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M H Chen

Publications and source records attributed to M H Chen.

At least 37 records · Page 2Linked to original sources
PubMed2001

Maximum likelihood methods for cure rate models with missing covariates.

We propose maximum likelihood methods for parameter estimation for a novel class of semiparametric survival models with a cure fraction, in which the covariates are allowed to be missing. We allow the covariates to be either categorical or continuous and specify a parametric distribution for the covariates that is written as a sequence of one-dimensional conditional distributions. We propose a novel EM algorithm for maximum likelihood estimation and derive standard errors by using Louis's formula (Louis, 1982, Journal of the Royal Statistical Society, Series B 44, 226-233). Computational techniques using the Monte Carlo EM algorithm are discussed and implemented. A real data set involving a melanoma cancer clinical trial is examined in detail to demonstrate the methodology.

Algorithms↗
PubMed2001

Bayesian semiparametric models for survival data with a cure fraction.

We propose methods for Bayesian inference for a new class of semiparametric survival models with a cure fraction. Specifically, we propose a semiparametric cure rate model with a smoothing parameter that controls the degree of parametricity in the right tail of the survival distribution. We show that such a parameter is crucial for these kinds of models and can have an impact on the posterior estimates. Several novel properties of the proposed model are derived. In addition, we propose a class of improper noninformative priors based on this model and examine the properties of the implied posterior. Also, a class of informative priors based on historical data is proposed and its theoretical properties are investigated. A case study involving a melanoma clinical trial is discussed in detail to demonstrate the proposed methodology.

Bayes Theorem↗
PubMed2001

Characterization of the RcsC-->YojN-->RcsB phosphorelay signaling pathway involved in capsular synthesis in Escherichia coli.

Escherichia coli and other enteric microorganisms produce an extracellular polysaccharide capsule, called colanic acid, under certain environmental conditions. This capsular synthesis is regulated by the RcsC (sensor kinase)-->YojN (phosphotransfer intermediate)-->RcsB (response regulator) phosphorelay signal transduction under certain growth conditions. Nonetheless, little is known about signals that exaggerate the Rcs-system. To gain insight into signals that activate the Rcs-system, here we searched for genes that activate the Rcs-system, provided that those on a multicopy plasmid were introduced into E. coli. We identified several such genes, namely, rcsB, rcsA, djlA, lolA, and ompG. The DjlA, LolA, and OmpG proteins are particularly interesting in that they are all located on the cell surface, where the primary sensor RcsC histidine-kinase is localized. Implications of these findings are discussed with special reference to the mechanism by which RcsC perceives external signals.

Bacterial Proteins↗
PubMed2001

Experimental and clinicopathologic study on the relationship between transcription factor Egr-1 and esophageal carcinoma.

AIM: To observe the growth suppression effect of exogenous introduction of early growth response gene-1 (Egr-1 gene) on esophageal carcinoma tissue as well as on esophageal carcinoma cell line Eca109 and to explore the potential application of Egr-1 gene in gene therapy of tumor. METHODS: Eukaryotic expression vector of PCMV-Egr-1 plasmid was introduced into Eca109 cell line which expressed no Egr-1 protein originally with lipofectamine transfection method. The introduction and expression of PCMV-Egr-1 plasmid into Eca109 cell line was confirmed by G418 selection culture, PCR amplification of neogene contained in the vector, Western blot analysis and immunocytochemical analysis. The cell growth curve, soft agar colony formation rate and tumorigenicity in SCID mice were examined to demonstrate the growth suppression effect of exogenous Egr-1 gene on Eca109 cell line. The Egr-1 mRNA and Egr-1 protein were also detected in 50 surgical specimens of esophageal carcinoma by in situ hybridization and immunohistochemistry. RESULTS: Exogenous Egr-1 gene was introduced successfully into Eca109 cell line and expressed Egr-1 protein stably. The transfected Eca109 cell line grew more slowly than control Eca109 as shown by cell growth curves, the soft agar colony formation rate (4.0% vs 6.9%, P < 0.01) and the average growth rate of tumor in SCID mice (35.5 +/- 7.6 vs 65.8 +/- 7.6, P < 0.05). The expression level of Egr-1 mRNA and protein significantly increased in dysplastic epithelia adjacent to cancer rather than in cancer tissues (65.8% vs 20.0% by ISH and 57.9% vs 0.01). CONCLUSION: Exogenous Egr-1 gene shows the strong effect of growth inhibition in Eca109 cell line. Egr-1 in the cancer tissue shows down-regulated expression that supports the inhibited function of Egr-1 in cancer growth and suggests Egr-1 may have an important role in gene therapy of esophageal carcinoma.

Animals↗
PubMed2001

Thyroidectomy or radioiodine? The value of ultrasonography and cytology in the assessment of nodular lesions in Graves' hyperthyroidism.

Although diffuse toxic goiter is a classical feature of Graves' disease (GD) nodular goiters are occasionally found in some patients. The aim of the present study was to investigate the ultrasonographic and corresponding cytological manifestations in GD patients with nodular lesions to decide on a therapeutic strategy. Twenty-seven consecutive GD patients with nodular goiter were included in this study (21 women and six men, mean age 41.2 years, range 22-77 years). All underwent thyroid ultrasonography and fine-needle aspiration cytology. Of the 27 patients eight underwent surgical intervention because papillary thyroid carcinoma or follicular neoplasm was diagnosed by cytology; five of these were shown to have papillary thyroid carcinomas. Ultrasonography revealed the malignant nodules to be hypoechogenic, heterogeneous, and with ill-defined margins in four of these five thyroid cancers, whereas the remaining sonogram showed a cystic change and cauliflower-like tumor formation with microcalcification. The volume and maximal diameter of cancerous nodules were significantly larger than those of benign nodules. In conclusion our results reveal that ultrasonography and fine-needle aspiration cytology are reliable and quick methods for diagnosing nodular goiters in GD patients. If thyroid neoplasms are found ablative therapy with thyroidectomy is indicated instead of radioactive iodine.

Adult↗
PubMed2000

Pathologic findings and prostate specific antigen outcome after radical prostatectomy for patients diagnosed on the basis of a single microscopic focus of prostate carcinoma with a gleason score </= 7.

BACKGROUND: Whether patients who are diagnosed on the basis of a single microscopic focus of prostate carcinoma with a Gleason score </= 7 (micro PC) have potentially life-threatening disease if they are not treated is unknown. METHODS: Pathologic findings and prostate specific antigen (PSA) outcome after radical prostatectomy (RP) for men who were diagnosed with micro PC were determined. Of 917 patients who were managed with RP during 1989-1999 at the Brigham and Women's Hospital, 66 patients (7%) were diagnosed on the basis of micro PC. Pathologic stage, tumor grade, tumor volume, margin status, and PSA outcome were investigated and are reported. Estimates of PSA outcome were calculated using the actuarial method of Kaplan and Meier. Pairwise comparisons were made using the log rank test. RESULTS: The finding of micro PC at biopsy was associated with macroscopic disease (involving at least half of a single lobe) in 92% of the patients in this series. Although these men had favorable pathologic findings (94% had organ confined disease, 89% had negative tumor margins, and 79% had a prostatectomy Gleason score </= 6), approximately 10% of the patients failed biochemically within 5 years after RP. CONCLUSIONS: The finding of micro PC at biopsy should not be used as a surrogate for clinically insignificant disease.

Biopsy↗
PubMed2000

Regulation of plasmodesmal transport by phosphorylation of tobacco mosaic virus cell-to-cell movement protein.

Cell-to-cell spread of tobacco mosaic virus (TMV) through plant intercellular connections, the plasmodesmata, is mediated by a specialized viral movement protein (MP). In vivo studies using transgenic tobacco plants showed that MP is phosphorylated at its C-terminus at amino acid residues Ser258, Thr261 and Ser265. When MP phosphorylation was mimicked by negatively charged amino acid substitutions, MP lost its ability to gate plasmodesmata. This effect on MP-plasmodesmata interactions was specific because other activities of MP, such as RNA binding and interaction with pectin methylesterases, were not affected. Furthermore, TMV encoding the MP mutant mimicking phosphorylation was unable to spread from cell to cell in inoculated tobacco plants. The regulatory effect of MP phosphorylation on plasmodesmal permeability was host dependent, occurring in tobacco but not in a more promiscuous Nicotiana benthamiana host. Thus, phosphorylation may represent a regulatory mechanism for controlling the TMV MP-plasmodesmata interactions in a host-dependent fashion.

Amino Acids↗
PubMed2000

Utilizing predictions of early prostate-specific antigen failure to optimize patient selection for adjuvant systemic therapy trials.

PURPOSE: Prostate-specific antigen (PSA) failure within 2 years after radical prostatectomy (RP) has been shown to be a clinically significant predictor of distant failure. This study was performed to estimate 2-year PSA failure rates on the basis of readily available clinical and pathologic factors to identify patients for whom effective adjuvant systemic therapy is needed. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies, PSA level, and the pathologic findings at RP in 1,728 men provided clinically relevant information about PSA outcome after RP. A bootstrapping technique with 2,000 replications was used to provide 95% confidence intervals for the predicted 2-year PSA failure rates, which were determined on the basis of the independent clinical and pathologic predictors of PSA outcome. RESULTS: The independent predictors of time to PSA failure included a percentage of positive prostate biopsies of greater than 34% (P: < or =.009), PSA level greater than 10 ng/mL (P: < or =.01), seminal vesicle invasion (P: =. 02), prostatectomy Gleason score of 8 to 10 (P: =.04), and positive surgical margins (P: =.0001). Predictions of 2-year PSA failure rates and bootstrap estimates of the 95% confidence intervals were arranged in a tabular format, stratified by independent clinical and pathologic predictors of PSA outcome. CONCLUSION: Patients who are most likely to benefit from effective adjuvant systemic therapy after RP can be identified using readily available clinical and pathologic data.

Biopsy↗
PubMed2000

Evaluation of stroke patients with the extended activities of daily living scale in Taiwan.

PURPOSE: This study examined the construct validity of the Nottingham Extended Activities of Daily Living scale (EADL) in stroke patients in Taiwan. METHODS: The EADL and the Barthel Index were administered via telephone interview. Minor revisions were made for the EADL to reflect cultural differences and the recommendations of two previous studies on the use of EADL. One hundred and fifty three stroke patients from the community participated in the study. RESULTS: Two items, 'make hot snack' and 'write letters', were deleted from the EADL because they appeared to be of little discriminative value. The results suggest that a changed hierarchical order was present among the domestic and leisure subscales. All of the subscales, then, fulfilled the Guttman scaling criteria (coefficient of reproducibility > 0.9, coefficient of scalability > 0.6). The scores of the revised EADL were significantly related to age and the Barthel Index scores (Spearman correlation coefficients = -0.41 and 0.69, respectively, p < 0.001). There was no significant difference between the overall scores of men and women (median = 10, 10, respectively, Mann-Whitney U test, p = 0.67). CONCLUSION: These data support the validity of the EADL with minor modifications in the evaluation of the functional performance in stroke patients in Taiwan and confirm it to be a useful outcome measure in stroke research.

Activities of Daily Living↗
PubMed2000

Histone deacetylases specifically down-regulate p53-dependent gene activation.

p53, the most commonly mutated gene in cancer cells, directs cell cycle arrest or induces programmed cell death (apoptosis) in response to stress. It has been demonstrated that p53 activity is up-regulated in part by posttranslational acetylation. In agreement with these observations, here we show that mammalian histone deacetylase (HDAC)-1, -2, and -3 are all capable of down-regulating p53 function. Down-regulation of p53 activity by HDACs is HDAC dosage-dependent, requires the deacetylase activity of HDACs, and depends on the region of p53 that is acetylated by p300/CREB-binding protein (CBP). These results suggest that interactions of p53 and HDACs likely result in p53 deacetylation, thereby reducing its transcriptional activity. In support of this idea, GST pull-down and immunoprecipitation assays show that p53 interacts with HDAC1 both in vitro and in vivo. Furthermore, a pre-acetylated p53 peptide was significantly deacetylated by immunoprecipitated wild type HDAC1 but not deacetylase mutant. Also, co-expression of HDAC1 greatly reduced the in vivo acetylation level of p53. Finally, we report that the activation potential of p53 on the BAX promoter, a natural p53-responsive system, is reduced in the presence of HDACs. Taken together, our findings indicate that deacetylation of p53 by histone deacetylases is likely to be part of the mechanisms that control the physiological activity of p53.

Acetylation↗
PubMed2000

Reduction of cardiac volume in left-breast treatment fields by respiratory maneuvers: a CT study.

PURPOSE: A previous study of healthy female volunteers suggested that deep inspiratory breath holding can reduce the cardiac volume in the treatment portals for left-breast cancer treatment. The reduction of irradiated cardiac volume may be important considering the reported late cardiac morbidity and mortality and the frequent coexistent use of potentially cardiotoxic chemotherapy in breast cancer patients. In the present study, we evaluated the heart volume in the fields and, thus, the true benefit of this respiratory maneuver in breast cancer patients undergoing CT simulation. MATERIALS AND METHODS: Fifteen patients (median age, 53) were studied. For each patient, CT scans were performed both when the patient breathed normally (quiet respiration) and when the patient held her breath after a deep inspiration. Tangential fields were planned using the same medial, lateral, superior, and inferior borders on skin for the normal breathing and the breath-holding configurations. The cardiac and left-lung volumes within the tangential fields were calculated for both breathing configurations. Multiple scan series were performed for the breath-holding configuration to provide a more accurate delineation of the cardiac tissue and to study the reproducibility of the patient's position between different cycles of deep inspiration. RESULTS: None of the patients had difficulty holding her breath for 20 s. The cardiac volume in the field was reduced (-86 +/- 24%; p < 0.001) when patients held their breath after a deep inspiration compared to when breathing normally. For 7 patients (47%), deep inspiration moved the heart completely out of the radiation fields. The expansion of the lung tissue due to deep inspiration also increased the absolute lung volume in the tangential fields (183 cm(3) vs 97 cm(3), p < 0.001). However, the fractional volume of the left lung in the field was essentially unchanged. For all but 1 patient, the maximum difference between the external body contours from different breath holding cycles was 5 mm and occurred at the lateral aspect of the breast. At the medial aspect, as indicated by the position of the midline marker, the variations were well within the currently accepted tolerance for patient positioning during tangential treatment. CONCLUSIONS: Deep-inspiration breath holding substantially reduces cardiac volume in the tangential fields for left-sided breast cancer treatment. The variation between patient positions at different cycles of breath holding was found to be reasonably small. Therefore, it appears feasible to reduce cardiac radiation by treating patients with intratreatment minifractions lasting 10-15 s while patients hold their breath.

Aged↗
PubMed2000

Risk factors for syncope in a community-based sample (the Framingham Heart Study).

The epidemiology of syncope has not been well described. Prior studies have examined risk factors for syncope in hospital-based or other acute or long-term care settings. To determine risk factors for syncope in a community-based sample, we performed a nested case-control study. We examined reports of syncope in Framingham Heart Study participants who underwent routine clinic visits from 1971 to 1990. For each syncope case (n = 543) 2 controls were matched for age, sex, and examination period. Mean age of subjects was 67 years (range 25 to 95); 59% were women. History of stroke or transient ischemic attack, history of myocardial infarction, high blood pressure, use of antihypertensive medication, use of other cardiac medication, smoking, alcohol intake, body mass index, systolic blood pressure, diastolic blood pressure, heart rate, atrial fibrillation, PR interval prolongation, interventricular block, and diabetes or elevated glucose level were examined as potential predictors. Using conditional logistic regression analysis, the predictors of syncope included a history of stroke or transient ischemic attack (odds ratio [OR] 2.56, 95% confidence interval [CI] 1.62 to 4.04), use of cardiac medication (OR 1.67, 95% CI 1.21 to 2. 30), and high blood pressure (OR 1.46, 95% CI 1.14 to 1.88). Lower body mass index was marginally associated with syncope (OR per 4 kg/m(2) decrement 1.10, 95% CI 0.99 to 1.22), as were increased alcohol intake (OR per 5 oz/week 1.11, 95% CI 0.99 to 1.26), and diabetes or an elevated glucose level (OR 1.29, 95% CI 0.96 to 1.75). To our knowledge, this study represents the first community-based study of risk factors for syncope.

Adult↗
PubMed2000

Paclitaxel and concurrent radiation for gastric cancer.

PURPOSE: To determine the activity and toxicity of paclitaxel and concurrent radiation for gastric cancer. METHODS AND MATERIALS: Twenty-seven patients were studied. Twenty-five had proximal gastric cancers, two had distal cancers. Eight had esophageal extension, 6 had celiac adenopathy, and 7 had retroperitoneal adenopathy. Patients received paclitaxel, 50 mg/m(2) by 3-hour intravenous (IV) infusion, weekly, on days 1, 8, 15, 22, and 29. Radiation was administered concurrently to a total dose of 45.0 Gy, in 1.80 Gy fractions, for 25 treatments. Patients who were medically or surgically inoperable received a sixth week of paclitaxel with a radiation boost to 50.4 Gy. RESULTS: Esophagitis and gastritis were the most important toxicities, Grade 3 in four patients (15%), and Grade 4 in three patients (11%). Five patients (19%) had Grade 3 nausea. The overall response rate was 56%, including three patients (11%) with a complete response. The 2-year progression-free and overall survival rates were 29% and 31%, respectively. CONCLUSION: Concurrent paclitaxel and radiation demonstrates substantial local-regional activity in gastric cancer. Future investigations combining paclitaxel and radiation with other local-regional and systemic treatments are warranted.

Aged↗
PubMed2000

Interaction between the tobacco mosaic virus movement protein and host cell pectin methylesterases is required for viral cell-to-cell movement.

Virus-encoded movement protein (MP) mediates cell-to-cell spread of tobacco mosaic virus (TMV) through plant intercellular connections, the plasmodesmata. The molecular pathway by which TMV MP interacts with the host cell is largely unknown. To understand this process better, a cell wall-associated protein that specifically binds the viral MP was purified from tobacco leaf cell walls and identified as pectin methylesterase (PME). In addition to TMV MP, PME is recognized by MPs of turnip vein clearing virus (TVCV) and cauliflower mosaic virus (CaMV). The use of amino acid deletion mutants of TMV MP showed that its domain was necessary and sufficient for association with PME. Deletion of the PME-binding region resulted in inactivation of TMV cell-to-cell movement.

Amino Acid Sequence↗
PubMed2000

Morphometric analysis of argyrophilic nucleolar organizer regions (AgNORs) in nasopharyngeal carcinoma.

BACKGROUND: Nucleolar organizer regions (NORs), which are loops of DNA containing ribosomal RNA genes, have been shown to correlate with cell proliferation and malignant transformation. Conventional eyeball measurement of silver staining NORs (AgNORs) is time-consuming and subject to error. The diagnostic value of AgNOR area in nasopharyngeal carcinoma (NPC) by computer-assisted morphometric analysis is evaluated. METHODS: Silver-staining of NORs was applied to 23 paraffin sections of NPC containing both normal squamous epithelial and malignant cells. Various parameters of the AgNORs of these two cell types were analyzed by a computer-assisted image analysis system and then compared. RESULTS: The mean AgNOR area, AgNOR/nuclear area ratio, and AgNOR area/count ratio of malignant tumors were statistically significantly higher than those for the normal epithelium. There was no significant difference in the AgNOR counts between the two cell types. CONCLUSIONS: Computer-assisted morphometric analysis of AgNOR is an objective and reliable assessment method applicable to paraffin sections of NPC. The AgNOR area and its derivatives may aid in the diagnosis of NPC.

Adult↗
PubMed2000

Endoscopic variceal ligation plus nadolol and sucralfate compared with ligation alone for the prevention of variceal rebleeding: a prospective, randomized trial.

Both beta-blockers and endoscopic variceal ligation (EVL) have proven to be valuable alternatives to sclerotherapy in the prevention of variceal rebleeding. Sucralfate is a mucosal protector. The effects of combinations of beta-blocker, band ligation, and sucralfate (triple therapy) remain unknown. A total of 122 patients with a history of esophageal variceal bleeding were randomized to receive EVL only (group A, 62 patients) or triple therapy (group B, 60 patients). The procedure for the triple therapy included ligation with the addition of sucralfate granules until variceal obliteration. In addition, nadolol was administered during the course of the study or until death. After a median follow-up of 21 months, recurrent upper gastrointestinal bleeding developed in 29 patients (47%) in group A and 14 patients (23%) in group B (P =.005). Recurrent bleeding from esophagogastric varices occurred in 18 patients in group A and 7 patients in group B (P =.001). Twenty-one patients in group A (50%) and 12 patients (26%) in group B experienced variceal recurrence after variceal obliteration (P <.05). Treatment failure occurred in 11 patients (18%) in group A and in 4 patients (7%) in group B (P =.05). Twenty patients from group A and 10 patients from group B died (P =.08); 9 and 4 of these deaths, respectively, were attributed to variceal hemorrhage (P =.26). The combination of ligation, nadolol, and sucralfate (triple therapy) proved more effective than banding ligation alone in terms of prevention of variceal recurrence and upper gastrointestinal rebleeding as well as variceal rebleeding.

Adrenergic beta-Antagonists↗
PubMed2000

Peroxisome proliferator-activated receptor gamma 2 Pro12Ala gene variant is strongly associated with larger body mass in the Taiwanese.

The peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) has been studied extensively because of its putative role in adipocyte differentiation and insulin sensitivity. The association of the Pro12Ala and Pro115Gln PPARgamma2 gene variants with type 2 diabetes mellitus, the body mass index (BMI), and other diabetes-related phenotypes was examined in the Taiwanese population. Genotypes were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. Allele frequencies were compared between 280 subjects with type 2 diabetes mellitus and 310 subjects without diabetes using the chi-square test. Continuous phenotype analysis was performed by multiple logistic regression adjusting for age and BMI where appropriate. There was no significant association between the Pro12Ala gene variant and type 2 diabetes; the frequency of the Ala12 allele was 0.03 in type 2 diabetics and 0.04 in nondiabetics (P = .40). The Gln115 allele was not detected in any of the cases or controls. In multiple linear regression analysis of all cases and controls combined adjusted for age, sex, and diabetic status, carriers of the Ala12 allele had a mean BMI of 25.9+/-0.5 kg/m2 (mean +/- SE), compared with 24.2+/-0.1 kg/m2 in Pro12 homozygotes (P < .001). In addition, carriers of the Ala12 allele have a 2.9 times (95% confidence interval [CI], 1.5 to 5.5) higher odds of having a BMI of at least 25 kg/m2. These results suggest that in the Taiwanese, the Pro12Ala PPARgamma2 gene variant may contribute to fat accumulation and a higher BMI independent of type 2 diabetes. These results need to be confirmed in future studies, as a linkage disequilibrium of this variant with other mutations cannot be ruled out.

Adult↗