Biomedical subjects

Y F Chang

Publications and source records attributed to Y F Chang.

At least 19 recordsLinked to original sources

PubMed1998

Experimental infection of the human granulocytic ehrlichiosis agent in horses.

Human blood collected from two patients from Westchester County, New York with human granulocytic ehrlichia (HGE) infection was inoculated into two ponies. Inoculated ponies developed clinical signs similar to a previous report (Madigan et al., 1995). Histopathological changes involved follicular hyperplasia of lymphoid tissues. HGE DNA was detected by PCR in muscle, fascia, peritoneum, and adrenal gland after the ponies produced a high level of antibodies to HGE. We suggest that HGE may reside in poorly vascularized connective tissues, where the antibodies may have some difficulties to penetrate, resulting in persistent infection. Since HGE and E. equi cause very similar diseases in both humans and horses, they may be the same organism with minor genetic differences.

Adrenal Glands↗

PubMed1998

High-affinity aptamers selectively inhibit human nonpancreatic secretory phospholipase A2 (hnps-PLA2).

A family of sequence-related 2'-aminopyrimidine, 2'-hydroxylpurine aptamers, developed by oligonucleotide-based combinatorial chemistry, SELEX (systematic evolution of ligand by exponential enrichment) technology, binds human nonpancreatic secretory phospholipase A2 (hnps-PLA2) with nanomolar affinities and inhibits enzymatic activity. Aptamer 15, derived from the family, binds hnps-PLA2 with a Kd equal to 1.7 +/- 0.2 nM and, in a standard chromogenic assay of enzymatic activity, inhibits hnps-PLA2 with an IC50 of 4 nM, at a mole fraction of substrate concentration of 4 x 10(-6) and a calculated Ki of 0.14 nM. Aptamer 15 is selective for hnps-PLA2, having a 25- and 2500-fold lower affinity, respectively, for the unrelated proteins human neutrophil elastase and human IgG. Contractions of guinea pig lung pleural strips induced by hnps-PLA2 are abolished by 0.3 microM aptamer 15, whereas contractions induced by arachidonic acid are not altered. The structure that is essential for binding and inhibition appears to be a 40-base hairpin/loop motif with an asymmetrical internal loop. The affinity and activity of the aptamers demonstrate the ability of the SELEX process to isolate antagonists of nonnucleic-acid-binding proteins from vast oligonucleotide combinatorial libraries.

Amino Acid Sequence↗

PubMed1998

Spinal cord injury incidence in Mississippi: a capture-recapture approach.

BACKGROUND: Many studies have investigated spinal cord injury incidence rates. Few, however, have adjusted for the underascertainment. The current study used the capture-recapture method to estimate the ascertainment-corrected spinal cord injury incidence rate in Mississippi. METHODS: Two sources were used for case ascertainment: Mississippi's spinal cord injury registry and hospital reports. The two-sample capture-recapture method was used to adjust for undercount. RESULTS: Two hundred one spinal cord injuries were reported to or found by the Mississippi State Department of Health in 1993, with a crude incidence rate of 7.8 per 100,000 population per year among hospital admissions and prehospital fatalities. Using the two-sample capture-recapture method, it is estimated that the incidence rate would be 9.3 per 100,000 population per year. CONCLUSION: Capture-recapture estimates suggest that Mississippi's spinal cord injury incidence rate is more than twice the national average.

Epidemiologic Methods↗

PubMed1998

Interpretations of antibody responses to Salmonella enterica serotype enteritidis gm flagellin in poultry flocks are enhanced by a kinetics-based enzyme-linked immunosorbent assay.

Many regulatory and diagnostic programs for the detection of Salmonella enterica serotype Enteritidis infection in commercial poultry flocks have relied on rapid Pullorum agglutination tests to screen birds because of the shared antigens of S. enterica Enteritidis and S. enterica Pullorum and Gallinarum; however, the use of the enzyme-linked immunosorbent assay (ELISA) format affords better analytical sensitivity than crude agglutination tests. In this study, we adapted our earlier conventional indirect ELISA, using gm flagellin as the antigen, to a kinetics-based, computer-controlled ELISA (KELA). The KELA was used to screen for flagellin antibody from three commercial flocks: (i) a large flock involved in a U.S. Department of Agriculture trace back from a human S. enterica Enteritidis foodborne outbreak (n = 3,209), (ii) a flock infected with the endemic S. enterica Enteritidis serotype but which also had multiple other Salmonella serotypes (n = 65), and (iii) an S. enterica Pullorum-infected flock (n = 12). The first flock (S. enterica Enteritidis prevalence of 2.45% based on culture) provided a field test of the KELA and allowed the calculation of diagnostic sensitivity (D-Sn) and diagnostic specificity (D-Sp). With a cutoff of 10 (used for screening flocks [i.e., high sensitivity]), the KELA has a D-Sn of 95.2% and a D-Sp of 18.5%; with a cutoff of 140 (used in confirmatory flock testing [i.e., high specificity]), the KELA has a D-Sn of 28.0% and a D-Sp of 99.1%. We found that with a cutoff of 60 (D-Sn = 63.1%; D-Sp = 91.6%), we could eliminate reactions in the KELA caused by other non-S. enterica Enteritidis salmonellae. The KELA was also compared to two commercial rapid Pullorum tests, the Solvay (D-Sn = 94.9%; D-Sp = 55.5%) and the Vineland (D-Sn = 62.0%; D-Sp = 75.3%).

Animals↗

PubMed1998

Detection of human granulocytic ehrlichiosis agent and Borrelia burgdorferi in ticks by polymerase chain reaction.

Adult ixodid ticks were collected from Westchester County, New York, and Ipswich, Massachusetts, to determine the presence of infection with a human granulocytic ehrlichiosis (HGE) agent by using the polymerase chain reaction (PCR). The presence of Borrelia burgdorferi in ticks collected from New York was also determined by PCR. Of the 229 ticks from New York and 47 ticks from Massachusetts, 9% (22/229) and 25% (12/47) of ticks contained HGE agent, respectively. Fifty-four percent (123/229) of the ticks collected from New York were B. burgdorferi positive; 4% (9/229) of these ticks contained both HGE agent and B. burgdorferi. This finding indicates that animals with Lyme borreliosis may be also exposed to the etiologic agent of HGE. More extensive laboratory diagnosis may be necessary when multiple tick-borne diseases are suspected in animals.

Animals↗

PubMed1998

Childhood diabetes in China. Enormous variation by place and ethnic group.

OBJECTIVE: To investigate the incidence rate of IDDM in China. RESEARCH DESIGN AND METHODS: The Chinese IDDM registry was established in 1991 as part of the World Health Organization's Multinational Project for Childhood Diabetes (DiaMond) project. Twenty-two centers were developed to monitor the incidence of IDDM in children < 15 years of age. The population under investigation includes > 20 million individuals, representing approximately 7% of the children in China. Capture-recapture methods were used to estimate the ascertainment. RESULTS: The overall ascertainment-corrected IDDM incidence rate in China was 0.51 per 100,000, the lowest rate ever reported. There was a 12-fold geographic variation (0.13-1.61 per 100,000). In general, the incidence rate was higher in the north and the east. There was a sixfold difference among ethnic groups (highest: Mongol group, 1.82 per 100,000; lowest: Zhuang group, 0.32 per 100,000). CONCLUSIONS: China has an extremely low overall IDDM incidence rate. China also has the greatest geographic and ethnic variation seen for any country.

Adolescent↗

PubMed1998

The prevalence of diabetes in a Swedish population of 280,411 inhabitants. A report from the Skaraborg Diabetes Registry.

OBJECTIVE: To estimate the prevalence of known diabetes in a Swedish county (Skaraborg) and to evaluate capture-recapture methods for validation of the diabetes prevalence. RESEARCH DESIGN AND METHODS: Four sources were used to find known diabetic patients: 1) the Skaraborg Diabetes Registry (SDR), a case-finding inventory, 2) an administrative hospital registry, 3) a registry for the retinopathy screening program, and 4) a pharmacy prescription inventory. The capture-recapture method was applied to various combinations of sources to determine the prevalence of diabetes. RESULTS: The completeness of the SDR was 88.4 +/- 1.3%, indicating a diabetes prevalence of 3.20 +/- 0.08%. When the SDR was not used as one of the sources, the estimated prevalence varied between 2.2 and 4.5%. CONCLUSIONS: A case-finding registry is important in reliably estimating the prevalence of diabetes.

Body Mass Index↗

PubMed1998

Response of Epstein-Barr virus-associated Ki-1+ anaplastic large cell lymphoma to 13-cis retinoic acid and interferon alpha.

The response of peripheral T-cell lymphoma to 13-cis retinoic acid (13-cis-RA) has been well established, especially in Ki-1+ anaplastic large cell lymphoma (ALCL) confined to the skin. Here, we report the use of 13-cis-RA in combination with interferon alpha in a patient with refractory ALCL. The patient, an 18-year-old man, suffered from retroperitoneal, hepatic, and splenic ALCL. Reactive hemophagocytic syndrome also developed. Active Epstein-Barr virus infection was demonstrated by serologic tests and in situ hybridization of Epstein-Barr virus early RNA-1. Although high-dose intravenous immunoglobulin (IgG), etoposide, and steroids were administered, only chemotherapy (methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, and dexamethasone) successfully controlled the progress of hemophagocytosis. However, the retroperitoneal mass and splenic tumor did not show a satisfactory response to three cycles of chemotherapy. Hence, interferon 4.5 MU/m2 every other day with 13-cis-RA 1 mg/kg/day was instituted. Abdominal computed tomogram after 58 days of treatment revealed that the tumor had significantly reduced in size. Bone marrow biopsy demonstrated alleviation of hemophagocytosis as well. However, lymphoma cells had begun to infiltrate the bone marrow. Our findings suggest that 13-cis-RA and interferon alpha may be partially effective in treating ALCL.

Adolescent↗

PubMed1997

Cloning and characterization of a cotton lipid transfer protein gene specifically expressed in fiber cells.

A cotton genomic library was screened using a fiber-specific cDNA (GH3) encoding a lipid transfer protein (LTP). One genomic clone (1.7 kb DNA insert) containing the Ltp gene (Ltp6) was sequenced and characterized. The Ltp6 contains an open reading frame of 360 bp, which is interrupted by a single intron (136 bp) located in the region corresponding to the C-terminal of the protein. The derived amino-acid sequence of LTP6 is 64% homologous to that of GH3. Like the GH3 gene, the Ltp6 is specifically expressed in fiber cells in a temporal manner. However, its expression level is lower than that of GH3.

Amino Acid Sequence↗

PubMed1997

L-alpha-aminoadipate inhibits kynurenate synthesis in rat brain hippocampus and tissue culture.

Intracerebral administration of L-alpha-aminoadipic acid (L-AAA) at 500 mg/kg body weight to rats caused a complex behavioral change with sporadic wet-dog shakes. Animals developed severe limbic seizures between 1 and 6 h after L-AAA injection, characterized by generalized convulsions. Twenty days after L-AAA injection kynurenine aminotransferase (KAT) activity measured in hippocampal brain tissue slices prepared with a McIlwain chopper at 30 microns showed a significant 43% decrease. Subcutaneous injection of kynurenine at 500 mg/kg showed a 63% increase in KAT activity twenty days later. This increase was offset by a concomitant administration of 500 mg/kg L-AAA stereotaxically on day one. In astrocyte culture kynurenic acid synthesis is inhibited by L-AAA and L-pipecolic acid. The possible involvement of kynurenic acid in the modulation of neuronal degeneration is discussed.

2-Aminoadipic Acid↗

PubMed1997

Potent 2'-amino-, and 2'-fluoro-2'-deoxyribonucleotide RNA inhibitors of keratinocyte growth factor.

Reiterative in vitro selection-amplification from random oligonucleotide libraries allows the identification of molecules with specific functions such as binding to specific proteins. The therapeutic usefulness of such molecules depends on their high affinity and nuclease resistance. Libraries of RNA molecules containing 2'amino-(2'NH2)- or 2'fluoro-(2'F)-2'-deoxypyrimidines could yield ligands with similar nuclease resistance but not necessarily with similar affinities. This is because the intramolecular helices containing 2'NH2 have lower melting temperatures (Tm) compared with helices containing 2'F, giving them thermodynamically less stable structures and possibly weaker affinities. We tested these ideas by isolating high-affinity ligands to human keratinocyte growth factor from libraries containing modified RNA molecules with either 2'NH2 or 2'F pyrimidines. We demonstrated that 2'F RNA ligands have affinities (Kd approximately 0.3-3 pM) and bioactivities (Ki approximately 34 pM) superior to 2'NH2 ligands (Kd approximately 400 pM and Ki approximately 10 nM). In addition, 2'F ligands have extreme thermo-stabilities (Tm approximately 78 degrees C in low salt, and specificities).

3T3 Cells↗

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

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↗