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Biomedical subjects

Minoru Tomita

Publications and source records attributed to Minoru Tomita.

22 records · Page 2Linked to original sources

Moment analysis of microflow histogram in focal ischemic lesion to evaluate microvascular derangement after small pial arterial occlusion in rats.

The authors' high-spatial-resolution optical method was used to examine microvascular derangement in a focal cerebral cortex lesion in 12 Sprague-Dawley rats anesthetized with alpha-chloralose-urethane. A pial artery (approximately 40- to 50 microm diameter) was occluded by laser-beam cauterization (n = 6). Diluted carbon black suspension was injected into the internal carotid artery, and images in a 2-mm x 2-mm region of interest during tissue dye-dilution were recorded. Sequential frames were analyzed with Matlab software to evaluate blood distribution and mean transit time, affording a two-dimensional microflow map and histogram with first, second, third, and fourth moments. In the early phase of ischemia, blood distribution and average flow decreased (both P < 0.01), and the second moment (microflow heterogeneity) and third moment (skew to the left owing to increase in low-flow components) increased (P < 0.05 and P < 0.01, respectively). At approximately 2 hours, blood distribution decreased further in 3 cases, apparently because capillary stasis prevented carbon black filling. However, average microflow unexpectedly increased in 4 of 5 rats, presumably due to exclusion of unperfused (low flow at the earlier stage) channels from the calculation. The authors conclude that flow in ischemic tissue is quite heterogeneous and that an averaged flow value tends to smear important information about ischemic microvascular derangement.

Animals↗

Marked increase in number of dendritic cells in autoimmune-prone (NZW x BXSB)F1 mice with age.

Here, we report that the number of CD11c(+)CD3(-) B220(-) cells increases in autoimmune-prone male (NZW x BXSB)F1 (W/BF1) mice with age. The CD11c(+)CD3(-)B220(-) cells from W/BF1 mice show a typical stellate shape and induce the proliferation of T cells. In the CD11c(+)CD3(-)B220(-) cells from W/BF1 mice, CD11b (Mac-1alpha), NK 1.1, and CD95 (Fas) are upregulated in comparison with normal mice, while the expression of CD8alpha, CD117 (c-kit), CD135 (Flk-2/Flt-3), and Sca-1 decreases. There is a significant increase in Flt-3L (FL) mRNA in the bone marrow of W/BF1 mice with age. Moreover, activated hemopoietic cells express high levels of FL. The injection of CD11c(+)CD3(-)B220(-) cells from old W/BF1 mice to young W/BF1 mice transiently induces autoimmune disease (thrombocytopenia). These results suggest that hyperproduction of FL from activated hemopoietic cells induces a dramatic increase in the number of dendritic cells in aged W/BF1 mice, followed by the acceleration of autoimmunity.

Animals↗

Bone marrow-derived stem cells can differentiate into retinal cells in injured rat retina.

It has recently been shown that bone marrow cells can differentiate into various lineage cells including neural cells in vitro and in vivo. We therefore examined whether bone marrow stem cells can differentiate into retinal neural cells in adult rats. PKH-67-labeled stem cell-enriched bone marrow cells (BMCs) were injected into the vitreous space of eyes in which the retinas had been mechanically injured using a hooked needle. Two weeks after the injection of these cells, immunohistochemical examinations were carried out. The stem cell-enriched BMCs had been incorporated and had differentiated into retinal neural cells in the injured retina. The stem cell-enriched BMCs had accumulated mainly in the outer nuclear layer around the injured sites. The incorporated cells expressed glial fibrillary acidic protein, calbindin, rhodopsin, and vimentin. These results raise the possibility that stem cell-enriched BMCs have the ability to differentiate into retinal neural cells, and that the injection of stem cell-enriched BMCs into the retina would help repair damaged retinal cells.

Amacrine Cells↗

Biodegradable polymer composite grafts promote the survival and differentiation of retinal progenitor cells.

Retinal progenitor cells (RPCs) are multipotent central nervous system precursors that give rise to all of the cell types of the retina during development. Several groups have reported that mammalian RPCs can be isolated and expanded in culture and can differentiate into retinal neurons upon grafting to the mature, diseased eye. However, cell delivery and survival remain formidable obstacles to application of RPCs in a clinical setting. Because biodegradable polymer/progenitor constructs have been shown to be capable of tissue generation in other compartments, we evaluated the survival, migration, and differentiation of RPCs delivered on PLLA/PLGA polymer substrates to the mouse subretinal space and compared these results to conventional injections of RPCs. Polymer composite grafts resulted in a near 10-fold increase in the number of surviving cells after 4 weeks, with a 16-fold increase in cell delivery. Grafted RPCs migrated into the host retina and expressed the mature markers neurofilament-200, glial fibrillary acidic protein, protein kinase C-alpha, recoverin, and rhodopsin. We conclude that biodegradable polymer/progenitor cell composite grafts provide an effective means of increasing progenitor cell survival and overall yield when transplanting to sites within the central nervous system such as the retina.

Absorbable Implants↗