Biomedical subjects

T H Lu

Publications and source records attributed to T H Lu.

At least 37 records · Page 2Linked to original sources

PubMed2000

Induction of the heme oxygenase-1 gene by metalloporphyrins.

Induction of expression of heme oxygenase-1 (HO-1) has been studied in primary cultures of chick embryo liver cells and in the LMH line of avian hepatoma cells. Cells were transiently transfected with selected constructs containing portions of the 5'-untranslated (promoter) region of the HO-1 gene linked to luciferase as reporter gene. LMH cells that had been stably transfected with selected wild type or mutant constructs were also studied. Metalloporphyrins, especially Fe protoporphyrin (heme) and Co protoporphyrin strongly induced luciferase expression in both types of transfected cells. Low concentrations of Zn mesoporphyrin, an inhibitor of HO activity, exerted a synergistic effect on heme-, but not Co protoporphyrin-dependent induction. The antioxidant and &bond;SH donor N-acetyl cysteine had little effect on the metalloporphyrin-dependent inductions of HO-1, in contrast to its marked inhibitory effect on the sodium arsenite-dependent induction of the HO-1 gene. Deletional analysis showed that the key element(s) required for the metalloporphyrin-dependent induction of HO-1 is located between -3.6 and -5.6 kb upstream of the transcription starting point. Data from electrophoretic mobility shift and site-directed mutagenesis experiments excluded a role for consensus AP-1 binding elements at -1576, -3647, or -4578 in the inductions produced by heme or Co protoporphyrin.

Animals↗

PubMed2000

Regional mortality from motor vehicle traffic injury: relationships among place-of-occurrence, place-of-death, and place-of-residence.

Regional mortality data, which are compiled according to place-of-residence of the decedent, are an important reference for regional health planning and resource allocation. However, it would be inappropriate to apply these data to studies of environmental risk factors if a large proportion of fatal motor vehicle traffic injuries (MVTI) in fact occur outside the resident county. The aim of this study was to determine the proportion and characteristics of residents of a rural area of Taiwan who died from MVTIs that occurred outside the county of residence. We also explored the relationships among the place-of-occurrence, place-of-death, and place-of-residence of these decedents. The families or neighbors of residents of Huatung Area (eastern Taiwan) who died from MVTIs in 1994 or 1995 were interviewed to identify the place-of-occurrence of the MVTI. Of the 882 Huatung Area residents who died as a result of an MVTI during the study period and for whom relevant data were available, the MVTI occurred outside the resident county in 207 (23%) cases. Residents whose MVTI occurred outside the county of residence were more likely to be youths (aged 15-24) or young adults (aged 25-44) and driving automobiles or trucks. Of the 866 cases in which the exact place was known, the place-of-occurrence and the place-of-death (recorded on the death certificate) were in the same county in 849 (98%). Because a high proportion of fatal MVTIs occurred outside the resident county, the mortality rate calculated according to place-of-residence does not accurately reflect the environmental risk factors in this area. The finding that the characteristics of those whose MVTI occurred outside the county differed from those decedents whose MVTI occurred within the county indicates that there are two target groups for prevention programs. In addition, at least in Huatung Area, the place-of-death recorded on the death certificate could serve as a surrogate for the place-of-occurrence in epidemiologic studies.

Accidents, Traffic↗

PubMed2000

Synthesis and structural characterization of a Re(V) complex with a 2N1S donor and the radiochemical behavior of its Tc analog.

A rhenium(V) complex with 2-(2-pyridylmethylthio)-aniline has been synthesized and characterized by UV-VIS absorption, IR, MS and X-ray crystallography. The complex contains a ReO3+ moiety and the amine compound, acting as a monobasic tridentate(NSN) ligand. The chemical behavior of its technetium analog has been studied radioanalytically by solvent extraction, TLC, electrophoresis and HPLC using 99mTc tracer.

Crystallography, X-Ray↗

PubMed2000

Upstream regulatory elements in chick heme oxygenase-1 promoter: a study in primary cultures of chick embryo liver cells.

Previously, chick heme oxygenase-1 (cHO-1) gene was cloned by us and two regions important for induction by sodium arsenite were identified. These two regions were found to contain consensus sequences of an AP-1 (-1580 to -1573) and a MRE/cMyc complex (-52 to -41). In the current study, the roles of these two elements in mediating the sodium arsenite or cobalt chloride dependent induction of cHO-1 were investigated further. DNA binding studies and site-directed mutagenesis studies indicated that both the AP-1 and MRE/cMyc elements are important for the sodium arsenite induction, while cobalt chloride induction involves only the AP-1 element. Electrophoretic mobility shift assays showed that nuclear protein binding to the AP-1 element was increased by both sodium arsenite or cobalt chloride treatment, whereas the binding of proteins to the MRE/cMyc element showed a high basal expression in untreated cells and the binding activity was only slightly increased by sodium arsenite treatment. Site-directed mutagenesis studies showed that, to completely abolish sodium arsenite induction, both the AP-1 and MRE/cMyc elements must be mutated; mutation of either element alone resulted in only a partial effect. In contrast, a single mutation at AP-1 element was sufficient to reduce the cobalt chloride induction almost completely. The MRE/cMyc complex plays a major role in the basal level expression, and shares some similarities to the upstream stimulatory factor element (USF) identified in the promoter regions of mammalian HO-1 genes and other stress regulated genes. Because sodium arsenite is known to cause oxidative stress and because activation of AP-1 proteins has been shown to be a key step in the oxidative stress response pathway, we also explored the possibility that the induction of the cHO-1 gene by sodium arsenite is mediated through oxidative stress pathway(s) by activation of AP-1 proteins. We found that pretreatment with antioxidants (N-acetyl cysteine or quercetin) reduced the induction of the endogenous cHO-1 message or cHO-1 reporter construct activities induced by sodium arsenite or cobalt chloride. These antioxidants also reduced the protein binding activities to the AP-1 element in the electrophoretic mobility shift assays. In summary, induction of the cHO-1 gene by sodium arsenite or cobalt chloride is mediated by activation of the AP-1 element located at -1,573 to -1,580 of the 5'UTR.

Animals↗

PubMed2000

Accuracy of cause-of-death coding in Taiwan: types of miscoding and effects on mortality statistics.

BACKGROUND: The objectives of this study were to assess the accuracy of cause-of-death coding, determine the extent to which coders follow the selection rules of coding set out in the International Classification of Diseases, 9th Revision (ICD-9), and the effects of miscoding on mortality statistics in Taiwan. METHOD: A systematic sample of 5621 death certificates was reviewed. The underlying cause of death (UCD) selected by the reviewer for each death certificate was compared with that selected by the original coder. The UCD was selected according to ACME (Automated Classification of Medical Entities) Decision Tables. RESULTS: The overall agreement rates between the reviewer and coders according to the three-digit and two-digit categories of ICD-9 were 80.9% and 83.9%, respectively. Good agreement was found for malignant neoplasms (kappa = 0.94) and injuries and poisoning (kappa = 0.97), but there was poor agreement for nephrotic diseases (kappa = 0.74), hypertension-related diseases (kappa = 0.74), and cerebral infarction (kappa = 0.77). Reasons for disagreements included disagreement in nomenclature (42.8%), inappropriate judgement of causal relationships (41.5%), and incorrect interpretation of Selection Rule 3 and Modification Rules (15.7%). CONCLUSION: This study showed various levels of agreement for different diseases between the reviewer and the original coders in selection of the UCD. Owing to the 'compensatory effect of errors', the national mortality statistics were not affected significantly. The national administration should undertake routine internal studies to control the quality of UCD coding practices.

Age Distribution↗

PubMed2000

Structure determination of porcine haemoglobin.

To investigate a potential candidate material for making artificial red blood cells to supplement blood transfusion, the X-ray structure of porcine haemoglobin at 1.8 A resolution was determined as part of research towards synthesizing human blood. Porcine haemoglobin was crystallized by the vapor-diffusion method, producing crystals of dimensions 0.3-0.5 mm after successive seeding. The crystals belong to the orthorhombic space group P2(1)2(1)2(1), with unit-cell parameters a = 68.10, b = 72.27, c = 114.85 A. The initial phase was determined by the molecular-replacement method, using human oxyhaemoglobin as a model. The final R factor was 21.1% for 36 820 reflections after validation of 574 water molecules. The r.m.s. deviations of bond lengths, angles, torsion angles and improper angles from their ideal values are 0.017 A, 3.0, 20.6 and 1.8 degrees, respectively. The average B factor is 33.63 A(2) for the haemoglobin molecule and 50.53 A(2) for the water molecules. The structure could be superimposed on a 2.8 A resolution structure with an r.m.s. difference of 0.59 A in main-chain atomic positions and 1. 27 A in side-chain atomic positions. Porcine and human haemoglobins are compared. A tentative model for artificial blood is proposed based on the complementarity relationship of the surface charges between haemoglobin and the surrounding cell membrane.

Amino Acid Sequence↗

PubMed2000

Crystallization of agglutinin from the seeds of Abrus precatorius.

Agglutinin protein purified from the seeds of Abrus precatorius has a high antitumour activity and was crystallized at room temperature with polyethylene glycol 8000 as the precipitant. The agglutinin crystal diffracted to 3.45 A and belongs to one of two possible tetragonal space groups, P4(1)2(1)2 or P4(3)2(1)2, with unit-cell parameters a = b = 141.91, c = 105.63 A. The asymmetric unit contains a heterotetrameric protein molecule of molecular weight 134 kDa and has a solvent content of approximately 38%.

Crystallization↗

PubMed1999

Demographic characteristics of fathers of infants born to adolescent mothers in Taiwan.

It has been well accepted that effective programs for prevention of adolescent pregnancy should involve adolescent women and their partners. Using data from certificates of live births in Taichung County, Taiwan, in 1994, the demographic characteristics of fathers whose infants were born to adolescent women were compared with a matched group fathers whose infants were born to women aged > or =20 years. Most of the fathers of infants born to adolescent women were adults: 57% of the fathers of infants born to women aged < or =15 years were > or =30 years of age. Fathers of infants born to adolescent women had a lower educational level than that of matched fathers. These demographic characteristics of fathers should be carefully interpreted and taken into consideration in developing intervention programs.

Adolescent↗

PubMed1998

Molecular cloning, characterization, and expression of the chicken heme oxygenase-1 gene in transfected primary cultures of chick embryo liver cells.

Using chick heme oxygenase-1 (cHO-1) cDNA as a probe, three independent clones were identified from screening a lambda FixII chick genomic library. Genomic Southern blots using this cDNA probe or a cHO-1 5' specific probe showed that cHO-1 is a single-copy gene. Based on restriction enzyme analysis, Southern blots, polymerase chain reaction analysis and DNA sequencing, it was confirmed that the three overlapping clones isolated cover the entire cHO-1 gene, as well as approximately 10 kb of the flanking regions on both ends. As with mammalian HO-1x, cHO-1 has five exons and four introns. Computer analysis of the DNA sequence obtained identified consensus sequences corresponding to numerous transcription factor recognition elements. These include AP-1, AP-2, NF-kB, C/EBP, c-Myc and a metal-responding element identified in the promoter region, and two Sp-1 elements in intron 1. Transient expression studies in transfected primary cultures of chick embryo liver cells showed that a CAT reporter gene construct containing 2.8 kb of the cHO-1 promoter region responded to sodium arsenite, H2O2, transition metals and 12-0-tetradecanoylphorbol 13-acetate, but not to heme. Studies with deletion mutants, consisting of various lengths of the cHO-1 promoter region, indicated that there are two regions important for sodium arsenite induction, one located between residues -1642 and -1293, and the second located in the first 263 base pairs of the cHO-1 promoter. DNA binding studies by electrophoretic mobility shift assay showed that nuclear protein isolated from primary cultures of chick embryo liver cells bound to the oligonucleotide probe containing an AP-1 element identified at -1573 to -1580. In addition, such binding was increased by cobalt or sodium arsenite treatment.

Animals↗

PubMed1998

Association of parental characteristics with adverse outcomes of adolescent pregnancy.

BACKGROUND: It is well-known that pregnancy in adolescence has an increased risk of adverse reproductive outcomes. It remains unclear whether this association is due mainly to the unfavourable sociodemographic status or due solely to biological immaturity of pregnant adolescents. OBJECTIVE: The purpose of this study was to determine the association of parental sociodemographic characteristics with the adverse outcomes of adolescent pregnancy. METHOD: Data from certificates of live births in Taichung County, Taiwan in 1994 of 7994 singleton, first-born babies whose mothers were 15-34 years of age were analysed. The relative risk of having adverse pregnancy outcomes for adolescent subgroups was obtained as compared with that among mothers 20-34 years of age with the same characteristics. The adjusted relative risk of having adverse pregnancy outcomes for each covariate was calculated by a multiple logistic regression analysis. RESULTS: Of 7994 babies born to mothers of 15-34 years of age, 8.3% were born to adolescent mothers. In all age groups, the younger adolescent mothers (15-17 years of age) had the highest percentage of both infants with low birth weight (10.6%) and preterm births (7.1 %). Younger adolescent mothers in almost all sociodemographic categories had higher risks of having both low-birth-weight and preterm births than those of older adolescent mothers. Multiple logistic regression analysis showed that a younger maternal age is the only significant risk factor for having infants with low birth weight (adjusted RR = 2.5, 95% Cl 1.8-4.5 and adjusted RR = 1.7, 95% Cl 1.2-2.6 for younger and older adolescent mothers, respectively) or preterm birth (adjusted RR = 1.9, 95% Cl 1.1-3.4 and adjusted RR = 1.5, 95% Cl 1.0-2.3 for younger and older adolescent mothers, respectively). CONCLUSIONS: Adolescent pregnancy carries an increased risk of having low-birth-weight and preterm births, and a younger maternal age is causally implicated.

Adolescent↗

PubMed1998

Trends in injury mortality among adolescents in Taiwan, 1965-94.

OBJECTIVES: To describe trends in injury mortality among adolescents in Taiwan for prioritising preventive interventions. METHODS: Adolescent injury mortality data for Taiwan were derived from official publications of vital statistics from 1965 to 1994 to determine trends by sex and cause of death. Simple linear regression was used to test the trends. RESULTS: The number of deaths due to injury among adolescents aged 10-19 years in Taiwan increased from 983 in 1965 to 1783 in 1994, an 81% increase. The injury mortality rate increased 42%, from 32.2 per 100,000 in 1965 to 45.6 per 100,000 in 1994. The proportion of injury deaths also increased, from 45.3% in 1965 to 72.8% in 1994. The trends in mortality from motor vehicle injury (MVI) among four demographic groups were all significantly positive (p < 0.001). The proportion of deaths due to MVI among injury was 14% in 1965 and increased to 63% in 1994. CONCLUSIONS: The increase in injury mortality rates among adolescents over the past three decades appears to be due largely to the increase in MVI mortality rates with males aged 15-19 years accounting for most of this increase. Priorities for adolescents in Taiwan are MVI (especially motorcyclists) and drownings.

Accidents↗

PubMed1998

Factors related to adolescents' perceptions of treatment outcomes in an adolescent health clinic.

To determine factors related to adolescents' perceived treatment outcomes of their health problems in an adolescent health clinic located at a college hospital, 246 adolescent patients between the ages of 11 and 21 who visited the clinic twice or more during the period January 1994 to December 1995 were included in this study. Information concerning adolescents' sociodemographic characteristics, family function, office visits and health problems of first visits was collected by reviewing subjects' medical and other clinic-related records. In addition, a structured questionnaire was mailed to assess subjects' satisfaction with physicians and the environment and services provided by the clinic as well as their perceived treatment outcomes. 148 patients completed the questionnaire, a response rate of 60.2%. Most of the respondents were in late-stage adolescence (71.0%) and were in school (71.0%). About half of respondents had normal family function, while the other half had moderate or severe family dysfunction. Most of the health problems of respondents were acute (64.2%) and were biological (76.4%) conditions. Most of the respondents were satisfied with the various characteristics of physicians except confidentiality emphasized by the physicians, while many fewer respondents were satisfied with the environment and services provided by the clinic. Family function, physicians' respect toward the adolescents, and the adolescents' satisfaction with the services provided in general were the factors significantly related to adolescents' perceived treatment outcomes based on a stepwise, multiple logistic regression analysis. We conclude that efforts to provided could result in better adolescent perceived treatment outcomes.

Adolescent↗

PubMed1997

Regulation of expression of the human heme oxygenase-1 gene in transfected chick embryo liver cell cultures.

Induction of heme oxygenase (HO) has been proposed as a protective cellular mechanism against oxidative damage. In previous work (Tyrrell et al., Carcinogenesis [1993] 14, 761-765), portions of the 5' promoter region of the human HO-1 gene linked to the reporter gene chloramphenicol acetyl transferase (CAT), had been transiently expressed in HeLa cells. To extend the study of human HO gene expression into primary liver cells, these reporter gene fusion constructs, containing 121 or 1416 base pairs of the untranscribed 5'-upstream sequences of the human HO-1 gene, were used along with pSV beta-Gal plasmid to dually transfect primary cultures of chick embryo liver cells (CELC). The transfected cells were treated with selected metals, heme, phorbol ester, and chemical agents that produce oxidative stress (H2O2 or sodium arsenite). Reporter gene activities were measured 18-20 h later. Our major findings are: (1) these HO-CAT constructs were expressed in CELC; (2) unlike HeLa cells, the expression of CAT was detected in CELC without the need for the SV40 enhancer; (3) sodium arsenite and cobalt chloride induced the expression of the HO-CAT constructs whereas heme had no effect on or decreased CAT expression for all of the transfected constructs; (4) study of endogenous chick HO-1 gene expression in CELC showed that HO-1 responded to sodium arsenite treatment in a dose-dependent fashion, and the response was rapid and transient. We conclude that, in chick liver cell cultures, induction of the HO-1 gene by heme is fundamentally different from that produced by transition metals or sodium arsenite. Furthermore, the results suggest that expression of the HO-1 gene is highly conserved across species.

Animals↗

PubMed1997

Actin-binding membrane proteins identified by F-actin blot overlays.

Actin and associated proteins at the cytoskeleton-plasma membrane interface stabilize the membrane bilayer, control cell shape, and delimit specialized membrane domains. To identify membrane proteins that bind directly to F-actin, we have developed a blot overlay assay with 125I-labeled F-actin. In the soil amoebae, Dictyostelium discoideum, the major proteins reactive in this assay are p30a, a 34-kD peripheral membrane protein that is concentrated in filopodia and at sites of cell-cell adhesion, and ponticulin, a 17-kD transmembrane glycoprotein required for efficient chemotaxis and for control of pseudopod dynamics. Proteins with apparent molecular masses of approximately 34- and approximately 17-kD also are observed on F-actin blot overlays of many mammalian cell lines. However, in mammalian cells, the most prominent F-actin binding proteins in this assay exhibit apparent molecular masses of 78-, 80-, 81-, approximately 120-, and 205-kD. Bovine neutrophils contain the 78-, 81-, and 205-kD proteins, all of which co-isolate with a plasma membrane-enriched fraction. We have previously identified the 78-, 80-, and 81-kD proteins as moesin, radixin, and ezrin, respectively. These proteins, which are members of the protein 4.1 superfamily, colocalize with actin in cell surface extensions and have been implicated in the protrusion of microvilli, filopodia, and membrane ruffles. The 205-kD protein (p205) appears to be absent from current databases, and its characteristics are still under investigation. We here report that the 120-kD protein is drebrin, a submembranous actin-binding protein originally identified as a developmentally regulated brain protein. Thus, it appears that F-actin blot overlays provide an efficient assay for simultaneous monitoring of a subset of F-actin binding proteins, including p30a, ponticulin, moesin, radixin, ezrin, p205, and drebrin.

3T3 Cells↗

PubMed1997

Characteristics of adolescent patients and their health problems at an adolescent health clinic.

In Taiwan, there has been an increase in biopsychosocial morbidity among adolescents in the past ten years, but neither an adolescent health care delivery system nor a subspecialty training program in adolescent medicine has been hitherto established. To better understand the characteristics of adolescent patients and their health problems, the sociodemography and health problems of all adolescent patients aged 11 to 21 years who visited the Adolescent Health Clinic twice or more during January, 1994 and December, 1995 at a college hospital, were analysed by reviewing patients' medical records and the adolescent registration records. There were totally 264 adolescent patients with an average age of 18.7 +/- 3.4 years. The number of female adolescents involved in the study (139 persons or 52.7%) was little more than that of male adolescents. Most of the adolescent patients (67.4%) were in late stage of adolescence; in addition, most of them (81.4%) were students. During the 2-year study period, there was a total of 350 independent health problems among 957 office visits made by the 264 patients, averaging 1.3 problems and 2.7 office visits per patient and per problem, respectively. Supplementary classification, mental disorders, and respiratory system diseases were the three leading disease classifications, occupying 66.6% of all disease classifications. General medical examination, upper respiratory tract infection, and immunization were more common among all individual diagnoses. Regarding gender difference in the encountered health problems, hepatitis B, office visiting for counseling, and conductive disorder, were more prominent in the male adolescents, whereas upper respiratory tract infection, goiter, acne vulgaris, peptic ulcer disease, migraine, and eating disorders were more common in the female adolescents. Moreover, the patients in the different stages of adolescence had their unique health problems. It was concluded that there were variations in the health problems encountered among adolescents of different genders and of the different stages of adolescence.

Adolescent↗

PubMed1996

Regulation of metallothionein gene expression. Studies in transfected primary cultures of chick embryo liver cells.

To study the regulation of expression of the metallothionein gene in normal liver cells, we transfected chick embryo liver cells in primary cultures with constructs containing luciferase or chloramphenicol acetyl transferase (as reporter genes) under the control of differing lengths of the 5'-promoter region of the chick metallothionein gene (containing 30, 122, 190, or 623 base pairs upstream of the transcriptional start site). We controlled for efficiency of transfection by co-transfections with a plasmid containing a bacterial beta-galactosidase gene under the control of the SV 40 promoter and enhancer. Treatment of the transfected cells with transition metallic ions (cadmium, cobalt, and zinc) or sodium arsenite produced increases in activities of luciferase or chloramphenicol acetyl transferase, relative to beta-galactosidase, and this activity mapped to the first 122 base pairs of the promoter. Although heme has recently been reported to induce the endogenous metallothionein gene in chick embryo liver cells, 10-50 microM heme did not increase reporter gene activities in transfected cells. Nevertheless, the heme-dependent induction of endogenous heme oxygenase-1 in these cells was normal. We conclude that the heme-dependent induction of the liver metallothionein gene depends upon DNA region(s) outside the regulatory region of the chick metallothionein gene studied here and that elements within the first 122 base pairs of the metallothionein promoter are sufficient to confer responsiveness to transition metals or sodium arsenite.

Animals↗

PubMed1995

Crystal structure of abrin-a at 2.14 A.

The crystal structure of abrin-a, a type II ribosome-inactivating protein from the seeds of Abrus precatorius, has been determined from a novel crystalline form by the molecular replacement method using the coordinates of ricin. The structure has been refined at 2.14 A to a R-factor of 18.9%. The root-mean-square deviations of bond lengths and angles from the standard values are 0.013 A and 1.82 degrees, respectively. The overall protein folding is similar to that of ricin, but there are differences in the secondary structure, mostly of the A-chain. Several parts of the molecular surface differ significantly; some of them are quite near the active site cleft, and probably influence ribosome recognition. The positions of invariant active site residues remain the same, except the position of Tyr74. Two water molecules of hydrogen-bonded active site residues have been located in the active site cleft. Both of them may be responsible for hydrolyzing the N-C glycosidic bond. The current abrin-a structure is lactose free; this is probably essential for abrin-a crystallization. The B-chain is a glycoprotein, and the positions of several sugar residues of two sugar chains linked to earlier predicted glycosylation sites were determined. One of the sugar chains is a bridge between two neighboring molecules, since one of its mannose residues is connected to the galactose binding site of the neighboring molecule. Another sugar chain covers the surface of the B-chain.

Abrin↗

PubMed1994

A new crystal form of abrin-a from the seeds of Abrus precatorius.

A new crystal form of abrin-a from the seeds of Abrus precatorius has been obtained by vapor diffusion method. The abrin-a crystals belong to monoclinic space group P2(1) with cell dimensions a = 84.58 A, b = 73.07 A, c = 48.23 A, beta = 96.20 degrees. An asymmetric unit contains one protein molecule of molecular weight 65 kDa and has a solvent content of approximately 46%.

Abrin↗