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Biomedical subjects

L Y Chang

Publications and source records attributed to L Y Chang.

At least 109 records · Page 6Linked to original sources

Association of RFLP of HLA class I genes with Chinese ankylosing spondylitis patients.

By serum typing, it is indicated that HLA B27 may be associated with the susceptibility to ankylosing spondylitis (AS). We analyzed DNA restriction fragment length polymorphism (RFLP) in 28 Chinese AS patients and 99 healthy controls, using a 1.4 Kb HLA class I cDNA probe. The results showed that the frequencies of the 8.1 Kb EcoRI, 5.2 Kb EcoRI and 21.9 Kb XbaI fragments were found to be significantly increased in affected patients (P less than 0.0001, P = 0.0015, respectively), but that of 19.2 Kb XbaI fragment was decreased (P = 0.0021). The data suggest that AS may be a polygenic disease; furthermore, B27 and 8.1 Kb EcoRI band may be two different factors responsible for the susceptibility or just in linkage disequilibrium with the susceptible gene(s).

Asian People↗

Prevalence of psychiatric disorders in Taiwan defined by the Chinese Diagnostic Interview Schedule.

The Taiwan Psychiatric Epidemiological Project, conducted from 1982 to 1986, used the multistage random sampling method with 5005, 3004 and 2995 subjects selected respectively from metropolitan Taipei (MT), 2 small towns (ST) and 6 rural villages (RV). The case identification tool was the Chinese modified Diagnostic Interview Schedule (DIS-CM). This study presents the lifetime and one-year prevalence of 27 and of 17 specific psychiatric disorders respectively. The lifetime prevalence of any disorder defined by the DIS-CM -- excluding tobacco dependence -- was 16.3%, 28.0% and 21.5% in the MT, ST and RV samples respectively. The differences in lifetime prevalence between the sexes and between the 3 sampling areas were significant for 15 and 8 disorders respectively. The ST sample seemed to have the most disorders, with the highest prevalence among 3 sampling areas. The mean ratio of one-year to lifetime prevalence was 0.67. The differences in prevalence rates between the 3 sampling areas and between the international studies are discussed from methodological, social and cultural points of view.

Adolescent↗

Human IgE and IgG antibodies to mosquito proteins detected by the immunoblot technique.

Immunoblot technique was used in this study to detect IgE and IgG antibodies in human sera against mosquito antigens. Mosquito proteins were separated on SDS-polyacrylamide gels and transferred electrophoretically to nitrocellulose papers. After incubation with sera from different individuals, the precipitated bands were analyzed with enzyme-labeled goat anti-human immunoglobulins. Distinct patterns of antigen were recognized by IgE and IgG antibodies.

Adolescent↗

Effects of low levels of NO2 on terminal bronchiolar cells and its relative toxicity compared to O3.

This report describes structural changes occurring in the terminal bronchioles of rats exposed to low levels of NO2 continuously for 6 weeks. In addition, the relative susceptibility of epithelial cells to oxidants and the comparative toxicity of NO2 and O3 are discussed. Terminal bronchioles isolated from rats exposed 5 days/week to 2.0 ppm NO2 (plus two 1-hr daily spikes to 6.0 ppm) were found to have 19% less ciliated cells per unit area of epithelial basement membrane. The remaining ciliated cells had a reduced mean surface area (-29%). The shape of the Clara cell changed with reduced size of the dome protrusions but increased cell contact with the basement membrane. These data indicate that exposure to 2.0 ppm NO2 (+ spikes) for 6 weeks caused injuries to cilia and ciliated cells and possible Clara cell differentiation in the terminal bronchioles of adult rats. Exposures of adult or juvenile rats to 0.5 ppm NO2 (+ two 1-hr daily spikes 5 days/week to 1.5 ppm) did not cause morphologically measurable injuries in the terminal bronchioles. The severity of the concentration-dependent epithelial cell reactions to NO2 and O3 in adult rat terminal bronchioles were compared to those occurring in the proximal alveolar regions (PAR). Epithelial cells in the PAR appeared to be more susceptible to oxidant insult since both 0.5 ppm NO2 and 0.25 ppm O3 were found to cause epithelial injury only in the PAR. Comparison of epithelial reactions to 6-week exposures to either NO2 or O3 indicated that 0.25 ppm O3 caused four times as much increase in the number of type I epithelial cells as did 2 ppm (+spikes) NO2. Therefore, O3 could be 40 times more toxic than NO2 in the PAR on the basis of the inspired concentration and the focal response. On the other hand, there was no loss of ciliated cells following the 0.25 ppm O3 exposure. This suggests that the ratio of O3 to NO2 toxicity in the terminal bronchioles is considerably less than 10. The relative toxicity of the two oxidant gases appears to be site specific.

Animals↗

Molecular immunocytochemistry of the CuZn superoxide dismutase in rat hepatocytes.

The distribution of CuZn superoxide dismutase (SOD) molecules in subcellular organelles in rat liver hepatocytes was studied using integrated biochemical, stereological, and quantitative immunocytochemical techniques. A known concentration of purified CuZn SOD in 10% gelatin was embedded alongside the liver tissue for the calculation of CuZn SOD concentrations in hepatocyte organelles and total CuZn SOD in the rat liver. Most of the CuZn SOD was located in the cytoplasmic matrix (73.1%) and in the nucleus (11.9%) with concentrations of 1.36 and 0.71 mg/cm3, respectively. Lysosomes contained the highest concentration (5.81 mg/cm3). Only low concentrations were measured in mitochondria (0.21 mg/cm3). Membrane-bound spaces of rough endoplasmic reticulum (ER), smooth ER, and the Golgi system did not contain significant concentrations of the enzyme. By adding up the concentrations in all subcellular compartments, a total liver content of CuZn SOD was established from the immunocytochemical measurements (0.386 +/- 0.028 mg/gm liver) that agreed closely with those obtained by biochemical assays (0.380 +/- 0.058 mg/gm liver). The average distances between two CuZn SOD molecules can be calculated from enzyme concentrations. It was determined that CuZn SOD molecules in the cytoplasmic matrix and nucleus were 34 and 42 nm apart, respectively. In peroxisomes and mitochondria, average intermolecular distance increased to approximately 60 nm and increased to 136 nm in smooth ER. CuZn SOD is a relatively abundant protein in the cytosol of hepatocytes and its distribution overlaps with major sites of O2- production. The efficiency of protection CuZn SOD can provide to cytosolic proteins from attacks by superoxide anion depends on the rate of O2- production, distribution of CuZn SOD relative to cytosolic proteins, and the relative reaction rates between O2- with both cytosolic proteins and CuZn SOD. Future studies of these substrate-enzyme relationships in vivo can lead to a greater understanding of how cells handle oxidant stress.

Animals↗

Alcoholism by Chinese diagnostic interview schedule: a prevalence and validity study.

A community survey in metropolitan Taipei (MT) and two small towns (ST) by using the Chinese modified diagnostic interview schedule (DIS-CM) revealed a significant difference in the prevalence of alcohol abuse (AA) defined by DSM-III between two study samples (MT 3.4%; ST 8.0%), but the prevalence of alcohol dependence (AD) was not different (MT 1.5%; ST 1.8%). These figures are significantly higher than that of an earlier Formosan study. Demographic data, psychiatric symptoms, medical complications and impairment of social functions were adopted as the variables to validate the nosological status of AA and AD. The results of this study substantiated that AA and AD identified by the DIS-CM were nosologically different from a non-alcoholic group. The possible reasons for an increasing prevalence of alcoholism in Taiwan Chinese were discussed. An etiological hypothesis was proposed for AA and AD on account of their differential prevalences.

Adult↗

Characteristics of five monoclonal antibodies to major allergens of the short ragweed pollen.

Monoclonal antibodies against major allergens of the short ragweed pollen were produced by fusion of NS-1 cells with splenic cells from BaLB/C mice that had been immunized separately with the major allergens, AgE-B + E-C and AgK, of the short ragweed pollen. These monoclonal antibodies were detected by enzyme-linked immunosorbent assay and further characterized by immunoblot analysis using the crude extract and highly purified allergens of the ragweed pollen. Three monoclonal antibodies obtained by immunization with AgE-B + E-C, designated as 36-6, 27-2 and 48-5, reacted mainly with the beta (36-6) and alpha (27-2) subunit of AgE and both AgE and AgK (48-5), respectively. Two monoclonal antibodies obtained by immunization with AgK, 4-7 and 8-5, had a similar reactivity with AgE-B + E-C, AgK, AgK-A and AgK-B. In addition, however, antibody 4-7 also reacted with AgE-B2 as well as the 36- and the 24- to 22-kilodalton antigens of the crude extract. All 5 monoclonal antibodies were characterized as IgGl subclass. Besides, monoclonal antibody 48-5 also showed cross-reactivity to components of sage pollen. Beyond academic interests, the monoclonal antibodies described here may also be useful in clinical allergy.

Allergens↗

Progressive lung cell reactions and extracellular matrix production after a brief exposure to asbestos.

Inhaled chrysotile asbestos fibers have been shown to deposit initially on the first alveolar duct bifurcations. In brief accidental exposure to asbestos, this would be the most likely site of a significant cellular or fibrotic reaction. The characteristics and progression of tissue reactions occurring at first alveolar duct bifurcations after a single brief asbestos exposure was defined using morphometric techniques. Seven-week-old rats were exposed, nose only, for 1 hour to chrysotile asbestos fibers. After the exposure, the animals were kept in air for 2 days or 1 month, and then their lungs were fixed by vascular perfusion or by intratracheal instillation of 2% glutaraldehyde. The first bifurcations of seven alveolar ducts in each animal were isolated from plastic-embedded tissue and thin-sectioned for electron-microscopic analysis. Two days after exposure, the volume of epithelium and interstitium in the duct bifurcations had increased by 78% and 28%, respectively (P less than 0.05). The total number and volume of alveolar macrophages on the bifurcations increased about 10 times (P less than 0.05), whereas the number and volume of interstitial macrophages increased threefold (P less than 0.05). Statistically significant increases in the numbers of Type I (82%) and Type II (29%) epithelial cells also occurred. One month after the 1-hour exposure, the volume of epithelium and the number of Type I and Type II cells were still greater than control values, but these differences no longer achieved statistical significance. The volume of the interstitium, on the other hand, increased 67% (P less than 0.05), and this was accompanied by a persistently high number of interstitial macrophages, accumulation of myofibroblasts/smooth muscle cells, and an increased volume of interstitial matrix. These results demonstrate that a brief exposure to chrysotile asbestos causes a rapid response that involves an influx of macrophages to the first alveolar duct bifurcations and alterations in the alveolar epithelium. These acute structural changes are followed by a progressive response manifested by increased numbers of interstitial cells and localized interstitial fibrosis.

Aerosols↗

Co-purification of an atrial natriuretic factor receptor and particulate guanylate cyclase from rat lung.

An atrial natriuretic factor (ANF) receptor from rat lung was solubilized with Lubrol-PX and purified by sequential chromatographic steps on GTP-agarose, DEAE-Sephacel, phenyl-agarose, and wheat germ agglutinin-agarose. The ANF receptor was enriched 19,000-fold. The purified receptor has a binding profile and properties that correspond to the affinity and specificity found in membranes and crude detergent extracts. Polyacrylamide gel electrophoresis of the purified preparation in the presence of sodium dodecyl sulfate and dithiothreitol showed the presence of one major protein band with a molecular mass of 120,000 daltons. When purified preparations were incubated with 125I-ANF, then cross-linked with disuccinimidyl suberate, the 120,000-dalton protein was specifically radiolabeled. This high affinity binding site for ANF co-purified with particulate guanylate cyclase. Particulate guanylate cyclase was purified to a specific activity of 19 mumol cyclic GMP produced/min/mg of protein utilizing Mn-GTP as substrate. This represented a 15,000-fold purification compared to the initial lung membrane preparation with Lubrol-PX. Gel permeation high performance liquid chromatography and glycerol density gradient sedimentation studies of the purified preparation also resulted in co-migration of specific ANF binding and guanylate cyclase activities. The co-purification of these activities suggests that both ANF binding and guanylate cyclase activities reside in the same macromolecular complex. Presumably ANF binding occurs at the external membrane surface and cyclic GMP synthesis at the internal membrane surface of this transmembrane glycoprotein.

Animals↗

Effects of subchronic inhalation of low concentrations of nitrogen dioxide. I. The proximal alveolar region of juvenile and adult rats.

Inhalation of nitrogen dioxide (NO2) produces injury to the epithelium of terminal airways and the alveoli proximal to the airways. Techniques were devised to isolate alveolar tissue from this region for morphometric studies to define the extent of alveolar septal injury caused by NO2. One-day-old and six-week-old rats were exposed to either room air or 0.5 ppm NO2 for 23 hr per day 7 days per week for 6 weeks. An additional group of 6-week-old rats were exposed to 2.0 ppm NO2 for the same duration. Two daily hour spikes to three times the background concentrations (0.5 to 1.5 ppm and 2.0 to 6.0 ppm) were applied Monday through Friday. At the end of the exposure, rat lungs were fixed by intratracheally infusing buffered 2% glutaraldehyde. Pieces of lung tissue were embedded in large plastic blocks which were softened with heat and thin (0.3 mm) sliced. Terminal bronchioles and their corresponding proximal alveolar regions were identified from the thin plastic slices, removed, and glued to cylindrical EM blocks for thin sectioning. Morphometric analysis revealed that epithelial injury occurred in all exposed animals. The juvenile rats which had been exposed to 0.5 ppm NO2 since 1 day of age exhibited changes in the characteristics of type II epithelial cells. These cells spread to cover more alveolar surface and became thinner. Adult animals exposed to 0.5 and 2.0 ppm NO2 showed changes in alveolar macrophages and in the alveolar interstitium in addition to changes in the epithelium. Animals exposed to 0.5 ppm NO2 showed spreading and hypertrophy of type II epithelial cells. Those animals exposed to the higher concentration of NO2 had similar changes in type II epithelial cells and in addition showed an increase in type I cell number. The type I epithelial cells were smaller and covered less alveolar surface area than normal type I cells, suggesting a regenerating population of type I cells. These results suggest that prolonged exposure to low concentrations of NO2 can cause injury to the alveolar epithelium indicated initially by spreading and hypertrophy of type II cells followed by differentiation into type I cells to compensate and repair the injury. Adult rats were as sensitive or more sensitive to NO2 injury than were juvenile rats.

Aging↗

Differential distribution of brush cells in the rat lung.

The distribution of brush cells in the rat lung was studied using electron microscopic morphometry. Samples were taken from six distinctive anatomical regions. Tissue from the trachea, lobar bronchi, terminal bronchioles, first alveolar duct bifurcations, proximal alveolar regions, and the distal alveolar region were isolated and embedded in Epox 812. Aside from the trachea and the lobar bronchi, the other four regions were isolated from embedded tissue using microdissection techniques. Electron micrographs taken from thin sections of these samples were analyzed. It was found that brush cells made up 10% of the volume of epithelium covering the first alveolar duct bifurcation. Approximately 2% of the proximal alveolar epithelium, 1.4% of the terminal bronchiolar epithelium, and 3% of the tracheal epithelium were made up of brush cells. No brush-bordered epithelium was found in the lobar bronchi or in the distal alveolar walls. We conclude that brush cells have a distinct spatial location in the lung, being in high concentration in the trachea and in areas where first generation alveolar ducts bifurcate. The highest density was on the bifurcation of the first alveolar ducts, and their density decreased radially from this region.

Animals↗

Chinese diagnostic interview schedule. I. Agreement with psychiatrist's diagnosis.

NIMH-DIS was translated into Chinese and modified to the Chinese version of DIS (DIS-CM). One hundred clinical patients and 187 community subjects were studied for diagnostic agreement between the DIS-CM and the psychiatrist's clinical diagnosis. In the community sample, DIS-CM overdiagnosed the cases of manic episode, phobic disorder, obsessive-compulsive disorder and alcoholic problem, while it underdiagnosed the cases of tobacco dependence in the community sample and manic episode in the clinical cases. Standard diagnostic criteria, method of symptom detection, and social desirability, were identified as the major factors contributing to the diagnostic disparity. Variables related to life situations, language habit and medical histories were also analysed to test the external validity of the DIS-CM in case identification. The results affirm that the DIS-CM is reliable as a psychiatric epidemiological tool.

Alcoholism↗

Chinese diagnostic interview schedule. II. A validity study on estimation of lifetime prevalence.

The validity of DIS-CM (Chinese modified version of Diagnostic Interview Schedule) was examined by analyzing lifetime prevalence of each age group, age at onset, and recency of illness. The magnitude of the discrepancy between the empirical and the estimated data was adopted as the criterion of the degree of deviation. Manic and depressive episodes were found to be seriously underestimated. Schizophrenic, panic, phobic and antisocial personality disorders were probably underestimated. The observed lifetime prevalence figures with DIS-CM are rather conservative for these disorders. The prevalence data of a recent 1-year period are less biased and more reliable. The nature of the disease, recall effect, active or passive psychological resistance, mortality, and uncooperative attitude are considered factors that induce an underestimate of lifetime prevalence.

Adolescent↗

Intestinal receptor for heat-stable enterotoxin of Escherichia coli is tightly coupled to a novel form of particulate guanylate cyclase.

A novel form of particulate guanylate cyclase tightly coupled by cytoskeletal components to receptors for heat-stable enterotoxin (ST) produced by Escherichia coli can be found in membranes from rat intestinal mucosa. Intestinal particulate guanylate cyclase was resistant to solubilization with detergent alone, with only 30% of the total enzyme activity being extracted with Lubrol-PX. Under similar conditions, 70% of this enzyme was solubilized from rat lung membranes. The addition of high concentrations of sodium chloride to the extraction buffer resulted in greater solubilization of particulate guanylate cyclase from intestinal membranes. Although extraction of intestinal membranes with detergent and salt resulted in greater solubilization of guanylate cyclase, a small fraction of the enzyme activity remained associated with the particulate fraction. This activity was completely resistant to solubilization with a variety of detergents and chaotropes. Particulate guanylate cyclase and the ST receptor solubilized by detergent retained their abilities to produce cyclic GMP and bind ST, respectively. However, ST failed to activate particulate guanylate cyclase in detergent extracts. In contrast, guanylate cyclase resistant to solubilization remained functional and coupled to the ST receptor since enzyme activation by ST was unaffected by various extraction procedures. The possibility that the ST receptor and particulate guanylate cyclase were the same molecule was explored. ST binding and cyclic GMP production were separated by affinity chromatography on GTP-agarose. Similarly, guanylate cyclase migrated as a 300,000-dalton protein, while the ST receptor migrated as a 240,000-dalton protein on gel filtration chromatography. Also, thiol-reactive agents such as cystamine and N-ethylmaleimide inhibited guanylate cyclase activation by ST, with no effect on receptor binding of ST. These data suggest that guanylate cyclase and the ST receptor are independent proteins coupled by cytoskeletal components in membranes of intestinal mucosa.

Animals↗

Chimpanzee fetal G gamma and A gamma globin gene nucleotide sequences provide further evidence of gene conversions in hominine evolution.

The fetal globin genes G gamma and A gamma from one chromosome of a chimpanzee (Pan troglodytes) were sequenced and found to be closely similar to the corresponding genes of man and the gorilla. These genes contain identical promoter and termination signals and have exons 1 and 2 separated by the conserved short intron 1 (122 bp) and exons 2 and 3 separated by the more rapidly evolving, larger intron 2 (893 bp and 887 bp in chimpanzee G gamma and A gamma, respectively). Each intron 2 has a stretch of simple sequence DNA (TG)n serving possibly as a "hot spot" for recombination. The two chimpanzee genes encode polypeptide chains that differ only at position 136 (glycine in G gamma and alanine in A gamma) and that are identical to the corresponding human chains, which have aspartic acid at position 73 and lysine at 104 in contrast to glycine and arginine at these respective positions of the gorilla A gamma chain. Phylogenetic analysis by the parsimony method revealed four silent (synonymous) base substitutions in evolutionary descent of the chimpanzee G gamma and A gamma codons and none in the human and gorilla codons. These Homininae (Pan, Homo, Gorilla) coding sequences evolved at one-tenth the average mammalian rate for nonsynonymous and one-fourth that for synonymous substitutions. Three sequence regions that were affected by gene conversions between chimpanzee G gamma and A gamma loci were identified: one extended 3' of the hot spot with G gamma replaced by the A gamma sequence, another extended 5' of the hot spot with A gamma replaced by G gamma, and the third conversion extended from the 5' flanking to the 5' end of intron 2, with G gamma replaced here by the A gamma sequence. A conversion similar to this third one has occurred independently in the descent of the gorilla genes. The four previously identified conversions, labeled C1-C4 (Scott et al. 1984), were substantiated with the addition of the chimpanzee genes to our analysis (C1 being shared by all three hominines and C2, C3, and C4 being found only in humans). Thus, the fetal genes from all three of these hominine species have been active in gene conversions during the descent of each species.

Animals↗

Morphological changes in rat tracheal cells during the adaptive and early growth phase in primary cell culture.

The purpose of our studies was to determine the fate of different cell types present in early primary cultures of tracheal epithelial cells and, if possible, to elucidate the role they play in the establishment of the cultures. Epithelial cells were isolated from rat tracheas with 0.5% Pronase and were cultured on collagen-coated dishes as described previously. Light and transmission electron microscopic studies showed that the cell population harvested from rat trachea was composed of approximately 30% ciliated cells, 50% granule-containing cells and 20% undifferentiated cells (presumably basal cells). Upon seeding the tracheal cell suspensions into culture, approximately 40% of the cells attached. Cell attachment was virtually complete after 16 h. Roughly 60% of the cells attaching during the first 12 h were neither ciliated nor granulated, suggesting that undifferentiated cells played a major role in establishment of the early cultures. Between 20 and 35% of the cells attaching during this time were identified as granulated cells (mucous cells). Ciliated cells did not start to attach in significant numbers until 8 h after seeding. They never amounted to more than 8-12% of the attached cell population. After 12 h of culture, the cell population underwent a progressive loss of differentiation. The number of poorly differentiated cells (i.e. those showing neither cilia nor mucous granules) increased correspondingly. This loss of differentiation preceded the onset of DNA synthesis and cell growth which began at about 24 and 40 h, respectively. Continuous [3H]thymidine-labelling studies showed that at 48 h after the start of culture about 90% of all attached cells had entered DNA synthesis at least once. This finding is consistent with the interpretation that the ciliated cells are terminally differentiated cells and are probably the only part of the tracheal cell inoculum not participating in the growth of the cultures. At 72 h, the cultures (now in mid-log growth phase) were composed of uniformly undifferentiated cells lacking cilia and mucous granules. The cells nevertheless showed unequivocal epithelial characteristics such as tight junctions and desmosomes. The studies suggest that both basal and mucous cells are responsible for the establishment and growth of the rat tracheal epithelial cell cultures.

Animals↗