Biomedical subjects

Y Ding

Publications and source records attributed to Y Ding.

At least 217 records · Page 12Linked to original sources

PubMed1998

[A monoclonal antibody that reacts with an antigen on both normal and malignant prostate cells].

OBJECTIVE: To study the YDPC--a monoclonal antibody that reacts with an antigen on both normal and malignant prostate cell. METHOD: A murine monoclonal antibody (MAb) designated YDPC was generated by treating the primed spleen cells with leucine methyl ester (LeuOMe) following immunization of mice with prostate cancer cell line PC-3M. RESULT: YDPC reacted uniformly with all adenocarcinomas of the prostate examined. It also reacted with the surface antigen on normal prostate epithelial cells and on cells from benign prostate hyperplasia. YDPC reacted with a limited number of normal tissues including renal tubules, adrenal and sweat gland. In addition, three lymph nodes metastasis and one bladder metastasis were found to be strongly positive, while four transitional cell carcinomas of the prostate negative. Preliminary experiments showed that this antibody does specifically localize to prostate cancer xenografts in nude mice. CONCLUSION: YDPC reacts with a differentiation antigen and this antigen continues to be expressed on all adenocarcinomas of the prostate. This antibody may be useful in the diagnosis of or therapy for prostate cancer.

Adenocarcinoma↗

PubMed1998

[The methods of surgical removal of glioblastoma multiform under functional cerebral cortex].

OBJECTIVE: To find the superlative way of surgical removal of glioblastoma multiform under functional cortex by comparative study of 123 patients. METHOD: Surgical approaches include direct and total resection of tumors, trans-functional cortex or adjacent area beyond functional cortex. They were compared with partial tumor resection plus external/internal decompressive procedure, total removal of tumor plus functional cortex resection. Comprehensive analysis was made. RESULT: Total removal of tumors both trans-functional or adjacent cortex prolonged the survival time of patients. As a result, minimal damage was observed in patients with both approaches, which are helpful for recovery of impaired cerebral function. On the other hand, partial resection of tumors in spite of combining with decompressive procedure or functional cortex resection did not show the same benefit. CONCLUSION: Surgical resection of glioblastoma multiform through trans-functional cortex or adjacent cortex beyond functional area is superior to other approaches both in dealing with total tumors removal and cerebral function recovery. But the resection through adjacent cortex beyond functional area in recovery of impaired cerebral function is more effective.

Brain Neoplasms↗

PubMed1998

[A new genus of oral bacteria in human].

A strain, No. 90-1, is isolated from the oral cavity of a patient with periodontophthy. This strain is a Gram-positive, non-endospore-forming, facultative anaerobe with spherical cells, 0.9-1.5 microns in diameter, occuring in pairs and seldom in short chains of four cells, and motile by one flagellum per cell. The optimum growing temperature is 35-37 degrees C; appreciable growth is not found below 10 degrees C, but growth at 53 degrees and tolerance to 60 degrees C for 30 min. This strain is microhalophilous and grows best, well and poorly in the medium containing 2%, 10%-15% and 25% NaCl respectively. Catalase and urease are positive and nitrate is reduced. Acid is produced from many carbohydrates, but no gas. Gelatin can be hydrolyzed, but starch, cellulose and dextrin do not. G + C content in DNA is 41.34 mol%(Tm). The strain(90-1) is considered to be a new species belonging to a new genus because its some characteristics are different from those of the known coccus genuera and designated as Stomatostreptococcus microhalophilus Ping, Zhou, Sun et Fan gen. nov. sp. nov. according to its source and microhalophilic trait.

Humans↗

PubMed1998

[Library search of UV spectra of organic environmental pollutants by artificial neural network].

In this paper, the artificial neural network (ANN) was applied to the library search of UV spectra of organic environmental pollutants. The optimization of network parameters was discussed and the effects of noise and impurity were investigated in detail. The use of derivative spectra for ANN library search was proposed to enhance the resolution of the UV spectra. This method could speed up the convergence of the network and could enhance the tolerance of impurity level, but was subject to noise comparing with the ANN using conventional UV spectra. Results show that the ANN is superior to the correlation coefficient method in resistance to noise and impurity.

Databases, Factual↗

PubMed1998

[Simultaneous determination of zinc, cadmium and lead chelated by porphyrin with partial least squares fluorimetry].

The fluorescence spectra of super-highly sensitive chelate systems containing multicomponent metal porphyrins are analysed by partial least squares method, and a computerized analysis for the simultaneous determination of zinc, cadmium and lead is developed. Zinc, cadmium and lead can quantitatively combine with meso-tetrakis-(4-methoxyphenyl)-porphyrin in a strong base medium and in the presence of Tween-80 when they are heated for 30 min in a boiling water-bath. The proposed method has been applied to the simultane ous determination of zinc, cadmium and lead in artificial and environmental water samples, and the recovery ratios are in the range of 93.2-107%.

English Abstract↗

PubMed1997

Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor-alpha and doxycycline.

Neutrophil collagenase (matrix metalloproteinase-8 or MMP-8) is regarded as being synthesized exclusively by polymorphonuclear neutrophils (PMN). However, in vivo MMP-8 expression was observed in mononuclear fibroblast-like cells in the rheumatoid synovial membrane. In addition, we detected MMP-8 mRNA expression in cultured rheumatoid synovial fibroblasts and human endothelial cells. Up-regulation of MMP-8 was observed after treatment of the cells with either tumor necrosis factor-alpha (10 ng/ml) or phorbol 12-myristate 13-acetate (10 nM). Western analysis showed a similar regulation at the protein level. The size of secreted MMP-8 was 50 kDa, which is about 30 kDa smaller than MMP-8 from PMN. Conditioned media from rheumatoid synovial fibroblasts contained both type I and II collagen degrading activity. However, degradation of type II collagen, but not that of type I collagen, was completely inhibited by 50 microM doxycycline, suggesting specific MMP-8 activity. In addition, doxycycline down-regulated MMP-8 induction, at both the mRNA and protein levels. Thus MMP-8 exerts markedly wider expression in human cells than had been thought previously, implying that PMN are not the only source of cartilage degrading activity at arthritic sites. The inhibition of both MMP-8 activity and synthesis by doxycycline provides an incentive for further studies on the clinical effects of doxycycline in the treatment of rheumatoid arthritis.

Arthritis, Rheumatoid↗

PubMed1997

Promoter attenuation in gene therapy: interferon-gamma and tumor necrosis factor-alpha inhibit transgene expression.

One of the major limitations to current gene therapy is the low-level and transient vector gene expression due to poorly defined mechanisms, possibly including promoter attenuation or extinction. Because the application of gene therapy vectors in vivo induces cytokine production through specific or nonspecific immune responses, we hypothesized that cytokine-mediated signals may alter vector gene expression. Our data indicate that the cytokines interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) inhibit transgene expression from certain widely used viral promoters/enhancers (cytomegalovirus, Rous sarcoma virus, simian virus 40, Moloney murine leukemia virus long terminal repeat) delivered by adenoviral, retroviral or plasmid vectors in vitro. A constitutive cellular promoter (beta-actin) is less sensitive to these cytokine effects. Inhibition is at the mRNA level and cytokines do not cause vector DNA degradation, inhibit total cellular protein synthesis, or kill infected/transfected cells. Administration of neutralizing anti-IFN-gamma monoclonal antibody results in enhanced transgene expression in vivo. Thus, standard gene therapy vectors in current use may be improved by altering cytokine-responsive regulatory elements. Determination of the mechanisms involved in cytokine-regulated vector gene expression may improve the understanding of the cellular disposition of vectors for gene transfer and gene therapy.

Adenoviruses, Human↗

PubMed1997

The kidney androgen-regulated protein promoter confers renal proximal tubule cell-specific and highly androgen-responsive expression on the human angiotensinogen gene in transgenic mice.

Transgenic mice were generated containing a 1542-base pair fragment of the kidney androgen-regulated protein (KAP) promoter fused to the human angiotensinogen (HAGT) gene with the goal of specifically targeting inducible expression of renin-angiotensin system components to the kidney. High level expression of both KAP-HAGT and endogenous KAP mRNA was evident in the kidney of male mice from two independent transgenic lines. Renal expression of the transgene in female mice was undetectable under basal conditions but could be strongly induced by administration of testosterone. Testosterone treatment did not cause a transcriptional induction in any other tissues examined. However, an analysis of six androgen target tissues in males revealed that the transgene was expressed in epididymis. No other extra-renal expression of the transgene was detected. In situ hybridization demonstrated that expression of HAGT (and KAP) mRNA in males and testosterone-treated females was restricted to proximal tubule epithelial cells in the renal cortex. Although there was no detectable human angiotensinogen protein in plasma, it was evident in the urine, consistent with a pathway of synthesis in proximal tubule cells and release into the tubular lumen. These results demonstrate that 1542 base pairs of the KAP promoter is sufficient to drive expression of a heterologous reporter gene in a tissue-specific, cell-specific, and androgen-regulated fashion in transgenic mice.

Angiotensinogen↗

PubMed1997

Inhibitory effects of HepG2 cell-derived apolipoprotein A-I-containing lipoproteins on cholesteryl ester accumulation in macrophages.

We investigated the mechanisms of inhibitory effects on foam cell formation of apolipoprotein A-I-containing lipoproteins secreted by HepG2 cells (HepG2-HDL) using mouse peritoneal macrophages. When macrophages were incubated with acetylated low-density lipoprotein (acetyl-LDL) in the presence of HepG2-HDL, cholesterol ester (CE) accumulation in cells was reduced by 63%. This inhibitory capacity was almost similar to that of plasma high-density lipoprotein (HDL). When macrophages were converted to foam cells with acetyl-LDL and then reacted with HepG2-HDL or plasma HDL, the HDL-induced CE reduction was 2.2-fold greater than HepG2-HDL. Similar results were obtained using apo E-free HepG2-HDL. Since the inhibitory effect of HDL on acetyl-LDL-induced CE accumulation in macrophages is due largely to its cholesterol efflux capacity, these results suggest the presence of an additional mechanism for the inhibition of CE accumulation by HepG2-HDL. To investigate the mechanism, acetyl-LDL was reisolated from HepG2-HDL by Sephacryl S-300 gel filtration after incubation in a cell-free system. Reisolated acetyl-LDL showed a significant reduction in electrophoretic mobility. The extent of CE accumulation by reisolated acetyl-LDL was reduced by 20% compared with control acetyl-LDL. Moreover, its endocytic degradation by macrophages was reduced by 28%. HepG2-HDL also inhibited macrophage degradation of acetyl-LDL as well as oxidized LDL, a likely atherogenic lipoprotein. This inhibitory effect was ascribed to the HepG2-HDL subfraction containing pre-beta HDL. Our results indicated that apo A-I-containing lipoproteins as a physiological model of nascent HDL may inhibit foam cell formation by reducing ligand activity of atherogenic lipoproteins. These data possibly suggest inhibitory function of nascent HDL for the formation of foam cells in vivo.

Animals↗

PubMed1997

Adenovirus-mediated gene transfer of viral interleukin-10 inhibits the immune response to both alloantigen and adenoviral antigen.

Although adenoviral vectors are attractive for gene transfer, their effectiveness is limited by host antiviral immune responses. In this study, we determined if host antiallograft and antiviral immunity could be diminished with an adenoviral vector encoding the immunosuppressive cytokine viral interleukin-10 (vIL-10). AdSV40vIL-10, a vIL-10-expressing adenoviral vector with an SV40 promoter, induced significant prolongation of murine cardiac allograft survival to 32.2 +/- 1.7 days compared to 14.2 +/- 1.0 days for controls (p < 0.01). This effect was specific for vIL-10 encoding vector and could be inhibited by anti-vIL-10 monoclonal antibody (mAb). In vivo administration of adenovirus facilitated the generation of adenovirus-specific cytotoxic T lymphocytes (CTL), whereas treatment with AdSV40vIL-10 prevented CTL priming and generation of virus-specific immunity. AdSV40vIL-10 also induced extended expression of a beta-galactosidase reporter from a co-injected LacZ-encoding adenoviral vector. These results demonstrate that adenovirus-mediated gene transfer and expression of vIL-10 prolong allograft survival and inhibit the immune response to adenoviral antigens, thereby improving the persistence of the vector and extending transgene expression. The efficacy of adenoviral vectors can be improved by incorporating immunosuppressive genes into the vector.

Adenoviridae↗

PubMed1997

Matrix metalloproteinase 13 (collagenase 3) in human rheumatoid synovium.

OBJECTIVE: To show the eventual presence and extent of production of matrix metalloproteinase 13 (MMP-13, or collagenase 3) in rheumatoid synovial tissue samples and extracts, and to assess the inhibition characteristics of recombinant MMP-13. METHODS: Immunohistochemical avidin-biotin-peroxidase complex staining/morphometry was used to analyze MMP-13-positive cells in situ. Neutral salt extraction of synovial tissue, electrophoresis of the extract in different buffer systems, and Western blotting were also used. The inhibitory properties of doxycycline, clodronate, pamidronate, and D-penicillamine for recombinant enzyme were determined with a soluble type II collagen assay. RESULTS: MMP-13 was detected in fibroblast- and macrophage-like mononuclear cells in the synovial lining and stroma and in vascular endothelial cells. The overall expression of MMP-13 in these cells in the synovial stroma was high in rheumatoid arthritis (86 +/- 12%) compared with osteoarthritis (17 +/- 5%) patient samples (P = 0.0027). In a high-pH native electrophoresis gel, immunoreactivity to anti-MMP-1 and anti-MMP-13 were clearly separated, with anti-MMP-13-immunoreactive material migrating faster than anti-MMP-1-immunoreactive material. Finally, in contrast to MMP-1 and MMP-8, MMP-13 was found to be relatively resistant to the inhibitory effects of doxycycline and clodronate in vitro. CONCLUSION: Due to its localization in synovial tissue, its substrate profile, increased expression, and relative resistance to known MMP inhibitors, MMP-13 is suggested to play a major role in the pathogenesis of tissue destruction in rheumatoid arthritis.

Adult↗

PubMed1997

Inhibition of matrix metalloproteinase-1 by dichloromethylene bisphosphonate (clodronate).

Interstitial collagenase present in human jaw cyst extract and purified human fibroblast-type collagenase (MMP-1) were both efficiently inhibited in vitro by clodronate, an osteoactive, antiresorptive bisphosphonate. The IC50 of clodronate to inhibit MMP-1 is 150 microM. These findings suggest an extended and hitherto undescribed properties for clodronate/biphosphonates in prevention and treatment of tissue degradation in both bone and soft tissue destructive diseases.

Bone Diseases↗

PubMed1997

Retinotopic order in the optic nerve and superior colliculus during development of the retinocollicular projection in the wallaby (Macropus eugenii).

Retinotopic order of optic axons in the optic nerve and superior colliculus of the marsupial mammal, the wallaby (Macropus eugenii), has been examined and compared during development of the retinocollicular projection to investigate the role of order in the nerve in map formation. Small groups of axons from different retinal quadrants were labelled in vivo with a carbocyanine dye from just after axons first reached the colliculus to when the projection was mature. The distribution and branching patterns of axons and their arbors on the colliculus were assessed quantitatively during this period, as was the degree of order in the nerve. Initially, axons accumulated in coarse retinotopic order in the colliculus, with little branching and no sign of arborization to form terminal zones. Axons labelled from deposits covering a mean of 2.2% of the retina reached a mean collicular coverage of around 30% at 41-47 days, at which time they began arborizing in their retinotopically correct positions. By 55 days axons from all retinal quadrants had formed terminal zones in their retinotopically correct positions. Axons did not arborise in incorrect positions as has been reported in the rat. By 61-68 days coverage had decreased to around 10%. By 90-95 days only axons supplying terminal zones were present and terminal zones were smaller. In the nerve, axons showed a coarse and consistent order throughout development. This order was retinotopic only immediately behind the eye. Temporal and nasal axons occupied corresponding halves of the nerve along its course. Axons from dorsal and ventral retina shifted from dorsal and ventral positions in the nerve, respectively, to opposite sides of the nerve just before the chiasm. This would assist in positioning them in the appropriate lateral and medial optic tracts, respectively, in the positions they occupied as they approached the colliculus. However, the position in the nerve was not related to the ability to arborize in the correct collicular position. In particular, the increase in retinotopic order in the colliculus late in development was not accompanied by an increase in order in the nerve. Since the final organization in the colliculus shows greater order than is ever seen in the nerve, additional mechanisms must be involved in the maturation of the collicular map.

Animals↗

PubMed1997

Analysis of the T beta gamma-binding domain of MEKA/phosducin.

MEKA/phosducin, a 33 kDa phosphoprotein in the photoreceptor cell, associates with transducin beta gamma (T beta gamma) with its N-terminal domain (N-terminal 105 amino acids of MEKA), and translocates T beta gamma from the photoreceptor disc membrane to the soluble fraction. The present study further localized the T beta gamma-binding domain to aa 17-105 of MEKA, and showed that the activity of MEKA to translocate T beta gamma depends on the domain. A series of deletion mutant MEKA proteins were prepared to investigate the domain of MEKA which binds to and translocates T beta gamma. Both binding and translocation activities were not impaired by the deletion of the N-terminal 16 amino acids of MEKA, but completely abolished by further deletion to 42Val. Although anti-MEKA serum inhibited the T beta gamma-MEKA association, the antiserum absorbed with a recombinant peptide corresponding to aa 17-105 of MEKA did not, confirming that aa 17-105 of MEKA directly interacts with T beta gamma.

Amino Acid Sequence↗

PubMed1997

Characterization of a nuclear factor that enhances DNA binding activity of SSCRE-BP/PUR alpha, a single-stranded DNA binding protein.

Pur alpha has been identified as a single-stranded DNA binding protein that specifically binds to the purine-rich strand present in the DNA replication initiation zone of the human c-myc gene. We have previously demonstrated that chronic morphine treatment decreases the DNA binding activity of ssCRE-BP (single-stranded cyclic AMP response element-binding protein), which has been shown to be identical to pur alpha by cDNA cloning, and is abundant in the brain. In this report we identified an activator of ssCRE-BP/pur alpha in the brain and characterized it. Although purified ssCRE-BP/pur alpha or its GST-fusion protein exhibited very low DNA binding activities, they were markedly enhanced by including nuclear extract in the binding assay. The enhanced binding activity is trypsin-sensitive, heat-stable and has a molecular weight of approximately 66 kDa. Casein could substitute for the activator and increased the DNA binding activity of ssCRE-BP/pur alpha by one order. A series of deletion mutants were prepared in order to determine the DNA binding and activator interacting domains, and both of them were found to reside in AA 50-215 of ssCRE-BP/pur alpha. These data suggest that the DNA binding activity of ssCRE-BP/pur alpha is augmented by a nuclear protein, which may modulate the ssCRE-BP/pur alpha activity to develop morphine dependence and tolerance.

Animals↗

PubMed1997

Lead-induced hypertension is not associated with altered vascular reactivity in vitro.

In confirmation of a previous study (Am J Hypertens 1993;6:723), mean arterial blood pressure (MBP), as determined by tail cuff plethysmography, was found to be significantly elevated in Sprague-Dawley rats after 3 months of feeding 0.48 mmol/L (100 ppm) lead acetate/day (144 +/- 3.3 [SEM], in lead-treated [L] v 107 +/- 3.3 mm Hg in controls [C], P < .001). Thoracic aorta was excised from L and C animals (n = 6). Segments were suspended in tissue baths with Krebs' bicarbonate solution, then tested sequentially for vasoreactivity to 68 mmol/L K+, followed by graded concentrations of phenylephrine (PE), 0.01 to 0.3 micromol/L, acetylcholine (Ach), 0.001 to 3 micromol/L, nitroprusside (SNP), 0.0001 to 0.1 micromol/L, norepinephrine (NE), 0.001 to 300 micromol/L. There were no differences between L and C animals with respect to either vasoconstrictors (PE and NE) or vasodilators (Ach and SNP). The tissue levels of cGMP measured with and without phosphodiesterase inhibition, and in the absence and presence of either Ach or SNP, were comparable in the two groups. We conclude that the intrinsic vascular responsiveness is unchanged in lead-treated animals. The elevation of MBP is due to the presence of circulating factor(s) and hemodynamic changes.

Acetylcholine↗

PubMed1997

Altered nitric oxide metabolism and increased oxygen free radical activity in lead-induced hypertension: effect of lazaroid therapy.

Chronic exposure to low levels of lead results in sustained hypertension (HTN) in humans and experimental animals. The mechanism of lead-induced HTN remains unclear. We investigated the possible role of reactive oxygen species (ROS) and their impact on nitric oxide (NO) metabolism in lead-induced HTN. Male Sprague-Dawley rats were treated with lead (100 ppm in drinking water) for twelve weeks. They were then treated with either the potent antioxidant, lazaroid (des-methyl-tirilazad, 5 mg/kg i.p., twice daily) (Pb-Lz group) or placebo (Pb group) for two weeks and monitored for an additional two weeks. A group of normal animals served as controls (N = 6 in each group). Lead administration resulted in marked HTN together with a significant rise in plasma concentration of lipid peroxidation product, malondialdehyde (MDA, reflecting increased ROS generation) and a twofold reduction in urinary excretion of NO metabolites, that is, total nitrates and nitrites (NOx). Lazaroid therapy led to prompt normalization of blood pressure, plasma MDA and urinary NOx. In contrast, blood pressure and plasma MDA remained elevated, and recovery of urinary NOx excretion was slow with placebo therapy. No significant difference was found in creatinine clearance between the study groups during the observation period. Thus, chronic lead exposure resulted in marked HTN coupled with increased ROS production and decreased urinary NOx excretion. Administration of the potent antioxidant, lazaroid, abrogated HTN and reversed the abnormalities of plasma MDA and urinary NOx excretion, thus supporting the role of ROS in lead-induced HTN in this model.

Animals↗

PubMed1997

Large-scale concatenation cDNA sequencing.

A total of 100 kb of DNA derived from 69 individual human brain cDNA clones of 0.7-2.0 kb were sequenced by concatenated cDNA sequencing (CCS), whereby multiple individual DNA fragments are sequenced simultaneously in a single shotgun library. The method yielded accurate sequences and a similar efficiency compared with other shotgun libraries constructed from single DNA fragments (> 20 kb). Computer analyses were carried out on 65 cDNA clone sequences and their corresponding end sequences to examine both nucleic acid and amino acid sequence similarities in the databases. Thirty-seven clones revealed no DNA database matches, 12 clones generated exact matches (> or = 98% identity), and 16 clones generated nonexact matches (57%-97% identity) to either known human or other species genes. Of those 28 matched clones, 8 had corresponding end sequences that failed to identify similarities. In a protein similarity search, 27 clone sequences displayed significant matches, whereas only 20 of the end sequences had matches to known protein sequences. Our data indicate that full-length cDNA insert sequences provide significantly more nucleic acid and protein sequence similarity matches than expressed sequence tags (ESTs) for database searching.

DNA Transposable Elements↗