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Biomedical subjects

Yong Du

Publications and source records attributed to Yong Du.

35 records · Page 2Linked to original sources

Ultraviolet photolysis of CH2I2 in methanol: O-H insertion and HI elimination reactions to form a dimethoxymethane product.

Ultraviolet photolysis of low concentrations of CH2I2 in methanol solution found that CH2I2 is converted into dimethoxymethane and some H+ and I- products. Picosecond time-resolved resonance Raman (ps-TR3) experiments observed that the isodiiodomethane (CH2I-I) photoproduct decayed faster as the concentration of methanol increases, suggesting that isodiiodomethane is reacting with methanol. Ab initio calculations indicate isodiiodomethane is able to react with methanol via an O-H insertion/HI elimination to form an iodoether (ICH2-O-CH3) and HI products. The iodoether can then further react via another O-H insertion/HI elimination reaction to form the dimethoxymethane (CH3-O-CH2-O-CH3) observed in the photochemistry experiments. A reaction mechanism consistent with these experimental and theoretical observations is proposed.

Journal Article↗

Water-catalyzed dehalogenation reactions of the isomer of CBr4 and its reaction products and a comparison to analogous reaction of the isomers of di-and trihalomethanes.

A combined experimental and theoretical study of the UV photolysis of a typical tetrahalomethane, CBr4, in water and acetonitrile/water was performed. Ultraviolet photolysis of low concentrations of CBr4 in water mostly leads to the production of four HBr leaving groups and CO2. Picosecond time-resolved resonance Raman (Ps-TR3) experiments and ab initio calculations indicate that water-catalyzed O-H insertion/HBr elimination of the isomer of CBr4 and subsequent reactions of its products lead to the formation of these products. The UV photolyses of di-, tri-, and tetrahalomethanes at low concentrations in water-solvated environments are compared to one another. This comparison enables a general reaction scheme to be deduced that can account for the different products produced by UV photolysis of low concentrations of di-, tri-, and tetrahalomethanes in water. The fate of the (halo)formaldehyde intermediate in the chemical reaction mechanism is the key to determining how many strong acid leaving groups are produced and which carbon atom final product is likely formed by UV photolysis of a polyhalomethane at low concentrations in a water-solvated environment.

Journal Article↗

Distinct novel mutations affecting the same base in the NIPA1 gene cause autosomal dominant hereditary spastic paraplegia in two Chinese families.

Hereditary spastic paraplegia (HSP) is a neurodegenerative disease characterized by lower-limb spasticity, hyperreflexia, progressive spastic gait abnormalities, and an extensor-plantar response. It is genetically very heterogeneous, with 28 Human Genome Organisation (HUGO)-approved IDs in the database (last search: August 8, 2004). Following the identification of the SPG6 gene, NIPA1, we have identified two novel mutations, c.316G>C and c.316G>A, in two independent Chinese families linked to the SPG6 locus. These two mutations would cause a p.G106R substitution, and cosegregated with the disease. Structural predictions suggest that p.G106 is located in the third transmembrane domain of the protein, and that the mutant p.G106R disrupts this structure, causing the intramembrane loop to descend into the cytoplasm. Our results identify two novel mutations responsible for HSP and suggest that c.316 of theNIPA1 gene may be a mutational hotspot.

Adult↗

Association of serum caffeine concentrations with blood lipids in caffeine-drug users and nonusers - results of German National Health Surveys from 1984 to 1999.

Previous studies regarding effects of caffeine on lipids focused mainly on coffee consumption, the real association of serum caffeine concentrations with blood lipids is unclear. 814 caffeine-drug users who had taken any caffeine/caffeine-containing pharmaceutical products and 623 nonusers without any drug use in the last seven days before the medical interview were identified from German National Health Surveys from 1984 to 1999. Serum caffeine concentrations were measured by using EIA for caffeine-drug users and nonusers in the same laboratory. Blood lipids were measured routinely for all survey participants. The association of caffeine concentrations with blood lipids was established by means of partial correlation analysis and regression analysis. After controlling for influence factors, caffeine concentrations were closely positively related to triglycerides in caffeine-drug users (male: r = 0.245, p < 0.001; female: r = 0.117, p = 0.018) and related to HDL-C in female nonusers (r = 0.245, p < 0.001). No associations were found between caffeine concentrations and total cholesterol and LDL-C levels in any groups of our study. Acute intake of caffeine might increase triglycerides levels especially in men while chronic intake of caffeine might be weakly but positively associated with HDL-C concentrations in women. The effects of caffeine on the pathogenesis of cardiovascular diseases should be further confirmed through epidemiological studies.

Adolescent↗

Partial volume effect compensation for quantitative brain SPECT imaging.

Partial volume (PV) effects degrade the quantitative accuracy of SPECT brain images. In this paper, we extended a PV compensation (PVC) method originally developed for brain PET, the geometric transfer matrix (GTM) method, to brain SPECT using iterative reconstruction-based compensations. In the GTM method a linear transform between the true regional activities and the measured results was assumed. Elements of the GTM were calculated by projecting and reconstructing maps with uniform regions representing different structures. However, with iterative reconstruction methods, especially when reconstruction-based compensation for detector response was applied, we found that it was important to treat the region maps as a perturbation to the reconstructed image in the estimation of the GTM. This modified method, termed perturbation-based GTM (pGTM) was evaluated using Monte Carlo (MC) simulated and experimentally acquired data. Results showed great improvement of the quantitative accuracy in brain SPECT imaging. For MC simulated data, PVC using pGTM reduced the underestimation of striatal activities from 30% to less than 1.2%. For experimental data, PVC using pGTM reduced the underestimation of striatal activities from 36% to less than 7.8%. The underestimation of the striatum to background activity ratio was also improved from 31% to 2.7%.

Algorithms↗

[Risk factors affecting the long-term outcome of IgA nephropathy].

OBJECTIVE: To study the risk factors predicting long-term renal survival of IgA nephropathy in Chinese. METHODS: Clinical and pathological data of 317 patients (124 males and 193 females) with IgA nephropathy confirmed by renal biopsy in our center from January 1987 to February 2003 were reviewed retrospectively and were correlated with outcomes. A semiquantitative scoring system was used to evaluate individual pathological lesion of the kidney. Patients were followed for at least 6 months and doubling of serum creatinine level was defined as endpoint of follow-up. Renal survival was calculated by Kaplan-Meier survival analysis and risk factors of progression were analyzed by using univariate and multi-variate Cox regression models. RESULTS: The average age at renal biopsy was (30.1 +/- 10.9) years and the average duration from onset of disease to the time of biopsy was (20.1 +/- 33.7) months. Thirty-two percent of the patients had 24 h-urinary protein excretion greater than 1.0 g at the time of biopsy. Thirty-two percent of the patients had hypertension and 20.8% had renal insufficiency. Thirty-five percent of the patients were of Lee's grade IV or above and 20.5% presented with small proportion of crescent formation (usually less than 20%). Patients were followed for an average duration of (43.5 +/- 32.2) months with 39 patients (12.3%) reaching the endpoint. The 1-, 3-, 5- and 10-year renal survival was 99.5%, 93.1%, 84.5% and 60.1% respectively. Univariate Cox regression analysis revealed that longer duration of the disease before biopsy, serum creatinine > 115 micromol/L, proteinuria > 1.0 g/d, hypertension, Lee's grading of IV-V, moderate-severe glomerulosclerosis, crescent formation, moderate-severe interstitial fibrosis and renal arteriolar lesion were risk factors of disease progression, with an odds ratio of 1.007, 9.61, 7.31, 3.97, 5.41, 5.78, 4.65, 14.05 and 2.28 respectively (P < 0.001). Episodic macro-hematuria had an odds ratio of 0.194 (P < 0.05). Age, sex, serum cholesterol and triglyceride level had no significant impact on prognosis. Proteinuria, elevated serum creatinine, glomerulosclerosis, crescent formation and interstitial fibrosis were confirmed to be independent risk factors by multi-variate Cox regression model while the remaining variables were not statistically significant. Patients with both renal insufficiency and proteinuria greater that 1.0 g/24 h at the time of biopsy had a very poor 5-year renal survival (41.8%). CONCLUSIONS: Proteinuria, renal insufficiency, glomerulosclerosis, crescent formation and interstitial fibrosis were independent risk factors predicting the renal survival. IgA nephropathy presented with proteinuria, hypertension and crescent formation may need intervention.

Adolescent↗

Comparison of the dehalogenation of polyhalomethanes and production of strong acids in aqueous and salt (NaCl) water environments: Ultraviolet photolysis of CH(2)I(2).

The ultraviolet photolysis of CH(2)I(2) was studied in water and salt water solutions using photochemistry and picosecond time-resolved resonance Raman spectroscopy. Photolysis in both types of environments produces mainly CH(2)(OH)(2) and HI products. However, photolysis of CH(2)I(2) in salt water leads to the formation of different products/intermediates (CH(2)ICl and Cl(2) (-)) not observed in the absence of salt in aqueous solutions. The amount of CH(2)(OH)(2) and HI products appears to decrease after photolysis of CH(2)I(2) in salt water compared to pure water. We briefly discuss possible implications of these results for photolysis of CH(2)I(2) and other polyhalomethanes in sea water and other salt aqueous environments compared to nonsalt water solvated environments.

Journal Article↗

Efficient dehalogenation of polyhalomethanes and production of strong acids in aqueous environments: water-catalyzed O--H-insertion and HI-elimination reactions of isodiiodomethane (CH2I-I) with water.

A combined experimental and theoretical study of the ultraviolet photolysis of CH2I2 in water is reported. Ultraviolet photolysis of low concentrations of CH2I2 in water was experimentally observed to lead to almost complete conversion into CH2(OH)2 and 2HI products. Picosecond time-resolved resonance Raman spectroscopy experiments in mixed water/acetonitrile solvents (25%-75% water) showed that appreciable amounts of isodiiodomethane (CH2I-I) were formed within several picoseconds and the decay of the CH2I-I species became substantially shorter with increasing water concentration, suggesting that CH2I-I may be reacting with water. Ab initio calculations demonstrate the CH2I-I species is able to react readily with water via a water-catalyzed O--H-insertion and HI-elimination reaction followed by its CH2I(OH) product undergoing a further water-catalyzed HI-elimination reaction to make a H2C=O product. These HI-elimination reactions produce the two HI leaving groups observed experimentally and the H2C=O product further reacts with water to produce the other final CH2(OH)2 product observed in the photochemistry experiments. These results suggest that CH2I-I is the species that reacts with water to produce the CH2(OH)2 and 2HI products seen in the photochemistry experiments. The present study demonstrates that ultraviolet photolysis of CH2I2 at low concentration leads to efficient dehalogenation and release of multiple strong acid (HI) leaving groups. Some possible ramifications for the decomposition of polyhalomethanes and halomethanols in aqueous environments as well as the photochemistry of polyhalomethanes in the natural environment are briefly discussed.

Journal Article↗

Assignment of charge transfer absorption band in optical absorption spectra of the adsorbate-silver colloid system.

In this paper we reported the UV-visible-NIR optical absorption properties of silver colloid, employed as a high efficient substrate in surface-enhanced Raman spectra (SERS), under various conditions. Experimental results revealed that the new absorption band, usually appearing in the longer wavelength region due to the addition of molecules, was related to the direct adsorption of molecules on colloidal silver surface. When the adsorption occurred, this new band would appear. Once the molecules were desorbed from silver surface, the new band could not be observed. Some evidences inferred that the new absorption band was associated with the effect of charge-transfer transition between adsorbates and colloidal silver particles, while not with the effect of the surface plasma resonance due to the silver particles aggregation which was usually attributed to in previous research work.

Colloids↗

Family-based association study showing that immunoglobulin A nephropathy is associated with the polymorphisms 2093C and 2180T in the 3' untranslated region of the Megsin gene.

Immunoglobulin A nephropathy (IgAN) is considered to be a multifactorial disease with genetic and environmental factors contributing to its pathogenesis. The genes involved in susceptibility and progression of the disease have not yet been clearly elucidated. Megsin (SERPINB7) is an important candidate gene, predominantly expressed in glomerular mesangium and upregulated in IgAN. To investigate the potential role of this and other genes in IgAN, patients with biopsy-proven IgAN were recruited, as were family members, for a family-based association study. The genotypes of the polymorphisms C2093T and C2180T within the 3' untranslated region of the gene were determined by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. The results were analyzed by transmission disequilibrium test (TDT) and haplotype relative risk (HRR). TDT analyses revealed that Megsin 2093C and 2180T alleles were significantly more transmitted from heterozygous parents to patients than expected (C2093T: 127 trios, P = 0.034, C2180T: 100 trios, P = 0.002). Extended TDT showed increased cotransmission of the 2093C and 2180T alleles (232 families, P < 0.001). HRR revealed that the 2093C and 2180T alleles were more often transmitted to patients (P = 0.014, <0.001, respectively). Genetic variation in Megsin confers susceptibility to IgAN.

3' Untranslated Regions↗

[Expression of prostate stem cell antigen (PSCA) and selection of its specific binding peptide].

Prostate stem cell antigen (PSCA), a homologue of the Ly-6/Thy-1 family of cell surface antigen, is expressed by a majority of human prostate cancers and is a promising target for prostate cancer immunotherapy. To obtain the specific peptide binding with PSCA for targeted immunotherapy, PSCA gene was obtained by RT-PCR from human prostate cancer cell line DU145 and the transcated PSCA (tPSCA) gene was cloned into vector pQE30 for soluble expression in E. coli. The identity of recombinant tPSCA was confirmed through ELISA and western blot by use of anti-PSCA monoclonal antibody. Then the 12-peptide phage display library was screened with the purified tPSCA protein for its specific binding peptide through 3 rounds panning. For identifying the peptide's specificity, the peptide was coupled with EGFP (enhanced green fluorecent protein) by recombinant DNA technology and the recombinant coupled protein was termed 11-EGFP. The binding specificity with tPSCA of 11-EGFP was further confirmed by ELISA and competitive inhibition experiment. Flow cytometry demonstrated its binding specificity with cell line DU145. In conclusion, a 12-amino-acid peptide which could bind with PSCA specifically was found and it may be a potential tool for targeted immunotherapy of prostate carcinoma.

Antibodies, Monoclonal↗

Antibody-induced intracellular signaling works in combination with radiation to eradicate lymphoma in radioimmunotherapy.

Radioimmunotherapy (RIT) has emerged as an effective treatment for lymphoma, however the underlying mechanisms are poorly understood. We therefore investigated the relative contributions of antibody and targeted radiation to the clearance of tumor in vivo, using 2 different syngeneic murine B-cell lymphoma models. Although RIT with (131)I-anti-major histocompatibility complex class II (MHCII) was effective in targeting radiation to tumor, no improvement in survival was seen by escalating the radiation dose alone and there were no long-term survivors. In contrast, using the combination of (131)I anti-MHCII in the presence of unlabeled anti-idiotype (anti-Id), 100% prolonged disease-free survival was seen in both B-cell lymphoma models at the higher radiation dose. Using in vivo tracking we show that treatment with radiation plus anti-Id monoclonal antibody (mAb) results in a substantially greater reduction of splenic tumor cells than with either treatment alone. Prolonged survival could also be achieved using (131)I anti-MHCII plus the signaling anti-CD19 mAb. Furthermore, the ability of these anti-B-cell mAbs to improve survival with targeted radiotherapy appeared to correlate with their ability to initiate intracellular signal transduction. Together these data illustrate that using 1 mAb to target radiation to tumor and a second to induce cell signaling is an effective new strategy in RIT.

Animals↗

Intragenic allelic loss and promoter hypermethylation of the RIZ1 tumor suppressor gene in parathyroid tumors and pheochromocytomas.

BACKGROUND: Loss of heterozygosity (LOH) at chromosome 1p is a common abnormality in both parathyroid tumors and pheochromocytomas. The recently characterized tumor suppressor gene RIZ1, located at 1p36, has emerged as a putative candidate to be involved in endocrine tumorigenesis. MATERIAL: Presence of allelic loss, promoter hypermethylation, and mutational aberrations of the RIZ1 gene were investigated using PCR-based techniques in 47 parathyroid tumors and 23 pheochromocytomas. Gene expression studies used the RNAse protection assay. RESULTS: RIZ1 mRNA is expressed in pathologic tissues of the parathyroid and adrenal medulla. Thirteen of 47 (28%) parathyroid tumors, and 9/23 (39%) pheochromocytomas displayed LOH within the RIZ1 gene locus. Promoter hypermethylation of RIZ1 was detected in 36% of the parathyroid tumors and was related to LOH at the RIZ1 locus (P=.01), and absence of somatic mutation of the MEN1 gene (P=.044). In the pheochromocytomas, none of the benign tumors, but 2/4 malignant specimens exhibited RIZ1 promoter hypermethylation. CONCLUSION: Alteration of the RIZ1 gene locus via intragenic allelic loss and promoter hypermethylation seem common in parathyroid tumors. Inactivation of the RIZ1 gene may cause parathyroid tumorigenesis via a mechanism in which genetic alteration of the MEN1 gene is redundant.

Adolescent↗

Hormone replacement therapy in Germany: determinants and possible health-related outcomes. Results of National Health Surveys from 1984 to 1999.

OBJECTIVES: To explore the determinants of hormone replacement therapy (HRT) use and possible health-related outcomes in Germany. METHODS: 827 current HRT users (age range 31-78 years, who had taken HRT products in the last 7 days before the medical interview) and 2371 age-matched nonusers were identified from five population-representative National Health Surveys performed from 1984 to 1999 in Germany. Cross-sectional comparisons between HRT users and nonusers were performed for socioeconomic factors and possible health-related outcomes. Regression models were used to obtain odds ratios of HRT use. RESULTS: HRT use increased dramatically from 3% in 1984/1985 to 21% in 1998/1999 among German women aged 40-69. Regression analysis and comparison between HRT users and nonusers suggested that HRT use was closely associated with socioeconomic factors and personal lifestyle that may favor better health. In HRT users, however, we did not observe any health-related benefits in satisfaction with life or health. While HRT users appeared superior to nonusers with respect to the glycemic status, histories of cardiovascular diseases, despite a favorable lipid profile, occurred not less than in the group of nonusers. CONCLUSIONS: In the settings of our cross-sectional studies in Germany HRT did not improve users' health benefits and did not show cardioprotective effects. The better glycemic status should be balanced against the higher risks of cardiovascular diseases and breast cancer.

Adult↗

The tumor suppressor gene RIZ in cancer gene therapy (review).

In recent years, significant progress has been made in understanding the nature of the human genome and the role that genes and their related proteins play in both normal and diseased cells. It has been proven that many cancers are caused by the mutation of certain genes or lack of gene function. The introduction of those genes into cancer cells where gene function is compromised, can work to restore gene function and stop tumor progression. There have been numerous clinical trials, which have shown that gene therapy products are efficacious in humans. The RIZ1 gene is a member of a superfamily of histone/protein methyltransferases. The gene is commonly inactivated in human cancers. Gene knock-out study has established RIZ1 as a tumor susceptibility gene in mice. The gene has potent tumor suppressive activities in causing apoptosis, G2/M arrest, or both. Preclinical animal studies have shown that a recombinant adenovirus expressing the gene, AdRIZ1, can suppress the growth of colon cancer xenografts. Therefore, AdRIZ1 shows promise as a new generation of gene therapy products to enter the clinic.

DNA-Binding Proteins↗