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Biomedical subjects

C Chang

Publications and source records attributed to C Chang.

At least 91 records · Page 5Linked to original sources
PubMed2000

Crystal structure of NAD(+)-dependent DNA ligase: modular architecture and functional implications.

DNA ligases catalyze the crucial step of joining the breaks in duplex DNA during DNA replication, repair and recombination, utilizing either ATP or NAD(+) as a cofactor. Despite the difference in cofactor specificity and limited overall sequence similarity, the two classes of DNA ligase share basically the same catalytic mechanism. In this study, the crystal structure of an NAD(+)-dependent DNA ligase from Thermus filiformis, a 667 residue multidomain protein, has been determined by the multiwavelength anomalous diffraction (MAD) method. It reveals highly modular architecture and a unique circular arrangement of its four distinct domains. It also provides clues for protein flexibility and DNA-binding sites. A model for the multidomain ligase action involving large conformational changes is proposed.

Amino Acid Sequence↗
PubMed2000

Temporal changes of cerebral metabolites and striatal lesions in acute 3-nitropropionic acid intoxication in the rat.

To investigate the mechanisms of neuronal death in neurodegeneration, in vivo localized proton magnetic resonance spectroscopy ((1)H-MRS) and diffusion-weighted MRI (DWI) were used to evaluate temporal changes in rat striata after administration of 3-nitropropionic acid. It was found that N-acetylaspartate (NAA) reduction, with nearly simultaneous evidence of striatal lesions in DWI, was preceded by a significant and progressive increase of acetate. Shortly before the NAA levels decreased to the lowest point, acetate levels peaked and began to gradually decline toward the control levels. These results suggest that acetate increase may arise from fatty acid degradation, inhibition of succinate dehydrogenase and possible NAA hydrolysis. The elevated acetate may provide a source of acetyl group for membrane repair during excitotoxic brain injury. Magn Reson Med 44:29-34, 2000.

Acetates↗
PubMed2000

Comparison of a single half-dose, long-acting form of gonadotropin-releasing hormone analog (GnRH-a) and a short-acting form of GnRH-a for pituitary suppression in a controlled ovarian hyperstimulation program.

OBJECTIVE: To compare the effect of a single low-dose leuprolide acetate depot (LA depot) and leuprolide acetate (LA) on pituitary down-regulation in women undergoing controlled ovarian hyperstimulation (COH). DESIGN: Retrospective study. SETTING: An IVF unit of an academic medical center. PATIENT(S): Women who underwent COH and IVF-ET. INTERVENTION(S): Pituitary down-regulation with half-dose LA depot (1.88 mg sc, group 1) or LA (0.5 mg/d sc, group 2) was started on menstrual days 21-23. MAIN OUTCOME MEASURE(S): The concentrations of estradiol (E(2)), FSH, LH, gonadotropin dosages, the numbers of oocytes retrieved, oocytes fertilized and embryos transferred, and pregnancy rates of the two groups were compared. RESULT(S): A total of 289 patients in group 1 and 158 in group 2 were included. There were no statistically significant differences between the two groups in baseline concentrations of E(2) and FSH, concentrations of E(2), FSH, and LH during hCG administration, gonadotropin dosage, the number of oocytes retrieved, the number of oocytes fertilized and embryos transferred, and pregnancy rates. CONCLUSION(S): Single half-dose LA depot offers a useful alternative for pituitary suppression in ovarian stimulation for IVF.

Adult↗
PubMed2000

Cryopreservation of human spermatozoa within human or mouse empty zona pellucidae.

OBJECTIVE: To compare the empty zona pellucidae (ZP) of different species for use in the cryopreservation of spermatozoa. DESIGN: Prospective study. SETTING: An IVF unit of a medical center. PATIENT(S): Patients with azoospermia, oligoasthenozoospermia, or normal spermatozoa. INTERVENTION(S): Human and mouse ZP were prepared by evacuating the cytoplasm of oocytes or embryos. The evacuated ZP were injected with spermatozoa from patients with severe oligoasthenozoospermia and from healthy, fertile men. After the freezing and thawing procedure, the spermatozoa were aspirated outside the ZP. MAIN OUTCOME MEASURE(S): The number of spermatozoa per ZP, the number of motile sperm before freezing and after thawing, the number of sperm lost per ZP after freezing, and the sperm recovery rate were compared according to the different origins of the ZP and the sperm. RESULT(S): The number of spermatozoa, number of motile sperm before freezing and after thawing, number of sperm lost per ZP, and sperm recovery rate were comparable in all groups. The total mean number of motile sperm before freezing and after thawing, the mean number of nonmotile sperm after thawing, the mean number of sperm lost after thawing, and the sperm recovery rate were 14.5%, 11. 8%, 1.0%, 1.5%, and 82%, respectively. CONCLUSION(S): Zona pellucidae are an ideal vehicle for the cryopreservation of sperm collected by testicular sperm extraction or microsurgical epididymal sperm aspiration or from patients with severe oligoasthenozoospermia. There were no differences when human and mouse ZP were used for sperm storage.

Animals↗
PubMed2000

Epidemiologic study of type 2 diabetes in Taiwan.

Diabetes mellitus (DM) in adults is a global health problem, although its prevalence varies widely between different populations and the rate has generally increased worldwide. In Taiwan, the mortality rate from DM has almost doubled over the past 10 years. The prevalence of DM in Taiwan was established between 1985 and 1996 and the rates were between 4.9 and 9.2%. The prevalence of impaired glucose tolerance (IGT) was 15.5% (men 15% and women 15.9%). The prevalence of DM and IGT increased significantly with age for both genders. The significant factors associated with newly diagnosed DM were age, BMI, family history of DM, systolic blood pressure (hypertension), physical activity and serum triglyceride levels. The prevalence of large vessel disease (LVD) in DM and non-diabetic subjects were 20.0 and 12.9%, respectively. Among diabetics, 15.8% had ischemic heart disease (IHD), 1.7% leg vessel disease (leg VD), and 2.5% stroke. In non-diabetics, the prevalence of the aforementioned macroangiopathies were 11.5, 0.2 and 1.2%, respectively. The diabetics had a significantly higher prevalence of macrovascular disease than non-diabetic subjects. The most significantly associated with the LVD was serum cholesterol levels. Serum cholesterol and HbA1(c) were significantly associated with the development of IHD. Cigarette smoking and female gender were significantly associated with the leg VD. The prevalence of diabetic retinopathy (DR) was 35.0%. (background DR 30%, preproliferative DR 2.8% and proliferative DR 2.2%, respectively.) The prevalence of DR for previously and newly diagnosed diabetics were 45.2 and 28.3% (men 42.8 vs. 33.3% and women 47.5 vs. 24.8%), respectively. From multiple logistic regression analysis, duration of DM was the most important risk factor related to DR. Diabetic subjects treated with insulin had a higher risk of developing retinopathy than those treated with dietary control. The prevalence of nephropathy and neuropathy were 12.9 and 23.5%, respectively. For those patients with and those without nephropathy and neuropathy, the duration of DM, percentage of insulin treatment, percentage of hypertension, and fasting plasma glucose were significantly different. Diabetic duration, hypertension, insulin treatment and glycemic control consistently correlated with nephropathy and neuropathy. In conclusion, the prevalence of DM in Taiwan was between 4.9 and 9.2%, and the prevalence of IGT was 15.5%. The possible risk factors of newly diagnosed diabetes were age, family history of DM, BMI, SBP (hypertension), physical activity and triglyceride levels. Diabetes in Chinese subjects share many characteristics similar to other Asian populations. The burden imposed by the chronic complications of diabetes is massive. In Taiwan, the mortality rates from DM have increased greatly over the past 10 years. Reduction of the modificable risk factors such as BMI, hypertenion and dyslipidemia, and increase of physical activity and good glycemic control through public health efforts may help to reduce the risk of DM and its chronic complications.

Adult↗
PubMed2000

Fetal renal volume in normal gestation: a three-dimensional ultrasound study.

To establish a reference chart of fetal kidneys in normal pregnancy, we performed a prospective and cross-sectional study. A total of 152 singleton fetuses ranging between 20 and 40 weeks' gestation and meeting the criteria of normal pregnancies were included. Three-dimensional ultrasound (3-D US) was used to measure the fetal renal volume. Our results revealed that both renal volumes are highly correlated with the fetal gestational age. Using gestational age (GA) as the independent variable and right renal volume (RRV) as the dependent variable, the best-fit regression equation was RRV (mL)=0.74053xGA (week)-13.318 (r = 0.89, p < 0.001). Similarly, the best-fit equation for the left renal volume (LRV) was LRV (mL)=0. 76093xGA (week)-13.421 (r = 0.86, p < 0.001). The normal growth centiles of both kidneys were established based on these two equations. There were no significant differences of the volumes between bilateral kidneys. In conclusion, our data of fetal renal volumes assessed by 3-D US may serve as a reference in evaluating fetal renal growth.

Cross-Sectional Studies↗
PubMed2000

Neuroprotective effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid: evaluation by magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy.

Magnetic resonance imaging and in vivo proton magnetic resonance spectroscopy were used to evaluate the therapeutic effect of lamotrigine and MK-801 on rat brain lesions induced by 3-nitropropionic acid. Systemic administration of 3-nitropropionic acid (15 mg/kg per day) to two-month-old Sprague-Dawley rats (n = 10 for each group) for five consecutive days induced selective striatal and hippocampal lesions and specific behavioral change. Pretreatment with lamotrigine (10 mg/kg or 20 mg/kg per day) or MK-801 (2 mg/kg per day) attenuated the lesions and behavioral change. There were no significant differences in T2 values of the striatum and hippocampus among rats pretreated with MK-801, lamotrigine (20 mg/kg) and sham controls. Significant elevations of succinate/creatine and lactate/creatine ratios and decreases of N-acetylaspartate/creatine and choline/creatine ratios were observed after 3-nitropropionic acid injections (P < 0.001). The changes were nearly prevented after pretreatment with lamotrigine (20 mg/kg). However, the N-acetylaspartate/creatine in rats pretreated with lamotrigine (10 mg/kg) (P < 0.01) and MK-801 (P < 0.05) still showed significant reduction as compared with sham controls. Thus we conclude that both lamotrigine and MK-801 are effective in attenuation of brain lesions induced by 3-nitropropionic acid. A higher dose of lamotrigine provides a better neuroprotective effect than MK-801. With a better therapeutic effect and fewer side effects, lamotrigine is more promising for potential clinical application.

Animals↗
PubMed2000

Lack of androgen receptor transcriptional activity in human keratinocytes.

Since detection of androgen receptor (AR) expression in keratinocytes by immunostaining is controversial, we investigated whether keratinocytes can act as androgen target cells using transient transfection assays. Chloramphenicol acetyltransferase (CAT) assays for the endogenous AR transcriptional activity in HaCaT keratinocytes indicated that DHT (10(-9)-10(-8) M) can induce less than 1.5-fold of mouse mammary tumor virus CAT, which is quite low, compared with 38-fold induction by 10(-7) M 1,25-dihydroxyvitamin D(3) of P450cc24-CAT. Furthermore, this low DHT-mediated induction could not be enhanced by the AR co-activators, ARA70 or ARA55. Western blotting analysis indicated that HaCaT and normal keratinocytes do not express AR protein. Transfection of exogenous AR into HaCaT keratinocytes, however, could install AR transcriptional activity, suggesting that HaCaT keratinocytes have all the necessary accessory factors for AR transcription activity. In conclusion, keratinocytes are unlikely to be target cells for androgen.

Animals↗
PubMed2000

A post-mid-blastula transition requirement for TGFbeta signaling in early endodermal specification.

In Xenopus, endodermal cell fate is determined gradually from late blastula to early gastrula stages; cell-cell interaction plays an important role in this process. Here we use a cell dissociation assay to show that extracellular signaling is required continuously before endoderm determination. Activin and Vg1, but not BMP2 or basic FGF, rescue the expression of endodermal markers in dissociated cells when provided at the mid-blastula transition (MBT, the time in which zygotic transcription begins). Removal of exogenously added activin or Vg1 before MBT results in reduction of endodermal gene expression in dissociated vegetal cells. In vivo, endogenous endodermal markers are reduced in vegetal explants when activin-like signaling is blocked with dominant negative receptors. VegT, a maternal transcription factor shown to be critical for endoderm specification, relies on an active TGFbeta pathway to induce endoderm in animal caps. These results indicate that TGFbeta signaling may be activated by the maternally expressed VegT to participate in endoderm determination. In addition, VegT function seems to be required in parallel with the TGFbeta pathway, as overexpression of activin does not relieve endoderm repression by a dominant negative VegT mutant in vegetal cells. Our data suggest that maternal VegT first activates a zygotic TGFbeta signal, then cooperates with this signal to determine the endodermal cell fate.

Activins↗
PubMed2000

A computer-aided design mammography screening system for detection and classification of microcalcifications.

This paper presents a prototype of a computer-aided design (CAD) diagnostic system for mammography screening to automatically detect and classify microcalcifications (MCCs) in mammograms. It comprises four modules. The first module, called the Mammogram Preprocessing Module, inputs and digitizes mammograms into 8-bit images of size 2048x2048, extracts the breast region from the background, enhances the extracted breast and stores the processed mammograms in a data base. Since only clustered MCCs are of interest in providing a sign of breast cancer, the second module, called the MCCs Finder Module, finds and locates suspicious areas of clustered MCCs, called regions of interest (ROIs). The third module, called the MCCs Detection Module, is a real time computer automated MCCs detection system that takes as inputs the ROIs provided by the MCCs Finder Module. It uses two different window sizes to automatically extract the microcalcifications from the ROIs. It begins with a large window of size 64x64 to quickly screen mammograms to find large calcified areas, this is followed by a smaller window of size 8x8 to extract tiny, isolated microcalcifications. Finally, the fourth module, called the MCCs Classification Module, classifies the detected clustered microcalcifications into five categories according to BI-RADS (Breast Imaging Reporting and Data System) format recommended by the American College of Radiology. One advantage of the designed system is that each module is a separate component that can be individually upgraded to improve the whole system. Despite that it is still is a prototype system a preliminary clinical evaluation at TaiChung Veterans General Hospital (TCVGH) has shown that the system is very flexible and can be integrated with the existing Picture Archiving and Communications System (PACS) currently implemented in the Department of Radiology at TCVGH.

Algorithms↗
PubMed2000

Differential regulation of testosterone vs. 5alpha-dihydrotestosterone by selective androgen response elements.

There are two major physiological androgens, testosterone (T), and 5alpha-dihydrotestosterone (DHT), which induce different responses in mammals. These androgens regulate the target gene transcription via binding to and activating the same androgen receptor (AR). The molecular mechanisms that differ between these two very close androgens through the same AR protein to target the distinct genomic responses remain unknown. Using yeast genetic selection, we identified two kinds of androgen response elements (ARE), which could respond differentially to T vs. DHT. These two AREs also show different T- vs. DHT-induced AR transactivation in mammalian Chinese hamster ovary (CHO) cells in terms of copy number and comparisons with the classic mouse mammary tumor virus ARE. Together, our results suggest that the selective ARE sequence may play an important role in the differential T- vs. DHT-induced AR transactivation.

Animals↗
PubMed2000

Differential contribution of the conserved tyrosine residues to activity and structural stability of Ophiophagus hannah alpha-neurotoxins.

Two alpha-neurotoxins, Oh-4 and Oh-7, from king cobra (Ophiophagus hannah) venom were subjected to Tyr modification with tetranitromethane. Selective nitration of Tyr4 in Oh-4 caused a slight decrease in lethal toxicity of 11% and a decrease in nicotinic acetylcholine receptor (nAchR)-binding activity of 28%, whereas nitration of Tyr4 in Oh-7 resulted in an approximately equal 60% decrease in lethality and nAchR-binding activity. When the Tyr23 in Oh-4 or Tyr22 in Oh-7 appears to be 'buried' in the toxin following further modification, the toxins lost their biological activity and conformational change concurrently. Nevertheless, the dinitrated Oh-4 retained a beta-sheet structure as revealed by CD spectra and exhibited a precipitin reaction with anti-Oh-4 sera. These results indicate that both Tyr4 and Tyr22 play a crucial role in the neurotoxicity of Oh-7, whereas intact Tyr23 is involved in the manifestation of the toxicity of Oh-4 to a greater extent. In contrast to Oh-4, the conformational stability of Oh-7 depends heavily upon the integrity of Tyr22.

Circular Dichroism↗
PubMed2000

Ligation-mediated PCR for quantitative in vivo footprinting.

Ligation-mediated polymerase chain reaction (LM-PCR) is a genomic analysis technique for determination of (1) primary DNA nucleotide sequences (2) cytosine methylation patterns (3) DNA lesion formation and repair, and (4) in vivo protein-DNA footprints. However, LM-PCR can be limited by the multiple steps required and the relatively short stretch of sequence (usually <200 bp) that can be analyzed per reaction. We report here a simplified, one-day LM-PCR protocol in which all pipetting steps can be performed by a robotic workstation and which, moreover, provides longer reads (>350 bp) and enhanced signal quality by use of nonradioactive detection and a LI-COR DNA sequencing instrument. Sensitivity comparable to radiolabeling is achieved using oligonucleotide primers that are 5'-end labeled with infrared fluorochromes. We showed that the technique could be used for sensitive and reproducible in vivo photofootprinting of the human phosphoglycerate kinase 1 (PGK1) promoter, as well as providing good Maxam-Gilbert sequence information. The methods described here should allow high-throughput, high-resolution analysis of transcription factor binding and chromatin structure, and also may be useful for sequencing gaps that are refractory to cloning.

Animals↗
PubMed2000

Expression of MHC class II in T cells is associated with increased HIV-1 expression.

HIV-1 replicates in activated T cells at significantly higher levels than in resting cells. Thus, certain molecules up-regulated during T cell activation appear to be important for HIV-1 replication. In this study, we present evidence suggesting that expression of MHC class II (class II) molecules on CD4+ T cells facilitate HIV-1 replication. T cells that expressed class II supported greater virus replication than T cells lacking class II. The class II+ cells, when either infected with HIV-1 or transfected with an env-minus HIV-1 provirus plasmid, produced 10-20-fold greater virus expression than class II- cells. Anti-class II antibody markedly inhibited virus expression in class II+ cells (but not class II- cells) and also decreased the nuclear binding activity of AP-1, an inducible transcription factor important in T cell activation and HIV-1 expression. Most importantly, the induction of class II expression by transfection of the MHC class II transactivator (CIITA) stimulated HIV-1 replication in Jurkat T cells. Taken together, these data suggest that expression of MHC class II molecules and/or CIITA in T cells enhances HIV-1 transcription.

CD4-Positive T-Lymphocytes↗
PubMed2000

Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis.

By using an HBV-producing cell line (MS-G2) in vitro culture system, we found that wogonin isolated from Scutellaria baicalensis can suppress HBV surface antigen production (P < 0.001) without evidence of cytotoxicity. By assaying the endogenous HBV DNA polymerase activity, we found that both the relaxed circular and the linear forms of HBV DNA are significantly reduced in the wogonin-treated group. Wogonin deserves to be further evaluated for the treatment of human HBV infection.

Flavanones↗
PubMed2000

Dipyridamole-thallium/sestamibi before vascular surgery: a prospective blinded study in moderate-risk patients.

PURPOSE: This study assessed in a prospective, blinded fashion whether a reversible defect on dipyridamole-thallium (DTHAL)/sestamibi (DMIBI) can predict adverse cardiac events after elective vascular surgery in patients with one or more clinical risk factors. METHODS: Consecutive patients with one or more clinical risk factors underwent a preoperative blinded DTHAL/DMIBI. Patients with recent congestive heart failure (CHF) or myocardial infarction (MI) or severe or unstable angina were excluded. RESULTS: Eighty patients (78% men; mean age, 65 years) completed the study. Diabetes mellitus was the most frequent clinical risk factor (73%), followed by age older than 70 years (41%), angina (29%), Q wave on electrocardiogram (26%), history of CHF (7%), and ventricular ectopy (3%). The results of DTHAL/DMIBI were normal in 36 patients (45%); a reversible plus or minus fixed defect was demonstrated in 28 patients (36%), and a fixed defect alone was demonstrated in 15 patients (19%). Nine adverse cardiac events (11%) occurred, including three cases of CHF, and one case each of unstable angina, Q wave MI, non-Q wave MI, and cardiac arrest (successfully resuscitated). Two cardiac deaths occurred (2% overall mortality), one after a Q wave MI and one after CHF and a non-Q wave MI. The cardiac event rate was 14% for reversible defect and 9.8% without reversible defect (P =.71). The cardiac event rate was 12.5% (one of eight cases) for two or more reversible defects, versus 11.1% (eight of 72 cases) for fewer than two reversible defects (P = 1.0). The sensitivity rate of two or more areas of redistribution was 11% (95% CI, 0.3%-48%), the specificity rate was 90%, and the positive and negative predictive values were 12.5% and 89%, respectively. CONCLUSION: Our study demonstrated no association between reversible defects on DTHAL/DMIBI and adverse cardiac events in moderate-risk patients undergoing elective vascular surgery.

Aged↗
PubMed2000

Requirements of multiple domains of SLI-1, a Caenorhabditis elegans homologue of c-Cbl, and an inhibitory tyrosine in LET-23 in regulating vulval differentiation.

SLI-1, a Caenorhabditis elegans homologue of the proto-oncogene product c-Cbl, is a negative regulator of LET-23-mediated vulval differentiation. Lack of SLI-1 activity can compensate for decreased function of the LET-23 epidermal growth factor receptor, the SEM-5 adaptor, but not the LET-60 RAS, suggesting that SLI-1 acts before RAS activation. SLI-1 and c-Cbl comprise an N-terminal region (termed SLI-1:N/Cbl-N, containing a four-helix bundle, an EF hand calcium-binding domain, and a divergent SH2 domain) followed by a RING finger domain and a proline-rich C-terminus. In a transgenic functional assay, the proline-rich C-terminal domain is not essential for sli-1(+) function. A protein lacking the SH2 and RING finger domains has no activity, but a chimeric protein with the SH2 and RING finger domains of SLI-1 replaced by the equivalent domains of c-Cbl has activity. The RING finger domain of c-Cbl has been shown recently to enhance ubiquitination of active RTKs by acting as an E3 ubiquitin-protein ligase. We find that the RING finger domain of SLI-1 is partially dispensable. Further, we identify an inhibitory tyrosine of LET-23 requiring sli-1(+) for its effects: removal of this tyrosine closely mimics the loss of sli-1 but not of another negative regulator, ark-1. Thus, we suggest that this inhibitory tyrosine mediates its effects through SLI-1, which in turn inhibits signaling upstream of LET-60 RAS in a manner not wholly dependent on the ubiquitin-ligase domain.

Amino Acid Motifs↗