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Biomedical subjects

Y F Chang

Publications and source records attributed to Y F Chang.

At least 37 records · Page 2Linked to original sources

Polysaccharide storage myopathy in Morgan, Arabian, and Standardbred related horses and Welsh-cross ponies.

Polysaccharide storage myopathy is an equine neuromuscular disorder characterized by accumulation of glycogen-related polysaccharide inclusions within skeletal muscle fibers. The pathologic criteria for diagnosis of this disorder are somewhat controversial; however, periodic acid-Schiff-positive, amylase-resistant inclusions are considered pathognomonic. Although these inclusions are most often found in affected horses related to the Quarter Horse, draft horse, and Warmblood breeds, this report describes these characteristic inclusions in muscle of five horses from nonrelated breeds (two Morgans, one Arabian, one Arabian x Thoroughbred, and one Standardbred) and two Welsh cross ponies. Affected horses had histories of recurrent exertional rhabdomyolysis, and one developed progressive weakness leading to increased recumbency. The affected ponies were part of an unrelated research project and had no apparent clinical signs.

Amylases↗

Site-directed selection of oligonucleotide antagonists by competitive elution.

Oligonucleotide ligands that bind a protein or a small molecule of interest are readily isolated by in vitro selection and amplification of rare sequences from combinatorial libraries of sequence-randomized oligonucleotides (Gold et al., 1995). Classic systematic evolution of ligands by exponential enrichment (SELEX) protocols are affinity based (Tuerk and Gold, 1990), but because many problems and applications require antagonists, protocols for selecting inhibitors are both desirable and valuable. A widely applicable approach for isolating inhibitors is competitive elution with a molecule that binds the targeted molecule's active or binding site. We have used this approach to isolate antagonists of wheat germ agglutinin (WGA) from a library of 2'NH2-pyrimidine, 2'OH-purine oligonucleotides by elution with N N' N"-triacetylchitotriose, (GlcNAc)3. The highest affinity aptamers have equilibrium dissociation constants of 1 nM-20 nM for WGA, a 10(3)-10(4)-fold improvement relative to (GlcNAc)3, and unlike the carbohydrate, are highly specific. In addition to competing for binding with (GlcNAc)3, aptamers inhibit WGA-mediated agglutination of sheep erythrocytes, demonstrating that they are able to compete with natural ligands presented on the surfaces of cells. These results illustrate the feasibility of isolating high-affinity, high-specificity antagonists by competitive elution with low molecular weight, relatively low-affinity, and low-specificity small molecules.

Animals↗

Evaluating the reported prevalence of type 2 diabetes mellitus by the Oguni diabetes registry using a two-sample method of capture-recapture.

BACKGROUND: Capture-recapture methods have been widely employed in the study of wildlife populations and have recently been applied to count various human diseases and conditions. We have estimated the prevalence of type 2 diabetes mellitus by adjusting for the degree of undercount using a two-sample model of capture-recapture among men and women aged 50-69 in Oguni town, Japan. METHODS: Oguni town diabetes registry data were utilized as the first source. In the registry, only those who had experienced fasting plasma glucose of > or = 7.8 mmol/l (140 mg/dl) or 2 h plasma glucose after a 75 g oral glucose tolerance test (OGTT) of > or = 11.1 mmol/l (200 mg/dl) were counted as having diabetes. A second source was a sample study selecting 200 men and 200 women aged 50-69 randomly, which was conducted in August 1991. A 75 g OGTT was done in the morning. The 1985 World Health Organization criteria were used to classify the diabetes status of the participants. A two-sample model of capture-recapture methods was employed to estimate the total number of cases of diabetes and determine the ascertainment rates of the registry. RESULTS: The prevalence estimated by the diabetes registry was 7.1%. The prevalence from the sample study was 8.8% with a participation rate of 74%. Estimated prevalence employing the capture-recapture method was 13.1%. The ascertainment rate of the registry was 53.8%. CONCLUSIONS: Little is known about the prevalence of type 2 diabetes in local areas in Japan, the US and the world. Capture-recapture methods are likely to provide a means to accurately assess the prevalence of diabetes.

Aged↗

Helicobacter felis infection in dogs: effect on gastric structure and function.

The relationship of Helicobacter felis, an organism that is observed in the stomachs of dogs, to gastric disease in dogs is unclear. The objective of this study was to determine if Helicobacter felis infection alters gastric morphology and gastric secretory function in dogs. Five specific-pathogen-free (SPF), Helicobacter-free Beagle dogs were examined before and for 26 weeks after inoculation with H. felis (ATCC 49179). Three SPF uninfected dogs served as controls. All five dogs became colonized by H. felis as determined by urease activity, histopathology, polymerase chain reaction, and transmission electron microscopic examination of serial gastric biopsies. The degree of colonization ranged from < 1 organism/400 x field to > 10 organisms/400 x field. The fundus, body, and cardia were most heavily colonized. Evaluation of gastric biopsies showed mild gastric inflammation and lymphoid follicles in both infected and uninfected dogs. There was no correlation between the number of organisms observed and the degree of gastric inflammation or number of lymphoid follicles. The gastric secretory axis, assessed by fasting and meal-stimulated plasma gastrin, mucosal gastrin and somatostatin immunoreactivity, fasting gastric pH, and pentagastrin-stimulated gastric acid secretion, was similar in both infected and uninfected dogs. Fasting gastric pH was not a reliable indicator of gastric secretory function. These findings suggest that H. felis may not be a gastric pathogen in dogs. However, the density of colonization and limited duration of infection should be considered when interpreting these findings.

Animals↗

The isolation and sequence of canine interleukin-8 receptor.

A cDNA corresponding to canine IL-8 receptor has been cloned and sequenced. The cDNA was synthesized using RT-PCR, with oligonucleotide primers designed from conserved regions of published IL-8 receptors. The 5'-end was cloned by 5'-RACE and the 3'-end was cloned by 3'-RACE. The cDNA encodes a predicted full length IL-8r protein of 356 amino acids. At the nucleic acid level, the canine cDNA shows 83.9%, 82.4%/78.8%, 81.5%/78%, 81.4%/77.7%, 77.8% and 77.3%/71.9% identity to published sequences of bovine, human, gorilla, rabbit, mouse and rat IL8RB/IL8RA, respectively. The derived protein from the cDNA sequences shows 75.3%/70.3%, 75.3%/70.1%, 74.8%/69.4%, 70%/59%, and 69.7% identity to that of human, rabbit, gorilla, rat and mouse IL8RB/IL8RA homolog.

5' Untranslated Regions↗

Capture-recapture analysis of batterer reassaults: an epidemiological innovation for batterer program evaluation.

Capture-recapture analysis is an analytical tool being used in epidemiological research to estimate incidence rates for missing cases and unreliable reporting. Its contribution to batterer program evaluations is examined through a capture-recapture analysis of a multisite evaluation of batterer programs (n = 853). Capture-recapture analysis is applied to various subsamples of the multisite study and to different outcomes (i.e., any reassault, "severe" reassault) to explore the utility of capture-recapture. Finally, the capture-recapture estimates are compared to only the women's reports and to adjusted women's reports (women's reports supplemented with arrest records and men's reports), which are the basis of existing batterer program evaluation. The capture-recapture reassault estimate for the 15-month follow-up is equal to the adjusted women's reports (39%), but is 7% greater than the women reports. The subsample estimates for the individual sites appear to vary as a result of unreliable or unavailable arrest records.

Battered Women↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗