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Biomedical subjects

Hua Yang

Publications and source records attributed to Hua Yang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Distinct endocytic pathways control the rate and extent of synaptic vesicle protein recycling.

Synaptic vesicles have been proposed to form through two mechanisms: one directly from the plasma membrane involving clathrin-dependent endocytosis and the adaptor protein AP2, and the other from an endosomal intermediate mediated by the adaptor AP3. However, the relative role of these two mechanisms in synaptic vesicle recycling has remained unclear. We now find that vesicular glutamate transporter VGLUT1 interacts directly with endophilin, a component of the clathrin-dependent endocytic machinery. In the absence of its interaction with endophilin, VGLUT1 recycles more slowly during prolonged, high-frequency stimulation. Inhibition of the AP3 pathway with brefeldin A rescues the rate of recycling, suggesting a competition between AP2 and -3 pathways, with endophilin recruiting VGLUT1 toward the faster AP2 pathway. After stimulation, however, inhibition of the AP3 pathway prevents the full recovery of VGLUT1 by endocytosis, implicating the AP3 pathway specifically in compensatory endocytosis.

Acyltransferases↗
PubMed2006

Quantum-sized carbon dots for bright and colorful photoluminescence.

We report that nanoscale carbon particles (carbon dots) upon simple surface passivation are strongly photoluminescent in both solution and the solid state. The luminescence emission of the carbon dots is stable against photobleaching, and there is no blinking effect. These strongly emissive carbon dots may find applications similar to or beyond those of their widely pursued silicon counterparts.

Carbon↗
PubMed2006

Angiostatin decreases cell migration and vascular endothelium growth factor (VEGF) to pigment epithelium derived factor (PEDF) RNA ratio in vitro and in a murine ocular melanoma model.

PURPOSE: Our previous experiments have shown that low dose angiostatin results in decreased hepatic micrometastasis in a mouse model of uveal melanoma. The purpose of these experiments is to evaluate the effect of angiostatin on in vitro migration of melanoma cells and to explore the in vivo mechanism of angiostatin in our model. METHODS: For in vitro studies, quantitative RT-PCR was used to detect VEGF and PEDF mRNA in mouse B16LS9 melanoma cells and Mel290 human uveal melanoma cells with or without supplemental 0.1 mug/ml murine or human recombinant angiostatin. A wound healing assay was used to measure cellular migration in these two groups of cells. For the in vivo mechanism, aliquots of tissue culture B16LS9 cells treated with or without 0.1 mug/ml murine angiostatin were heterotopically inoculated into the posterior compartments of the right eyes of C57BL/6 mice. Frozen hepatic tissue was prepared and stained with hematoxylin using an RNase-free technique. Hepatic micrometastatic uveal melanoma cells were obtained by laser capture microdissection (LCM). Levels of VEGF and PEDF mRNA were detected by real time RT-PCR in the hepatic micrometastases. RESULTS: After in vitro treatment of the cell lines with angiostatin, the ratio of VEGF/PEDF mRNA significantly decreased in the B16LS9 (0.88+/-0.11 [mean+/-standard deviation] versus 2.70+/-0.15 in the control group; p=0.00006) and Mel290 (0.12+/-0.02 versus 0.68+/-0.04 in the control group; p=0.00346). However, the absolute VEGF mRNA and PEDF mRNA did not significantly change (p>0.08 for both cell lines). The migration assay showed significantly decreased migration at 24 h and 48 h after angiostatin treatment for both B16LS9 (p<0.01) and Mel290 (p<0.01) cell lines. For the in vivo experiments, pretreatment with angiostatin resulted in a decreased VEGF/PEDF mRNA ratio in B16LS9 cells compared to controls (0.0274+/-0.0070 versus 0.1726+/-0.0313; p=0.0014). Additionally, there was significantly increased PEDF mRNA (2.14+/-0.12 versus 0.30+/-0.05 in the control group; p=0.00002) in the liver metastases after pretreatment with angiostatin. CONCLUSIONS: Angiostatin inhibits the migration of melanoma cells in vitro. Angiostatin significantly decreases the ratio of VEGF/PEDF mRNA level in vitro and in hepatic micrometastatic melanoma cells. Angiostatin increases PEDF mRNA in melanoma metastases.

Angiostatins↗
PubMed2006

Design, synthesis, and progress toward optimization of potent small molecule antagonists of CC chemokine receptor 8 (CCR8).

Activation of CCR8 by its ligand CCL1 may play an important role in diseases such as asthma, multiple sclerosis, and cancer. The study of small molecule CCR8 antagonists will help establish the validation of these hypotheses. We report the design, synthesis, and progress toward optimization of potent small molecule CCR8 antagonists identified from a high-throughput screen. These analogues exhibit good potency in binding and chemotaxis assays, show good selectivity versus the hERG channel, and have good eADME (early absorption, distribution, metabolism, and excretion) profiles.

Amination↗
PubMed2006

[The prevalence of disc hemorrhage and papillary atrophy in Beijing Eye Study].

OBJECTIVE: To evaluate the prevalence of disc hemorrhage and papillary atrophy in Beijing defined area. METHODS: To review 4163 right eyes consecutive plain color fundus photographs of 4163 subjects (male/female = 1832/2331) who attended the eye screening. RESULTS: The prevalence of glaucoma is 3.0% (135/4439). Disc hemorrhage was found in 42 eyes of 42 subjects (1.0%), and more frequently in women. The prevalences of papillary atrophy (alpha zone and beta zone) were 70.98% (2955/4163) and 20.95% (872/4163), respectively. The prevalence of beta zone was greater in glaucoma group than in non-glaucomatous group (Fisher's test, P < 0.01). CONCLUSION: The prevalence of disc hemorrhage is low in whole population and women are easier to have disc hemorrhage with aging. Disc hemorrhage and papillary atrophy have different prevalences in defined-population study and might have close association on the early onset of glaucoma.

Adult↗
PubMed2006

Rapid TNFR1-dependent lymphocyte depletion in vivo with a selective chemical inhibitor of IKKbeta.

The transcription factor NF-kappaB plays a central role in regulating inflammation and apoptosis, making it a compelling target for drug development. We identified a small molecule inhibitor (ML120B) that specifically inhibits IKKbeta, an Ikappa-B kinase that regulates NF-kappaB. IKKbeta and NF-kappaB are required in vivo for prevention of TNFalpha-mediated apoptosis. ML120B sensitized mouse bone marrow progenitors and granulocytes, but not mature B cells to TNFalpha killing in vitro, and induced apoptosis in vivo in the bone marrow and spleen within 6 hours of a single oral dose. In vivo inhibition of IKKbeta with ML120B resulted in depletion of thymocytes and B cells in all stages of development in the bone marrow but did not deplete granulocytes. TNF receptor-deficient mouse thymocytes and B cells were resistant to ML120B-induced depletion in vivo. Surprisingly, surviving bone marrow granulocytes expressed TNFR1 and TNFR2 after dosing in vivo with ML120B. Our results show that inhibition of IKKbeta with a small molecule in vivo leads to rapid TNF-dependent depletion of T and B cells. This observation has several implications for potential use of IKKbeta inhibitors for the treatment of inflammatory disease and cancer.

Animals↗
PubMed2006

Heterogeneity of the Ca2+ sensitivity of secretion in a pituitary gonadotrope cell line and its modulation by protein kinase C and Ca2+.

Modulation of the Ca2+ sensitivity and cooperativity of secretion is an important means of regulating neurotransmission and hormone secretion. Employing high-time resolution measurement of membrane capacitance (Cm) stimulated by step-like or ramp [Ca2+]i elevation, we have identified the co-existence of both a high and low Ca2+-sensitive exocytosis in an immortal pituitary gonadotrope cell line, LbetaT2. Ramp [Ca2+]i generated by slow uncaging elicited a biphasic C(m) response. The first phase of response, which represents a highly Ca2+-sensitive pool (HCSP) of vesicles, began to secrete at low [Ca2+]i concentration (<1 microM) with low Ca2+ cooperativity. In contrast, the second phase, which represents a lowly Ca2+-sensitive pool (LCSP) of vesicles, only exocytozed at higher [Ca2+]i (>5 microM) and displayed a steep Ca2+ cooperativity. The co-existence of vesicle populations with different Ca2+ sensitivities was further confirmed by flash photolysis stimuli. The size of the HCSP was approximately 30 fF under resting conditions, but was dramatically increased (approximately threefold) by application of phorbol-12-myristate-13-acetate (PMA, an activator of protein kinase C). Forskolin (an activator of protein kinase A), however, exerted no significant effect on the size of both HCSP and LCSP. GnRH (gonadotropin releasing hormone) augmented the size of both pools to a larger extent (5- and 1.7-fold increase for HCSP and LCSP, respectively). The heterogeneity of Ca2+ sensitivity from different pools of vesicles and its differential modulation by intracellular signals suggests that LbetaT2 cells are an ideal model to further unravel the mechanism underlying the modulation of Ca2+-sensing machineries for exocytosis.

Animals↗
PubMed2006

Influence of the site of small bowel resection on intestinal epithelial cell apoptosis.

Massive small bowel resection (SBR) results in a significant increase in intestinal epithelial cell (EC) proliferation as well as apoptosis. Because the site of SBR (proximal (P) vs. distal (D)) affects the degree of intestinal adaptation, we hypothesized that different rates of EC apoptosis would also be found between P-SBR and D-SBR models. Wild-type C57BL/6J mice underwent: (1) 60% P-SBR, (2) 60% D-SBR, or (3) SHAM-operation (transaction-reanastomosis) at the mid-gut point. Mice were sacrificed after 7 days. EC apoptosis was measured by TUNEL staining. EC-related apoptotic gene expression including intrinsic and extrinsic pathways was measured with reverse transcriptase-polymerase chain reaction. Bcl-2 and bax protein expression were analyzed by Western immunoblotting. Both models of SBR led to significant increases in villus height and crypt depth; however, the morphologic adaptation was significantly higher after P-SBR compared to D-SBR (P<0.01). Both models of SBR led to significant increases in enterocyte apoptotic rates compared to respective sham levels; however, apoptotic rates were 2.5-fold higher in ileal compared to jejunal segments (P<0.01). P-SBR led to significant increases in bax (pro-apoptotic) and Fas expression, whereas D-SBR resulted in a significant increase in TNF-alpha expression (P<0.01). EC apoptosis seems to be an important component of intestinal adaptation. The significant difference in EC apoptotic rates between proximal and distal intestinal segments appeared to be due to utilization of different mechanisms of action.

Adaptation, Physiological↗
PubMed2006

Prevalence of visual impairment among adults in China: the Beijing Eye Study.

PURPOSE: To estimate the prevalence and distribution of blindness and low vision in Northern China. DESIGN: Population-based cohort study. METHODS: The Beijing Eye Study included 4438 subjects with an age of 40+ years. Mean age was 56.2 +/- 10.6 years (range, 40 to 101 years). RESULTS: Forty-three (1.0%) individuals had low vision (<20/60 and >/=20/400 best-corrected vision), and 17 (0.4%) individuals were blind (best-corrected visual acuity in the better-seeing eye <20/400). Low vision/blindness were significantly associated with age (P < .001), myopic refractive error (P < .001), and level of educational background (P = .035). It was not associated with gender (P = .76) and rural vs urban area (P = .88). CONCLUSIONS: Blindness or low vision affects approximately one in 100 Chinese older than 40 years. An estimated 4.1 million Chinese older than 40 years have low vision, and an estimated 1.6 million Chinese older than 40 years are blind.

Adult↗
PubMed2006

Frequency of optic disk hemorrhages in adult chinese in rural and urban china: the Beijing eye study.

PURPOSE: To determine the frequency of optic disk hemorrhages in the adult Chinese population. DESIGN: Population-based prevalence survey. METHODS: The study included 4439 subjects out of 5324 subjects invited to participate (response rate 83.4%) with an age of 40+ years. Mean age was 56.2 +/- 10.6 years. Color optic disk photographs (45 degrees) were morphometrically examined. RESULTS: Optic disk photographs were available for 8655 eyes of 4378/4439 (98.6%) subjects. Prevalence of disk hemorrhages was 107/8655 (1.24%; 95% confidence interval (CI): 1.00%, 1.47%) eyes. Occurrence of disk hemorrhages was significantly associated with glaucomatous optic nerve damage (P < .001; OR: 9.3; 95% CI: 5.6, 15.4) and age (P = .008; 95% CI: 1.01, 1.05). The occurrence of disk hemorrhages was not significantly associated with intraocular pressure (IOP) (P = .63; 95% CI: 0.97, 1.06), refractive error (P = .06; 5% CI: 0.87, 2.18), and visual field score (P = .81; 95% CI: 0.96, 1.03). Defining glaucoma as glaucomatous optic disk appearance, 20/107 (18.7%; 95% CI: 11.2%, 26.2%) disk hemorrhages were found in glaucomatous eyes. Out of 226 glaucomatous eyes, 20/226 (8.8%; 95%CI: 5.12%, 12.58%) eyes showed a disk hemorrhage. Hypertensive glaucoma eyes and normotensive glaucoma eyes did not vary considerably in frequency of disk hemorrhages (P = .44; OR: 1.82; 95% CI: 0.59, 5.68). CONCLUSIONS: Disk hemorrhages occur in a frequency of approximately 1.2% in adult Chinese. Major associated factors are glaucomatous optic neuropathy and age. Presence of a disk hemorrhage suggested glaucomatous optic nerve damage with a positive predictive value of approximately 20%. About 9% of glaucomatous eyes showed a disk hemorrhage at the time of examination.

Adult↗
PubMed2006

Preoperative pulmonary hypertension is associated with postoperative left ventricular dysfunction in chronic organic mitral regurgitation: an echocardiographic and hemodynamic study.

BACKGROUND: Some degree of pulmonary hypertension (PHTN) is common in patients with chronic mitral regurgitation. The aim of this study was to determine whether preoperative PHTN is associated with postoperative left ventricular (LV) dysfunction. METHODS: The study included 79 patients with chronic organic mitral regurgitation. Preoperative and postoperative LV function was assessed by echocardiography. Preoperative and postoperative hemodynamics were evaluated by a pulmonary artery catheter. RESULTS: Pulmonary artery systolic pressure decreased postoperatively (pre 49 +/- 14 vs. post 36 +/- 11 mm Hg, P < .01). Postoperative LV ejection fraction was significantly reduced in patients with preoperative PHTN (pre 61 +/- 11% vs post 49 +/- 12%, P < .01). A stepwise multivariate regression analysis showed that preoperative pulmonary artery systolic pressure and LV end-systolic dimension were independent predictors of postoperative LV ejection fraction (r = -0.53, P < .001, and r = -0.34, P < .05, respectively). CONCLUSION: Preoperative PHTN is associated with postoperative LV dysfunction in patients with chronic organic mitral regurgitation undergoing mitral valve operation.

Chronic Disease↗
PubMed2006

Enterogenesis in a clinically feasible model of mechanical small-bowel lengthening.

BACKGROUND: Recent work indicates that mechanical force induces small-bowel growth, although methods reported do not have direct clinical application. We report a clinically feasible technique of enterogenesis and describe intestinal function in this model. METHODS: Using a pig model (n = 11), we stretched isolated small intestinal segments mechanically for 7 days in vivo with an intraluminal device. Control segments were not stretched. Morphology, histology, and epithelial proliferation were assessed. Absorption and epithelial barrier function were examined in an Ussing chamber. RESULTS: Stretch segments were significantly longer than Control segments and had nearly 2-fold greater surface area (P < .001). Mucosal thickness was much greater in Stretch than Control segments (772 +/- 134 vs. 647 +/- 75 microm, P = .02). Although villus height was reduced in Stretch and Control segments (353 +/- 76 vs. 324 +/- 76 microm, P = .6) versus native jejunum (522 +/- 87, P < .0005), crypt depth was increased dramatically in Stretch (450 +/- 95 microm) versus Control segments (341 +/- 64, P = .005). This observation was accompanied by a 2-fold increase in cellular proliferation (26.3 +/- 3.8 vs 12.1 +/- 6.6 % bromodeoxyuridine+, P < .05). Barrier function was intact ([3H]-mannitol permeation, 0.16 +/- 0.08%, vs native jejunum, 0.17 +/- 0.08%, P = .81). Glucose-mediated sodium transport was similar in Stretch versus native jejunum segments (60.0 +/- 23.5 vs 82.3 +/- 47.3 microA/cm2, P = .31), as was carbachol-induced chloride transport (82.4 +/- 72.2 vs 57.2 +/- 33.4 microA/cm2, P = .54) and alanine absorption (16.46 +/- 12.94 vs 23.53 +/- 21.31 microA/cm2, P = .53). CONCLUSIONS: Mechanical stretching induces small intestinal growth, while maintaining function. Epithelial architecture does change, such that a decrease in villus height is offset by a marked increase in crypt depth and a 2-fold increase in epithelial proliferation. Epithelial barrier and absorptive functions remain intact. The device described may have direct clinical applicability.

Animals↗
PubMed2006

Combined immunologic and anti-angiogenic therapy reduces hepatic micrometastases in a murine ocular melanoma model.

PURPOSE: To evaluate the combined effect of neoadjuvant intracameral interferon alpha -2b and adjuvant low-dose angiostatin in reducing the number of hepatic micrometastases in a murine model of ocular melanoma. METHODS: The posterior compartments of the right eyes of C57BL6 mice were inoculated with 5 x 10(5) cells/2.5 microl of cells from the Queens, B16F10, or B16LS9 melanoma cell lines. The right eyes were enucleated at 7 days, and the mice were sacrificed at 28 days postinoculation, respectively. Hepatic micrometastases were counted. There were four treatment groups (n = 15 each) for each cell line as follows: group 1, intraperitoneal injections of 20 KIU interferon alpha -2b for 4 days prior to enucleation; group 2, intramuscular injections of 100 microl 0.1 microg/microl murine angiostatin every day for 14 days starting on day 1 after enucleation; group 3, treatment of group 1 and group 2 combined; group 4, intraperitoneal and intramuscular injections of equal volumes of phosphate-buffered saline (PBS) (control group). RESULTS: Results showed decreased micrometastases for groups 1 through 3 compared with group 4, with the greatest reduction in group 3 (p < 0.006). CONCLUSIONS: This study suggests that combined neoadjuvant interferon alpha -2b and adjuvant low-dose angiostatin therapy act synergistically to decrease hepatic micrometastases in a murine ocular melanoma model.

Angiogenesis Inhibitors↗
PubMed2006

Analysis of fecal microbial flora for antibiotic resistance in ceftiofur-treated calves.

To evaluate the impact of ceftiofur treatment in calves on fecal shedding of ceftriaxone-resistant bacteria, 3 female Holstein dairy calves were treated by intramuscular injection with EXCENEL RTU (ceftiofur hydrochloride, Pharmacia and Upjohn) at a therapeutic dosage of 2.2 mg/kg/day for 5 consecutive days following label directions. Three untreated calves were housed separately and served as controls. One to 3 days following the initial administration of ceftiofur, there was a 14% and 2% increase of fecal bacteria resistant to 16 and 64 microg ceftriaxone/mL, respectively. This response remained unchanged from days 6 to 13, and increased resistance was seen at day 17. Randomly selected isolates of gram-positive and gram-negative bacteria with elevated resistance to ceftriaxone (minimal inhibitory concentration (MIC) >or=64 microg ceftriaxone/mL) were isolated from calf feces and identified. In vitro conjugation experiments revealed that both the ceftriaxone-resistance gene bla (CMY-2) and class 1 integron were transferred from two bacterial species to Salmonella spp. at a frequency of 10(7) to 10(5). MIC data revealed that Salmonella transconjugants acquired either reduced susceptibility or resistance to ceftriaxone as well as to multiple antibiotics. This genetic transfer occurred both within and between genera. Treatment of calves with therapeutic dosages of ceftiofur can significantly increase for at least 17 days following the initial treatment the fecal excretion of ceftriaxone-resistant bacteria, including Salmonella species.

Animals↗
PubMed2006

Initial diagnosis and treatment follow up of neuroblastoma invasion of inferior vena cava with I-123 metaiodobenzylguanidine scintigraphy.

Neuroblastoma is a common malignancy diagnosed during childhood. Metastatic neuroblastoma frequently involves regional lymph nodes, bone, and bone marrow. In contrast, neuroblastoma involvement of the inferior vena cava (IVC) is extremely rare. We report a case of neuroblastoma with IVC invasion visualized with I-123 metaiodobenzylguanidine (I-123 MIBG) scintigraphy during a diagnostic workup while a follow-up I-123 MIBG scan showed resolution of tumor uptake in the IVC with treatment.

Child, Preschool↗