3,027 research outputs found
KINETIC ANALYSIS OF LOWER EXTREMITY DURING SIDESTEP CUITING UNDER DIFFERENT DIRECTIONS
The purpose of this study was to investigate the ground reaction forces, joint reaction forces, net muscle joint moments of the ankle, knee and hip during elite lhandball athletes executed typical cutting maneuver under four different directions. Four male elite handball players were tested during fast running (4.5-5.5 m/s) and then performed cutting to the right off (30°, 400 50°, 600 A JVC camera (60 Hz) and synchronized with force plate (1200 Hz) were used to collect the relative parameters of braking leg during cutting maneuver. Each participant's braking leg (right leg) was modeled as a system of rigid bodies. The inverse dynamics approach was used to integrate the body segment parameter, kinetic and force plate data, and to solve the resultant joint moments. The results showed that sidestep cutting maneuver would produce a load and according to the increase of cutting angles, the lower extremity could receive a strike force and moment during the braking phase. Besides, while the knee angle of f1exion was small and repeated loading of this magnitude were enough to produce the fatigue of lower extremity joints that would eventually resu'lt in complete disruption and clinical lower extremity joints injury
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Fucosylation of LAMP-1 and LAMP-2 by FUT1 correlates with lysosomal positioning and autophagic flux of breast cancer cells.
Alpha1,2-fucosyltransferases, FUT1 and FUT2, which transfer fucoses onto the terminal galactose of N-acetyl-lactosamine via α1,2-linkage have been shown to be highly expressed in various types of cancers. A few studies have shown the involvement of FUT1 substrates in tumor cell proliferation and migration. Lysosome-associated membrane protein 1, LAMP-1, has been reported to carry alpha1,2-fucosylated Lewis Y (LeY) antigens in breast cancer cells, however, the biological functions of LeY on LAMP-1 remain largely unknown. Whether or not its family member, LAMP-2, displays similar modifications and functions as LAMP-1 has not yet been addressed. In this study, we have presented evidence supporting that both LAMP-1 and 2 are substrates for FUT1, but not FUT2. We have also demonstrated the presence of H2 and LeY antigens on LAMP-1 by a targeted nanoLC-MS(3) and the decreased levels of fucosylation on LAMP-2 by MALDI-TOF analysis upon FUT1 knockdown. In addition, we found that the expression of LeY was substantial in less invasive ER+/PR+/HER- breast cancer cells (MCF-7 and T47D) but negligible in highly invasive triple-negative MDA-MB-231 cells, of which LeY levels were correlated with the levels of LeY carried by LAMP-1 and 2. Intriguingly, we also observed a striking change in the subcellular localization of lysosomes upon FUT1 knockdown from peripheral distribution of LAMP-1 and 2 to a preferential perinuclear accumulation. Besides that, knockdown of FUT1 led to an increased rate of autophagic flux along with diminished activity of mammalian target of rapamycin complex 1 (mTORC1) and enhanced autophagosome-lysosome fusion. This may be associated with the predominantly perinuclear distribution of lysosomes mediated by FUT1 knockdown as lysosomal positioning has been reported to regulate mTOR activity and autophagy. Taken together, our results suggest that downregulation of FUT1, which leads to the perinuclear localization of LAMP-1 and 2, is correlated with increased rate of autophagic flux by decreasing mTOR signaling and increasing autolysosome formation
High expression FUT1 and B3GALT5 is an independent predictor of postoperative recurrence and survival in hepatocellular carcinoma.
Cancer may arise from dedifferentiation of mature cells or maturation-arrested stem cells. Previously we reported that definitive endoderm from which liver was derived, expressed Globo H, SSEA-3 and SSEA-4. In this study, we examined the expression of their biosynthetic enzymes, FUT1, FUT2, B3GALT5 and ST3GAL2, in 135 hepatocellular carcinoma (HCC) tissues by qRT-PCR. High expression of either FUT1 or B3GALT5 was significantly associated with advanced stages and poor outcome. Kaplan Meier survival analysis showed significantly shorter relapse-free survival (RFS) for those with high expression of either FUT1 or B3GALT5 (P = 0.024 and 0.001, respectively) and shorter overall survival (OS) for those with high expression of B3GALT5 (P = 0.017). Combination of FUT1 and B3GALT5 revealed that high expression of both genes had poorer RFS and OS than the others (P < 0.001). Moreover, multivariable Cox regression analysis identified the combination of B3GALT5 and FUT1 as an independent predictor for RFS (HR: 2.370, 95% CI: 1.505-3.731, P < 0.001) and OS (HR: 2.153, 95% CI: 1.188-3.902, P = 0.012) in HCC. In addition, the presence of Globo H, SSEA-3 and SSEA-4 in some HCC tissues and their absence in normal liver was established by immunohistochemistry staining and mass spectrometric analysis
Online assessment of patients' views on hospital performances using Rasch model's KIDMAP diagram
<p>Abstract</p> <p>Background</p> <p>To overcome the drawback of individual item-by-item box plots of disclosure for patient views on healthcare service quality, we propose to inspect interrelationships among items that measure a common entity. A visual diagram on the Internet is developed to provide thorough information for hospitals.</p> <p>Methods</p> <p>We used the Rasch rating scale model to analyze the 2003 English inpatient questionnaire data regarding patient satisfactory perception, which were collected from 169 hospitals, examined model-data fit, and developed a KIDMAP diagram on the Internet depicting the satisfaction level of each hospital and investigating aberrant responses with Z-scores and MNSQ statistics for individual hospitals. Differential item functioning (DIF) analysis was conducted to verify construct equivalence across types of hospitals.</p> <p>Results</p> <p>18 of the 45 items fit to the model's expectations, indicating they jointly defined a common construct and an equal-interval logit scale was achieved. The most difficult aspect for hospitals to earn inpatients' satisfaction were item 29 (staff told you about any medication side effects to watch when going home). No DIF in the 18-item questionnaire was found between types of hospitals, indicating the questionnaire measured the same construct across hospitals. Different types of hospitals obtained different levels of satisfaction. The KIDMAP on the Internet provided more interpretable and visualized message than traditional item-by-item box plots of disclosure.</p> <p>Conclusion</p> <p>After removing misfit items, we find that the 18-item questionnaire measures the same construct across types of hospitals. The KIDMAP on the Internet provides an exemplary comparison in quality of healthcare. Rasch analysis allows intra- and inter-hospital performances to be compared easily and reliably with each other on the Internet.</p
Malignant phyllodes tumors display mesenchymal stem cell features and aldehyde dehydrogenase/disialoganglioside identify their tumor stem cells.
IntroductionAlthough breast phyllodes tumors are rare, there is no effective therapy other than surgery. Little is known about their tumor biology. A malignant phyllodes tumor contains heterologous stromal elements, and can transform into rhabdomyosarcoma, liposarcoma and osteosarcoma. These versatile properties prompted us to explore their possible relationship to mesenchymal stem cells (MSCs) and to search for the presence of cancer stem cells (CSCs) in phyllodes tumors.MethodsParaffin sections of malignant phyllodes tumors were examined for various markers by immunohistochemical staining. Xenografts of human primary phyllodes tumors were established by injecting freshly isolated tumor cells into the mammary fat pad of non-obese diabetic-severe combined immunodeficient (NOD-SCID) mice. To search for CSCs, xenografted tumor cells were sorted into various subpopulations by flow cytometry and examined for their in vitro mammosphere forming capacity, in vivo tumorigenicity in NOD-SCID mice and their ability to undergo differentiation.ResultsImmunohistochemical analysis revealed the expression of the following 10 markers: CD44, CD29, CD106, CD166, CD105, CD90, disialoganglioside (GD2), CD117, Aldehyde dehydrogenase 1 (ALDH), and Oct-4, and 7 clinically relevant markers (CD10, CD34, p53, p63, Ki-67, Bcl-2, vimentin, and Globo H) in all 51 malignant phyllodes tumors examined, albeit to different extents. Four xenografts were successfully established from human primary phyllodes tumors. In vitro, ALDH+ cells sorted from xenografts displayed approximately 10-fold greater mammosphere-forming capacity than ALDH- cells. GD2+ cells showed a 3.9-fold greater capacity than GD2- cells. ALDH+/GD2+cells displayed 12.8-fold greater mammosphere forming ability than ALDH-/GD2- cells. In vivo, the tumor-initiating frequency of ALDH+/GD2+ cells were up to 33-fold higher than that of ALDH+ cells, with as few as 50 ALDH+/GD2+ cells being sufficient for engraftment. Moreover, we provided the first evidence for the induction of ALDH+/GD2+ cells to differentiate into neural cells of various lineages, along with the observation of neural differentiation in clinical specimens and xenografts of malignant phyllodes tumors. ALDH+ or ALDH+/GD2+ cells could also be induced to differentiate into adipocytes, osteocytes or chondrocytes.ConclusionsOur findings revealed that malignant phyllodes tumors possessed many characteristics of MSC, and their CSCs were enriched in ALDH+ and ALDH+/GD2+ subpopulations
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