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Biomedical subjects

Y F Chang

Publications and source records attributed to Y F Chang.

At least 55 records · Page 3Linked to original sources
PubMed1997

Borrelia burgdorferi migrates into joint capsules and causes an up-regulation of interleukin-8 in synovial membranes of dogs experimentally infected with ticks.

Twenty 6-week-old specific-pathogen-free beagles were infected with Borrelia burgdorferi by tick challenge, and five uninfected dogs served as controls. During the study, all dogs were monitored for infection, clinical signs, and antibody response against B. burgdorferi. During episodes of lameness or postmortem, synovial fluids from each dog were examined for volume, cell number, polymorphonuclear leukocyte (PMN) content, cell viability, and chemotactic activity. Twenty-five tissues collected postmortem from each dog were tested for interleukin-8 (IL-8) mRNA, tumor necrosis factor alpha (TNF-alpha) mRNA, presence of live spirochetes, and histopathological changes. Thirteen infected dogs (group A), which seroconverted rapidly (maximum titers within 50 to 90 days), developed acute and severe mono- or oligoarthritis almost exclusively in the limb closest to the tick bite (median incubation period, 66 days). Synovial fluids of the arthritic joints collected during episodes of lameness had significantly elevated volume, cell count, PMN proportion, cell viability, and chemotactic activity for PMNs. The remaining joints of the same animals contained synovial fluids with elevated chemotactic activity and cell viability. Twelve dogs tested positive for IL-8 mRNA in multiple tissues (synovia, pericardium, and peritoneum), and 10 dogs expressed TNF-alpha mRNA, but only in the tributary lymph nodes of the inflamed joints. Histological examinations revealed severe poly- or oligoarthritis and moderate to severe cortical hyperplasia in draining lymph nodes of the inflamed joints in all 13 dogs. Seven infected dogs with mild or no clinical signs (group B) seroconverted slowly (peak titers after 90 days), and only some joint fluids showed chemotactic activity, which on average was lower than that in inflamed and noninflamed joints from dogs in group A. Four dogs expressed IL-8 mRNA (in the synovia and pericardium), and three dogs had TNF-alpha mRNA in tributary lymph nodes. Histologically, nonsuppurative arthritis was found in multiple joints, and mild to moderate cortical hyperplasia was found in draining lymph nodes. Five uninfected dogs without lameness (group C) had normal synovial fluids and tissues. In all infected dogs, live spirochetes were demonstrated more frequently in tissues of the somatic quadrant closest to the tick bite than in tissues further from the site of infection, suggesting that dissemination of B. burgdorferi occurs more by migration than by blood-borne spread. From these studies employing a canine model of B. burgdorferi infection, we conclude that IL-8 is involved in the pathogenesis of acute Lyme arthritis.

Animals↗
PubMed1997

Persistence of Borrelia burgdorferi in experimentally infected dogs after antibiotic treatment.

In specific-pathogen-free dogs experimentally infected with Borrelia burgdorferi by tick exposure, treatment with high doses of amoxicillin or doxycycline for 30 days diminished but failed to eliminate persistent infection. Although joint disease was prevented or cured in five of five amoxicillin- and five of six doxycycline-treated dogs, skin punch biopsies and multiple tissues from necropsy samples remained PCR positive and B. burgdorferi was isolated from one amoxicillin- and two doxycycline-treated dogs following antibiotic treatment. In contrast, B. burgdorferi was isolated from six of six untreated infected control dogs and joint lesions were found in four of these six dogs. Serum antibody levels to B. burgdorferi in all dogs declined after antibiotic treatment. Negative antibody levels were reached in four of six doxycycline- and four of six amoxicillin-treated dogs. However, in dogs that were kept in isolation for 6 months after antibiotic treatment was discontinued, antibody levels began to rise again, presumably in response to proliferation of the surviving pool of spirochetes. Antibody levels in untreated infected control dogs remained high.

Animals↗
PubMed1997

Dog bite incidence in the city of Pittsburgh: a capture-recapture approach.

OBJECTIVES: The purpose of this study was to estimate the number of dog bite injuries occurring in the city of Pittsburgh in 1993. METHODS: The capture-recapture method was used, along with long-linear modeling. Three sources were used to identify victims hospital reports, animal control reports, and police/victim reports. RESULTS: In 1993, 790 dog bites were reported. The capture-recapture method estimated that there were 1388 unreported dog bites, with an estimated incidence rate of 58.9 per 10,000. CONCLUSIONS: Dog bite is a common our preventable injury. To improve surveillance, the focus should be on educating the general public about the serious consequences of dog bite injuries.

Animals↗
PubMed1997

Evaluation of CLO test and polymerase chain reaction for biopsy-dependent diagnosis of Helicobacter pylori infection.

Helicobacter pylori is now recognized as possibly playing an etiologic role on the development of chronic gastritis, peptic ulcers and adenocarcinoma of the distal stomach. CLO test and polymerase chain reaction (PCR) assay are rapid, biopsy-dependent diagnostic tests for H. pylori identification. In this study, we assessed four diagnostic methods (CLO test, PCR assay, culture and histological examination) for H. pylori detection in biopsy specimens from 78 patients with gastroduodenal diseases and investigating the efficiency of CLO test and PCR assay for the diagnosis of H. pylori infection. H. pylori was identified in 75.6%, 75.6%, 64.1%, 69.2% of patients by CLO test, PCR assay, culture and histological examination, respectively. Compared with the detection of H. pylori by culture and/or histological examination, the sensitivity and specificity of the CLO test were 98.2% and 81.8%, respectively, whereas the sensitivity and specificity of PCR assay were 96.4% and 77.3%, respectively. According to the H. pylori infection state as determined from the results of three concordant tests, the sensitivities of culture, CLO test, histological examination, and PCR assay were 90.9%, 96.4%, 98.2% and 100%, respectively. Whereas, the specificity was 100%, 95%, 95% and 90% for culture, CLO test, histological examination, and PCR assay, respectively. We found that both CLO test and PCR assay were highly sensitive and specific for H. pylori identification; however, PCR assay was more sensitive than other methods for detecting the specimens after patients received treatment. The results of this study suggest that CLO test is a rapid and sensitive method of screening for H. pylori infection and that PCR assay could provide an accurate indication of the state of infection both during treatment for eradication of H. pylori and at follow-up.

Biopsy↗
PubMed1997

Sequence of a human E2F-4 pseudogene with shortened AGC trinucleotide repeats.

We have isolated a human genomic DNA fragment of 0.7 kb by polymerase chain reaction (PCR) using human E2F-4 gene primers. Sequence analysis indicates that this DNA comes from a processed E2F-4 pseudogene. Its sequence is 75% identical to the human E2F-4 cDNA, and bears several deletions and insertions. A 30 bp deletion shortens the 13 AGC repeats in the E2F-4 gene by 10 repeats. The sequence data also suggest that another 65 bp deletion and some small insertions may be generated by replication errors on template pairing.

Amino Acid Sequence↗
PubMed1996

DNA aptamers block L-selectin function in vivo. Inhibition of human lymphocyte trafficking in SCID mice.

Selectins participate in the initial events leading to leukocyte extravasation from the blood into tissues. Thus the selectins have generated much interest as targets for antiinflammatory agents. Therapeutic molecules based on the monomeric carbohydrate ligand sialyl Lewis X (SLe(X)) have low affinities and are not specific for a given selectin. Using SELEX (Systematic Evolution of Ligands by EXponential Enrichment) technology, we have generated aptamers specific for L-selectin that require divalent cations for binding and have low nanomolar affinity. In vitro, the deoxyoligonucleotides inhibit L-selectin binding to immobilized SLe(X) in static assays and inhibit L-selectin-mediated rolling of human lymphocytes and neutrophils on cytokine-activated endothelial cells in flow-based assays. These aptamers also block L-selectin-dependent lymphocyte trafficking in vivo, indicating their potential utility as therapeutics.

Animals↗
PubMed1996

Characterization of L-alpha-aminoadipic acid transport in cultured rat astrocytes.

The mechanism of the selective gliotoxicity of L-alpha-aminoadipate (L-alpha AA) is thought to involve its entry into glia as a substrate for glutamate transporters or, alternatively, its ability to inhibit glial glutamate transport. To clarify the properties of L-alpha AA as a transport substrate, we explored the ionic dependence, kinetics and pharmacology of L-[3H] alpha AA uptake in rat cortical astrocytes. We observed two components of saturable L-alpha AA uptake, one Na(+)-dependent and the other Na(+)-independent. These components exhibited the characteristics of system X-AG, the widespread family of Na(+)-cotransporters of aspartate and glutamate, and system x-c, a Cl(-)-dependent glutamate/cystine exchanger, respectively. The K(m) value of Na(+)-dependent L-alpha AA uptake was 629 +/- 42 microM, and Vmax was 62 +/- 4 nmol.min-1.mg-1 protein, which was more than twice the capacity of Na(+)-dependent glutamate uptake. The kinetic parameters of Na(+)-dependent L-alpha AA uptake (K(m) of 20 +/- 2 microM, Vmax of 1.7 +/- 0.4 nmol.min-1.mg-1 protein did not differ from the values for Na(+)-independent glutamate uptake, indicating that L-alpha AA and glutamate are equally good substrates for system x-c.

2-Aminoadipic Acid↗
PubMed1996

Identification of a locus involved in the utilization of iron by Actinobacillus pleuropneumoniae.

The cloned afu locus of Actinobacillus pleuropneumoniae restored the ability of an Escherichia coli K-12 mutant (aroB) to grow on iron-limited media. DNA sequence analysis of the fragment showed that there are three genes designated afuA, afuB and afuC (Actinobacillus ferric uptake) that encode products similar to the SfuABC proteins of Serratia marcescens, the HitABC proteins of Haemophilus influenzae, the FbpABC proteins of Neisseria gonorrhoeae and the YfuABC proteins of Yersinia enterocolitica. The three genes encode a periplasmic iron-binding protein (AfuA), a highly hydrophobic integral cytoplasmic membrane protein with two consensus permease motifs (AfuB) and one hydrophilic peripheral cytoplasmic membrane protein with Walker ATP-binding motifs (AfuC), respectively. This system has been shown to constitute a periplasmic binding protein-dependent iron transport system in these organisms. The afuABC operon is locating approximately 200 bp upstream of apxIC gene, but transcribed in opposite direction to the ApxI-toxin genes.

Actinobacillus pleuropneumoniae↗
PubMed1996

Calcium-dependent oligonucleotide antagonists specific for L-selectin.

The selectins are calcium-dependent C-type lectins that recognize complex anionic carbohydrate ligands, initiating many cell-cell interactions in the vascular system. Selectin blockade shows therapeutic promise in a variety of inflammatory and postischemic pathologies. However, the available oligosaccharide ligand mimetics have low affinities and show cross-reaction among the three selectins, precluding efficient and specific blockade. The SELEX (systematic evolution of ligands by exponential enrichment) process uses combinatorial chemistry and in vitro selection to yield high affinity oligonucleotides with unexpected binding specificities. Nuclease-stabilized randomized oligonucleotides subjected to SELEX against recombinant L-selectin yielded calcium-dependent antagonists with approximately 10(5) higher affinity than the conventional oligosaccharide ligand sialyl LewisX. Most of the isolated ligands shared a common consensus sequence. Unlike sialyl LewisX, these antagonists show little binding to E- or P-selectin. Moreover, they show calcium-dependent binding to native L-selectin on peripheral blood lymphocytes and block L-selectin-dependent interactions with the natural ligands on high endothelial venules.

Base Sequence↗
PubMed1996

Paclitaxel-induced apoptosis in human gastric carcinoma cell lines.

BACKGROUND: Gastric cancer is one of the most common cancers in Asia. Chemotherapy and radiation therapy have had limited success. Recently, paclitaxel has been found to be effective against a variety of cancers, including lung, breast, ovary, melanoma, and prostate. Whether paclitaxel is effective in the treatment of gastric cancer is not known and is worthy of investigation. METHODS: Human gastric carcinoma cell lines NUGC-3 and SC-M1 were examined for response to paclitaxel treatment. Cancer cells were treated with paclitaxel (0.001, 0.01, 0.1, and 1 microM) for 1-3 days. Cell number was counted by hemocytometer and cell viability was determined by the trypan blue exclusion method. Cell cycle progression and expression of proliferating cell nuclear antigen (PCNA) were examined by flow cytometry. The percentage of apoptotic cells was determined after staining with hematoxylin and eosin. RESULTS: Paclitaxel was cytotoxic to the two human gastric carcinoma cell lines examined. The growth-inhibiting dose was 0.01 microM. Paclitaxel-treated gastric carcinoma cells were arrested mainly in G2/M phases before apoptosis. However, treatment with 0.01 microM of paclitaxel resulted in a decrease of cells at G0/G1 phases without an increase of cells at G2/M phase indicating that paclitaxel was also cytotoxic to gastric carcinoma cells at G0/G1 phases. In addition, the expression of PCNA was significantly increased in 0.1 and 1 microM paclitaxel-treated cells, suggesting that DNA repair was increased in these cells. CONCLUSIONS: Paclitaxel is effective in growth inhibition of gastric carcinoma cell lines in clinically attainable concentrations. Our results suggest that paclitaxel is a potential chemotherapeutic drug for gastric carcinoma.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Global epidemiology and public health in the 21st century. Applications of new technology.

Epidemiology and public health need to change for the upcoming problems of the 21st century and beyond. We outline a four-point approach to produce this change. The first one is to take a systems approach to disease. The second approach discussed is the use of new techniques to "count" disease using capture-recapture. The third represents the application of telecommunications, especially the Internet, to public health. The fourth and final component represents the application, at the local health department level, of a total quality approach, as espoused by Deming, for the prevention of disease.

Computer Communication Networks↗
PubMed1996

Calendar time trends of the insulin-dependent diabetes mellitus mortality in Allegheny county, Pennsylvania.

This study applied a Cox proportional hazard model to investigate the calendar time trends of insulin-dependent diabetes mellitus (IDDM) mortality. The study population was the IDDM patients who were diagnosed in the period 1965-1979, less than or equal to 19 years of age at diagnosis, and were residents of Allegheny County, PA. The mortality follow-up for each individual was recorded from the diagnosis of IDDM and till 31 December 1990. There were 999 individuals in this study, and 68 deaths (6.8%) occurred during this 26-year investigation period. Overall, for the patients with the same IDDM duration, non-whites were 1.7 times more likely to die than white group; female IDDM patients had a higher risk of death than male IDDM patients (1.27:1); and the risk of mortality increased as the age at diagnosis increased. When controlling for the gender, ethnic groups and age at onset effect, the risk of dying in different calendar years appeared to be a quadratic form. The highest mortality appeared in the late 60's, and the lowest was in the period of 1975-1979. Disappointingly the mortality has begun to rise again in the latest time frame.

Adolescent↗
PubMed1996

Lyme disease: laboratory diagnosis of infected and vaccinated symptomatic dogs.

Serological assays for detection of canine antibodies to the Lyme agent generally have been difficult to validate because an acceptable standard of comparison such as unequivocal proof of infection status has not been available. For practical and logistical reasons, it has not been possible to use culture of organism from infected animals, seroconversion in a large number of field dogs, or clinical criteria as the standard of comparison for validation of assays. Therefore, estimates of diagnostic sensitivity and specificity based on an appropriate gold standard have not been available. When it was discovered how to infect laboratory dogs via ticks infected with Borrelia burgdorferi, it was possible to define the kinetics and magnitude of the antibody response that might be expected in nature. ELISA and Western immunoblot data from experimental dogs were then compared and correlated with results of the same tests on dogs from endemic and nonendomic areas. Coupled with studies on cross-reactive antibodies elicited from other infectious agents or autoimmune phenomena, it was possible to account for interfering antibodies and to establish estimates of diagnostic sensitivity and specificity for the ELISA based on objective criteria. Such validated assays can predict, with a relatively high degree of proficiency, the infection and/or vaccinal status of animals. These assays have shown that some dogs, vaccinated with the commercially available whole-cell Lyme bacterins develop typical signs of Lyme disease but have no evidence of an underlying infection; antibody elicited only by the vaccine and not by infection is detectable in these animals. Western immunoblot can also confirm infection in animals of equivocal ELISA status if their bands have been evaluated for specificity of antibodies to B burgdorferi. Serology can be a very useful aid in the diagnosis of Lyme disease, but it requires that the assays used have been subjected to rigorous validation criteria. When that is not performed, an unacceptable level of false-positive and false-negative test results is virtually assured.

Animals↗
PubMed1995

Interaction of streptokinase and plasminogen. Studied with truncated streptokinase peptides.

The interaction of streptokinase (SK) with human plasminogen (HPlg) was investigated using truncated SK peptides prepared by gene cloning techniques. SK(16-414) and SK(16-378) could activate HPlg as efficiently as the authentic SK. SK(60-414), which had been preincubated with SK(1-59), could also activate HPlg. SK(91-414), SK(127-414), and SK(158-414), at a concentration of one-tenth of HPlg, all failed to activate HPlg. However, the truncated SK peptides in complexes with equimolar HPlg could form amidolytically active virgin enzymes that slowly converted to human plasmin (HPlm) after a lag period of 15 min. SK(16-316) could not activate HPlg. No virgin enzyme was detected when SK(16-316) was incubated with equimolar HPlg, but the HPlg in the complex was modified to HPlm after reaction for 20 min. SK(220-414) and SK(16-251) had no ability to transform HPlg to virgin enzyme or to HPlm in equimolar complex with HPlg, although they could bind to HPlg. The functions of five regions in the SK molecule (a, Ile1-Lys59; b, Ser60-Asn90; c, Val158-Arg219; d, Tyr252-Ala316; e, Ser317-Ala378) in interaction with HPlg are deduced. Region a is important in stabilizing the conformation of the SK molecule, and region b is essential for HPlg activation. Region c is required for induction of the conformational changes of HPlg to virgin enzyme. Regions c and d are required for the conversion of HPlg to HPlm in the HPlg.SK equimolar complex. Coordination of regions c, d, and e of SK is essential for a virgin enzyme formation, and coordination of regions b, c, d and e is required for an effective SK-type HPlg activator.

Base Sequence↗
PubMed1995

Efficiency and accuracy of disease monitoring systems: application of capture-recapture methods to injury monitoring.

Capture-recapture methods were employed to determine the most accurate and efficient approaches to monitor adolescent injuries. Multiple sources were used to ascertain cases of adolescent injuries that occurred between September 1 and December 31, 1991, in a single school district in metropolitan Pittsburgh, Pennsylvania. Eliminating the duplicate cases between the sources revealed 144 verified injuries; 127 (88.2%) were identified by student monthly recalls, 33 (22.9%) by daily attendance records, 58 (40.3%) by medical excuses, and 72 (50.0%) by a 4-month student recall. Capture-recapture analyses were undertaken to assess potential dependencies between the sources, to estimate the degree of underascertainment in the population, and to evaluate the efficiency of the individual sources and the combinations between them. It was estimated that 91% of the cases in the population were ascertained when all four methods of case finding were utilized. Furthermore, the analysis indicated that accurate injury estimates could be achieved using combinations of only two or three of the sources. An analysis of the efficiency of the methods of ascertainment revealed a trade-off between effort (the number of hours needed to identify cases) and the precision (coefficient of variation) of the injury estimates. Capture-recapture analysis not only provided an approach to evaluate and adjust for undercount but also offered a formal means to evaluate the most efficient combination of the sources to maximize completeness while minimizing effort. The use of these techniques has the potential to evaluate and improve injury surveillance as well as other disease monitoring systems.

Adolescent↗
PubMed1995

Uptake and metabolism of delta 1-piperidine-2-carboxylic acid by synaptosomes from rat cerebral cortex.

delta 1-Piperidine-2-carboxylic acid (P2C), an intermediate of the L-lysine metabolic pathway in the brain, was studied for its uptake and metabolism in the synaptosome of the rat cerebral cortex. The results of this study showed that the uptake of P2C into the synaptosome was NA+- and temperature-dependent with a two-tier transport kinetic (Km = 2.6 and 0.7 microM; Vmax = 1.6 and 0.73 pmol/min/mg). P2C uptake was only moderately inhibited (approximately 20%) by L-lysine and its metabolites, L-pipecolic acid and L-alpha-aminoadipic acid at up to 100 microM, and the putative amino acid neurotransmitters, gamma-aminobutyric acid, L-glutamic acid and L-aspartic acid (25-31%) at 5-500 microM. The synaptosomal preparation only has a very low activity for metabolizing P2C to its product L-pipecolic acid. The metabolic activity for P2C was mainly contained in the 27,000 x g supernatant S2 fraction. Since P2C is the precursor of the putative neuromodulator L-pipecolic acid, the understanding of its uptake and metabolic characteristics in the brain should be of significance.

Animals↗
PubMed1995

L-lysine is a barbiturate-like anticonvulsant and modulator of the benzodiazepine receptor.

Our earlier observations showed that L-lysine enhanced the activity of diazepam against seizures induced by pentylenetetrazol (PTZ), and increased the affinity of benzodiazepine receptor binding in a manner additive to that caused by gamma-aminobutyric acid (GABA). The present paper provides additional evidence to show that L-lysine has central nervous system depressant-like characteristics. L-lysine enhanced [3H]flunitrazepam (FTZ) binding in brain membranes was dose-dependent and stimulated by chloride, bromide and iodide, but not fluoride. Enhancement of [3H]FTZ binding by L-lysine at a fixed concentration was increased by GABA but inhibited by pentobarbital between 10(-7) to 10(-3)M. While GABA enhancement of [3H]FTZ binding was inhibited by the GABA mimetics imidazole acetic acid and tetrahydroisoxazol pyridinol, the enhancement by pentobarbital and L-lysine of [3H]FTZ binding was dose-dependently increased by these two GABA mimetics. The above results suggest that L-lysine and pentobarbital acted at the same site of the GABA/benzodiazepine receptor complex which was different from the GABA binding site. The benzodiazepine receptor antagonist imidazodiazepine Ro15-1788 blocked the antiseizure activity of diazepam against PTZ. Similar to pentobarbital, the anti-PTZ effect of L-lysine was not blocked by Ro15-1788. Picrotoxinin and the GABA, receptor antagonist bicuculline partially inhibited L-lysine's enhancement of [3H]FTZ binding with the IC50s of 2 microM and 0.1 microM, respectively. The convulsant benzodiazepine Ro5-3663 dose-dependently inhibited the enhancement of [3H]FTZ binding by L-lysine. This article shows the basic amino acid L-lysine to have a central nervous system depressant characteristics with an anti-PTZ seizure activity and an enhancement of [3H]FTZ binding similar to that of barbiturates but different from GABA.

Animals↗