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Biomedical subjects

K Y Chang

Publications and source records attributed to K Y Chang.

At least 19 recordsLinked to original sources
PubMed2006

Evaluation of wound healing effect on skin-defect nude mice by using human dermis-derived mesenchymal stem cells.

We report that human dermis-derived mesenchymal stem cells (hDMSCs) possess differentiation potential of epidermis facilitating wound healing in skin-defect nude mice in combination with the treatment using gelatin/thermosensitive poly N-isopropylacrylamide (pNIPAAm)/polypropylene (PP). The results showed that the rate of cell growth and wound recovery in the hDMSC and gelatin/pNIPAAm/PP-treated group was significantly greater than those in the gelatin/pNIPAAm/PP-treated only group (P < .01). The reepithelialization marker of human pan-cytokeratin was also significantly increased on days 14 and day 21 in the wound site of hDMSCs and gelatin/pNIPAAm/PP-treated group. Furthermore, the stem cell marker of human CD13 gradually decreased during the period of wound healing. In sum, this novel method provided a transferring system for stem cell therapy, maintaining its temperature-sensitive property of easy peeling by lower temperature treatment.

Animals↗
PubMed2001

Effect of orthographic and phonological similarity on false recognition of drug names.

Health professionals and patients tend to confuse drugs with similar names, thereby threatening patient safety. One out of four medication errors voluntarily reported in the US involves this type of drug name confusion. Cognitive psychology offers insight into how and why these errors occur. The objective of this investigation was to examine the effect of orthographic (i.e., spelling) and phonological (i.e., sound) similarity on the probability of making recognition memory errors (i.e., false recognitions). Prospective, computer-based, recognition memory experiments on 30 pharmacists and 66 college students were conducted. Participants viewed a study list of drug names and then a test list. The test list was twice as long as the study list and contained distractor names at progressively increasing levels of similarity to the study words. The task was to identify which test names were on study list and which were new. The main outcome measure was probability of making a false recognition error (i.e., of saying a new name was on the study list). Among pharmacists and college students, there was a strong and significant effect of similarity on the probability of making a false recognition error. It was concluded that both orthographic (i.e., spelling) and phonological (i.e., sound) similarity increase the probability that experts and novices will make false recognition errors when trying to remember drug names. Similarity is easily and cheaply measured, and therefore, steps should be taken to monitor and reduce similarity as a means of reducing the likelihood of drug name confusions.

Humans↗
PubMed2001

Mitogen-activated protein kinase kinase inhibitor PD98059 blocks the trans-activation but not the stabilization or DNA binding ability of hypoxia-inducible factor-1alpha.

Under low oxygen tension, cells increase the transcription of specific genes that are involved in angiogenesis, erythropoiesis, and glycolysis. Hypoxia-induced gene expression primarily depends on the stabilization of the alpha-subunit of hypoxia-inducible factor-1 (HIF-1alpha), which acts as a heterodimeric trans-activator. Our results indicate that stabilization of HIF-1alpha protein by treatment of proteasome inhibitors, is not sufficient for hypoxia-induced gene activation, and an additional hypoxia-dependent modification is necessary for gene expression by HIF-1alpha. Here, we demonstrate that mitogen-activated protein kinase kinase-1 (MEK-1) inhibitor PD98059 does not change either the stabilization or DNA binding ability of HIF-1alpha but it inhibits the trans-activation ability of HIF-1alpha, thereby it reduces the hypoxia-induced transcription of both an endogenous target gene and a hypoxia-responsive reporter gene. We found that hypoxia induced p42/p44 mitogen-activated protein kinases (MAPKs) that are target protein kinases of MEK-1, and that expression of dominant-negative p42 and p44 MAPK mutants reduced HIF-1-dependent transcription of the hypoxia-responsive reporter gene. Our results are the first to identify that hypoxia-induced trans-activation ability of HIF-1alpha is regulated by different mechanisms than its stabilization and DNA binding, and that these processes can be experimentally dissociated. MEK-1/p42/p44 MAPK regulates the trans-activation, but not the stabilization or DNA binding ability, of HIF-1alpha.

Cell Hypoxia↗
PubMed2001

Normalization of retinal vascular permeability in experimental diabetes with genistein.

PURPOSE: To study the effects of genistein, a tyrosine kinase inhibitor, on retinal vascular permeability in an experimental diabetic rat model. METHODS: Seventy-two rats were equally divided into four groups: (1) nondiabetic control group, (2) diabetic control group, (3) diabetic rats receiving 150 mg genistein/kg food, and (4) diabetic rats receiving 300 mg genistein/kg food. Diabetes was induced by streptozotocin injection in the three diabetic groups. Rats were fed diets with or without genistein and followed for 6 months. Retinal vascular permeability was assessed by measuring radiolabeled sucrose leakage into the retina and by Western blot analysis for total retinal albumin. Retinal phosphotyrosine levels and proliferating cell nuclear antigen (PCNA) were also evaluated by Western blot analysis. RESULTS: Diabetic control rats had markedly increased retinal vascular leakage of radiolabeled sucrose compared with nondiabetic control rats. Diabetic rats receiving oral genistein had significantly less retinal vascular leakage of radiolabeled sucrose than diabetic control rats in a dose-response fashion. Diabetic control rats had increased levels of phosphotyrosine, retinal albumin, and PCNA by Western blot analysis compared with nondiabetic control rats. Rats receiving 300 mg of genistein had decreased retinal albumin by Western blot analysis. Western blot analysis demonstrated a dose-response decrease in retinal phosphotyrosine levels and PCNA in genistein-treated diabetic rats compared with diabetic control rats. CONCLUSIONS: Long-term oral administration of genistein significantly inhibits retinal vascular leakage in experimentally induced diabetic rats. Tyrosine kinase inhibition may be a useful pharmacological approach for the treatment of diabetic-induced retinal vascular leakage.

Administration, Oral↗
PubMed2000

CM1, a possible novel activation molecule on human lymphocytes.

CM1 (centrocyte/-blast marker 1) defined by a mAb developed against concanavalin-A activated PBMC, is expressed specifically on some tonsillar germinal center (GC) B cells. In single flow cytometric analysis, the bone marrow did not express these molecules nor did the PBMC or the thymocytes. The peripheral B lymphocytes showed more than 90% positive, while the peripheral T lymphocytes showed approximately 60% positive at 48 h after activation by PMA/ionomycin, respectively. A western blot analysis and an immunoprecipitation for CM1 showed a band at 70 kDa. Cross-linking of CM1 with anti-CM1 mAb induced apoptosis of the GC B cells (CD38(+)IgD(-)). Immunohistochemical staining revealed that the CM1 molecule is distributed over the entire area except the proximal dark zone of the tonsillar germinal centers. These results suggest that the CM1 molecule might be involved in differentiation of the germinal center B cells as one of the novel centrocyte markers.

ADP-ribosyl Cyclase↗
PubMed2000

Role of follicular dendritic cells in the apoptosis of germinal center B cells.

Follicular dendritic cells (FDCs) provide the most obvious source of antigens, which are essential for the differentiation of GC B cells. It has been reported that most proliferating B cells in germinal centers undergo apoptosis. Quantitative histology shows macrophages with apoptotic debris throughout the germinal center, the highest frequency of these cells being found in the dense FDC network. Based on these findings, we hypothesized that FDC may be involved in an apoptotic pathway of the germinal center B cells. To prove this hypothesis, we performed double immunohistochemical analysis using anti-FDC mAb and peanut agglutinin (PNA), with their respective TUNEL kits. Collated data showed that a great proportion of the apoptotic cells, most of which were positive for PNA, were in close contact with FDC, which indicated an interaction between FDC and B cells in the apoptotic pathway. Further studies using double immunohistochemical staining and FACS analyses demonstrated the expression of Fas-ligand (FasL) in a subset of the FDC. These results suggest that FDC may play a role in the apoptosis of germinal center B cells via Fas-FasL interaction.

Animals↗
PubMed2000

Contrast-enhanced dynamic computed tomography does not aggravate the clinical severity of patients with severe acute pancreatitis: reevaluation of the effect of intravenous contrast medium on the severity of acute pancreatitis.

BACKGROUND: Contrast-enhanced abdominal computed tomography (CT) is useful in demonstrating pancreatitis necrosis, but the administration of contrast medium in animal models with acute pancreatitis may worsen the severity. HYPOTHESIS: The use of contrast-enhanced CT in clinical patients with acute pancreatitis may actually aggravate the severity of the disease. DESIGN: A randomized prospective study. SETTING: Chang Gung Memorial Hospital, Taipei, Taiwan. PATIENTS: Twenty patients with severe acute pancreatitis were randomly divided into 2 groups. Those in group A (n = 10) underwent a CT examination with a contrast-enhanced medium, and those in group B (n = 10) underwent a CT examination without a contrast-enhanced medium. MAIN OUTCOME MEASURES: The patients' serum amylase, lipase, C-reactive protein, leukocyte, glutamicoxaloacetic transaminase, creatinine, calcium, and phosphate levels were serially checked before the CT examination and at 2, 4, 6, 8, 12, and 24 hours after the examination was performed. The biochemical data between the 2 groups were compared. The morbidity, length of stay, and mortality were also compared. RESULTS: There were no significant changes in the level of pancreatic enzymes, C-reactive proteins, and leukocytes and in the biochemical data of either group before or after the CT examination. The difference in the previously examined values between the 2 groups was also not significant. There was also no difference in the morbidity, length of hospital stay, and mortality between the 2 groups. CONCLUSION: Contrast-enhanced abdominal CT does not aggravate the severity of clinical patients with severe acute pancreatitis.

Adult↗
PubMed2000

Age-related retinal pigment epithelium and Bruch's membrane degeneration in senescence-accelerated mouse.

PURPOSE: To investigate age-related changes in the retinal pigment epithelium (RPE), Bruch's membrane, and choriocapillaris in the senescence-accelerated mouse (SAM). METHODS: The external and eyecup features and light and electron microscopic findings were examined in three male and two female mice of a senescence-prone mouse strain (SAM P(8)) monthly for 12 months. These results were compared with those in age-matched mice of similar background but senescence resistant (SAM R(1)). Choroidal vascular casts were prepared at 12 months in seven mice each of the SAM P(8) and SAM R(1) strains. Quantitative analysis of area of choriocapillaris was performed by automated image analysis, and the results were analyzed by paired Student's t-test. RESULTS: We found in the SAM P(8) strain that hair loss, coarseness of hair texture, and ulceration of skin appeared and increased as the age advanced (at approximately 5-9 months). Eyecup examination showed no differences. Light and electron microscopy revealed progressively more prominent abnormalities in the RPE and Bruch's membrane mice older than 10 months. Two of the five SAM P(8) mice older than 11 months showed what appeared to be intra-Bruch's membrane choroidal neovascularization. The RPE and Bruch's membrane appeared normal in the SAM R(1) strain. In the SAM P(8), vascular casts of the choriocapillaris showed a mild but significant decrease in vascular area when compared with the SAM R(1) strain at 12 months (P = 0.011). CONCLUSIONS: Senescence accelerated mice develop progressive age-related changes in the RPE-Bruch's-choriocapillaris complex that have features that may be relevant in the study of age-related macular changes in humans.

Aging↗
PubMed1999

Correlation of deformability at a tRNA recognition site and aminoacylation specificity.

The fidelity of protein synthesis depends on specific tRNA aminoacylation by aminoacyl-tRNA synthetase enzymes, which in turn depends on the recognition of the identity of particular nucleotides and structural features in the substrate tRNA. These features generally reside within the acceptor helix, the anticodon stem-loop, and in some systems the variable pocket of the tRNA. In the alanine system, fidelity is ensured by a G.U wobble base pair located at the third position within the acceptor helix of alanine tRNA. We have investigated the activity of mutant alanine tRNAs to explore the mechanism of enzyme recognition. Here we show that the mismatched pair C-C is an excellent substitute for G.U in alanine-tRNA-knockout cells. A structural investigation by NMR spectroscopy of the C-C RNA acceptor end reveals that the two cytosines are intercalated into the helix, and that C-C exists in multiple conformations. Structural heterogeneity also is present in the wild-type G.U RNA, whereas inactive Watson-Crick helices are structurally rigid. The correlation between functional and structural data suggests that the G.U pair provides a distinctive structure and a point of deformability that allow the tRNA acceptor end to fit into the active site of the alanyl-tRNA synthetase. Fidelity is ensured because noncognate and inactive mutant tRNAs are bound in the active site in an incorrect conformation that reduces enzymatic activity.

Acylation↗
PubMed1999

Cecropin D-like antibacterial peptides from the sphingid moth, Agrius convolvuli.

Two major antibacterial peptides were isolated and purified from immunized larval hemolymph of Agrius convolvuli. Acid extraction, gel filtration, ultrafiltration, and reversed-phase FPLC were used for purification of peptides. These peptides had similar molecular mass and amino acid composition. Moreover, 21 of the first 23 N terminal residues were identical. The peptides were highly homologous with cecropin D in size and primary sequence, and named Agrius cecropin D1 and D2. The molecular masses of Agrius cecropin D1 and D2 were 3,879.39 and 3,839.27, respectively. In antibacterial and hemolytic assays, Agrius cecropin D showed potent antibacterial activities against a panel of Gram positive and negative bacteria without hemolytic activity against human red blood cells. Notably, our antibacterial assay revealed Agrius cecropin D possessed stronger or at least equivalent activities against B. megaterium than cecropin A. It suggests that Agrius cecropin D, which has an alternative structure from cecropin D, could be the model for the development of peptide antibiotics. Arch.

Amino Acid Sequence↗
PubMed1999

Proliferation not apoptosis as a prognostic indicator in retinoblastoma.

The balance between proliferation and cell death is the major determinant of tumour growth. We analysed the proliferative and apoptotic indices (PI and AI, respectively) of 33 children with retinoblastoma. PI and AI were assessed by immunohistochemistry for Ki-67 antigen and TUNEL staining, respectively. The mean PI was 21.0+/-21.1%, and higher PI was associated with more advanced tumour stage (P<0.0001) and poor clinical outcome (P<0.05). Patients in whom amplified N-myc oncogene was found (n=6) determined by the multiplex polymerase chain reaction tended to have a higher PI (37.6+/-27.2%) than those without amplified N-myc (n=27; PI=17.3+/-18.1). A PI value of over 40% was clearly associated with an unfavourable prognosis. The AI, however, did not correlate with any of the other variables analysed. The findings suggest that proliferation, but not apoptosis, is of critical significance in retinoblastoma biology. PI, as determined by the Ki-67 antigen labelling index, seems to be a relevant histopathological parameter that can predict the clinical outcome of retinoblastoma.

Apoptosis↗
PubMed1999

Similarity as a risk factor in drug-name confusion errors: the look-alike (orthographic) and sound-alike (phonetic) model.

BACKGROUND: One of every four medication errors reported in the United States is a name-confusion error. The rate of name-confusion errors might be reduced if new and confusing names were not allowed on the market and if safeguards could be put in place to avoid confusion between existing names. OBJECTIVES: To evaluate several prognostic tests of drug-name confusion, alone and in combination, with respect to their sensitivity, specificity, and overall accuracy. RESEARCH DESIGN: Case-control study. Twenty-two different computerized measures of orthographic similarity, orthographic distance, and phonetic similarity were used to compute similarity/distance scores for n = 1,127 cases (ie, pairs of names that appeared in published error reports or national error databases) and n = 1,127 controls. MAIN OUTCOME MEASURES: Mean similarity/distance scores were compared across cases and controls. The performance of each measure at distinguishing between cases and controls was evaluated by tenfold crossvalidation. Dose-response relationships were examined. Univariate and multivariate logistic regression models were formed and evaluated by 10 fold crossvalidation. RESULTS: Cases had significantly higher similarity scores than controls. Every measure of similarity proved to be a significant risk factor for error. There was a significant increasing trend in the odds-ratio as a function of similarity. A three-predictor logistic regression model had crossvalidated sensitivity of 93.7%, specificity of 95.9% and accuracy of 94.8%. CONCLUSIONS: A sensitive and specific test of drug-name confusion potential can be formed using objective measures of orthographic similarity, orthographic distance, and phonetic distance.

Analysis of Variance↗
PubMed1999

Purification and characterization of the venom phospholipases A2 from Asian monotypic crotalinae snakes.

Phospholipases A2 were purified from the venoms of Asian monotypic crotalinae snakes including Callosellasma, Hypnale, Deinagkistrodon, and Tropidolaemus by a combination of gel filtration and reversed-phase chromatographic methods. One to four isoforms of the enzyme were found in each of the venoms. The venom enzymes were subjected to N-terminal sequencing up to the 30th amino acids, and their molecular weights were analyzed by electrospray-ionization mass spectrometry. Homologous antiplatelet phospholipase with a conserved Glu 6 residue was found in each of the venoms. Basic phospholipases with Trp 6 (W6) but without detectable enzyme activities were also isolated from the venom of C. rhodostoma, H. hypnale, and T. wagleri. These W6 enzymes showed strong heparin-binding affinity and capable of inducing edema in rat paws. The fact that the venoms of Callosellasma and Hypnale contain similar types of phospholipases is in accord with recent reports that these two taxa formed a clade. Deinagkistrodon venom does not contain phospholipase variants other than the Glu-6 subtype as Trimeresurus, Agkistrodon, and Protobothrops venoms do. Interestingly, the Glu-6 enzyme from T. wagleri venom has a molecular weight of 15,319 Daltons, higher than those of most other venom phospholipases. Our results show that new types of the enzyme are more likely to be found in the venom of monotypic species; the amino acid sequence data or the subtypes of venom-phospholipases are potentially useful as markers or a character system for studying higher-order systematics of venomous snakes.

Amino Acid Sequence↗
PubMed1998

Localization of transferrin binding protein in relation to iron, ferritin, and transferrin receptors in the chicken cerebellum.

We have demonstrated that transferrin binding protein (TfBP), ferritin, and iron, are specifically localized in Bergmann glia, while the transferrin receptor is confined to Purkinje cells in the chicken cerebellum. The results of this study suggest that Bergmann glia have previously undescribed functions related to iron regulation such as sequestration of iron and the maintenance of iron homeostasis in the cerebellum.

Animals↗
PubMed1997

The structure of an RNA "kissing" hairpin complex of the HIV TAR hairpin loop and its complement.

We have used nuclear magnetic resonance (NMR) to obtain the structure of an RNA "kissing" hairpin complex formed between the HIV-2 TAR hairpin loop and a hairpin with a complementary loop sequence. Kissing hairpins are important in natural antisense reactions; their complex is a specific target for protein binding. The complex has all six nucleotides of each loop paired to form a bent quasicontinuous helix of three coaxially stacked helices: two stems plus a loop-loop interaction helix. Experimental constraints derived from heteronuclear and homonuclear NMR data on 13C and 15N-labeled RNA led to a structure for the loop-loop helix with an average root-mean-square deviation of 0.83 (+/-0.10) A for 33 converged structures relative to the average structure. The loop-loop helix of the kissing complex is distorted compared to A-form RNA. Its major groove is blocked by the phosphodiester bonds that connect the first loop residue of each hairpin with its own stem, and it is flanked by two negatively charged phosphate clusters. The loop-loop helix has alternating helical twists between adjacent base-pairs. The base-pairs at the helix junctions are overwound and three base-pairs near the helix junctions adopt high propeller twists. All these changes reduce the distance needed for the bridging phosphodiester bonds connecting each stem and loop to cross the major groove of the loop-loop helix, and result in a deformed RNA helix with localized perturbations in the minor groove surface. The alternating helical twist pattern, plus other distortions in the loop-loop helix may be important for Rom protein recognition of the kissing hairpin complex.

Bacterial Proteins↗
PubMed1997

Effects of n-3 and n-6 fatty acids on plasma eicosanoids and liver antioxidant enzymes in rats receiving total parenteral nutrition.

The effect of total parenteral nutrition (TPN) enriched with n-3 or n-6 fatty acids on the concentration of plasma eicosanoids was evaluated in rats. Rats were divided into three groups: the control group (n = 6) was fed a chow diet and infused with saline only. Two experimental groups (n = 11, 13) received TPN solutions at an energy level of 30 kcal/100g body weight with 40% energy provided as fat. The experimental groups were maintained on TPN for a period of 7 d. The basal TPN solutions were isonitrogenous and identical in nutrient composition except for differences in lipid source. One experimental group received a safflower oil emulsion, whereas the other group received a fish oil emulsion. At the end of the experimental period, plasma 6-keto prostaglandin F1 alpha, thromboxane B2, bleeding time, lipid peroxidation products, and antioxidant enzymes of liver were analyzed. The results demonstrated that the fish oil group had lower 6-keto prostaglandin F1 alpha concentration than the safflower oil group. Also, plasma thromboxane B2 was the lowest in the fish oil group among the three groups. There was no difference in bleeding time among the groups. With regard to liver lipid peroxidation products, malondialdehyde concentration was not higher in the fish oil group, whereas superoxide dismutase and glutathione peroxidase activities were lower in the fish oil group compared with the control and safflower oil groups. The results suggest that TPN prepared with fish oil fat emulsion causes less accumulation of lipid peroxidation products in the liver of rats, and may be beneficial in preventing platelet aggregation.

6-Ketoprostaglandin F1 alpha↗