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Biomedical subjects

H J Chen

Publications and source records attributed to H J Chen.

At least 73 records · Page 4Linked to original sources
PubMed2000

Atopic cataracts in a child with atopic dermatitis: a case report and review of the literature.

Cataracts induced by atopic dermatitis rarely occur in adolescent and young adult patients suffering from this problem. Lenticular opacity is an important ocular complication in atopic dermatitis. Although the cause of atopic dermatitis and its ocular complications are unknown, cataracts have been observed to develop and progress during periods of exacerbation of the dermatitis. We report the case of a 16-year-old boy with atopic dermatitis who abruptly developed cataracts in both eyes while suffering from severe skin itching which began 2 months before the initial examination. His peroxidation test result was very high, and we postulate the retinal peroxidation might play a key role in cataractogenesis. Lens aspiration and intraocular artificial lens implantation were performed smoothly with restoration of visual acuity in both eyes.

Adolescent↗
PubMed1999

Favorable clinical outcome of cervical cancers infected with human papilloma virus type 58 and related types.

To determine whether the status of human-papillomavirus (HPV) infection affects the clinical outcome of cervical carcinoma (CC), HPV genotype was prospectively determined in 94 consecutive CC cases subsequently followed for a median duration of 37.5 months. With a consensus PCR-RFLP method of HPV genotyping, 81 (86.2%) cancers were positive for HPV DNA. They were classified, according to the phylogenic similarities, into HPV-16-related (type 16, n = 45; type 31, n = 2), HPV-58-related (type 58, n = 17; type 33, n = 3; type 52, n = 2) and HPV-18-related (type 18, n = 8; type 68, n = 1) groups, and analyzed in relation to clinical outcome. The following results were observed: (i) Type-58-related HPVs were more prevalent in the old age (older than the median age of 52) group than in the young age group (41% vs. 14.6%, p = 0.045); (ii) 63% (5/8) of patients with advanced stages (III and IV) were HPV-negative, a figure much higher than that (9.3%, 8/84) of patients with early stages (stage I and II) (p = 0.002); (iii) the occurrence of adenocarcinoma or adenosquamous carcinoma was higher in the HPV-18-related group (50%) than in the HPV-16-related (33.3%) or the HPV-58-related (16.7%) groups (p = 0.024); (iv) the status of lymph-node metastasis and tumor grade did not correlate with HPV status; (v) 5-year survival rates were 90.2%, 80% and 74% for HPV-58-, HPV-16- and HPV-18-related groups, respectively (p = 0.03, after adjustment for tumor stage); (vi) in comparison with the HPV-16-related group, the relative risk of death in the HPV-58- and the HPV-18-related groups were 0.32 [95% CI, 0.07-1.49] and 1.87 [0.36-14.9] respectively. HPV genotype appears to affect the clinical behavior and outcome of cervical cancer. HPV-58-related types are prevalent in the older population, and appear to confer a favorable prognosis. Int. J. Cancer (Pred. Oncol.) 84:553-557, 1999.

Adult↗
PubMed1999

Binding of ATP to human DNA topoisomerase I resulting in an alteration of the conformation of the enzyme.

It has been known for some time that ATP inhibits the DNA relaxation activity of human DNA topoisomerase I. However, the underlying mechanism of this inhibitory effect remains largely unknown. Using filter binding assays, the binding of human DNA topoisomerase I to DNA was decreased in the presence of ATP. This result suggests that the inhibition of DNA relaxation activity of human DNA topoisomerase I by ATP is at the binding step rather than at the nicking or resealing step. DNA topoisomerase I cleavage assay further supports this notion. ATP-agarose binding and UV cross-linking assays also demonstrate that ATP directly and specifically binds human DNA topoisomerase I. To address whether the ATP binding results in conformational changes in human DNA topoisomerase I, various proteases were employed for detecting potential protein conformational changes. Our results indicated that the proteolytic susceptibilities of trypsin and chymotrypsin were altered in the presence of ATP. The result suggests that the conformation of human DNA topoisomerase I was altered upon ATP binding. In addition, the binding between ATP and human DNA topoisomerase I was also reduced by increasing concentrations of DNA. Our data suggests that human DNA topoisomerase I exhibits at least two incompatible conformations. One conformation is in the form of a topoisomerase I-ATP complex, which inhibits DNA relaxation activity of human DNA topoisomerase I, and the other, a topoisomerase I-DNA complex, which exerts DNA relaxation activity. Our studies identify the role of ATP in the regulation of human DNA topoisomerase I and provide a substantial implication of how human DNA topoisomerase I compromises its versatile functions.

Adenosine Triphosphate↗
PubMed1999

Inhibition of DNA synthesis by downregulation of cyclin A but not Skp 2 overexpression in human hepatocellular carcinoma cells.

Cyclin A is an S and G2/M phase regulatory protein and associates with Skp 2 in many transformed cells. Our previous results showed that 12 (39%) and 17 (55%) out of 31 hepatocellular carcinoma (HCC) patients exhibited higher protein expression levels of cyclin A and Skp 2, respectively, in their tumorous compared to non-tumorous tissues. In the present study, we used Western blot analysis to show that 3 out of 6 HCC cell lines, HA59T, HA22T and HCC36, exhibited overexpression of cyclin A, among which the HCC36 cell line also expressed a higher Skp 2 protein level. Moreover, we used the antisense oligonucleotide phosphorothioates to down regulate the overexpression of cyclin A and Skp 2 proteins to determine whether or not these two proteins are involved in the mitogenesis of HCC36 cells. After treatment with antisense oligonucleotide phosphorothioates, the gene product of cyclin A or Skp 2 was suppressed dose-dependently as revealed by Western blot analyses. By [3H]thymidine incorporation assay, we found that downregulation of cyclin A but not Skp 2 overexpression could inhibit the DNA synthesis ability of HCC36 cells, suggesting that abnormal Skp 2 expression is not directly correlated with the HCC proliferation.

Carcinoma, Hepatocellular↗
PubMed1999

Detection of protease activities using specific aminoacyl or peptidyl p-nitroanilides after sodium dodecyl sulfate - polyacrylamide gel electrophoresis and its applications.

A general method for detecting protease activities on acrylamide or agarose gels after sodium dodecyl sulfate - polyacrylamide gel electrophoresis (SDS-PAGE) using specific aminoacyl p-nitroanilide (NA) or peptidyl NA as substrate is described. This method is extended from the spectrophotometric assay of p-nitroaniline, which is a chromogenic product liberated by protease action on aminoacyl NA or peptidyl NA. The acrylamide gel containing protein bands was dipped directly into a solution which contained specific synthetic aminoacyl NA or peptidyl NA as a substrate or had been overlaid with an agarose gel containing the same substrate. The p-nitroaniline released on the acrylamide or agarose gel by the specific protease was diazotized with sodium nitrite and then coupled to N-(1-naphthyl)-ethylenediamine to produce distinct activity band(s). The substrates used for protease activity staining on gels were identical to those used for spectrophotometric assays. Some applications are described.

Benzoylarginine Nitroanilide↗
PubMed1999

Aerodynamic measurements of patients with Parkinson's disease.

Patients with Parkinson's disease commonly complain of voice dysfunction. Most of these complaints can be attributed to the known muscular control disorders that occur with Parkinson's disease. However, the manifestations of Parkinson's disease muscular dysfunction on parameters of phonation such as airflow, laryngeal resistance, and subglottal pressure necessary to sustain phonation have not been reported. The purpose of this study was to examine the aerodynamic characteristics of flow, laryngeal resistance, and phonation pressure threshold in a heterogeneous population of patients with Parkinson's disease who had varying voice complaints and to compare the data to similar studies for human subjects who have no voice complaints. The studies used a noninvasive method of detecting flow and acoustic signal from the lips, oral cavity and nose during phonation and used an external flow interruption technique to estimate subglottal pressure and phonation threshold pressure. About one third of the patients could not produce phonation at regular and loud intensities that were comfortable for normal subjects. The mean subglottal pressure (SGP) of patients with Parkinson disease who could produce 3 levels of intensity comparable to normal subjects was significantly higher than the mean SGPs for normal subjects for the same intensities of vocal production. The mean flow rates measured from patients with Parkinson's disease at the same 3 intensities of phonation was not significantly greater than in normal subjects. This indicated that the mean laryngeal resistance calculated for patients with Parkinson's disease was notably and significantly greater than mean laryngeal resistance calculated for normal subjects at the same intensity levels. The mean vocal efficiency (VE) for normal subjects was not significantly different than the mean VE for patients with Parkinson's disease, because greater pressure was used to generate similar flow and acoustic energy. These findings correlate with the perception of patients with Parkinson's disease that they are working harder to produce phonation. The observation of notably greater laryngeal resistance and phonation threshold pressure in patients with Parkinson's disease suggests that further studies of the glottic aperture in patients with Parkinson' disease may be useful for understanding how this common motor disorder disturbs phonation.

Aged↗
PubMed1999

Dioscorin, the major tuber storage protein of yam (Dioscorea batatas decne) with carbonic anhydrase and trypsin inhibitor activities.

Dioscorin, the tuber storage protein of yam (Dioscorea batatas Decne), was purified successively by ammonium sulfate fractionation, DE-52 ion exchange chromatography, and Sephadex G-75 column. Two protein bands (82 and 28 kDa) were found under nonreducing conditions after SDS-PAGE; but only one band (32 kDa) was detected under reducing conditions. The first 21 amino acids in the N-terminal region of the 28 kDa form were VEDEFSYIEGNPNGPENWGNL, which was highly homologous to deductive sequence of dioscorin from cDNA of another yam species (Dioscoreacayenensis Lam) reported by Conlan et al. (Plant Mol. Biol. 1995, 28, 369-380). Hewett-Emmett and Tashian (Mol. Phylogenet. Evol. 1996, 5, 50 -77) mentioned that, according to DNA alignments, dioscorin from yam (D. cayenensis) was alpha-carbonic anhydrase (alpha-CA) related. In this report, we found that the purified dioscorin showed both CA dehydration activity using sodium bicarbonate as a substrate and CA activity staining after SDS-PAGE. A polyclonal antibody, which was raised against trypsin inhibitor (TI), a storage protein of sweet potato (Ipomoea batatas [L.] Lam var. Tainong 57), cross-reacted with dioscorin, which also showed TI activity determined by both activity staining after SDS-PAGE and trypsin inhibition determination.

Amino Acid Sequence↗
PubMed1999

Detection and quantification of 1,N(6)-ethenoadenine in human placental DNA by mass spectrometry.

Exocyclic DNA adducts have been reported to derive from various exogenous as well as endogenous sources, such as lipid peroxidation. Among them, 1,N(6)-ethenoadenine (epsilonAde) has previously been detected in tissue DNA of untreated rodents and humans by an immunoaffinity/(32)P-postlabeling method. This study reports detection and quantification of the endogenous epsilonAde adduct in the same human placental DNA by three independent assays, namely, GC/MS, LC/MS, and HPLC/fluorescence. Using a recently reported gas chromatography/negative ion chemical ionization/mass spectrometry (GC/NICI/MS) method [Chen, H.-J. C., et al. (1998) Chem. Res. Toxicol. 11, 1474], the level of epsilonAde in human placental DNA from a commercial source was found to be 2.3 adducts per 10(6) Ade bases. To confirm these findings, a liquid chromatography/electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) method was developed for epsilondAdo. With this LC/MS assay, epsilondAdo was detected at the level of 2.5 adducts per 10(6) dAdo nucleosides in the same human placental DNA. The stable isotopes of epsilonAde and epsilondAdo were added as internal standards in both GC/MS and LC/ESI/MS/MS assays, respectively, and thus provided high specificity, reproducibility, and accurate quantification. The relatively high levels of epsilonAde in this human placental DNA detected by mass spectrometry were further verified by HPLC/fluorescence analysis. The GC/MS method was validated by the HPLC/fluorescence assay using calf thymus DNA treated with chloroacetaldehyde or by the LC/MS method with 2, 3-epoxy-4-hydroxynonanal-modified calf thymus DNA. The epsilonAde level in human placental DNA freshly isolated in the presence of an antioxidant was similar to that in DNA from the commercial source. Since epsilonAde is a potential mutagenic lesion, analysis of epsilonAde by the specific and sensitive GC/NICI/MS method may provide a useful biomarker in cancer risk assessment.

Adenine↗
PubMed1999

Management of choroidal melanomas with linear accelerator-based stereotactic radiosurgery.

PURPOSE: To discuss the technical aspect, dose prescription, clinical results, and biological responsiveness of linear accelerator-based stereotactic radiosurgery for choroidal melanoma. METHODS: From March 1995 to December 1995, three choroidal melanoma patients were treated with Linac-based radiosurgery in our department. Two patients underwent one dose of radiosurgery with 18 and 20 Gy in single fraction, respectively. The third patient received two doses of radiosurgery with a total dose of 35 Gy. RESULTS: Follow-up time ranged from 19 to 25 months (median: 24 months). One patient had near-total regression, while the other two patients had partial response on the last MR images. Visual acuity was deteriorated in all patients. One patient developed a radiation-induced cataract in the treated eye. CONCLUSION: Linac-based radiosurgery is technically feasible for management of choroidal melanoma. Although visual acuity was not improved in these patients, they appreciated the preserving of the eyeball without affecting their general appearance.

Adult↗
PubMed1999

Development of a prefabricated treatment plant for diluted pig wastewater.

In order to develop a prefabricated treatment and reuse plant for diluted pig wastewater, an entrapped-mixed-microbial-cell (EMMC) process was evaluated for its process performance and economic analysis. At the hydraulic retention time (HRT) of 30 hrs (loading rate of 1.0 g TCOD/L/d) and intermittent aeration of 1 hr of aeration and 1 hr of non-aeration, it was found that, by using the pretreatment of the ammonium crystallization, both the medium and large carriers were able to reduce TCOD, SCOD, and T-N by 83.51, 84.11, and 95.10%, respectively. The EMMC unit and lime post-treatment followed by ammonium crystallization can reduce BOD5, TCOD, SCOD, TSS, T-N, and T-P, respectively by 99.22, 93.85, 92.67, 97.73, 96.43, and 97.27%. The treated wastewater, after disinfection, is able to meet the requirements of the standards issued by the USEPA for reuse of food crops. The economic analysis indicates that based on the process performance of the EMMC unit, a prefabricated wastewater treatment plant for 2000 pigs has comparable net present worth (NPW) comparing intermittent aerated biological systems and less operation and maintenance and land requirement than conventional biological processes for removal carbon and nitrogen. A farm operation of more than 2000 pigs meets the unit cost of US$4.91/pig/yr. This will minimize the problems pertaining to technical factors or considerations that heavily influence planning, construction and operation of a pig wastewater treatment system.

Animals↗
PubMed1999

Porous balloon delivery of S-dC28 does not prevent restenosis in the porcine coronary artery model of balloon injury.

Phosphorothioate (PS) oligodeoxynucleotides (ODN) inhibit vascular smooth muscle cell proliferation through antisense and G-quartet aptameric mechanisms. PS-ODN such as the cytidine homopolymers, have been demonstrated to have non-G-quartet, nonsequence-specific inhibitory effects in a rat carotid balloon injury model of neointimal proliferation. We sought to test the efficacy of S-dC28, a cytidine homopolymer lacking G-quartets, on neointimal proliferation in the porcine coronary artery model of balloon injury. A total of 23 animals (11 controls, 12 treated) were subjected to balloon injury in a coronary artery, followed by infusion of control solution or S-dC28 via porous balloon, the Scimed Dispatch Coronary Infusion Catheter. After a mean interval of 49 days, the animals were killed, and the target coronary segments were examined histologically. S-dC28 did not significantly inhibit neointimal formation. Fluorescein isothiocyanate (FITC)-labeled S-dC28 was present in the intima and media immediately after administration but was present mainly within the adventitia 3 hours after administration. S-dC28, when delivered by a Scimed Dispatch Coronary Infusion Catheter (Maple Grove, MN), did not significantly affect neointimal proliferation after balloon injury in a porcine coronary artery model.

Angioplasty, Balloon, Coronary↗
PubMed1999

Cerebral sparganosis: case report.

A 19-year-old man visited our hospital following an attack of general tonic-clonic convulsion. Multiple lesions were noted over bilateral frontal areas on brain computed tomography and magnetic resonance images. The diagnosis was confirmed by positive antibody for sparganum using enzyme-linked immunosorbent assay (ELISA). Praziquantel, 2400 mg/d for one month, was prescribed before the antibody test results came out and the treatment failed. Total removal of the lesion and the enclosed parasite cured the patient. Although the features of cerebral sparganosis on brain computed tomography and magnetic resonance images have been previously described, the findings were not specific and the present case exhibited some different patterns including bilateral multiple calcifications and ventricular compression. The significance of the bilateral involvement is not known but the ventricular compression suggests that the disease was in an active stage. Imaging studies appear to only provide some clues for the diagnosis of sparganosis. Bilateral involvement may be seen as in the present case. The final diagnosis depends on pathologic or immunologic examination results. Surgical intervention either using stereotactic techniques or total removal of the lesion is the treatment of choice while antiparasitic agents are ineffective.

Adult↗
PubMed1998

Effect of patient position and hypotensive anesthesia on inferior vena caval pressure.

STUDY DESIGN: This is a prospective study to measure the inferior vena caval pressure of 20 patients in different positions and different states of blood pressure. OBJECTIVES: Because the inferior vena caval pressure could affect the vertebral venous pressure, which in turn may influence blood loss during lumbar spinal surgery, this study was designed to provide the quantitative data necessary to stress the importance of patient positioning and to assess the effect of controlled hypotension on inferior vena caval pressure. SUMMARY OF BACKGROUND DATA: Positioning patients with a pendulous abdomen and controlled hypotension has been practiced widely during lumbar spinal surgery. It is generally believed that the former will help reduce vertebral venous engorgement and the latter will produce a bloodless surgical wound. However, there have been no complete studies in which quantitative changes of inferior vena caval pressure resulting from different positions was examined. In addition, it would be interesting to know what happens to inferior vena caval pressure during induced hypotension. Could there be an adverse effect on the inferior vena caval pressure during the hypotensive state? METHODS: An intravenous catheter was introduced into the inferior vena cava in each of 20 patients undergoing spinal surgery. In each patient, the inferior vena caval pressure was measured when the patient was supine, prone on a conventional pad, and prone on a Relton-Hall frame. It was followed by isoflurane-induced hypotension with reduction of mean arterial pressure by 20 mm Hg. RESULTS: In this series, the inferior vena caval pressure ranged from 8.2 to 23.4 mm Hg (with a mean of 15.3 mm Hg) when patients were positioned prone on a conventional pad. However, when they were subsequently positioned prone on a Relton-Hall frame, the inferior vena caval pressure decreased dramatically to a range of 4.6 to 13.6 mm Hg (with a mean of 8.2 mm Hg). In each patient the measured inferior vena caval pressure when positioned prone on a conventional pad was 1.5 times greater than that measured with the patient positioned on a Relton-Hall frame. There was a statistically significant difference between these two positions (F = 75.996; P < 0.05). The patients' mean arterial pressure ranged from 92 to 105 mm Hg before induced hypotension. During this time, the inferior vena caval pressure ranged from 4.1 to 13.1 mm Hg (mean, 8.2 mm Hg). During the hypotensive state, the patients' inferior vena caval pressure was found to range from 4.2 to 13.6 mm Hg (mean, 8.1 mm Hg). In each patient the hypotensive interior vena caval pressure may be slightly higher or lower than the baseline pressure. However, the variation never exceeded 1.7 mm Hg. Statistically, there was no significant difference between these two periods (t = 0.956; P > 0.05). CONCLUSIONS: A device allowing the patient's abdominaL viscera to hang freely while the patient is in a prone position significantly reduces their inferior vena caval pressure. The patients also has a constant inferior vena caval pressure during isoflurane-induced hypotension.

Adult↗
PubMed1998

Closed reduction of bilateral locked facets of the cervical spine under general anaesthesia.

BACKGROUND: Bilateral facet interlocking of the cervical spine is a relatively uncommon type of cervical spinal injury. It is frequently associated with devastating neurological symptoms and signs. Early reduction of the locked facets is thought to be critical in preventing progressive secondary spinal cord injury. Whereas skull tong traction remains our primary option for closed reduction of bilateral locked facets of the cervical spine, it is not always successful, even with heavy traction weights. Other more aggressive measures may occasionally be required. The authors report their experience in reducing bilateral locked facets of the cervical spine by manual closed reduction. METHODS: This small series consists of six cases of cervical spinal injury with bilateral locked facets in which manual closed reduction under general anaethesia and muscle relaxation was used. Three of them presented with complete quadriplegia (Frankel class A). One case presented with incomplete but severe neurological deficits (Frankel class B). After unsuccessful closed reduction with skull traction, these patients were treated by manual closed reduction under general anaesthesia and muscle relaxation, followed by anterior discectomy, interbody fusion and stabilization. RESULTS: All cases made neurological improvement after the procedures. Even in cases with initial severe neurological deficits, the recovery was remarkable. The recovery was dramatic in two cases. Case 1 improved from Frankel class B to E; and Case 5 from Frankel class A to D. No case deteriorated neurologically after the procedures. Pneumonia occurred in Case 3; and stress ulcer accompanied by haemorrhage was noted in Case 4. None of these complications was directly related to the procedures. CONCLUSION: The potential for improvement of neurological function following early and successful reduction and fixation of the dislocated spine is emphasized. With meticulous techniques, manual closed reduction may be an effective alternative to skull tong traction when the latter fails.

Adult↗
PubMed1998

A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II.

Ca2+ influx through N-methyl-D-aspartate- (NMDA-) type glutamate receptors plays a critical role in synaptic plasticity in the brain. One of the proteins activated by the increase in Ca2+ is CaM kinase II (CaMKII). Here, we report a novel synaptic Ras-GTPase activating protein (p135 SynGAP) that is a major component of the postsynaptic density, a complex of proteins associated with synaptic NMDA receptors. p135 SynGAP is almost exclusively localized at synapses in hippocampal neurons where it binds to and closely colocalizes with the scaffold protein PSD-95 and colocalizes with NMDA receptors. The Ras-GTPase activating activity of p135 SynGAP is inhibited by phosphorylation by CaMKII located in the PSD protein complex. Inhibition of p135 SynGAP by CaMKII will stop inactivation of GTP-bound Ras and thus could result in activation of the mitogen-activated protein (MAP) kinase pathway in hippocampal neurons upon activation of NMDA receptors.

Animals↗
PubMed1998

DNA adducts of 2,3-epoxy-4-hydroxynonanal: detection of 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine and 1,N6-ethenoadenine by gas chromatography/negative ion chemical ionization/mass spectrometry.

2,3-Epoxy-4-hydroxynonanal (EH) is a bifunctional aldehyde formed by epoxidation of trans-4-hydroxy-2-nonenal, a peroxidation product of omega-6 polyunsaturated fatty acids. EH is mutagenic and tumorigenic and capable of modifying DNA bases forming etheno adducts in vitro. Recent studies showed that etheno adducts are present in tissue DNA of humans and untreated rodents, suggesting a potential endogenous role of EH in their formation. A sensitive assay is needed so we can determine whether EH is involved in etheno adduct formation in vivo and study the biological significance of the etheno adducts in DNA. In this study, we developed a gas chromatography/negative ion chemical ionization/mass spectrometry assay for the analysis of 1, N6-ethenoadenine (epsilonAde) and 7-(1', 2'-dihydroxyheptyl)-3H-imidazo[2,1-i]purine (DHH-epsilonAde) in DNA; both are products from the reaction of adenine with EH. The assay entails the following sequence of steps: (1) addition of [15N5]epsilonAde and [15N5]DHH-epsilonAde to DNA as internal standards, (2) acid hydrolysis of DNA, (3) adduct enrichment by C18 solid phase extraction (SPE), (4) derivatization by pentafluorobenzylation (PFB), (5) separation of PFB-epsilonAde and PFB-DHH-epsilonAde on a Si SPE column, (6) acetonide (ACT) formation of PFB-DHH-epsilonAde, and (7) GC/MS analysis with selective ion monitoring (SIM). The limit of detection by on-column injection for PFB-epsilonAde monitoring of the (M - PFB)- ion at m/z 158 was 30 amol and for ACT-PFB-DHH-epsilonAde monitoring of the (M - PFB)- ion at m/z 328 was 0.4 fmol; the detection limits for the entire assay were 6.3 fmol for epsilonAde and 36 fmol for DHH-epsilonAde. In calf thymus DNA modified with EH at 37 degreesC for 50 h, both epsilonAde and DHH-epsilonAde were detected at high levels by this method, 4.5 +/- 0.7 and 90.8 +/- 8.7 adducts/10(3) adenine, respectively. These levels were also verified by HPLC fluorescence analysis, indicating that EH extensively reacts with adenine in DNA, forming etheno adducts. The high sensitivity of the assay suggests that it may be used in the analysis of ethenoadenine adducts in vivo.

Adenine↗
PubMed1998

A comparison of guanosine-quartet inhibitory effects versus cytidine homopolymer inhibitory effects on rat neointimal formation.

Phosphorothioate oligodeoxynucleotides (PS oligos) manifest antisense and G-quartet aptameric inhibitory effects on vascular smooth muscle cell (SMC) proliferation. PS oligo cytidine homopolymers also have nonsequence-specific, non-G-quartet inhibitory effects on in vitro and in vivo SMC proliferation. In this study, we compared the effects of S-dC18 and S-dC28, 18-mer and 28-mer cytidine homopolymers, respectively, which lack guanosines, with those of ZK10, a G-tetrad forming compound, on in vitro SMC proliferation and in vivo neointimal formation. ZK10 significantly inhibited in vitro human aortic SMC proliferation. At the same molar concentration, ZK10 had significantly greater inhibitory potency on SMC proliferation than either S-dC18, S-dC28, or 7DG-ZK10, which is a modified ZK10 with ten 7-deaza guanosine substitutions. ZK10 was significantly more potent than S-dC18 and S-dC28 in inhibiting PDGF-induced in vitro SMC migration. S-dC18, S-dC28, and ZK10 treatment significantly reduced the intima/media area ratio after rat carotid artery balloon injury compared with the values of the control groups. ZK10 was a more potent inhibitor of neointimal formation than the same chain length S-dC18. ZK10 formed higher-order structures, as shown on gel electrophoresis, in contrast to S-dC28 and 7DG-ZK10. Therefore, the 18-mer ZK10 has comparable in vivo SMC inhibitory effects to the 28-mer S-dC28, a fact that may have ramifications for the development of optimal PS oligos to inhibit angioplasty restenosis.

Angioplasty, Balloon↗