Hepatocyte growth factor prevents intimal hyperplasia in rabbit carotid expanded polytetrafluoroethylene grafting

AbstractPurpose: The major cause of vascular prosthesis failure is anastomotic intimal hyperplasia caused by the proliferation and migration of smooth muscle cells. Hepatocyte growth factor (HGF) is an endothelium-specific growth factor that exerts a mitogenic action on endothelial cells. This study was designed to examine the effect of HGF on the suppression of intimal hyperplasia after small-caliber expanded polytetrafluoroethylene (ePTFE) grafting. Methods: An ePTFE graft, 2 mm in diameter and 30 mm in length, was implanted in the left common carotid arteries of Japanese white rabbits, after which the animals were fed with a 1.0% cholesterol diet. HGF was infused intravenously immediately and then every day for 7 days at doses of 0.3 mg/body (the 0.3-mg HGF group; n = 20) or 1.0 mg/body (the 1.0-mg HGF group; n = 17). A control group (n = 20) underwent infusion with saline solution. The rabbits were killed on postoperative days (PODs) 1, 2, 3, 5, 7, and 28. Results: The patency rates on POD 28 were 33%, 55%, and 100% in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and the 1.0-mg HGF group (P <.05). Endothelial-like cells were seen on the intraluminal surface of the graft only near the anastomotic site on POD 5 in the 1.0-mg HGF group. Intimal thickness at the distal anastomosis was 284 ± 140 μm, 106 ± 18 μm, and 67 ± 10 μm in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.05). The number of anti-embryonic smooth muscle antibody positive cells at the distal anastomosis was 28.6 ± 0.8, 3.8 ± 2.8, and 3.9 ± 0.9 in the control, the 0.3-mg HGF, and the 1.0-mg HGF groups, respectively, with a significant difference between the control and both HGF groups (P <.01). Conclusion: HGF might suppress intimal thickness at the anastomotic site and improve the patency rate via rapid reendothelialization by POD 28 in a rabbit carotid ePTFE grafting model. (J Vasc Surg 2002;35:786-91.

A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression

SummarySignaling mechanisms underlying self-renewal of leukemic stem cells (LSCs) are poorly understood, and identifying pathways specifically active in LSCs could provide opportunities for therapeutic intervention. T-cell immunoglobin mucin-3 (TIM-3) is expressed on the surface of LSCs in many types of human acute myeloid leukemia (AML), but not on hematopoietic stem cells (HSCs). Here, we show that TIM-3 and its ligand, galectin-9 (Gal-9), constitute an autocrine loop critical for LSC self-renewal and development of human AML. Serum Gal-9 levels were significantly elevated in AML patients and in mice xenografted with primary human AML samples, and neutralization of Gal-9 inhibited xenogeneic reconstitution of human AML. Gal-9-mediated stimulation of TIM-3 co-activated NF-κB and β-catenin signaling, pathways known to promote LSC self-renewal. These changes were further associated with leukemic transformation of a variety of pre-leukemic disorders and together highlight that targeting the TIM-3/Gal-9 autocrine loop could be a useful strategy for treating myeloid leukemias

Possible Progression of Mass-flow Processes around Young Intermediate-mass Stars Based on High-resolution Near-infrared Spectroscopy. I. Taurus

We used the WINERED spectrograph to perform near-infrared high-resolution spectroscopy (resolving power R = 28,000) of 13 young intermediate-mass stars in the Taurus star-forming region. Based on the presence of near- and mid-infrared continuum emission, young intermediate-mass stars can be classified into three different evolutionary stages: Phases I, II, and III in the order of evolution. Our obtained spectra (λ = 0.91–1.35 μm) depict He i λ10830 and Pβ lines that are sensitive to magnetospheric accretion and winds. We also investigate five sources each for Pβ and He i lines that were obtained from previous studies along with our targets. We observe that the Pβ profile morphologies in Phases I and II corresponded to an extensive variety of emission features; however, these features are not detected in Phase III. We also observe that the He i profile morphologies are mostly broad subcontinuum absorption lines in Phase I, narrow subcontinuum absorption lines in Phase II, and centered subcontinuum absorption features in Phase III. Our results indicate that the profile morphologies exhibit a progression of the dominant mass-flow processes: stellar wind and probably magnetospheric accretion in the very early stage, magnetospheric accretion and disk wind in the subsequent stage, and no activities in the final stage. These interpretations further suggest that opacity in protoplanetary disks plays an important role in mass-flow processes. Results also indicate that He i absorption features in Phase III sources, associated with chromospheric activities even in such young phases, are characteristics of intermediate-mass stars