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Biomedical subjects

D M Cheng

Publications and source records attributed to D M Cheng.

At least 19 recordsLinked to original sources

Effect of local restaurant smoking regulations on progression to established smoking among youths.

BACKGROUND: While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis. OBJECTIVE: To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents. DESIGN, SETTING, AND SUBJECTS: A cohort of 2623 Massachusetts youths, ages 12-17 years at baseline, was interviewed via random digit dial telephone survey in 2001-2002 and followed up two years later. A generalised estimating equations (GEE) logistic regression analysis was used and controlled for potential individual, household, and town level confounding factors. MAIN OUTCOME MEASURE: Progression to established smoking during the two year follow up period (defined as having smoked 100 or more cigarettes in one's life). RESULTS: Compared to youths living in towns with weak regulations, those living in towns with strong regulations (complete restaurant smoking bans) had less than half the odds of progression to established smoking (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.24 to 0.66). The association was stronger for youths in towns with strong regulations in effect for two or more years (OR 0.11, 95% CI 0.03 to 0.37), although it was still present for those in towns with strong regulations in effect for less than two years (OR 0.55, 95% CI 0.33 to 0.90). No relationship was found between living in a town with a medium restaurant smoking regulation (restriction of smoking to enclosed, separately ventilated areas) and rates of progression to established smoking. CONCLUSIONS: Local restaurant smoking bans may be an effective intervention to prevent youth smoking.

Adolescent↗

Relation between local restaurant smoking regulations and attitudes towards the prevalence and social acceptability of smoking: a study of youths and adults who eat out predominantly at restaurants in their town.

OBJECTIVE: To examine the relation between strength of local restaurant smoking regulations and smoking related social norms among youths and adults. DESIGN: We used generalised estimating equations logistic regression analysis to examine the relation between regulation strength and youths' and adults' perceptions of adult smoking prevalence and the social acceptability of smoking in their town, while controlling for baseline anti-smoking sentiment in the town. SETTING: Each of the 351 Massachusetts towns were classified as having strong (complete smoking ban), medium (restriction of smoking to enclosed, separately ventilated areas), or weak (all others) restaurant smoking regulations. SUBJECTS: 1147 Massachusetts youths ages 12-17 years and 2116 adults who reported that they often or always eat out in their own town, drawn from a random digit dial survey. MAIN OUTCOME MEASURES: Perceived adult smoking prevalence and perceived social acceptability of smoking in restaurants, in bars, or in general. RESULTS: Compared to youths from towns with weak regulations, youths from towns with strong regulations were more likely to perceive lower adult smoking prevalence (odds ratio (OR) 1.71; 95% confidence interval (CI) 1.02 to 2.84) and social unacceptability of adult smoking (OR 2.00, 95% CI 1.29 to 3.08) in their town. Adults from towns with strong regulations were not more likely to perceive lower adult smoking prevalence, but had more than twice the odds of perceiving that smoking was unacceptable in restaurants (OR 2.19, 95% CI 1.58 to 3.02) or bars (OR 2.51, 95% CI 1.90 to 3.31). CONCLUSIONS: Strong local restaurant smoking regulations are associated with favourable smoking related social norms among youths and adults.

Adolescent↗

Effect of highly active antiretroviral therapy on survival in patients with AIDS-associated pulmonary Kaposi's sarcoma treated with chemotherapy.

PURPOSE: Kaposi's sarcoma (KS) is the most common AIDS-related malignancy. Pulmonary involvement by KS (PKS) has carried a poor prognosis with median reported survival ranging from 3 to 10 months. We studied whether the introduction of highly active antiretroviral therapy (HAART; triple antiretroviral therapy including a protease inhibitor and two reverse transcriptase inhibitors) has been associated with improved survival for AIDS patients with PKS. PATIENTS AND METHODS: A retrospective study was performed of 37 consecutive patients with PKS and human immunodeficiency virus infection in the tumor registry at a large municipal hospital in New York City between 1994 to 1997. There were 16 patients from 1994 to 1995 (pre-HAART period) and 21 patients from 1996 to 1997 (post-HAART period). The primary end point was survival, which was defined as time from start of chemotherapy until death from any cause. RESULTS: Patients were analyzed by the date of diagnosis (pre- v post-HAART period) and whether or not they received HAART. Kaplan-Meier analysis showed significantly better survival in patients diagnosed in the post-HAART period (P =.0025). Additional Kaplan-Meier analysis indicated that patients on HAART had substantially better survival (P <.0001). Cox multivariate analyses showed that HAART therapy was associated with a reduced risk of death (hazard ratio = 0.09; 95% confidence interval, 0.03 to 0.69). CONCLUSION: In patients with AIDS-associated PKS and undergoing chemotherapy, administration of HAART was associated with increased survival.

Acquired Immunodeficiency Syndrome↗

Biosynthetic response and mechanical properties of articular cartilage after injurious compression.

Traumatic joint injury is known to produce osteoarthritic degeneration of articular cartilage. To study the effects of injurious compression on the degradation and repair of cartilage in vitro, we developed a model that allows strain and strain rate-controlled loading of cartilage explants. The influence of strain rate on both cartilage matrix biosynthesis and mechanical properties was assessed after single injurious compressions. Loading with a strain rate of 0.01 s(-1) to a final strain of 50% resulted in no measured effect on the cells or on the extracellular matrix, although peak stresses reached levels of about 12 MPa. However, compression with strain rates of 0.1 and 1 s(-1) caused peak stresses of approximately 18 and 24 MPa, respectively, and resulted in significant decreases in both proteoglycan and total protein biosynthesis. The mechanical properties of the explants (compressive and shear stiffness) were also reduced with increasing strain rate. Additionally, cell viability decreased with increasing strain rate, and the remaining viable cells lost their ability to exhibit an increase in biosynthesis in response to low-amplitude dynamic mechanical stimulation. This latter decrease in reparative response was most dramatic in the tissue compressed at the highest strain rates. We conclude that strain rate (like peak stress or strain) is an important parameter in defining mechanical injury, and that cartilage injuriously compressed at high strain rates can lose its characteristic anabolic response to low-amplitude cyclic mechanical loading.

Animals↗

MEIS1 and HOXA7 genes in human acute myeloid leukemia.

Co-activation of Meisl with Hoxa7 or Hoxa9 homeobox genes by retroviral gene insertion has recently been reported to be leukemogenic in murine myeloid leukemia. In this study we determined their expression in human leukemia. Most human myeloid leukemia cell lines co-expressed MEIS1 with HOXA7 and HOXA9. Among patients with acute leukemia, 50% of AML patients expressed MEIS1, while the majority of ALL patients were negative. A total of 89.5% of patients expressing MEIS1 co-expressed HOXA7. In unadjusted models, poorer response to chemotherapy was associated with expression of HOXA7 regardless of MEIS1 status and older patients were more likely to express either gene.

Cell Line↗

Covariate analysis of viral eradication studies.

An important issue arising in therapeutic studies of hepatitis C and HIV is the identification of and adjustment for covariates associated with viral eradication and resistance. Analyses of such data are complicated by the fact that eradication is an occult event that is not directly observable, resulting in unique types of censored observations that do not arise in other competing risks settings. This paper proposes a semiparametric regression model to assess the association between multiple covariates and the eradication/resistance processes. The proposed methods are based on a piecewise proportional hazards model that allows parameters to vary between observation times. We illustrate the methods with data from recent hepatitis C clinical trials.

Journal Article↗

The one-sample problem from eradication studies of chronic viral infections.

In studies of chronic viral infections, the objective is to estimate probabilities of developing viral eradication and resistance. Complications arise as the laboratory methods used to assess eradication status result in unusual types of censored observations. This paper proposes nonparametric methods for the one-sample analysis of viral eradication/resistance data. We show that the unconstrained nonparametric maximum likelihood estimator of the subdistributions of eradication and resistance are obtainable in closed form. In small samples, these estimators may be inadmissible; thus, we also present an algorithm for obtaining the constrained MLEs based on an isotonic regression of the unconstrained MLEs. Estimators of several functionals of the eradication and resistance subdistributions are also developed and discussed. The methods are illustrated with results from recent hepatitis C clinical trials.

Biometry↗

[Study on rearrangements of immunoglobulin genes in acute nonlymphocytic leukemia].

OBJECTIVE: To explore the mechanism of infidelity of immunoglobulin gene rearrangements in acute nonlymphocytic leukemia and its significance in genotyping of acute leukemia. METHODS: Immunoglobulin gene rearrangement was studied in 25 patients with acute nonlymphocytic leukemia in various stages by polymerase chain reaction. RESULTS: Immunoglobulin heavy chain gene rearrangements were detected in three of 25 patients, one of whom in complete remission was found to have tendency of relapse one month later. CONCLUSION: Lineage infidelity of immunoglobulin gene rearrangements does exist in acute nonlymphocytic leukemia, therefore, immunoglobulin rearrangements probably can not be regarded as an absolutely reliable marker for acute lymphocytic leukemia. Immunoglobulin rearrangements may have some significance in the detection of minimal residual disease of acute leukemia.

Adolescent↗

Structural and conformational studies on deoxyguanosyl-3',5'-deoxyadenosine monophosphate and its ethyl phosphotriester analogs--left-handed dimers.

The mode of base-base stacking, the handedness and the sugar(dGpA)phosphate backbone conformation of deoxyguanosyl 3'-5' deoxyadenosine and its diastereomeric ethyl phosphotriester analogs were studied by 1H NMR, UV and CD spectroscopy. The results indicate the three dimers are left-handed, while the sugar phosphate backbone is comprised predominantly of C2-endo,gg(C4-C5) and g'g (C5-O) conformers. The two bases are extensively stacked and interact about 90 degrees along the dyad axes. The extent of base overlap in dGpA is slightly greater than in either ethyl phosphotriester analog. The absolute configurations of the two ethyl phosphotriester diastereoisomers of dGpA can be assigned by one-dimensional and two-dimensional 1H NMR nuclear Overhauser enhancement experiments.

Alkylation↗

Nuclear Overhauser effect as a tool for the complete assignment of nonexchangeable proton resonances in short deoxyribonucleic acid helices.

A new strategy for the assignment of nonexchangeable proton resonances in oligonucleotide duplexes is presented and used to interpret the spectra of the oligonucleotide helix d(CpGpCpGpCpG) X d(CpGpCpGpCpG) in low salt (B form). This procedure is based on the use of sequential homodecoupling (1D) or COSY (2D) for the interconnection of the sugar resonances pertaining to the same residue and on the measurement of nuclear Overhauser effect (NOE) (1D or 2D) between critically located protons in order to establish the connectivity between the base protons and the sugar protons, as well as between consecutive base-sugar residues. The assignment performed by this method was found in perfect agreement with the one made previously by the incremental procedure [Cheng, D. M., Kan, L.-S., Frechet, D., Ts'o, P. O. P., Uesugi, S., Shida, T., & Ikehara, M. (1983) Biopolymers (in press)]. Also, this method is demonstrated to be applicable to DNA short helices containing A X T base pairs.

Base Sequence↗

Synthesis and characterization of the dinucleoside monophosphates containing 2'-fluoro-2'-deoxyadenosine.

Three dinucleoside monophosphates containing 2'-fluor-2'-deoxyadenosine (dAfl), dAfl-dAfl, dAfl-A, and A-dAfl, were synthesized chemically. Characterization of these dimers has been performed by UV absorption, CD, and 1H NMR spectroscopies. The results showed that all three dimers have a stacked conformation with a geometry similar to that of A-A but with greater extent of base-base over-lapping than A-A. This interpretation is verified by the data of chemical shifts and coupling constants of 1H NMR study on these dimers (D. M. Cheng, L. S. Kan, P. O. P. Ts'o. S. Uesugi, Y. Takatsuka, and M. Ikehara unpublished data). All three dimers form 2U.1A complexes with poly(uridylic acid). The Tm of dAfl-dAfl.2poly(U) is higher than that of dAfl-A.2poly(U), which in turn is higher than that of A-dAfl.2poly(U). The NMR results clearly indicate that the conformation of the furanose of dAfl moiety in these dimers is more favored toward 3'-endo than 2'-endo puckering in comparison with the adenosine. The effects of 3' substituents on oligo- and polynucleotide conformation are also discussed.

Circular Dichroism↗

Variation in nucleolar organizer activity in lymphocytes of females with adenocarcinoma.

With the use of Ag staining and conventional light microscopy, a difference is visualized in the frequency of nucleolar organizer regions between PHA-stimulated lymphocytes from normal females and females with various types of adenocarcinoma. This difference in NOR activity is more pronounced in G chromosome than D chromosomes. It is feasible that rDNA gene activity in PHA-stimulated lymphocytes is augmented in patients with adenocarcinoma due to the presence of plasma mediators arising from cellular malignancies. The NOR regions located on G chromosomes are considered to be more sensitive to these mediators than those on D chromosomes.

Adenocarcinoma↗