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Biomedical subjects

J Mallery

Publications and source records attributed to J Mallery.

5 recordsLinked to original sources

Survival of rat or mouse ventral mesencephalon neurons after cotransplantation with rat sertoli cells in the mouse striatum.

Transplanting cells across species (xenotransplantation) for the treatment of Parkinson's disease has been considered an option to alleviate ethical concerns and shortage of tissues. However, using this approach leads to decreased cell survival; the xenografted cells are often rejected. Sertoli cells (SCs) are testis-derived cells that provide immunological protection to developing germ cells and can enhance survival of both allografted and xenografted cells. It is not clear whether these cells will maintain their immunosuppressive support of cografted cells if they are transplanted across species. In this study, we investigated the immune modulatory capacity of SCs and the feasibility of xenografting these cells alone or with allografted and xenografted neural tissue. Transplanting xenografts of rat SCs into the mouse striatum with either rat or mouse ventral mesencephalon prevented astrocytic infiltration of the graft site, although all transplants showed activated microglia within the core of the graft. Surviving tyrosine hydroxylase-positive neurons were observed in all conditions, but the size of the grafts was small at best. SCs were found at 1 and 2 weeks posttransplant. However, few SCs were found at 2 months posttransplant. Further investigation is under way to characterize the immune capabilities of SCs in a xenogeneic environment.

Animals↗

Formation and structure of transplantable tissue constructs generated in simulated microgravity from Sertoli cells and neuron precursors.

Cell transplantation therapy for Parkinson's disease (PD) has received much attention as a potential treatment protocol for this neurodegenerative condition. Although there have been promising successes with this approach, it remains problematic, especially regarding the inability to provide immediate trophic support to the newly grafted cells and the inability to prevent acute and/or long-term graft rejection by the host. To address these issues of cell graftability, we have created a novel tissue construct from isolated rat Sertoli cells (SC) and the NTerra-2 immortalized human neuron precursor cell line (NT2) utilizing NASA-developed simulated microgravity technology. The two cell types were cocultured at a 1:4 (SC/NT2) ratio in the High Aspect Rotating Vessel (HARV) biochamber for 3 days, after which a disc-shaped aggregate (1-4 mm diameter) was formed. Sertoli neuron aggregated cells (SNAC) were collected by gravity sedimentation and processed either for light and electron microscopy or for fluorescent immunocytochemistry. Intra-SNAC clusters of SC and NT2 cells were identified by anti-human mitochondrial protein (huMT--specific for NT2 cells) and cholera toxin subunit B (CTb--specific for SC). There was little evidence of cell death throughout the aggregate and the absence of central necrosis, as might be expected in such a large aggregate in vitro. Ultrastructurally, SC did not express junctional modifications with NT2 cells nor with adjacent SC as is typical of SC in vivo and, in some protocols, in vitro. NT2 cells, however, showed distinct intercellular junction-like densities with adjacent NT2 cells, often defining canaliculi-like channels between the microvillus borders of the cells. The results show that the use of simulated microgravity coculture provides a culture environment suitable for the formation of a unique and viable Sertoli-NT2 (i.e., SNAC) tissue construct displaying intra-aggregate cellular organization. The structural integration of SC with NT2 cells provides a novel transplantable tissue source, which can be tested to determine if SC will suppress rejection of the grafted NT2 cells and provide for their short- and long-term trophic support in situ in the treatment of experimental PD.

Animals↗

Intravascular ultrasound imaging of human coronary arteries in vivo. Analysis of tissue characterizations with comparison to in vitro histological specimens.

BACKGROUND: Intravascular ultrasound imaging was performed in 27 patients after coronary balloon angioplasty to quantify the lumen and atheroma cross-sectional areas. METHODS AND RESULTS: A 20-MHz ultrasound catheter was inserted through a 1.6-mm plastic introducer sheath across the dilated area to obtain real-time images at 30 times/sec. The ultrasound images distinguished the lumen from atheroma, calcification, and the muscular media. The presence of dissection between the media and the atheroma was well visualized. These observations of tissue characterization were compared with an in vitro study of 20 human atherosclerotic artery segments that correlated the ultrasound images to histological preparations. The results indicate that high-quality intravascular ultrasound images under controlled in vitro conditions can provide accurate microanatomic information about the histological characteristics of atherosclerotic plaques. Similar quality cross-sectional ultrasound images were also obtained in human coronary arteries in vivo. Quantitative analysis of the ultrasound images from the clinical studies revealed that the mean cross-sectional lumen area after balloon angioplasty was 5.0 +/- 2.0 mm2. The mean residual atheroma area at the level of the prior dilatation was 8.7 +/- 3.4 mm2, which corresponded to 63% of the available arterial cross-sectional area. At the segments of the coronary artery that appeared angiographically normal, the ultrasound images demonstrated the presence of atheroma involving 4.7 +/- 3.2 mm2, which was a mean of 35 +/- 23% of the available area bounded by the media. CONCLUSIONS: Intravascular ultrasound appears to be more sensitive than angiography for demonstrating the presence and extent of atherosclerosis and arterial calcification. Intracoronary imaging after balloon angioplasty reveals that a significant amount of atheroma is still present, which may partly explain why the incidence of restenosis is high after percutaneous transluminal coronary angioplasty.

Angiography↗

Laser-assisted thermal angioplasty in human peripheral artery occlusions: mechanism of recanalization.

Recanalization of completely occluded superficial femoral or popliteal arteries was attempted in 18 patients with use of an Argon laser-mediated thermal probe. The length of the occluded segments varied between 0.5 and 26.0 cm, but 67% of the occlusions were greater than 9 cm long. The initial success rate was 67%. Arterial perforation occurred in six patients but was not associated with major complications. To study the mechanism of the laser-mediated thermal probe, thermal recanalization was performed on 11 human arterial segments in vitro obtained after amputation, and mechanical recanalization was performed in vitro in 10 human peripheral arteries with use of a guide wire and catheter technique. An additional four arteries were studied with the laser probe as a non-heated mechanical device. Both the mechanical and thermal devices appear to follow a similar pathway through a complete obstruction. These studies suggest that the thermal probe burns through soft fibrous tissue but is mechanically deflected away from hard fibrocalcific plaque. The probe then advances along the plane between the intimal plaque and the media for a variable length before perforating through the adventitia. These observations suggest that the major mechanism of thermal probe recanalization may be a mechanical process. It appears that thermal probe devices do not inherently seek the true lumen of an occluded artery and that better guidance systems need to be developed.

Aged↗

Correlation of minimum coronary lumen diameter with left ventricular functional impairment induced by atrial pacing.

To understand whether quantitative measurement of minimal coronary luminal diameter is a better method than percent diameter narrowing for assessing the functional impairment of myocardial contractility produced by coronary artery stenoses, measurements were made from 37 stenotic segments in 27 patients with coronary artery disease and from corresponding segments in 10 subjects without coronary artery narrowing. An assessment of the reliability of the 2 types of measurements was made by correlating them with the physiologic parameters of both segmental wall motion and global ejection fraction response induced by atrial pacing. Digitally acquired coronary angiograms were used to facilitate quantitative analysis. Measurements by edge detection and videodensitometry correlated closely (r = 0.94). Percent diameter narrowing correlated moderately with the change in ejection fraction (r = -0.41) or with the change in segmental wall motion (r = -0.44). The measurement of minimal lumen diameter correlated with the change in global ejection fraction (r = 0.61) and did so even better with the change in segmental wall motion (r = 0.78, p less than 0.05). A minimal lumen diameter of less than or equal to 1.5 mm identified patients likely to have a functional impairment during atrial pacing as assessed by either global ejection fraction or segmental wall motion defects. We conclude that minimal coronary luminal diameter provides a better method than percent diameter narrowing calculations to measure the anatomic severity of coronary artery narrowing.

Angiography↗