Search PubMed⌕ Search

Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 163 records · Page 9Linked to original sources

Function and sequence analyses of tumor suppressor gene p53 of CHO.K1 cells.

The tumor suppressor gene p53 plays an important role in guarding genomic integrity. When induced in response to environmental results, the gene product of p53 functions as a transcription factor to transactivate genes involved in arresting the cell cycle and as a facilitator of DNA repair. In contrast, the status of p53 in Chinese hamster ovary (CHO) cells, commonly used as a model system for various studies including those involving the cell cycle and transformation, remains an enigma. In this study, the function and sequence of p53 in CHO.K1 cells were investigated. The level of p53 proteins was elevated on ultraviolet (UV) irradiation of the cells, and the proteins formed specific complexes as probed with DNA containing p53-binding sequences. Its activities toward responsive promoters were inducible by UV in a dose-dependent manner. Although p53 in CHO.K1 contained a single missense mutation at codon 211, the mutation apparently had no effect on the functional properties of the protein. The CHO.K1 cells on X-ray irradiation failed to arrest at G1 phase even when the cells were transfected with a wildtype human p53 gene, indicating that the failure probably was not caused by dysfunction of its p53, but by some other mechanism. This result is consistent with the finding that p21(Waf1/Cip1) is undetectable in UV-treated CHO.K1 cells, whereas Gadd45 is induced by UV light in the cells.

3T3 Cells↗

Elliptocytes and tailed poikilocytes correlate with severity of iron-deficiency anemia.

This study examines the relationships between abnormal RBC morphology, RBC indices measured with an automated hematology analyzer, serum iron studies, and severity of anemia in patients with findings indicative of iron-deficiency anemia. Counts and morphologic classification of 1,000 RBCs from each of 22 patients were performed, and correlations were determined between parameters. The Student t test was used to determine the level of significance for correlations between parameters. Several significant relationships were found. As the percentage of elliptocytes increased, hemoglobin concentration, hematocrit, RBC concentration, and mean corpuscular hemoglobin level decreased (r = .48, .44, .40, and .49, respectively; P < .05). As the percentage of tailed poikilocytes increased, hemoglobin concentration, hematocrit, and RBC concentration decreased (r = .70, .77, and .71, respectively; P < .01) and RBC distribution width increased (r = .73; P < .01). Of significance, serum ferritin levels, long considered the best single indicator of iron deficiency, showed no correlation with the morphologic abnormalities assessed, severity of anemia, or any of the analyzer-generated indices. Our results indicate that microscopic evaluation of RBC morphology remains an important tool for the pathologist to evaluate the severity of anemia in patients with iron deficiency.

Anemia, Iron-Deficiency↗

Cerebral blood flow in patients with normal pressure hydrocephalus.

Mean cerebral blood flow (CBF) of the whole brain was measured in 48 patients who underwent cerebrospinal fluid shunt surgery for normal pressure hydrocephalus (NPH) by performing first-pass radionuclide angiography using 99Tcm-hexamethylpropylene amine oxime. Patients were divided according to outcome into an 'excellent' improvement group, a 'good' improvement group, a 'fair' improvement group and a 'poor' improvement group. Patients with excellent and good improvement had a preoperative mean CBF of 40.4 +/- 3.9 ml.100 g-1.min-1 and 37.1 +/- 5.5 ml.100 g-1.min-1, respectively, both of which were significantly (P < 0.005) higher than that in 11 patients who showed fair improvement (30.8 +/- 3.2 ml.100 g-1.min-1) and six patients who showed poor improvement (31.8 +/- 2.5 ml.100 g-1.min-1). Patients with a clinical improvement after shunting had an increased postoperative mean CBF. We conclude that patients with a preoperative mean CBF of over 35 ml.100 g-1.min-1 can show favourable improvement after a shunting procedure, and that the preoperative mean CBF of 32 ml.100 g-1.min-1 can be considered the critical level for treatment.

Adult↗

Functional analysis of two maize cDNAs encoding T7-like RNA polymerases.

We have characterized two maize cDNAs, rpoTm and rpoTp, that encode putative T7-like RNA polymerases. In vivo cellular localization experiments using transient expression of the green fluorescent protein suggest that their encoded proteins are targeted exclusively to mitochondria and plastids, respectively. An antibody raised against the C terminus of the rpoTp gene product identified mitochondrial polypeptides of approximately 100 kD. Their presence was correlated with RNA polymerase activity, and the antibody inhibited mitochondrial in vitro transcription activity. Together, these results strongly suggest that the product of rpoTm is involved in maize mitochondrial transcription. By contrast, immunoblot analysis and an antibody-linked polymerase assay indicated that rpoTp specifies a plastid RNA polymerase component. A quantitative reverse transcription-polymerase chain reaction assay was used to study the transcription of rpoTp and rpoTm in different tissues and under different environmental conditions. Although both genes were constitutively expressed, rpoTm transcripts were generally more prevalent in nonphotosynthetic tissues, whereas an increase in rpoTp transcripts paralleled chloroplast development. We suggest that these two genes encode constitutive components of the organelle transcription machinery but that their expression is nonetheless subject to modulation during plant development.

Amino Acid Sequence↗

Normal approximation diagnostics for the Cox model.

We discuss two diagnostic methods for assessing the accuracy of the normal approximated confidence region to the likelihood-based confidence region for the Cox proportional hazards model with censored data. The proposed diagnostic methods are extensions of the contour measures of Hodges (1987, Journal of the American Statistical Association 82, 149-154) and Cook and Tsai (1990, Journal of the American Statistical Association 85, 770-777) and the curvature measures of Jennings (1986, Journal of the American Statistical Association 81, 471-476) and Cook and Tsai (1990). These methods are also illustrated in a study of hepatocyte growth factor in patients with lung cancer and a Mayo Clinic randomized study of participants with primary biliary cirrhosis.

Biometry↗

Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: specific regulation of iepsilon transcription and immunoglobulin E switching.

The BCL-6 proto-oncogene encodes a POZ/zinc-finger transcription factor that is expressed in B cells and a subset of CD4(+) T cells within germinal centers. Recent evidence suggests that BCL-6 can act as a sequence-specific repressor of transcription, but the target genes for this activity have not yet been identified. The binding site for BCL-6 shares striking homology to the sites that are the target sequence for the interleukin-4 (IL-4)-induced Stat6 (signal transducers and activators of transcription) signaling molecule. Electrophoretic mobility shift assays demonstrate that BCL-6 can bind, with different affinities, to several DNA elements recognized by Stat6. Expression of BCL-6 can repress the IL-4-dependent induction of immunoglobulin (Ig) germ line epsilon transcripts, but does not repress the IL-4 induction of CD23 transcripts. Consistent with the role of BCL-6 in modulating transcription from the germ line epsilon promoter, BCL-6(-/-) mice display an increased ability to class switch to IgE in response to IL-4 in vitro. These animals also exhibit a multiorgan inflammatory disease characterized by the presence of a large number of IgE(+) B cells. The apparent dysregulation of IgE production is abolished in BCL-6(-/-) Stat6(-/-) mice, indicating that BCL-6 regulation of Ig class switching is dependent upon Stat6 signaling. Thus, BCL-6 can modulate the transcription of selective Stat6-dependent IL-4 responses, including IgE class switching in B cells.

Animals↗

Metabolic control of peroxisome abundance.

Zellweger syndrome and related disorders represent a group of lethal, genetically heterogeneous diseases. These peroxisome biogenesis disorders (PBDs) are characterized by defective peroxisomal matrix protein import and comprise at least 10 complementation groups. The genes defective in seven of these groups and more than 90% of PBD patients are now known. Here we examine the distribution of peroxisomal membrane proteins in fibroblasts from PBD patients representing the seven complementation groups for which the mutant gene is known. Peroxisomes were detected in all PBD cells, indicating that the ability to form a minimal peroxisomal structure is not blocked in these mutants. We also observed that peroxisome abundance was reduced fivefold in PBD cells that are defective in the PEX1, PEX5, PEX12, PEX6, PEX10, and PEX2 genes. These cell lines all display a defect in the import of proteins with the type-1 peroxisomal targeting signal (PTS1). In contrast, peroxisome abundance was unaffected in cells that are mutated in PEX7 and are defective only in the import of proteins with the type-2 peroxisomal targeting signal. Interestingly, a fivefold reduction in peroxisome abundance was also observed for cells lacking either of two PTS1-targeted peroxisomal beta-oxidation enzymes, acyl-CoA oxidase and 2-enoyl-CoA hydratase/D-3-hydroxyacyl-CoA dehydrogenase. These results indicate that reduced peroxisome abundance in PBD cells may be caused by their inability to import these PTS1-containing enzymes. Furthermore, the fact that peroxisome abundance is influenced by peroxisomal 105-oxidation activities suggests that there may be metabolic control of peroxisome abundance.

Cells, Cultured↗

A case of extraadrenal pheochromocytoma associated with adrenal cortical nodular hyperplasia and papillary thyroid carcinoma.

A 64-year-old woman was admitted in November, 1996 for fluctuating blood pressure. There was multinodular goiter in her neck. High urine VMA and serum aldosterone were noted. Computed tomography showed an oval lesion in the left adrenal gland. Left adrenalectomy was performed and the pathology was proved to be adrenal cortical nodular hyperplasia. Fluctuating blood pressure and high urine VMA persisted after the operation. CT scan of the abdomen revealed a soft tissue mass in lower abdomen. The patient was admitted again in September, 1997. Laboratory examinations showed normal serum aldosterone, normal plasma renin activity and high urine VMA. Aspiration cytology of the thyroid gland disclosed papillary thyroid carcinoma. [131I]-metaiodobenzylguanidine image revealed a high uptake lesion in the right L-3 paravertebral area. Tumor excision and thyroidectomy were performed. The pathology was reported as extraadrenal pheochromocytoma and papillary thyroid carcinoma. Papillary thyroid carcinoma is rarely associated with pheochromocytoma. To our knowledge, this paper is the first report of a patient with extraadrenal pheochromocytoma associated with papillary thyroid carcinoma and adrenal cortical nodular hyperplasia.

Adrenal Cortex↗

Prediction of effectiveness of shunting in patients with normal pressure hydrocephalus by cerebral blood flow measurement and computed tomography cisternography.

Measurement of cerebral blood flow (CBF) and computed tomography (CT) cisternography were performed in 37 patients with a tentative diagnosis of normal pressure hydrocephalus (NPH) to predict their surgical outcome. The mean CBF of the whole brain was measured quantitatively by single photon emission computed tomography with technetium-99m-hexamethylpropylene amine oxime before surgery. The results of CT cisternography were classified into four patterns: type I, no ventricular stasis at 24 hours; type II, no ventricular stasis with delayed clearance of cerebral blush; type III, persistent ventricular stasis with prominent cerebral blush; type IV, persistent ventricular stasis with diminished cerebral blush and/or asymmetrical filling of the sylvian fissures. The mean CBF was significantly lower than that of age-matched controls (p < 0.005). Patients with a favorable outcome had a significantly higher mean CBF than patients with an unfavorable outcome (p < 0.005). Patients with the type I pattern did not respond to shunting. Some patients with type II and III patterns responded to shunting but improvement was unsatisfactory. Patients with type IV pattern responded well to shunting, and those with a mean CBF of 35 ml/100 g/min or over achieved a favorable outcome. The combination of CBF measurement and CT cisternography can improve the prediction of surgical outcome in patients with suspected NPH.

Adult↗

Bartonella henselae and Bartonella clarridgeiae infection in domestic cats from The Philippines.

One hundred seven domestic cats from The Philippines were serologically tested to establish the prevalence of Bartonella infection. A subset of 31 of these cats also had whole blood collected to tentatively isolate Bartonella strains. Bartonella henselae and B. clarridgeiae were isolated from 19 (61%) of these cats. Bartonella henselae type I was isolated from 17 (89%) of the 19 culture-positive cats. Six cats (31%) were infected with B. clarridgeiae, of which four were coinfected with B. henselae. Sixty-eight percent (73 of 107) and 65% (70 of 107) of the cats had antibodies to B. henselae and B. clarridgeiae, respectively, detected by an immunofluorescence antibody (IFA) test at a titer > or = 1:64. When tested by enzyme immunoassay (EIA), 67 cats (62.6%) had antibodies to B. henselae and 71 cats (66.4%) had antibodies to B. clarridgeiae. Compared with the IFA test, the B. henselae EIA had a sensitivity of 90.4% and a specificity of 97%, with positive and negative predictive values of 98.5% and 82.5%, respectively. Similarly, the B. clarridgeiae EIA had a sensitivity of 97% and a specificity of 92% specificity, with positive and negative predictive values of 95.8% and 94.4%, respectively. The presence of antibodies to Bartonella was strongly associated with flea infestation. Domestic cats represent a large reservoir of Bartonella infection in the Philippines.

Animals↗

Severe intrahepatic cholestasis caused by amiodarone toxicity after withdrawal of the drug: a case report and review of the literature.

Cholestasis has been reported as a rare presentation among patients with severe liver injury secondary to amiodarone hepatic toxicity. We report an unusual case of amiodarone-induced cholestatic hepatotoxicity occurring after amiodarone had been discontinued and the initial abnormal liver function findings had improved. The patient, without jaundice at the initial presentation, developed severe jaundice about 4 months after withdrawal of amiodarone. Light and transmission electron microscopic examination of a specimen secured by computed tomographically guided liver biopsy was consistent with amiodarone hepatic toxicity as the cause of intrahepatic cholestasis. An abdominal ultrasound, endoscopic retrograde cholangiography, and dimethyl iminodiacetic acid and computed tomographic scans of the abdomen all failed to demonstrate any other causes for jaundice other than amiodarone toxicity. Thus, amiodarone hepatic toxicity may occur after drug withdrawal even if results of liver function tests improve. Histopathologic examination of a liver biopsy specimen is of value for diagnosis and prognosis. The liver biopsy findings, clinical course, and liver function test results are discussed, and the English-language literature on amiodarone cholestatic hepatotoxicity is reviewed.

Aged↗

Prenatal diagnosis of dyssegmental dysplasia. A case report.

BACKGROUND: Since the first use of sonography, most fetal dwarfism has been detectable prenatally. The correct differentiation of the subtype of dwarfism is difficult at times. Dyssegmental dysplasia is probably an exception to these subtypes because the vertebral disorganization and occipital encephalocele at times permits prenatal diagnosis. CASE: A 34-year-old woman, gravida 3, para 1, elective abortion 1 for dwarfism, was referred at 27 weeks' gestation for cystic hygroma. Further sonographic findings included: cystic hygroma with massive ascites, micromelia, occipital encephalocele, spinal disorganization and hydramnios. The fetus and both parents appeared to have a normal karyotype. Later the pregnancy was terminated with vaginal delivery. The fetus had micromelia, camptomelia, cystic hygroma, a flat face, short neck, short trunk, narrow thorax with protuberant abdomen, scoliosis and clubfeet. CONCLUSION: Sonography is effective in prenatal diagnosis of dyssegmental dysplasia. With sonography, diagnosis of dyssegmental dysplasia becomes possible as early as the first trimester.

Abnormalities, Multiple↗

A comparison of various ultrasound technologies.

Ultrasound-assisted lipoplasty represents a new and exciting adjunct to traditional suction-assisted lipoplasty techniques. With the development of this new field, a variety of special equipment needs have arisen. Most important among these needs are the ultrasonic generator, handpiece, and probe. This article critically examines, compares, and contrasts some of the most popular technological equipment currently available.

Humans↗

The prenatal diagnosis of Pierre-Robin sequence.

The purpose of this study was to evaluate the spectrum of prenatal sonographic and chromosomal findings, associated anomalies and perinatal and neonatal outcomes in cases with Pierre-Robin sequence. All cases (20) with Pierre Robin sequence, who were born at China Medical College Hospital between 1990 and 1997, were included and analysed in this series. 12 pregnancies (60 per cent) were complicated by polyhydramnios and 9 (45 per cent) were combined with cleft palate. Four cases (20 per cent) with cardiac anomalies were also observed. Two fetuses (10 per cent) had abnormal karyotyping (one trisomy 21, one trisomy 18). All fetuses were delivered at or near term. Male deviation was observed in cases with isolated Pierre-Robin sequence or combined mild anomalies (male female ratio: 13:3). Two neonatal mortalities and three with mental retardation were observed. This investigation provides a basis for counselling patients with fetal micrognathia or neonatal Pierre-Robin sequence. The main prenatal sonographic findings of Pierre-Robin sequence are micrognathia, polyhydramnios and cleft palate. In cases of polyhydramnios, sonographic examination of the facial profile and palate are recommended. After the finding of polyhydramnios, micrognathia, and even cleft palate, clinicians should be aware of the possibility of neonatal Pierre-Robin sequence. Cardiac evaluation and karyotyping is also recommended.

Abnormalities, Multiple↗

Twin vs. singleton pregnancy. Clinical characteristics and latency periods in preterm premature rupture of membranes.

OBJECTIVE: To compare the clinical characteristics and latency periods (latencies) of preterm premature rupture of the membranes (PPROM) in twin vs. singleton pregnancy. STUDY DESIGN: Between January 1986 and December 1996, data on all women with singleton and twin gestations complicated by PPROM were reviewed. Perinatal morbidity, mortality and latencies between singleton and twin pregnancies were compared. A further division according to PPROM at < 30 and > or = 30 weeks' gestation was made in both groups. Their latencies were compared. RESULTS: A total of 131 singleton and 48 twin pregnancies with PPROM between 20 and 36 weeks' gestation were included in this series. Regardless of the gestational age at PPROM, the mean latencies of singleton and twin pregnancies were statistically similar (4.4 +/- 3.3 vs. 3.4 +/- 2.9 days, nonsignificant). When PPROM occurred at > or = 30 weeks, the latency of twin pregnancies was shorter than that of singleton pregnancies (2.5 +/- 1.9 vs. 3.7 +/- 2.6 days, P < .05). In both groups, the latencies of PPROM at < 30 weeks were longer than that at > or = 30 weeks (singleton, 5.6 +/- 4.0 vs. 3.7 +/- 2.6 days, P < .005; twin, 4.8 +/- 3.5 vs. 2.5 +/- 1.9 days, P < .05). We also observed a higher percentage of deliveries within the initial 48 hours in twin pregnancies: 50% of women delivered within 48 hours after PPROM and 91.7% within 7 days. In contrast, 26.7% and 85.5% of singleton pregnancies with PPROM were delivered within 48 hours and 7 days, respectively. Perinatal and neonatal outcomes in both groups were similar. CONCLUSION: This investigation provides the basis for patient counseling and management in twin pregnancies with PPROM. In general, singleton and twin pregnancies with PPROM had similar latencies. Latency in PPROM at < 30 was longer than that of PPROM at > or = 30 weeks' gestation in both singleton and twin pregnancies. When PPROM occurred at < 30 weeks' gestation, both groups appeared to have similar latencies. In pregnancies with PPROM at > or = 30 weeks' gestation, latency in twins was shorter than in singleton pregnancies. In twin pregnancies with PPROM after 30 weeks' gestation, prompt steroid administration for fetal lung maturity should be considered.

Adult↗

Prenatal diagnosis of thoracopelvic dysplasia. A case report.

BACKGROUND: Thoracopelvic dysplasia, a variant of asphyxiating thoracic dysplasia (Jeune syndrome), is an uncommon skeletal disorder characterized by a small thorax, pelvic abnormalities and other complex, combined anomalies, including hypomelia, polydactyly and renal anomalies. CASE: A 32-year-old woman, gravida 1, para 0, was referred at 27 weeks' gestation due to polyhydramnios. Sonography revealed hydramnios, low fetal thoracic circumference (TC) and abdominal circumference (AC) ratio (0.78), skull and skin edema, increased nuchal translucency (7 mm), micrognathia, low-set ears, left cardiac deviation (66 degrees), overriding fingers, and club and rock-buttock feet. Amniocentesis revealed a normal karyotype (46, XY). Asphyxiating thoracic dysplasia was considered. At 40 weeks' gestation, a male infant was delivered vaginally. Besides the prenatal findings, cryptorchidism and high-arched palate were noted. Radiography of the infant revealed a narrow, funnel-shaped thorax and small pelvis with short, flared iliac bones; poorly developed acetabulum; and small, shallow sciatic notch. No dyspnea was observed at five months postpartum. CONCLUSION: Thoracopelvic dysplasia should be considered when a low TC/AC ratio (< 0.8) is observed. In this case the final diagnosis was made after detailed exclusion of other disorders combined with observation of a small thorax. Prenatal diagnosis of thoracopelvic dysplasia is possible.

Adult↗

Epigenetic toxicology as toxicant-induced changes in intracellular signalling leading to altered gap junctional intercellular communication.

Communication mechanisms [extra-, intra-, and gap junctional inter-cellular communication (GJIC)] control, from the fertilized egg, through embryogenesis to maturity and aging, whether a cell proliferates, differentiates, dies by apoptosis, or if differentiated, adaptively responds to endogenous and exogenous signals. From the egg to the 100 trillion cells in the human body, health is maintained when these communication processes between stem, progenitor and terminally differentiated cells are integrated. Each cell choice involves 'epigenetic' mechanisms to alter the expression of genes at the transcriptional, translational or post-translational levels. Disruption of the communication mechanisms can be either adaptive or maladaptive. Modulation of extra-cellular communication, either by genetic imbalances of growth factors, hormones or neurotransmitters or by environmental, exogenous chemicals can trigger signal transducing intra-cellular mechanisms. These intra-cellular signals can modulate gene expression at the transcriptional, translational or post-translational levels while also modulating GJIC. Untimely or chronic disruption of GJIC during embryonic or fetal development could lead to embryonic lethality or teratogenesis. By modulation of GJIC, homeostatic control of cell growth, differentiation or apoptosis could lead to specific diseases, such as neurological, cardiovascular, reproductive or endocrinological dysfunction. Chemical modulation or oncogene down-regulation of GJIC in initiated tissues has been shown to lead to tumor promotion. Genetic syndromes carrying a mutated gap junction gene, together with some transgenic and knock-out gap junction gene mice, provide evidence for the importance of this organelle found only in metazoans. Implications for 'thresholds' to toxicants and for risk assessment are evident.

Animals↗

Recombinant acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) purified to essential homogeneity utilizes cholesterol in mixed micelles or in vesicles in a highly cooperative manner.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an integral membrane protein located in the endoplasmic reticulum. It catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty acyl coenzyme A. The first gene encoding the enzyme, designated as ACAT-1, was identified in 1993 through an expression cloning approach. We isolated a Chinese hamster ovary cell line that stably expresses the recombinant human ACAT-1 protein bearing an N-terminal hexahistidine tag. We purified this enzyme approximately 7000-fold from crude cell extracts by first solubilizing the cell membranes with the zwitterionic detergent 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, then proceeding with an ACAT-1 monoclonal antibody affinity column and an immobilized metal affinity column. The final preparation is enzymologically active and migrates as a single band at 54 kDa on SDS-polyacrylamide gel electrophoresis. Pure ACAT-1 dispersed in mixed micelles containing sodium taurocholate, phosphatidylcholine, and cholesterol remains catalytically active. The cholesterol substrate saturation curves of the enzyme assayed either in mixed micelles or in reconstituted vesicles are both highly sigmoidal. The oleoyl-coenzyme A substrate saturation curves of the enzyme assayed under the same conditions are both hyperbolic. These results support the hypothesis that ACAT is an allosteric enzyme regulated by cholesterol.

Acyl Coenzyme A↗