of their own children in the same subdivision (r approximately 0.1-0.3). An additional correlation was introduced to see if geographically-based differentials of EFS can account for the differential of founders' regional genetic contribution. The analysis shows that EFS correlation has a definite impact on the concentration of a population's gene pool (it increases it by approximately 20%-45%), and partly accounts for the differences between subdivisions in this regard.

Family Characteristics↗

Contribution of in vivo models of thrombosis to the discovery and development of novel antithrombotic agents.

Cardiovascular and cerebrovascular diseases continue to be the leading cause of death throughout the world. Over the past two decades, great advances have been made in the pharmacological treatment and prevention of thrombotic disorders (e.g., tissue plasminogen activators, platelet GPIIb/IIIa antagonists, ADP receptor antagonists such as clopidogrel, low-molecular weight heparins, and direct thrombin inhibitors). New research is leading to the next generation of antithrombotic compounds such as direct coagulation FVIIa inhibitors, tissue factor pathway inhibitors, gene therapy, and orally active direct thrombin inhibitors and coagulation Factor Xa (FXa) inhibitors. Animal models of thrombosis have played a crucial role in discovering and validiting novel drug targets, selecting new agents for clinical evaluation, and providing dosing and safety information for clinical trials. In addition, these models have provided valuable information regarding the mechanisms of these new agents and the interactions between antithrombotic agents that work by different mechanisms. This review briefly presents the pivitol preclinical studies that led to the development of drugs that have proven to be effective clinicallly. The role that animal models of thrombosis are playing in the discovery and development of novel antithrombotic agents is also described, with specific emphasis on FXa inhibitors. The major issues regarding the use of animal models of thrombosis, such as the use of positive controls, appropriate pharmacodynamic markers of activity, safety evaluation, species-specificity, and pharmacokinetics, are highlighted. Finally, the use of genetic models in thrombosis/hemostasis research and pharmacology is presented using gene-therapy for hemophilia as an example of how animal models have aided in the development of these therapies that are now being evaluated clinically. In summary, animal models have contributed greatly to the discovery of currently available antithrombotic agents and will play a primary role in the discovery and characterization of the novel antithrombotic agents that will provide safe and effective pharmacological treatment for life-threatening thrombotic diseases.

Animals↗

Comparison between the end-diastolic images and the summed images of gated 99mTc-sestamibi SPECT perfusion study in detection of coronary artery disease in women.

BACKGROUND: End-diastolic images (EDI) can be easily derived from technetium 99m-sestamibi gated single photon emission computed tomography (SPECT) perfusion study (SGS). This may reduce the effect of myocardial wall thickening during systole and potentially improve the sensitivity of radionuclide perfusion imaging, especially in patients with small hearts. METHODS: This prospective study was conducted in 53 consecutive female patients to compare the diagnostic accuracy of EDI with that of the summed images (SI) of SGS. Fifty-three patients with suspected coronary artery disease (CAD), scheduled for coronary angiography within 2 months, were evaluated with SGS. Treadmill stress testing was used in 28 patients, and dipyridamole injection was used in the remaining 25 patients. A 2-day protocol was used as follows: stress test with 25 to 30 mCi of 99mTc-sestamibi and a rest study performed at least 24 hours later with the same dose. Sixteen frames per cardiac cycle were acquired for both the rest and the stress studies. Three end-diastolic frames were used for EDI, and all the 16 frames were summed for SI. SI and EDI data reconstruction were interpreted by 3 experienced blinded observers (consensus reading) during two distinct reading sessions, one with SI alone and the second with EDI alone. The heart was divided into 17 segments. RESULTS: Coronary angiography showed > or = 50% stenoses in 1 or more major coronary arteries in 38 patients and was normal in 15 patients. The sensitivity was 73.7% (28/38) and 84.2% (32/38), respectively, for SI and EDI. Three of 4 patients with CAD not detected by SI but seen with EDI were considered to have relatively small hearts. The specificity was 86.7% (13/15) and 80.0% (12/15) for SI and EDI, respectively. On a total of 901 segments, 106 ischemic defects were detected by SI and 173 by EDI (P = .001). The segmental agreement between the two techniques was 88.6% (798/901 segments). CONCLUSION: EDI showed more ischemic defects than SI, and there was also a nonsignificant trend toward an improved sensitivity of EDI in comparison to SI in detection of coronary artery disease in women, especially in patients with small hearts. EDI may be a useful adjunct to the standard perfusion imaging with SGS in such a clinical situation.

Adult↗

TSH receptor in adipose cells.

Although there have been reports supporting the presence of the TSH receptor (TSHR) in human adipose tissue, these findings are still not universally accepted. Contributing to the controversy is a paucity of data about the physiological role the TSH receptor might play in adipose cells. In addition to mature lipid-filled adipocytes, adipose tissue also harbors a pool of specialized, fibroblast-like preadipocytes within the stromal-vascular compartment. Upon appropriate induction, preadipocytes can either differentiate into adipocytes or undergo apoptosis. Since TSHR has been detected in preadipocytes and adipocytes, its potential impact on adipose tissue function may relate to differentiation stage-specific cellular properties.

Adipocytes↗

Epididymal epithelial cells cultured in vitro prolong the motility of bovine sperm.

It is well known that the epididymis is an excellent environment to maintain sperm viability. Therefore, we used different sections of bovine epididymis (caput, corpus, and cauda) to develop epithelial cell culture monolayers to identify factors that will increase sperm survival in the freezing-thawing process. Each epididymal section was dissected and treated with collagenase to obtain epithelial cell clusters. The cells were cultured in RPMI-1640 medium with 10% serum at 38.5 degrees C. A confluent monolayer was obtained after 5-7 days in culture and preliminary characterization using cytokeratin antibody indicated that the cell culture contained 85%-95% of epithelial cells. These cellular cultures were tested for their ability to maintain motility of epididymal and frozen-thawed spermatozoa. Washed spermatozoa were added to obtain a final dilution of 1 x 10(6) spermatozoa/mL. The motility of frozen-thawed spermatozoa was also recorded after incubation in conditioned media. Our results show that cocultures of spermatozoa and epididymal cell monolayers for 24 and 48 hours were beneficial for maintaining epididymal and frozen-thawed sperm motility (36.0% and 20.4%) compared with spermatozoa cultured with fibroblast cells or in the absence of a cell monolayer (0%; P < .01). The conditioned medium provides favorable conditions for sperm motility. Results with conditioned medium on maintenance of frozen-thawed sperm motility suggest that epididymal cells in vitro secrete beneficial factors that prolong the sperm survival.

Animals↗

Addition of specific metabolites to bovine epididymal cell culture medium enhances survival and motility of cryopreserved sperm.

We have developed a cell culture system of bovine epididymal epithelium in which cryopreserved bovine sperm motility was efficiently maintained for many hours. The culture conditions to maintain viable epididymal cells are quite different from conditions normally used to incubate sperm cells. Thus, we have modified a previously described principal cell medium (PCM; Moore et al, 1992) using HEPES as a buffer and supplemented media with myo-inositol, pyruvate, lactate, glycerol, and carnitine to mimic epididymal intraluminal conditions. In the first experiments the effects of PCM and our epididymal cell medium (ECM) on sperm motility were compared in the absence of cells and evaluated by microscopic analysis under a phase contrast microscope or using the Hamilton Thorn Image Analyzer System. Our results showed that motility of cauda epididymal sperm was significantly higher in ECM than in PCM during a 48-hour incubation period when both media were supplemented with 10% fetal bovine serum (FBS). We then replaced FBS with bovine serum albumin (BSA) or no proteins at all to verify if ECM was able to enhance sperm survival. To test this aspect we used frozen-thawed sperm, which survived up to 48 hours when sperm cells were coincubated with epididymal cell monolayers. Hence, PCM, ECM, and different media containing each metabolite of ECM were supplemented with 0.5% BSA to assess motility of thawed sperm after an incubation period of 6 hours. A positive effect on sperm motility was observed in all fresh and unconditioned media containing 1 mM pyruvate. Motion parameters were more efficiently maintained in all conditioned media than in unconditioned media. Our results showed, however, that pyruvate was almost completely oxidized or consumed by epididymal cells during preincubation of culture media. We conclude that motility of frozen-thawed bovine spermatozoa can be improved using a culture medium or a medium conditioned by epididymal cell cultures without carnitine but containing mainly pyruvate, inositol, glycerol, and lactate.

Animals↗