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A M Chen

Publications and source records attributed to A M Chen.

32 records · Page 2Linked to original sources
PubMed1997

Review: proximity effects in the production of chromosome aberrations by ionizing radiation.

After ionizing radiation has induced double-strand DNA breaks (dsb), misrejoining produces chromosome aberrations. Aberration yields are influenced by "proximity' effects, i.e., by the dependence of misrejoining probabilities on initial dsb separations. We survey proximity effects, emphasizing implications for chromosome aberration-formation mechanisms, for chromatin geometry, and for dose-response relations. Evidence for proximity effects comes from observed biases for centric rings and against three-way interchanges, relative to dicentrics or translocations. Other evidence comes from the way aberration yields depend on radiation dose and quality, tightly bunched ionizations being relatively effective. We concludes (1) that misrejoining probabilities decrease as the distance between dsb at the time of their formation increases, and almost all misrejoining occurs among dsb initially separated by < 1/3 of a cell nucleus diameter; (2) that chromosomes occupy (irregular) territories during the G0/G1 phase of the cell cycle, having dimensions also roughly 1/3 of a cell nucleus diameter, (3) that proximity effects have the potential to probe how much different chromosomes intertwine on move relative to each other: and (4) that incorporation of proximity effects into the classic random breakage-and-reunion model allows quantitative interrelation of yields for many different aberration types and of data obtained with various FISH painting methods or whole-genome scoring.

Chromosome Aberrations↗
PubMed1997

A rapid method for measuring pericentric inversions using fluorescence in situ hybridization (FISH).

We used three common fluorescent probes to measure pericentric inversion frequencies in 2.9 Gy 60Co gamma-irradiated human lymphocytes. For a given chromosome, the first probe is specific to one telomeric region, the second probe is specific to one subcentromeric region and the third probe is specific to the centromere. A pericentric inversion is made observable by the change in position (switching) of the fluorescent signals relative to the chromosome centromere. Our data showed equality between pericentric inversions and centric rings. The calculated whole-genome F-ratio of apparently simple translocations to pericentric inversions was 5.6.

Animals↗
PubMed1997

Intra-arm and interarm chromosome intrachanges: tools for probing the geometry and dynamics of chromatin.

Many chromosome-type, exchange-type chromosomal aberrations produced by radiation are intrachanges, i.e. involve only one chromosome. It is assumed such intrachanges are formed by illegitimate reunion of two double-strand breaks (DSBs) on the chromosome. The yield of intra-arm intrachanges (acentric rings or paracentric inversions) relative to that of interarm intrachanges (centric rings or pericentric inversions) is larger than would occur if production and illegitimate reunion of DSBs were spatially random. The excess of intra-arm intrachanges is presumably due to proximity effects for illegitimate reunions, i.e. enhancement of the intrachange probability when two DSBs are formed close to one another. Radiation track structure may also play a role. Using a polymer description for "large-scale" chromatin geometry (>2 Mb), and using two alternate (rapid or slow motion) models for the way that DSBs move after they are produced, theoretical estimates are given for size distributions of intrachanges at low or high linear energy transfer (LET). The ratio of intra-arm to interarm intrachanges is derived from the size distribution and compared with data from the literature on centric rings, inversions, interstitial deletions and excess acentric fragments. Proximity effects enhance yields of intra-arm relative to interarm intrachanges at least severalfold and perhaps as much as 10-fold compared to expectations based on spatial randomness. We argue that further measurements of intra-arm and interarm intrachanges would be informative about large-scale chromatin structure and chromosome motion. Because inversions are more frequent than estimates of randomness would indicate, and are transmissible to daughter cells, their size distribution could also help characterize past exposure to high-LET radiation.

Chromatin↗
PubMed1997

Computer simulation of data on chromosome aberrations produced by X rays or alpha particles and detected by fluorescence in situ hybridization.

With fluorescence in situ hybridization (FISH), many different categories of chromosome aberrations can be recognized-dicentrics, translocations, rings and various complex aberrations such as insertions or three-way interchanges. Relative frequencies for the various aberration categories indicate mechanisms of radiation-induced damage and reflect radiation quality. Data obtained with FISH support a proximity version of the classic random breakage-and-reunion model for the formation of aberrations. A Monte Carlo computer implementation of the model, called the CAS (chromosome aberration simulator), is generalized here to high linear energy transfer (LET) and compared to published data for human cells irradiated with X rays or 238Pu alpha particles. For each kind of radiation, the CAS has two adjustable parameters: the number of interaction sites per cell nucleus and the number of reactive double-strand breaks (DSBs) per gray. Aberration frequencies for various painted chromosomes, of varying lengths, and for 11 different categories of simple or complex aberrations were simulated and compared to the data. The optimal number of interaction sites was found to be approximately 13 for X irradiation and approximately 25 for alpha-particle irradiation. The relative biological effectiveness (RBE) of alpha particles for the induction of reactive DSBs (which are a minority of all DSBs) was found to be approximately 4. The two-parameter CAS model adequately matches data for many different categories of aberrations. It can use data obtained with FISH for any one painting pattern to predict results for any other kind of painting pattern or whole-genome staining, and to estimate a suggested overall numerical damage indicator for chromosome aberration studies, the total misrejoining number.

Alpha Particles↗
PubMed1996

Proximity effects for chromosome aberrations measured by FISH.

A Monte Carlo simulation computer program for radiation-produced chromosome aberrations, based on the breakage-and-reunion model, was extended to include proximity effects due to localization of chromosomes and limited range for break-break interactions. Two adjustable parameters were used. One corresponds to total dose: the other determines proximity effects by specifying the number of 'interaction regions' in a cell nucleus. The use of additional adjustable parameters was avoided by assuming randomness of break induction and aberration production. FISH chromosome painting data were obtained from 1.9 Gy 60Co gamma-rays-irradiated human lymphocytes. The data were compared with the computer simulation results, taking individual chromosome lengths into account. With about 13 interaction regions, agreement between the experiment and the simulation was good, even when detailed categories of damage were scored. An estimated average dsb-dsb interaction distance, based on 13 interaction regions, is about 1.3 micron. Monte Carlo methods give useful quantitative estimates of relative aberration yields, with a minimum of adjustable parameters and the theoretical assumptions, and indicated proximity effects. Computer simulation of FISH experiments can be adapted to any number of colours, any scoring criteria and any method of grouping aberrations into categories. Simulation allows systematic extrapolation of aberration data on painted chromosomes to whole-genome aberration frequencies.

Chromosome Aberrations↗
PubMed1996

Theoretical predictions on the equality of radiation-produced dicentrics and translocations detected by chromosome painting.

Existing models of chromosome aberrations produced by ionizing-radiation predict equal numbers of dicentrics and translocations if the dose is so low that complex aberrations can be ignored. We show that, for a specific subset of aberrations detected by FISH, dicentric/translocation equality is predicted even at higher doses. Assuming one-colour whole-chromosome painting (with unpainted chromosomes counterstained and centromeres recognizable) the relevant restriction is that the final metaphase pattern be, in the terminology of Simpson and Savage, 'apparently simple'. This means that the painted pattern is required to have the colour/centromere appearance corresponding to a single complete reciprocal exchange but its actual formation, as reflected for example in lengths, is allowed to be more complicated. The restriction to apparent simplicity is significantly less limiting than ignoring all complex aberrations. Our analysis of predicted dicentric/translocation equality in this case uses examples, a combinatorial counting method, Monte Carlo computer programs, and a duality proof. However, we argue that for 'visibly complex' dicentrics or translocations, no similar equality is expected in general. Corresponding experimental results are briefly surveyed. Checking dicentric/translocation equality experimentally can provide a significant test of current chromosome aberration models.

Chromosome Aberrations↗
PubMed1995

Chromosome aberrations produced by ionizing radiation: Monte Carlo simulations and chromosome painting data.

Monte Carlo simulations are used to analyze the reshuffling of chromosome segments which occurs when DNA is damaged by ionizing radiation. Programs are based on either Sax's classic breakage-and-reunion model or Revell's exchange model for chromosome aberrations. The simulations quantify the predictions of the two models in complete detail, using only one adjustable parameter which corresponds to total radiation dose. While testing subroutines, new analytic results on the chromosome/arm/break method of classifying aberrations were obtained. The model predictions were tested by using three-color fluorescence in situ hybridization (FISH) 'chromosome painting' on human lymphocyte cells irradiated with gamma-rays. Some of the per-cell aberration frequencies were observed to be intermediate between the predictions of the two models. This result indicates proximity 'effects', due to localization of chromosome interactions in space and time. Predictions based on chromosome arm lengths were found to be in good agreement with experiment. Monte Carlo simulations are a powerful, flexible way to compare models of chromosome aberration production with experiments quantitatively, using a minimum of theoretical presumptions.

Algorithms↗
PubMed1987

Indoor 222Rn measurements in the region of Beijing, People's Republic of China.

Passive integrating activated C detectors were used to study the regional distribution and temporal variation of 222Rn in indoor air in dwellings in the Beijing region. Measurements were made in 537 dwellings, which were either detached houses or multi-family apartments. The city-wide study was completed in 1985. The distributions are approximately log-normal with 90% of the dwellings having 222Rn levels less than 60 Bq m-3. The weighted average 222Rn concentration has been found to be 22.4 Bq m-3. Averages for detached houses and multi-family dwellings are 25.9 and 15.2 Bq m-3, respectively. Assuming an equilibrium factor of 0.5 and an occupancy factor of 0.8, the average equilibrium equivalent concentration of 222Rn progeny is 11.2 Bq m-3 and the annual average effective dose equivalent is 1.1 mSv.

Air Pollutants↗
PubMedDate not supplied

Mammography and clinical breast examination among Korean American women in two California counties.

BACKGROUND: Mammography and clinical breast examination (CBE) are underutilized, especially by women from some racial/ethnic minorities. Few published studies of screening practices or correlates for these subgroups exist. METHODS: A population-based telephone survey of 1,090 Korean Americans living in two California counties was conducted. To produce population estimates of mammography and CBE testing, we adjusted frequencies to account for different selection probabilities. Multivariable logistic regression was performed to determine independent correlates of testing. RESULTS: Only 34% [95% confidence intervals (CI) 30%, 39%] of Korean American women age 50 and older were estimated to have had a mammogram in the past 2 years. Only 32% (95% CI 28%, 37%) had had a CBE in the past 2 years. The strongest independent correlate of testing was having a regular medical checkup [odds ratio (OR) for mammogram = 9.21, 95% CI 3.98, 21.35; OR for CBE = 11.58, 95% CI 4.71, 28.46]. CONCLUSIONS: These estimates are lower than the Healthy People 2000 objectives as well as published estimates for other populations in the United States. Planning and implementing tailored programs to improve screening are best done using a community-sensitive approach, which, because racial/ethnic subgroups are growing, will assume increasing public health importance.

Aged↗
PubMedDate not supplied

Routine myocardial revascularization with the radial artery: a multicenter experience.

BACKGROUND: Current literature documents use of the radial artery (RA) for myocardial revascularization only as an alternative conduit in cases where the saphenous veins have been previously harvested or are unsuitable for use. Large-scale routine clinical use of the RA as the conduit of choice has not been reported. METHODS: This prospective study evaluated the harvest of the RA from 933 patients and the subsequent use of the conduit as a preferred coronary artery bypass graft second only to the left internal thoracic artery in 930 of these patients. RESULTS: Unilateral RA harvest was performed in 786 patients and 147 patients had bilateral RA harvest. A total of 1080 RAs were harvested; 214 (19.8%) originated from the dominant forearm. There was a mean of 3.30+/-0.93 grafts per patient of which 2.43+/-0.83 were arterial grafts. The mean number of RA grafts was 1.43+/-0.53. Operative mortality was 2.3% with none due to the RA graft(s). There was no ischemia nor motor dysfunction in the operated hands. Thirty-two (3.4%) patients experienced transient thenar dysesthesia that resolved in 1 day to 6 weeks. CONCLUSIONS: Our results demonstrate that routine total or near total arterial myocardial revascularization may be achieved safely and effectively with the use of one or both RAs in conjunction with the internal thoracic artery.

Adolescent↗
PubMedDate not supplied

Correlates of cigarette smoking among Korean American adults in Alameda County, California.

OBJECTIVE: To estimate the prevalence of cigarette smoking and to determine the sociodemographic correlates of smoking among Korean American adults in Alameda County, California, 1994-1995. METHOD: Korean surname-based telephone survey; contingency table and multinomial logistic regression analyses. FINDINGS: Almost 39% of Korean American men and 6% of Korean American women were current smokers. Among Korean American men those who attended religious activities less than monthly had nearly three times the odds of being current smokers, and those who did not speak English well had 2 1/2 times the odds of being current smokers as compared to never smokers. Those 18 to 24 years of age had more than 8 1/2 times the odds, and those who attended religious activities less than monthly had more than 3 1/2 times the odds of being current smokers as compared to former smokers. Among Korean American women those who were not married had more than 3 times the odds of being current smokers, and those who attended religious activities less than monthly had 22 times the odds of being current smokers as compared to never smokers. Those who attended religious activities less than monthly had almost 8 times the odds of being current smokers as compared to former smokers. CONCLUSIONS: This study increases our understanding about the prevalence and correlates of cigarette smoking among Korean Americans and can contribute to the development of effective smoking cessation and prevention strategies in this understudied population.

Adult↗
PubMedDate not supplied

Breast-conserving therapy in the setting of collagen vascular disease.

BACKGROUND: It is unclear whether the presence of collagen vascular disease should be considered a contraindication to irradiation. This study was undertaken to determine whether women with pre-existing collagen vascular disease have an increased incidence of complications after breast-conserving therapy. METHODS AND MATERIALS: A cohort of 36 patients with documented collagen vascular disease was conservatively treated for early-stage breast cancer between 1975 and 1998. All of these patients were treated with conventional radiation therapy to a total medium dose of 64 Gy. Seventeen had rheumatoid arthritis; four, scleroderma; four, Raynaud's phenomenon; five, lupus erythematosus; two, Sjögren's disease; and four, polymyositis. Each of these patients was matched to two control patients without a history of collagen vascular disease on the basis of age, radiation therapytechnique, chemotherapy or hormone therapy use, tumor histology, and date of treatment. Acute and late complications were assessed using a six-point scale from the toxicity criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer. The scoring system for both acute and late reactions ranged from 0 (no change over baseline) to 5 (radiation led to death). For the purpose of statistical analysis, patients were classified as having a significant complication if they had a score of 3 or greater. RESULTS: With a median clinical follow-up time of 12.5 years (range, 3.0-22.5 years), no significant difference was detected between the collagen vascular disease and control groups with respect to acute complications (14% vs 8%). With respect to late complications, a significant difference was observed (17% vs 3%) between the two groups. However, when patients in the collagen vascular disease group were analyzed by specific disease, this significance disappeared in all but the scleroderma group. CONCLUSIONS: Patients with scleroderma have a statistically significant increased incidence of radiation therapy complications after breast-conserving surgery and radiation therapy. The presence of other collagen vascular diseases should not be considered a contraindication for this treatment modality.

Adult↗
PubMedDate not supplied

"Health is strength": a research collaboration involving Korean Americans in Alameda County.

INTRODUCTION: This is a preliminary report from a research collaboration between Asian Health Services (community health center); Koreans in Alameda County, California; and the University of California at Berkeley School of Public Health. This five-year Centers for Disease Control and Prevention project supports a collaborative community intervention to improve breast and cervical cancer screening behavior among Korean women. METHODS: A Korean Community Advisory Board and Korean-American staff were recruited, and community sensitive research (CSR) and participatory action research (PAR) principles were applied: (1) building community infrastructure for sustainable action, (2) cultural appropriateness, (3) assuring responsiveness to community needs, and (4) a prevention focus that would assist health care providers. We conducted a population-based telephone survey on 676 Korean adults (272 men and 404 women). RESULTS: The collaborative process yielded (1) a high response rate (79%), (2) baseline health information on Korean Americans, (3) broadening of the original research topic, (4) survey responses that will guide intervention design, (5) culturally competent strategies, and (6) expanded Korean-American Community capacity for local action. CONCLUSIONS: Research collaboration between universities, community-based organizations, and ethnic communities can yield high-quality research. CSR and PAR approaches help break through cultural barriers in otherwise "hard to reach" API sub-populations. Determinants of success include sharing common goals; trust, honesty, and integrity; shared decision making; mutual respect of each partner's expertise; cultural sensitivity and cultural competence; flexibility, good communication, and mutual learning; and continuity of partners. Actively engaging members of the study population in the research process builds community capacity, thus laying the foundation for future projects that improve health status.

Adult↗