Biomedical subjects

Hong Du

Publications and source records attributed to Hong Du.

43 records · Page 3Linked to original sources

PubMed2003

Distinct endosomal compartments in early trafficking of low density lipoprotein-derived cholesterol.

We previously studied the early trafficking of low density lipoprotein (LDL)-derived cholesterol in mutant Chinese hamster ovary cells defective in Niemann-Pick type C1 (NPC1) using cyclodextrin (CD) to monitor the arrival of cholesterol from the cell interior to the plasma membrane (PM) (Cruz, J. C., Sugii, S., Yu, C., and Chang, T.-Y. (2000) J. Biol. Chem. 275, 4013-4021). We found that newly hydrolyzed cholesterol derived from LDL first appears in certain CD-accessible pool(s), which we assumed to be the PM, before accumulating in the late endosome/lysosome, where NPC1 resides. To determine the identity of the early CD-accessible pool(s), in this study, we performed additional experiments, including the use of revised CD incubation protocols. We found that prolonged incubation with CD (>30 min) caused cholesterol in internal membrane compartment(s) to redistribute to the PM, where it became accessible to CD. In contrast, a short incubation with CD (5-10 min) did not cause such an effect. We also show that one of the early compartments contains acid lipase (AL), the enzyme required for liberating cholesterol from cholesteryl ester in LDL. Biochemical and microscopic evidence indicates that most of the AL is present in endocytic compartment(s) distinct from the late endosome/lysosome. Our results suggest that cholesterol is liberated from LDL cholesteryl ester in the hydrolytic compartment containing AL and then moves to the NPC1-containing late endosome/lysosome before reaching the PM or the endoplasmic reticulum.

Animals↗

PubMed2003

An enhancer region determines hSP-B gene expression in bronchiolar and ATII epithelial cells in transgenic mice.

Regulation of the surfactant protein B gene (SP-B) is developmentally controlled and highly tissue specific. To elucidate the SP-B gene temporal/spatial expression pattern in lung development at the transcriptional level, a transgenic mouse model line carrying the human SP-B (hSP-B) 1.5-kb 5'-flanking regulatory region and the lacZ gene was established. Expression of hSP-B 1.5-kb lacZ gene started at the onset of lung formation [embryonic day 9 (E9)] and was restricted to epithelial cells throughout prenatal and postnatal lung development. In the adult lung, hSP-B 1.5-kb lacZ gene expression was restricted to bronchiolar and alveolar type II epithelial cells. In lung explant culturing studies, the hSP-B 1.5-kb lacZ gene was highly expressed in newly formed epithelial tubules during the respiratory branching process. In a second transgenic mouse line, an enhancer region, which binds to thyroid transcription factor-1, retinoic acid receptor, signal transducers and activators of transcription 3, and nuclear receptor coactivators (SRC-1, ACTR, TIF2, and CBP/p300), was deleted from the hSP-B 1.5-kb lacZ gene. The deletion abolished hSP-B lacZ gene expression in bronchiolar epithelial cells and significantly reduced its expression level in alveolar type II epithelial cells in transgenic mice.

Animals↗

PubMed2003

[Natural course and prognosis of visual acuity in patients of age-related macular degeneration with occult choroidal neovascularization].

OBJECTIVE: To investigate the natural course and the final visual acuity in patients of age-related macular degeneration with choroidal neovascularization. METHODS: Thirty five eyes of 29 patients diagnosed as AMD with occult choroidal neovascularization were studied. The eyes which had laser, radiation therapy or surgical treatment were excluded. Visual acuity, fundus examination, fluorescent angiography (FFA) and perimetry test were performed at the first time visit and 5 years following-up at an interval of 1 to 3 months. The average following-up period of time was 8 years (range from 5 to 16 years) which started in 1985 and ended in 2001. RESULTS: Initial visual acuity 0.1 or less was shown in 10 eyes (28.5%, only hands movement can be seen in 4 of 10 eyes), 23 eyes (65.7%) with visual acuity of 0.1 or less (14 eyes with vision acuity of hands movement) on the last visit. 7 of 35 eyes, the final visual acuity improved more than 2 lines, 12 eyes remained the same and 16 eyes had been lost vision more than two lines. At the baseline examination, 25 eyes had macular hemorrhages and 4 eyes had vitreous hemorrhages. The fundus hemorrhages occurred repeatedly 1 to 4 times in 23 eyes during following-up, the macular hemorrhages was detected in 7 eyes at the last visit. At the initial fundus examination, fibrotic membranes were found in 7 eyes; all 35 eyes had disc form scarring with various size in most recent following-up. CONCLUSION: The natural course of Age-related macular degeneration with choroidal neovascularization is prolonged and the final visual prognosis was poor especially in the cases with recurrent macular hemorrhages.

Age Factors↗

PubMed2003

[Study on the relationship between smoking, alcohol intake and hyperlipidemia in fishermen].

OBJECTIVE: To identify the relationship between smoking, alcohol intake and hyperlipidemia in fishermen. METHODS: 115 fishermen were randomly recruited and divided into case and control groups according to the result of blood lipoprotein. A questionnaire was used to record general information and the history of smoking and alcohol intake. Statistics were gathered to compare the difference of lipoprotein and apolipoprotein level between exposure and control groups and to calculate the OR value of smoking and alcohol intake. RESULTS: The OR of smoking was 3.417 (95% CI: 1.132 - 10.308), with significant dosage-effect relationship between smoking index and hyperlipidemia. The serum low density lipoprotein-cholesterol (LDL-C) and apolipoprotein (apo) B levels in smoking group was higher than that of control group. The OR value of alcohol intake at early age (early than 20) were 3.275 (95% CI: 1.249 - 8.580) and 4.016 (95% CI: 1.475 - 10.952) respectively. The LDL-C, apoB, the serum total cholesterol (TC)/high density lipoprotein-cholesterol (HDL-C) levels in alcohol abuse group were higher than that of control group. CONCLUSION: Smoking and alcohol abuse were important risk factors of hyperlipidemia, through changing the level of LDL-C and apoB. There was synergistic action between smoking and alcohol abuse in the development of hyperlipidemia.

Adolescent↗

PubMed2002

Lysosomal acid lipase deficiency: correction of lipid storage by adenovirus-mediated gene transfer in mice.

Lysosomal acid lipase (LAL) is the essential enzyme for hydrolysis of triglycerides (TGs) and cholesteryl esters (CEs) in lysosomes. Its deficiency produces two human phenotypes: Wolman disease (WD) and cholesteryl ester storage disease (CESD). The LAL null (lal(-/-)) mouse mimicks aspects of human WD and CESD. The potential for gene therapy of LAL deficiency was tested with first-generation adenoviral vectors containing human LAL cDNA (Ad-hLAL) by intravenous injection into lal(-/-) mice. Compared with phosphate-buffered saline-injected controls, the mice receiving Ad-hLAL had increased hepatic LAL activity, decreased hepatomegaly, and normalization of histopathology. hLAL protein and mRNA were detected by immunohistochemical staining and in situ hybridization in hepatic parenchymal and sinusoid lining cells, splenic sinusoidal cells, lung macrophages, and adrenal cortical cells. Mice showed TG reductions in liver, spleen, and small intestine of 68, 54, and 50%, respectively, and cholesterol reductions of 55, 52, and 34%, respectively, at 20 days postinjection. These studies provide the basis for the use of gene therapy, in the form of gene transfer via intravenously administered adenovirus, to correct deficiency states, such as WD and CESD, and histopathology of a variety of tissues.

Adenoviridae↗

PubMed2002

Spatial repression of PCNA by p53 during kidney development.

Transcriptional repression is a key mechanism for the spatial specification of gene expression and cell fate determination. During kidney development, proliferating cell nuclear antigen (PCNA) is expressed in the nephrogenic zone and is downregulated rapidly as renal epithelial cells enter terminal differentiation and acquire functional characteristics. Our laboratory reported that the transcription factor p53 stimulates the terminal differentiation of renal epithelial cells by means of transcriptional activation of renal function genes (Saifudeen Z, Dipp S, and El-Dahr SS. J Clin Invest 109: 1021-1030, 2002). Because p53-induced growth arrest correlates with downregulation of PCNA gene expression, we examined the impact of p53 inactivation on PCNA expression in mice and evaluated the effect of p53 on PCNA transcription. Immunohistochemistry revealed that the transition from nephrogenesis to terminal epithelial cell differentiation correlates with accumulation of the transcription factor p53. Importantly, the spatially restricted pattern of PCNA expression is disrupted in kidneys of p53-deficient pups, in which there was a redistribution of PCNA expression into the differentiation zone (without a change in total kidney PCNA content) and distortion of the tubular architecture. Electrophoretic mobility shift assays revealed that the binding of kidney nuclear extracts to the p53 response elements in human and rat PCNA promoters is developmentally regulated. Transient transfection assays performed in p53-deficient HeLa cells revealed that exogenous p53 strongly represses transcription from human PCNA promoter-reporter constructs. Interestingly, deletion of the p53-binding site confers enhanced responsiveness to p53-mediated repression, suggesting that transcriptional repression of PCNA by p53 is achieved by a mechanism other than direct DNA binding. On the basis of these results, we propose the hypothesis that p53-mediated transcriptional repression plays a role in the spatial restriction of PCNA gene expression during normal renal development.

Amino Acid Sequence↗

PubMed2002

[Vogt-Koyanagi-Harada syndrome: glucocorticoid therapy and visual prognosis].

OBJECTIVE: To evaluate the efficacy of glucocorticoid therapy in patients with Vogt-Koyanagi-Harada (VKH) syndrome. METHODS: One hundred and thirty-six patients with VKH were treated with two regimens of oral prednisone. Regimen 1: Fifty-one patients with VKH were treated at the uveitic stage with prednisone, starting from 2 mg/kg/day tapering gradually and shifting to alternate-day treatment. The patients were treated for approximately 8 months. Regimen 2: Eighty-five patients with VKH were referrals who were treated elsewhere with systemic glucocorticoid more than 2 months with total dose equivalent to prednisone more than 2 000 mg. Systemic and ocular complications were found in some of these patients. The hypothalamus-pituitary-adrenal axis was markedly inhibited as indicated by decrease in urine free cortisol (UFC). These patients were treated for 6 - 10 months based on the patients' individual ocular situations. The visual results, frequency of recurrence of uveitis and incidence of ocular complications were compared between the two groups. RESULTS: Visual acuity >/= 0.5 and >/= 0.8 were found to be 94.1% and 79.4% respectively in patients treated with regimen 1 which was far better than the patients treated with regimen 2. On the other hand, recurrence of uveitis and ocular complications were found significantly lower in the patients treated with regimen 1, as compared with that in patients treated with regimen 2 (23.5% vs. 63.5% and 9.8% vs. 49.4% respectively). All the differences are highly significant (P < 0.001). The UFC level in the patients treated with regimen 2 was increased from (5.3 +/- 5.8) microgram/24 h to (21.9 +/- 7.2) microgram/24 h (P < 0.001). CONCLUSIONS: These results indicate that both regimens are feasible for treating patients with VKH. However, regimen 1 is far better than regimen 2 with respect to visual prognosis, frequency of recurrence of uveitis as well as incidence of ocular complications.

Adolescent↗