Faculty Bibliography

RATIONALE AND OBJECTIVES: Evaluation of the T2 relaxation time of articular cartilage holds great potential for quantitative assessment of internal changes of the cartilage matrix. The purpose of the present study was to assess the validity of multiecho-based cartilage T2 quantitation in a clinical MRI setting at 1.5 T. METHODS: Four multisection multiecho sequence variants dedicated for quantitative T2 mapping of human articular cartilage were implemented on a 1.5 T whole-body imager and tested for accuracy in CuSO4-agarose gel phantoms and human patellar cartilage. Sequence design was varied to minimize errors in T2 quantitation due to stimulated echoes. RESULTS: As compared with single spin-echo experiments, the apparent T2 values calculated from the multiecho sequence variants showed mean deviations ranging from +26% to -32% (phantoms) and from +42% to -18% (cartilage). The patellar cartilage T2 covered a range from about 25 milliseconds to 55 milliseconds, with longer T2 values observed in the more superficial layers. In cartilage, best results were obtained from the sequence design using improved section profiles and a spoiler gradient scheme for suppression of stimulated echoes. CONCLUSIONS: Our results revealed a clear dependence of apparent T2 relaxation times on the pulse sequence design, emphasizing that the 'true' T2 is hard to find. In addition, the effect on the apparent T2 values resulting from the specific modification of any sequence variant varied according to the respective tissue's properties. Therefore, the acquisition technique in conjunction with the specific tissue on which T2 mapping is performed need to be reported in detail and should kept consistent to allow large-scale comparisons and monitoring of treatment strategies, e.g., in osteoarthritis

The four-cell C. elegans embryo contains two sister cells called ABa and ABp that initially have equivalent abilities to produce ectodermal cell types. Multiple Notch-mediated interactions occur during the early cell divisions that diversify the ABa and ABp descendants. The first interaction determines the pattern of ectodermal cell types produced by ABp. The second interaction induces two ABa granddaughters to become mesodermal precursors. We show that T-box transcription factors called TBX-37 and TBX-38 are essential for mesodermal induction, and that these factors are expressed in ABa, but not ABp, descendants. We provide evidence that the first Notch interaction functions largely, if not entirely, to prevent TBX-37, TBX-38 expression in ABp descendants. Neither the second Notch interaction nor TBX-37, TBX-38 alone are sufficient for mesodermal induction, indicating that both must function together. We conclude that TBX-37, TBX-38 play a key role in distinguishing the outcomes of two sequential Notch-mediated interactions

In Alzheimer disease (AD) patients, early memory dysfunction is associated with glucose hypometabolism and neuronal loss in the hippocampus. Double transgenic (Tg) mice co-expressing the M146L presenilin 1 (PS1) and K670N/M671L, the double 'Swedish' amyloid precursor protein (APP) mutations, are a model of AD amyloid-beta deposition (Abeta) that exhibits earlier and more profound impairments of working memory and learning than single APP mutant mice. In this study we compared performance on spatial memory tests, regional glucose metabolism, Abeta deposition, and neuronal loss in APP/PS1, PS1, and non-Tg (nTg) mice. At the age of 2 months no significant morphological and metabolic differences were detected between 3 studied genotypes. By 8 months, however, APP/PS1 mice developed selective impairment of spatial memory, which was significantly worse at 22 months and was accompanied by reduced glucose utilization in the hippocampus and a 35.8% dropout of neurons in the CA1 region. PS1 mice exhibited a similar degree of neuronal loss in CA1 but minimal memory deficit and no impairment of glucose utilization compared to nTg mice. Deficits in 22 month APP/PS1 mice were accompanied by a substantially elevated Abeta load, which rose from 2.5% +/- 0.4% at 8 months to 17.4% +/- 4.6%. These findings implicate Abeta or APP in the behavioral and metabolic impairments in APP/PS1 mice and the failure to compensate functionally for PS1-related hippocampal cell loss

The impact of inhibitors of tumor angiogenesis (endostatin, angiostatin) on the neovascularization required for the healing of transferred tissue has not been examined. We investigated the effect of endostatin on the functional neovascularization of random pattern flaps. C57BL6 mice were pretreated with endostatin beginning 3 days prior to surgery (n = 10), and daily injections continued throughout the study. Dorsal random cutaneous flaps were raised in both treatment and control (saline-treated) groups. The remaining cranial attachment was divided on day 9. Oxygen tension (PO2) was measured using a microprobe on days 1, 3, 5 and 16. Flaps were harvested and the vasculature was stained with CD31 on day 16. We found that endostatin significantly decreased flap survival. Mice that were treated with endostatin had fewer CD31+ blood vessels, worse flap perfusion at all time points, and lower oxygen tensions throughout the length of the flap. These findings have potential implications for the patients undergoing antiangiogenesis therapy who require surgical reconstruction

The vascular system is highly conserved in all vertebrates in the aspects of anatomy as well as in the genetic mechanism governing it. The embryo of the medaka, Oryzias latipes is small and transparent, providing many advantages for the experimental analysis of the vertebrate vascular system. We isolated a novel medaka transglutaminase gene, termed embryonic transglutaminase, and found that it showed the highest homology to the coagulation factor XIII A subunit of mammals. This gene is expressed in the anterior lateral plate mesoderm, and then expressed specifically in yolk veins consisting two ducts of Cuvier and the vitellocaudal vein. Our data is the first finding that a coagulation factor XIII-like gene is expressed in the early vascular development of vertebrates.

OBJECTIVE: To assess differences in pregnancy and implantation rates as a function of the embryo placement. DESIGN: Prospective cohort study. SETTING: A tertiary care center. SUBJECT(S): All fresh, nondonor IVF cycles performed in 2001. INTERVENTION(S): Alteration in embryo transfer (ET) target location from the fundal region to the middle to lower uterine segment. MAIN OUTCOME MEASURE(S): Clinical pregnancy rate (sonographic sac evidence/number of transfer cycles), implantation rate (number of sacs/number of embryos transferred), patient age, peak E(2), and fertilization rate. RESULT(S): A total of 393 fundal and 273 lower to middle uterine segment ETs were performed. The pregnancy (PR), implantation, and birth rates were significantly higher after a middle to lower uterine segment ET compared with fundal ET (39.6% vs. 31.2%; 21% vs. 14%; and 34.1% vs. 26.2%, respectively). Groups did not differ regarding patient age, basal FSH, peak E(2), number of intracytoplasmic sperm injection (ICSI) cycles, fertilization rate, embryo quality, or number of embryos transferred. CONCLUSION(S): Both PR and implantation rates are favorably affected by directing embryo placement to the lower to middle uterine segment. By some unknown mechanism, it appears that this endometrial location provides a more favorable region for embryo deposition

In adults and children over two years of age, large cranial defects do not reossify successfully, posing a substantial biomedical burden. The osteogenic potential of bone marrow stromal (BMS) cells has been documented. This study investigates the in vivo osteogenic capability of adipose-derived adult stromal (ADAS) cells, BMS cells, calvarial-derived osteoblasts and dura mater cells to heal critical-size mouse calvarial defects. Implanted, apatite-coated, PLGA scaffolds seeded with ADAS or BMS cells produced significant intramembranous bone formation by 2 weeks and areas of complete bony bridging by 12 weeks as shown by X-ray analysis, histology and live micromolecular imaging. The contribution of implanted cells to new bone formation was 84-99% by chromosomal detection. These data show that ADAS cells heal critical-size skeletal defects without genetic manipulation or the addition of exogenous growth factors.

Many pathfinding axons must locate target fields that are themselves positioned by active migration. A hypothetical method for ensuring that these migrations are coordinated is towing, whereby the extension of axons is entirely dependent on the migration of their target cells. Here we combine genetics and time-lapse imaging in the zebrafish to show that towing by migrating cells is a bona fide mechanism for guiding pathfinding axons in vivo