Biomedical subjects

Ben Wu

Publications and source records attributed to Ben Wu.

6 recordsLinked to original sources

PubMed2006

A soluble BAFF antagonist, BR3-Fc, decreases peripheral blood B cells and lymphoid tissue marginal zone and follicular B cells in cynomolgus monkeys.

BAFF (also known as BLyS), a member of the tumor necrosis factor superfamily, plays a critical role in the maturation and development of B cells. BAFF has three receptors on B cells, the most crucial of which is BR3. In this study, we demonstrate the biological outcome of BAFF blockade in cynomolgus monkeys using a soluble fusion protein consisting of human BR3 and human IgG1 Fc. In vitro, BR3-Fc blocked BAFF-mediated survival and proliferation of cynomolgus monkey B cells. Weekly treatment of cynomolgus monkeys with BR3-Fc for 13 to 18 weeks resulted in significant B-cell reduction in the peripheral blood and in lymphoid organs. CD21(high) B cells in lymphoid tissues, a subset analogous to human marginal zone B cells, expressed nearly twofold higher BR3 levels than did CD21(med) B cells. Lymphoid tissue flow cytometric analysis showed that BR3-Fc reduced this CD21(high) B-cell subset to a greater extent than it reduced CD21(med) B cells. Dual-label immunohistochemistry and morphometric image analysis supported these results by demonstrating that BR3-Fc reduced a significant proportion of the B cells within the splenic inner and outer marginal zones. These findings should prove very useful in guiding the desired therapeutic use of BR3-Fc for autoimmune diseases in the clinic.

Animals↗

PubMed2004

Mucosal regeneration of a duodenal defect using small intestine submucosa.

Intestinal tissue engineering has the potential of developing new treatment strategies for patients with a deficit in intestinal surface area. The purpose of this study was to investigate the capacity of small intestine submucosa (SIS) to regenerate intestinal epithelia in a rodent model for a duodenal defect. A duodenotomy was created in 20 Sprague-Dawley rats and was repaired with a circular patch of SIS. The repaired sites were retrieved 1, 2, 4, and 12 weeks after implantation. The size of the residual mucosal defect was measured. The retrieved tissues were fixed in formalin and processed by standard histologic techniques. The animals tolerated the procedure well. The mean size of the mucosal defects significantly decreased with time. Complete epithelialization of the defects was noted within 4 weeks in three of five samples. Histologically, the defects were lined with crypts and villi, but the muscularis layer did not regenerate. In the rodent model, SIS can be used as a patch to repair a duodenotomy. Mucosal regeneration was observed in the area of the defect. Further studies will determine whether SIS may be used to preserve or increase mucosal surface area in patients whose bowel length is compromised.

Animals↗

PubMed2003

Oral fibroblast expression of wound-inducible transcript 3.0 (wit3.0) accelerates the collagen gel contraction in vitro.

Wounds of the oral mucosa show faster closure with less scar formation than skin wounds in other areas. A differentially expressed cDNA, wound-inducible transcript 3.0 (wit3.0), was isolated from oral mucosal wound in rats (Sukotjo, C., Abanmy, A. A., Ogawa, T., and Nishimura, I. (2002) J. Dent. Res. 81, 229-235). The purpose of this study was to characterize the wit3.0 gene structure and the function of its deduced peptide. Human and rat genome databases revealed that the gene for wit3.0 was located in human chromosome 12p11.23 and rat chromosome 4q44. Its human and rat gene structures were well conserved, composed of 7 exons spread over 20 kb. Exon 5 was alternatively spliced generating two transcripts encoding deduced peptides of 215 and 253 amino acids (wit3.0 alpha and wit3.0 beta, respectively). The protein families data base of alignments (Pfam) analysis suggested the wit3.0 peptide sequence shared similarity with a portion of the myosin II coiled-coil domain consensus sequence. Fibroblasts isolated from the rat oral wound up-regulated wit3.0 expression and exhibited greater ability to contract collagen gel in vitro than fibroblasts isolated from untreated oral mucosa/gingiva. NIH3T3 and rat oral fibroblasts transfected with expression vector containing the coding sequences of wit3.0 alpha or wit3.0 beta increased in vitro collagen gel contraction. When treated with TGF beta-1, NIH3T3 fibroblast expression of wit3.0 showed no significant change, whereas alpha smooth muscle actin was increased in a dose-dependent manner. These data suggest that there may be a novel wound healing pathway involving wit3.0 underlying the favorable early wound closure characteristics of oral mucosa.

Actins↗

PubMed2003

Coenzyme Q(10) supplementation inhibits aortic lipid oxidation but fails to attenuate intimal thickening in balloon-injured New Zealand white rabbits.

Oxidized lipoproteins are implicated in atherosclerosis, and some antioxidants attenuate the disease in animals. Coenzyme Q(10) (CoQ(10)) in its reduced form, ubiquinol-10, effectively inhibits lipoprotein oxidation in vitro and in vivo; CoQ(10) supplements also inhibit atherosclerosis in apolipoprotein E gene knockout (apoE-/-) mice. Here we tested the effect of dietary CoQ(10) supplements on intimal proliferation and lipoprotein lipid oxidation in balloon-injured, hypercholesterolemic rabbits. Compared to nonsupplemented chow, CoQ(10) supplementation (0.5% and 1.0%, w/w) significantly increased the plasma concentration of CoQ(10) and the resistance of plasma lipids to ex vivo oxidation. CoQ(10) supplements also increased the content of CoQ(10) in the aorta and liver, but not in the brain, skeletal muscle, kidney, and heart. Surprisingly, CoQ(10) supplementation at 1% increased the aortic concentrations of all lipids, particularly triacylglycerols, although it significantly inhibited the proportion of triacylglycerols present as hydroperoxides by > 80%. The observed increase in vessel wall lipid content was reflected in elevated plasma concentrations of cholesterol, cholesteryl esters and triacylglycerols, and hepatic levels of mRNA for 3-hydroxy-3-methylglutaryl-coenzyme A reductase. CoQ(10) supplements did not attenuate lesion formation, assessed by the intima-to-media ratio of injured aortic vessels. Thus, like in apoE-/- mice, a high dose of supplemented CoQ(10) inhibits lipid oxidation in the artery wall of balloon-injured, hypercholesterolemic rabbits. However, unlike its antiatherosclerosis activity in the mice, CoQ(10) does not inhibit intimal hyperplasia in rabbits, thereby dissociating this disease process from lipid oxidation in the vessel wall.

Animals↗

PubMed2003

Precursor tissue analogs as a tissue-engineering strategy.

Natural tissues are composed of functionally diverse cell types that are organized in spatially complex arrangements. Organogenesis of complex tissues requires a coordinated sequential transformation process, with individual stages involving time-dependent expression of cell-cell, cell-matrix, and cell-signal interactions in three dimensions. The common theme of temporal-spatial patterning of these cellular interactions is also observed in other physiological processes, such as growth and development, wound healing, and tumor migration. The "precursor tissue analog" (PTA) applies the temporal-spatial patterning theme to tissue engineering. The goal of PTA in tissue engineering is not to fabricate the final transplantable tissue but rather to guide the dynamic organization, maturation, and remodeling leading to the formation of normal and functional tissues. We describe the critical design principles of PTA. First, structural, mechanical, and physiological requirements of the PTA as a temporary scaffold must be met by a fabrication method with flexibility. The fabrication potential incorporating biological materials such as living cells and plasmid DNA has been addressed. Second, the PTA concept is considered suitable for future tissue engineering in light of the use of undifferentiated stem cells, and may possess a capability to guide stem cells toward diverse differentiation characteristics in situ. To this end, the behavior of the engineered cell and tissue must be monitored in detail. The development of a practical phenotype monitoring system such as a DNA microarray may be integral to the fabrication strategies of PTA. Third, the microtopographical and microenvironmental control on the liquid-solid interaction may lead to a critical design for PTA to provide soluble factors, nutrients, and gases to the cells embedded within the scaffold. We suggest that the level set numerical simulation method may be utilized to engineer the consistent circulation of bioactive liquid throughout the PTA microenvironment.

Animals↗

PubMedDate not supplied

Comparing cutting efficiencies of diamond burs using a high-speed electric handpiece.

This study sought to compare the cutting efficiency of different diamond burs on initial use as well as during repeated use, alternating with sterilization. Long, round-end, tapered diamond burs with similar diameter, profile, and diamond coarseness (125-150 microm grit) were used. A high-torque, high-speed electric handpiece (set at 200,000 rpm) was utilized with a coolant flow rate of 25 mL/min. Burs were tested under a constant load of 170 g while cuts were made on a machinable ceramic substrate block. Each bur was subjected to five consecutive cuts for 30 seconds of continuous operation and the cutting depths were measured. All burs performed similarly on the first cut. Cutting efficiencies for three of the bur groups decreased significantly after the first cycle; however, by the fifth cycle, all bur groups performed similarly without any significant differences (p > 0.05). A scanning electron microscope revealed significant crystal loss after each use.

Ceramics↗