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J T Chang

Publications and source records attributed to J T Chang.

53 records · Page 3Linked to original sources
PubMed1997

Using the radial distributions of physical features to compare amino acid environments and align amino acid sequences.

We have performed a comprehensive analysis of the microenvironments surrounding the twenty amino acids. Our analysis includes comparison of amino acid environments with random control environments as well as with each of the other amino acid environments. We describe the amino acid environments with a set of 21 features summarizing atomic, chemical group, residue, and secondary structural features. The environments are divided into radial shells of 1 A thickness to represent the distance of the features from the amino acid C beta atoms. We make the results of our analysis available graphically over the world wide web. To illustrate the validity and utility of our analysis, we used the amino acid comparative profiles to construct a substitution matrix, the WAC matrix, based on a simple summary of the computed environmental differences. We compared our matrix to BLOSUM62 and PAM250 in BLAST searches with query sequences selected from 39 protein families found in the PROSITE database. Although BLOSUM62 was the most sensitive matrix overall, our matrix was more sensitive for some families, and exhibited overall performance similar to PAM250. Our results suggest that the radial distribution of biochemical and biophysical features is useful for comparing amino acid environments, and that similarity matrices based on the geometric distribution of features around amino acids may produce improved search sensitivity.

Amino Acid Sequence↗
PubMed1996

The role of brachytherapy in early-stage nasopharyngeal carcinoma.

PURPOSE: To present the treatment results and assess the optimal radiation dose and the role of brachytherapy in early stage nasopharyngeal cancer (NPC). METHODS AND MATERIALS: One hundred eighty-three patients with Stage I and II (American Joint Committee on Cancer Staging System, 1987) NPC completed the planned radiotherapy in our institution from 1979 to 1991. In 133 patients, radiotherapy was given to the nasopharynx by external beam to 64.8-68.4 Gy. Further boost was done by high dose rate (HDR) brachytherapy for 5-16.5 Gy in one to three fractions. For the remaining 50 patients, a course of external radiotherapy to the nasopharynx for 68.4-72 Gy was given to nasopharynx. Age (>40 or not), sex, neck boost or not, brachytherapy, and irradiation dose were analyzed to determine significant factors that influence the probabilities of local control and actuarial survival. RESULTS: The 5-year disease-specific survival was 85.8% and local control was 83%. Only the brachytherapy and irradiation dose significantly affected the results. The use of the brachytherapy had significant impact on overall survival and local control. Furthermore, we compared the prognostic effect of various radiation dosage among Group I of 50 patients (<72.5 Gy, no brachytherapy, excluding four patients who received brachytherapy), Group II of 71 patients (72.5-75 Gy; one to two fractions of brachytherapy), and Group III of 58 patients (>75 Gy; three fractions of brachytherapy). Five-year disease-specific survival rates of Group I, Group II, and Group III were 77, 95.5, and 82.4%, respectively. Five-year local control rates were: 73.7, 93.9, and 79.5%. We found that the Group II had the best actuarial survival and local control rate (log-rank test,p < 0.05). Most patients receiving brachytherapy encountered foul odor because of nasopharynx crust; 12 of them had palate or sphenoid sinus floor perforation or nasopharynx necrosis. None of the patients without brachytherapy experienced the same complications. CONCLUSIONS: The optimal radiotherapy dose to the nasopharynx area in early stage NPC may be within 72.5 to 75 Gy by our treatment protocol. A dose of more than 75 Gy did not have significant local control or survival advantage. The use of brachytherapy to elevate radiation dose had significant local control and survival benefit for early stage NPC patients, but the fractionation size should be decreased to reduce the complications.

Adult↗
PubMed1996

Full reconstruction of Markov models on evolutionary trees: identifiability and consistency.

A Markov model of evolution of characters on a phylogenetic tree consists of a tree topology together with a specification of probability transition matrices on the edges of the tree. Previous work has shown that, under mild conditions, the tree topology may be reconstructed, in the sense that the topology is identifiable from knowledge of the joint distribution of character states at pairs of terminal nodes of the tree. Also, the method of maximum likelihood is statistically consistent for inferring the tree topology. In this article we answer the analogous questions for reconstructing the full model, including the edge transition matrices. Under mild conditions, such full reconstruction is achievable, not by using pairs of terminal nodes, but rather by using triples of terminal nodes. The identifiability result generalizes previous results that were restricted either to characters having two states or to transition matrices having special structure. The proof develops matrix relationships that may be exploited to identify the model. We also use the identifiability result to prove that the method of maximum likelihood is consistent for reconstructing the full model.

Animals↗
PubMed1996

Inconsistency of evolutionary tree topology reconstruction methods when substitution rates vary across characters.

A fundamental problem in reconstructing the evolutionary history of a set of species is to infer the topology of the evolutionary tree that relates those species. A statistical method for estimating such a topology from character data is called consistent if, given data from more and more characters, the method is sure to converge to the true topology. A number of popular methods are based on modeling the evolution of each character as a Markov process along the evolutionary tree. The standard models further assume that each character has in fact evolved according to the same Markov process. This homogeneity assumption is unrealistic; for example, different types of characters are known to experience substitutions at different rates. Certain distance and maximum likelihood methods for topology estimation have been shown to be consistent under the homogeneity assumption. Here we give examples showing that these methods can fail to be consistent when the homogeneity assumption is relaxed. The examples are very simple, requiring only four taxa, binary characters, and characters that evolve at two different rates.

Animals↗
PubMed1996

Role of oxidative DNA damage in hydroxychavicol-induced genotoxicity.

Chewing betel quid has been linked to the development of oral cancer. In Taiwan, fresh Piper betle inflorescence is uniquely added to betel quid, and hydroxychavicol is the major phenolic components of P.betle inflorescence. In this study, we tested the mutagenic potential of hydroxychavicol in Salmonella typhimurium TA97, TA98, TA100 and TA102 with and without Aroclor-1254 induced S9 fraction. The results showed that hydroxychavicol was positive in S.typhimurium TA102 without metabolic activation. This increase in revertants was partially inhibited by catalase and superoxide dismutase. In Chinese hamster ovary (CHO-K1) cells, hydroxychavicol induced chromosome aberrations in a dose-dependent manner (10-50 microM) and the majority were chromosome-type aberrations. Hydroxychavicol also significantly increased the frequency of micronuclei in CHO-K1 cells up to 3-fold at a concentration of 40 microM. In addition, hydroxychavicol dose-dependently (0.1-20 microM) induced copper-dependent strand breaks in plasmid DNA. We further tested the oxidative DNA damage potential of hydroxychavicol by measuring 8-hydroxydeoxyguanosine (8-OH-dG) formation in CHO-K1 cells following an 18-h incubation and found that hydroxychavicol (6.25-100 microM) induced 8-OH-dG levels dose-dependently. The increase of 8-OH-dG formation was positively correlated (r = 0.79) with the hydroxychavicol-induced cytotoxicity. In conclusion, hydroxychavicol may exert its genotoxic potential through oxidative DNA damage.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1995

Steady-state mRNA levels of G protein subunits in developing rabbit myocardium.

Cardiac responsiveness to beta-adrenergic stimulation changes with age. Developmental changes in expression of guanine nucleotide-binding coupling protein (G protein) subunits may account for these physiologic changes. We measured steady-state levels of mRNA encoding the alpha-subunit of the specific G protein that stimulates adenylyl cyclase (Gs alpha) and three isoforms of beta-subunit of G proteins (G beta) in developing myocardium. Total RNA prepared from the right and left ventricles of fetal, neonatal, juvenile, and adult rabbits was size-fractionated, blotted, and probed with 32P-labeled cDNAs encoding rat Gs alpha, bovine G beta-1, human G beta-2, and human G beta-3. For standardization, these blots were subsequently hybridized with a 32P-labeled cDNA encoding glyceraldehyde 3-phosphate dehydrogenase (GAPD). Two-dimensional densitometric analysis of autoradiographs was used to quantify relative hybridization intensities. An age-dependent decrease in mRNAs encoding Gs alpha, G beta-1, and G beta-2 relative to mRNA encoding GAPD was observed in both ventricles, while G beta-3 mRNA was not detected. At all ages studied, levels of Gs alpha and G beta-1 mRNA were similar in the two ventricles. However, G beta-2 mRNA declined more in the left ventricle than in the right ventricle during maturation. Our results demonstrate developmental control in heart for mRNAs encoding several G protein subunits. In addition, differential declines in G beta-1 and G beta-2 mRNA in the right ventricle suggest that these G beta isoforms are regulated uniquely and may reflect functional roles for these G beta isoforms in different signaling cascades.

Adenylyl Cyclases↗
PubMed1995

Inhibition of translation initiation on Escherichia coli gnd mRNA by formation of a long-range secondary structure involving the ribosome binding site and the internal complementary sequence.

Previous research has indicated that the growth rate-dependent regulation of Escherichia coli gnd expression involves the internal complementary sequence (ICS), a negative control site that lies within the 6-phosphogluconate dehydrogenase coding sequence. To determine whether the ICS acts as a transcriptional operator or attenuator, we measured beta-galactosidase-specific activities in strains carrying gnd-lac operon and protein fusions containing or lacking the ICS. Whereas the presence of the ICS repressed beta-galactosidase expression from a protein fusion by 5-fold during growth on acetate and by 2.5-fold during growth on glucose, it had no effect on beta-galactosidase expression from an operon fusion. In vitro ribosome binding experiments employing the primer extension inhibition (toeprint) assay demonstrated that the presence of the ICS in gnd mRNA reduces both the maximum extent and the rate of ternary complex formation. Moreover, the effects of deletions scanning the ICS on in vivo gene expression were highly correlated with the effects of the deletions on ribosome binding in vitro. In addition, the distal end of the ICS element was found to contribute more to ICS function than did the proximal portion, which contains the complement to the Shine-Dalgarno sequence. Finally, RNA structure mapping experiments indicated that the presence of the ICS in gnd mRNA reduces the access of the nucleotides of the ribosome binding site to the single-strand-specific chemical reagents dimethyl sulfate and kethoxal. Taken together, these data support the hypothesis that the role of the ICS in the growth rate-dependent regulation of gnd expression is to sequester the translation initiation region into a long-range mRNA secondary structure that blocks ribosome binding and thereby reduces the frequency of translation initiation.

Acetates↗
PubMed1995

COPD in the elderly. A reversible cause of functional impairment.

OBJECTIVES: To determine the frequency of referral of patients age 69 years and older to the pulmonary function laboratory at a tertiary-care hospital for airflow limitation studies; to determine the point prevalence of a significant reversible component in patients with COPD as an age-related function; and to determine the proportion of patients who were prescribed bronchodilators following a pulmonary function test (PFT) demonstrating significant reversibility. DESIGN: A retrospective review of pulmonary function tests of patients 69 years and older within calendar year 1990 was performed. Chart review of those showing significant reversibility to bronchodilators during a PFT was performed to determine level of follow-up. SETTING: Referral-based pulmonary division in a tertiary-care hospital. PATIENTS: Men and women 69 years and older who had interpretable PFTs at Northwestern Memorial Hospital (NMH) during the calendar year 1990 (n = 405). Patients whose PFTs were uninterpretable due to poor effort (n = 10) were excluded from the study. INTERVENTIONS: No specific interventions were performed as a part of the study. Referring physicians may have requested a PFT with postbronchodilator (albuterol by nebulizer) testing and may have subsequently prescribed bronchodilators for their patients. MEASUREMENTS: We studied the effect of age, gender, smoking history, and degree of airflow obstruction on changes in spirometry values and reversibility status after bronchodilator (if applicable) as determined by a PFT. MAIN RESULTS: Of the 405 consecutive elderly patients studied, 193 (47.7%) received bronchodilators and 60 (31.1%) of these patients had significant improvement as judged by the criteria listed in the Methods section. The improvement occurred equally across all age groups (p > 0.05) and the percent responding to bronchodilators increased as the degree of obstruction increased (p < 0.001). Those who had never smoked were twice as likely to respond than were current or former smokers; men were more likely to respond than women. Most patients (84%) who responded were subsequently prescribed bronchodilators. CONCLUSIONS: Responses to inhaled bronchodilators occur at all ages. Older patients showed greater reversibility as the degree of obstruction increased, while a smoking history reduced the likelihood of a bronchodilator response. COPD in the elderly may differ from the traditional form of the disease.

Administration, Inhalation↗
PubMed1992

Identification of beta-subunit of GTP-binding regulatory protein in mitotic spindle.

BACKGROUND: The heterotrimeric GTP-binding regulatory protein (G protein) is important in membrane signal transduction. Since the function of the beta-subunit of G protein (G beta) in tumor cells is not well-documented, identification of G beta in tumor cells was performed. EXPERIMENTAL DESIGN: Immunolocalization, Western blotting, and immunoprecipitation of G beta in mammalian tumor and normal cells were investigated using rabbit antisera against amino and carboxyl terminal peptide fragments of G beta. A human nasopharyngeal carcinoma cell line (NPC-TW039) was used as the cell model because of its short doubling time. RESULTS: Anti-G beta immunoreactivity was found to be associated with the plasma membrane and the mitotic spindle throughout the mitotic phase of cell replication. Colcemid pretreatment resulted in random distribution of the anti-G beta reaction product in the mitotic cells. The same phenomenon was also seen in various other tumor and normal cell lines. When solubilized membranous, cytosolic, and mitotic spindle fractions were analyzed by Western blotting, G beta (35 +/- 1 kDa) was found to be associated with the plasma membrane and mitotic spindle fractions. Immunoprecipitation of isolated mitotic spindles with anti-G beta further confirmed these results. CONCLUSIONS: These findings indicate that G beta is closely associated with the mitotic spindle as well as the plasma membrane and may be important in regulation of cell mitosis in addition to transmembrane signal transduction.

Amino Acid Sequence↗
PubMedDate not supplied

MRI of nasopharyngeal carcinoma with emphasis on relationship to radiotherapy.

MRI has been used increasingly in the evaluation of nasopharyngeal carcinoma (NPC) because of its good tissue contrast and multiplanar capacity. Although there are some controversies in assessing skull base invasion and cervical metastatic adenopathy, recent reports demonstrate that MRI is currently better than or as good as CT in defining the extent of NPC. During follow-up of patients with NPC after radiotherapy, MRI is also more effective than CT in demonstrating tumor recurrence and in detecting postradiation complications. However, the difficulty of using MRI to detect early mucosal recurrence and to differentiate postradiation tissue changes from local tumor recurrence should be recognized. This paper reviews the literature regarding MRI of NPC related to radiotherapy, with special emphasis on treatment planning, recurrence assessment, and complication detection.

Carcinoma↗
PubMedDate not supplied

Sugar content of selected pharmaceuticals.

Medications may contain significant amounts of various sugars. Data provided by 67 manufacturers have been tabulated to provide specific qualitative and quantitative information on sugar content of selected drug products. Since diabetic individuals may tolerate various sugar forms differently, it is useful to know specific sugar forms and content present in medications. This listing should prove to be a convenient guide to clinicians caring for diabetic individuals.

Carbohydrate Metabolism↗
PubMedDate not supplied

Non-invasive thermal assessment of tissue phantoms using an active near field microwave imaging technique.

An active microwave imaging system for non-invasive temperature sensing has been developed and evaluated. The system is designed to assess biological tissues undergoing thermal therapy. This paper presents results that demonstrate the imaging capabilities of the microwave method using simulated and experimental phantom materials. Results from both numerical studies and laboratory experiments have been analysed and are presented. The imaging system uses a 16 channel fixed monopole array transceiver unit operating over a bandwidth of 300-900 MHz. The annular array diameter is 14.75 cm and is immersed in a 0.9% saline solution. Standard heterodyning principles are used for signal detection leading to a dynamic range of the system of better than 115dB. Image formation is accomplished with a 2-D finite element based, near-field iterative technique. This allows the simultaneous reconstruction of both the real and imaginary components of the dielectric property distribution in tissue equivalent phantoms. Data acquisition currently captures 144 complex field measurements per image. Image reconstruction requires approximately 2 min per iteration with a typical convergence in less than 10 steps. Experiments performed to evaluate the temperature dependence of biological phantoms (saline with variable salt concentrations) are described. The numerical accuracy and precision of the reconstruction algorithm based upon these phantom studies are presented. Simple laboratory models of localized hyperthermia have been used to evaluate the experimental accuracy and precision of the imaging system. A numerical precision of 0.02 degrees C and an accuracy of 0.37 degrees C have been observed with the current algorithm. In laboratory experiments, images have been reconstructed at different target temperatures and target saline concentrations. The effect of placing high contrast biological phantoms (i.e. bone/fat simulants) along with the heated objects have also been studied. Localized heating of the biological phantom is achieved by pumping a saline solution of pre-selected concentration through enclosed ends of hollow dielectric cylinders having approximately 5cm inner diameter and 4 mm wall thickness. The temperature of the heated zone is preset and maintained to +/-0.2 degrees C by an external heater and circulator. The results currently show that a maximum temperature precision of 0.98 degrees C and maximum relative accuracy of 0.56 degrees C has been achieved in the laboratory using the current generation of the prototype system.

Algorithms↗