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D T Chen

Publications and source records attributed to D T Chen.

15 recordsLinked to original sources
PubMed2005

The impact of privacy protections on recruitment in a multicenter stroke genetics study.

The authors reviewed the recruitment of stroke-affected sibling pairs using a letter-based, proband-initiated contact strategy. The authors randomly sampled 99 proband enrollment forms (Phase 1) and randomly sampled 50 sibling reply cards (Phase 2). The sibling response rate was 30.6%, for a pedigree response rate of 58%. Of the siblings who replied, 96% authorized further contact. Median time from proband enrollment to pedigree DNA banking, which required 3+ probands, was 134 days.

Brain Ischemia↗
PubMed2003

Bulb of penis as a marker for prostatic apex in external beam radiotherapy of prostate cancer.

PURPOSE: To investigate the relationship between the bulb of the penis and the peak of the urethrogram, and to compare this measurement with the ischial tuberosities (ITs) to peak distance. METHODS AND MATERIALS: Pelvic CT scans from 50 consecutive patients with localized prostate cancer were analyzed to identify the penile bulb. Each patient was required to undergo retrograde urethrography during CT-based treatment planning with 3-mm slices. The peak of the urethrogram was defined as the last CT slice in which the contrast dye in the urethra could be visualized. Measurements were taken from the slice containing the most superior aspect of the penile bulb to the last slice of the urethrogram peak. The superior aspect of the penile bulb was defined as the CT slice nearest the peak that contained a bulbous structure at the base of the penis. This distance was defined as the bulb-peak distance. Similarly, the IT-peak distance was recorded for comparison. RESULTS: The mean bulb-peak and IT-peak distances were calculated for 47 of 50 patients. The peak of the urethrogram was unable to be evaluated in 3 patients. The mean, median, and range bulb-peak distance was 2.4 mm (SD 1.8), 3 mm, and 0-6 mm, respectively. The mean, median, and range IT-peak distance was 20.1 mm (SD 6.6), 21 mm, and 6-33 mm, respectively. No patient had the bulb located above the apex of the urethrogram. CONCLUSION: The bulb of the penis is a relatively consistent soft-tissue landmark compared with the ITs and is located an average of 3 mm below the peak of the urethrogram. Therefore, the bulb of the penis is another landmark for the identification of the prostatic apex and is less invasive than retrograde urethrography.

Humans↗
PubMed2003

Rheological microscopy: local mechanical properties from microrheology.

We demonstrate how tracer microrheology methods can be extended to study submicron scale variations in the viscoelastic response of soft materials; in particular, a semidilute solution of lambda-DNA. The polymer concentration is depleted near the surfaces of the tracer particles, within a distance comparable to the polymer correlation length. The rheology of this microscopic layer alters the tracers' motion and can be precisely quantified using one- and two-point microrheology. Interestingly, we found this mechanically distinct layer to be twice as thick as the layer of depleted concentration, likely due to solvent drainage through the locally perturbed polymer structure.

Bacteriophage lambda↗
PubMed2001

Androgen regulation of the cell-cell adhesion molecule-1 (Ceacam1) gene.

Previous studies have established that the cell-cell adhesion molecule-1 (CEACAM1, previously known as C-CAM1) functions as a tumor suppressor in prostate cancer and is involved in the regulation of prostate growth and differentiation. However, the molecular mechanism that modulates CEACAM1 expression in the prostate is not well defined. Since the growth of prostate epithelial cells is androgen-regulated, we investigated the effects of androgen and the androgen receptor (AR) on CEACAM1 expression. Transient transfection experiments showed that the AR can enhance the Ceacam1 promoter activity in a ligand-dependent manner and that the regulatory element resides within a relatively short (-249 to -194 bp) segment of the 5'-flanking region of the Ceacam1 gene. This androgen regulation is likely through direct AR-promoter binding because a mutant AR defective in DNA binding failed to upregulate reporter gene expression. Furthermore, electrophoretic mobility shift assays demonstrated that the AR specifically binds to this sequence, and mutation analysis of the potential ARE sequences revealed a region within the sequence that was required for the AR to activate the Ceacam1 gene. Therefore, the regulation of Ceacam1 gene expression by androgen may be one of the mechanisms by which androgen regulates prostatic function.

Androgens↗
PubMed2001

Signal transduction by the CEACAM1 tumor suppressor. Phosphorylation of serine 503 is required for growth-inhibitory activity.

CEACAM1 is a cell-cell adhesion molecule that mediates homophilic cell adhesion. In addition, CEACAM1 was also shown to suppress the growth of prostate, breast, and colon tumors. Structural and functional analyses showed that the adhesion activity of CEACAM1 is mediated by its extracellular domain while its cytoplasmic domain is necessary and sufficient for growth-inhibitory activity. The signal pathways leading to CEACAM1-mediated growth suppression are not known. We studied the importance of phosphorylation of serine 503 in this growth-inhibitory signaling pathway. Full-length CEACAM1 was found to be phosphorylated in vivo in both tyrosine and serine residues. Mutation of tyrosine 488 to phenylalanine did not abolish the tumor-suppressive activity of CEACAM1, suggesting that phosphorylation at tyrosine 488 is not critical for CEACAM1's tumor-suppressive activity. Although expression of CEACAM1's cytoplasmic domain inhibited the growth of DU145 prostate cancer cells in vivo, mutation of serine 503 to alanine abolished the growth-inhibitory activity. In addition, the change of serine 503 to aspartic acid produced tumor-suppressive activity similar to that of the wild-type CEACAM1. These results suggested that phosphorylation at serine 503 is essential for CEACAM1's growth-inhibitory function in vivo.

Alanine↗
PubMed2001

Ethical and methodological issues in pedigree stroke research.

BACKGROUND: Stroke is a complex genetic disorder with a variable phenotype. Investigations of heritable factors in complex genetic disorders use pedigree and genetic techniques, which pose different ethical and methodological challenges than those routinely encountered in therapeutic research. Building consensus on acceptable research practices in this field is vital to the success of multicentered collaborations. SUMMARY OF REVIEW: We review important ethical and methodological concerns related to the collection, storage, and release of pedigree research information. The human studies aspects of pedigree research are complicated methodologically because individuals can be active or passive participants and pedigrees can be proband derived, partially validated, or fully validated. Current research ethics frameworks do not work well outside of a dyadic researcher-subject relationship. Privacy and confidentiality for family members must be considered in pedigree research. Investigators should anticipate potential conflicts of interest among family members when designing a pedigree research protocol. CONCLUSIONS: We propose a "proband-initiated contact" methodology in which the proband or the proband's designate allows identification of potential families without breaching the privacy of individuals in the family. In situations in which family history data are collected without direct contact between researchers and individuals in the proband's family, an Institutional Review Board may waive consent by family members after appropriate review of the protocol and application of rules for granting waivers of consent. Certificates of Confidentiality should be considered.

Confidentiality↗
PubMed1999

Analysis of drug dissolution data.

Drug absorption in the human body depends on the dissolution rate of the drug. Suitable dissolution characteristics are important to ensure that the drug will achieve the desired therapeutic effects. To assess the similarity of dissolution rates of several drug lots, we apply a general growth curve model with different covariance structures. The Box-Cox power transformation and the naive log transformation are applied to a function of the dissolution rate. The predictive sample-reuse, or cross-validation, method is employed in selecting an appropriate model with best predictive accuracy. A testing procedure for examining the similarity among the drug lots is also conducted. A partially Bayesian approach is used for the assessment of dissolution equivalence.

Bayes Theorem↗
PubMed1999

Life expectancy and causes of death in a population treated for serious mental illness.

OBJECTIVE: This cross-sectional mortality linkage study describes the prevalence of specific fatal disease and injury conditions in an adult population with serious mental illness. The large sample of decedents and the use of multiple-cause-of-death data yield new clinical details relevant to those caring for persons with serious mental illness. METHODS: Age-adjusted frequency distributions and years of potential life lost were calculated by gender and causes of death for persons in the population of 43,274 adults served by the Massachusetts Department of Mental Health who died between 1989 and 1994. Means and frequencies of these variables were compared with those for persons in the general population of the state who did not receive departmental services and who died during the same period. RESULTS: A total of 1,890 adult decedents served by the department of mental health were identified by electronic linkage of patient and state vital records. They had a significantly higher frequency of deaths from accidental and intentional injuries, particularly poisoning by psychotropic medications. Deaths from cancer, diabetes, and circulatory disorders were significantly less frequently reported. On average, decedents who had been served by the department of mental health lost 8.8 more years of potential life than decedents in the general population-a mean of 14.1 years for men and 5.7 for women. The differential was consistent across most causes of death. CONCLUSIONS: Findings in this study are consistent with previous findings identifying excess mortality in a population with serious mental illness. The high rate of injury deaths, especially those due to psychotropic and other medications, should concern providers.

Adolescent↗
PubMed1994

Nicotine increases diazepam binding inhibitor (DBI) mRNA in primary cultured neurons.

The effect of nicotine on the expression of diazepam binding inhibitor (DBI) mRNA in primary cultured cerebral cortical neurons was examined using Northern blot analysis. Nicotine exposure (0.001-10 microM) for 24 h increased the DBI mRNA level in a dose-dependent manner, whereas the beta-actin mRNA level showed no change. This effect of nicotine was faded out over 48 h of its exposure. Hexamethonium (100 microM) completely abolished the nicotine-induced increase in DBI mRNA expression. These results indicate that nicotine increases the expression of DBI mRNA in cerebral cortical neurons via the activation of nicotinic acetylcholine receptor.

Animals↗
PubMed1993

Safety of moclobemide in clinical use.

The reversible monoamine oxidase-A (MAO-A) inhibitors were developed by researchers in response to safety concerns about the old irreversible MAO inhibitors. Scientists devised this new class of MAO-A inhibitors with the hope that selectivity for the MAO-A receptor and reversibility of the inhibition would result in efficacy in depression with improved safety. Moclobemide is the first reversible MAO-A inhibitor to be widely marketed and is currently approved for marketing in approximately 50 countries. In determining the safety profile of a drug, the following strategy is generally employed by a manufacturer: (a) comparison of the drug to placebo in clinical trials to identify the more commonly occurring adverse reactions; (b) comparison of the drug to other known drugs in clinical trials to determine relative frequencies of adverse reactions; (c) examination of reports from practitioners, the so-called spontaneously reported adverse event reports to confirm that what is seen under the experimental conditions of clinical trials is also seen in "real life" and to generate hypotheses about rare adverse reactions to the drug; (d) identification of further adverse reactions from overdose reports; and (e) the conduct of postmarketing studies to further determine drug-drug interactions. Such a strategy was employed by the manufacturer for moclobemide, and this article reviews the results of data accumulated concerning moclobemide safety.

Antidepressive Agents↗
PubMed1985

Retinoic acid embryopathy.

Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively. The outcomes in this cohort were 8 spontaneous abortions, 23 normal infants, and 5 malformed infants. Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5). Among the 21 malformed infants we found a characteristic pattern of malformation involving craniofacial, cardiac, thymic, and central nervous system structures. The malformations included microtia/anotia (15 infants), micrognathia (6), cleft palate (3), conotruncal heart defects and aortic-arch abnormalities (8), thymic defects (7), retinal or optic-nerve abnormalities (4), and central nervous system malformations (18). The pattern of malformation closely resembled that produced in animal studies of retinoid teratogenesis. It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations.

Abnormalities, Drug-Induced↗