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Biomedical subjects

Y Chiang

Publications and source records attributed to Y Chiang.

54 records · Page 3Linked to original sources
PubMed1994

Preventive eye care in people with diabetes is cost-saving to the federal government. Implications for health-care reform.

OBJECTIVE: Diabetic retinopathy, which leads to macular edema and retinal neovascularization, is the leading cause of blindness among working-age Americans. Previous research has demonstrated significant cost savings associated with detection of eye disease in Americans with type I diabetes. However, detection and treatment of eye disease among those with type II diabetes was previously thought not to be cost-saving. Our purpose was to estimate the current and potential federal savings resulting from the screening and treatment of retinopathy in patients with type II diabetes, based on recently available data concerning efficacy of treating both macular edema and neovascularization along with new data on federal budgetary costs of blindness. RESEARCH DESIGN AND METHODS: We used computer modeling, incorporating data from population-based epidemiological studies and multicenter clinical trials. Monte Carlo simulation was used, combined with sensitivity analysis and present value analysis of cost savings. RESULTS: Screening and treatment for eye disease in patients with type II diabetes generates annual savings of $247.9 million to the federal budget and 53,986 person-years of sight, even at current suboptimal (60%) levels of care. If all patients with type II diabetes receive recommended care, the predicted net savings (discounted at 5%) exceeds $472.1 million and 94,304 person-years of sight. Nearly all savings are associated with detection and treatment of diabetic macular edema. Enrolling each additional person with type II diabetes into currently recommended ophthalmological care results in an average net savings of $975/person, even if all costs of care are borne by the federal government. CONCLUSIONS: Our analysis indicates that prevention programs aimed at improving eye care for patients with diabetes not only reduce needless vision loss but also will provide a financial return on the investment of public funds.

Blindness↗
PubMed1994

Local IL-4 delivery enhances immune reactivity to murine tumors: gene therapy in combination with IL-2.

Tumor cells transduced with the IL-4 gene demonstrate reduction of growth associated with macrophage and eosinophilic infiltrates, generation of cytotoxic T-cells, and protective immunity. Using murine IL-4 retroviral vectors, murine fibroblasts and tumors that produce from 50 to 5000 U of IL-4/10(6) cells per 24 hours as determined by ELISA and bioassay were successfully transduced. In blinded studies using C57BL/6 and BALB/c mice, we have shown that tumor growth can be inhibited (mean delay of 10 days compared with controls; P < .05) and in some cases, completely suppressed by the coinjection of viable tumor with IL-4-producing fibroblasts (tumor free > 100 days; P < .001). Animals that are able to reject an initial tumor inoculate can also completely reject subsequent parental tumor challenge of 10(5) cells (P < .001) while challenge of 10(6) parental tumor cells results in a significant delay of tumor induction (P < .05). In addition, immunization with IL-4 transduced fibroblasts and irradiated tumor cells resulted in complete suppression of parental tumor challenge in animals that received the high-dose IL-4 delivery. Finally coadministration of systemic IL-2 led to enhancement of IL-4 gene therapy resulting in a 20-day delay of preestablished tumor growth compared with controls (P < .05).

Animals↗
PubMed1993

Annexin II expression is regulated during mammalian cell cycle.

Annexin II is a substrate for oncogene and growth factor-associated protein-tyrosine kinases. Elevated expression of annexin II is seen in different types of cancers and recent evidence indicates a role for annexin II in DNA synthesis and cell proliferation. In this report we show that the level of annexin II is subject to cell cycle regulation. Chinese hamster ovary cells were selected without the use of drugs, by the mitotic cell selection technique. As the mitotic cells progressed synchronously through the cell cycle, we determined the steady-state levels of annexin II mRNA and protein. The half-life of annexin II mRNA was approximately 2 h as measured by pulse-chase and ribonuclease protection analyses. Steady-state levels of both annexin II mRNA and protein were high in mitotic cells. As the cells divided and entered G1, there was a reduction in the levels of both annexin II mRNA and protein. New synthesis of annexin II mRNA and protein occurred in early G1 and maximal expression of annexin II mRNA and protein occurred as the cells entered S-phase. A gradual reduction in steady-state levels of annexin II mRNA and protein occurred as cells progressed through S-phase. Similar results were obtained in HeLa cells. In HeLa cells, collected at various cell cycle stages by countercurrent centrifugal elutriation, we observed peak expression of annexin II in G1-S and S-G2 cells. We conclude from our results that annexin II expression is regulated during the mammalian cell cycle.

Animals↗
PubMed1993

Arg15-Lys17-Arg18 turkey ovomucoid third domain inhibits human furin.

Turkey ovomucoid third domain with Leu18 in its reactive site is a potent inhibitor of many serine proteinases: subtilisins, chymotrypsins, and elastases. Previous studies showed that an L18K mutation made it a moderately strong inhibitor of trypsin, while an L18E mutation made it a strong inhibitor of Glu-specific Streptomyces griseus proteinase (GluSGP). For human furin substrates the consensus optimal sequence is RXKR decreases. Therefore the A15R, T17K, and L18R mutations were made in turkey ovomucoid third domain. The mutant inhibits human furin with a Ka of 1.1 x 10(7) M-1. As human furin catalyzes an obligatory step in human immunodeficiency virus proliferation, this inhibitor, along with the others already available, deserves further study.

Amino Acid Sequence↗
PubMed1993

Functional and molecular characterization of tumor-infiltrating lymphocytes transduced with tumor necrosis factor-alpha cDNA for the gene therapy of cancer in humans.

TNF is effective in causing the regression of selected murine tumors when administered at high concentrations. Therapeutic levels in humans cannot be obtained systemically, however, because of dose-limiting toxicity. The development of immunotherapy with IL-2 and tumor-infiltrating lymphocytes (TIL), which can accumulate at tumor sites in some patients, and of efficient retroviral techniques for gene transfer into eukaryotic cells has allowed new therapeutic approaches using TNF. We have retrovirally transduced human TIL with the gene for TNF in an attempt to deliver high concentrations of TNF to the tumor site without dose-limiting systemic toxicity. Successful gene insertion was confirmed by Southern hybridization in 16 of 16 transduced and selected TIL cultures from 15 different patients, with an estimated 28 to 93% transduced cells within each culture. Transduced selected TIL cultures produced greater amounts of TNF, compared with nontransduced controls, in 11 of 16 cultures evaluated. However, overall production of TNF was > 30-fold lower, compared with a transduced and highly selected tumor cell line control (MEL-TNF). In addition, steady state levels of vector-derived transcript in nine of 10 transduced selected TIL cultures were < 14% of the amount seen in the MEL-TNF control line. In an attempt to increase TNF production, TIL were transduced with a mutated form of TNF containing the IFN-gamma signal peptide in place of the transmembranous region, to enhance secretion into the endoplasmic reticulum. By using this vector, TNF production increased by an average of fivefold. These studies demonstrate that TIL can be genetically modified to express and secrete a protein for use in targeted cancer therapy but that partial expression blockades exist that prevent maximal cytokine production by introduced genes in TIL.

DNA↗
PubMed1993

Characterization of mutation-induced changes in the maize (Zea mays L.) ADH1-1S1108 alcohol dehydrogenase.

The homodimeric alcohol dehydrogenase gene produce of maize (Zea mays L.) Adh1-1S1108 mutation was purified and compared with the parental Adh1-1S enzyme. The mutant alcohol dehydrogenase activity had pH optima and substrate specificity similar to those of the parental enzyme, but exhibited somewhat increased and decreased Km values for acetaldehyde and NADH, respectively. The mutant enzyme was also markedly less stable than the enzyme from parental tissues to temperatures as low as 50 degrees C. Sequence analysis of a polymerase chain reaction (PCR)-generated cDNA clone revealed a G-to-C mutation at position 406 and a C-to-T mutation at position 974. These would result in residue 103 of each protein subunit being changed from an alanine to a proline and residue 292 being changed from an alanine to a valine. Whether one or both of these changes in primary sequence is responsible for the altered substrate affinities and stability is not yet understood.

Alcohol Dehydrogenase↗
PubMed1993

Enhanced expression of annexin II in human pancreatic carcinoma cells and primary pancreatic cancers.

Annexin II is a calcium and phospholipid binding protein and a substrate for protein-tyrosine kinases. Recent investigations have revealed involvement of annexin II in DNA synthesis and cell proliferation. Increased levels of annexin II are observed in cancer cells and tissues. To investigate the expression of annexin II in pancreatic adenocarcinoma cells and primary tumors, we measured the levels of annexin II mRNA and protein in normal human pancreas, five established human pancreatic adenocarcinoma cell lines, three primary pancreatic cancers and one metastatic tumor. All five cell lines examined had 5- to 15-fold higher levels of annexin II as compared to normal pancreas. Significant elevations (2- to 8-fold) of annexin II expression were observed in the three primary pancreatic tumors and one metastatic tumor examined. Immunocytochemical analysis indicates that the increased expression of annexin II is limited to proliferating ductular adenocarcinoma, and annexin II expression co-localizes with cells that express PCNA. In normal pancreas, annexin II expression is seen in ductal and ductular cells and no expression is seen in acinar or islet cells. We conclude from these findings that annexin II has a role in cell proliferation and its regulation is altered in pancreatic cancer.

Adenocarcinoma↗
PubMed1993

Space-resolved fluoroimmunoassay for quantifying alpha-fetoprotein in serum.

A nickel-coated surface was used to adsorb a monolayer of anti-human alpha-fetoprotein antibody. After incubation with a patient's serum, the sample was stained with fluorescein isothiocyanate (FITC)-conjugated anti-human alpha-fetoprotein antibody. These slides were then read with a space-resolved fluorometer to determine the amount of FITC adsorbed onto the metal surface. We used an argon laser as the light source in the fluorometer. The parallel laser beam was tilted at about 45 degrees to the sample surface. The fluorescence from FITC was read with a perpendicular photon counter to reduce noise. The CV for these tests was approximately 10%. Comparison of these results (y) with those of a conventional radioimmunoassay (x) produced the regression equation y = 0.99x + 0.5, over the range 10-140 micrograms/L (n = 51).

Adsorption↗
PubMed1988

A space-resolved fluorometer and its application to immunoassay.

A metal surface has been added into a fluorometer to reflect the excited light and to reduce the light scattering. Due to the total separation of the fluorescent signal and the noise by directing them into different spaces, the resolution could be improved by several orders of magnitude. The same metal surface could also be used for immunoassays. The detection of alpha-fetoprotein in normal rat serum and human standard serum are given as examples. The results indicate that the apparatus and the method have significant advantages.

Antibodies, Anti-Idiotypic↗
PubMed1980

Localization and origin at rat intestinal cholesterol esterase determined by immunocytochemistry.

Monospecific rabbit antisera to rat pancreas cholesterol esterase were employed in the unlabeled antibody enzyme method of immunocytochemistry in combination with the horseradish peroxidase--antihorseradish peroxidase complex to localize this pancreatic enzyme within the wall of rat small intestine. Intestinal rings were fixed in paraformaldehyde with satisfactory preservation of structure and retention of cholesterol esterase antigenic determinants. Fixed sections, 6 micrometers thick, were stained. In the light microscope, specific reaction product, represented by intense brown areas, was uniformly distributed within the absorptive cells but was notably absent from the microvillar membrane. Reaction product was also seen within the laminapropria and submucosa. In contrast, reaction product was absent from sections of proximal intestine surgically deprived of pancreatic juice for 72 hours. Furthermore, the intensity of staining in sections of normal intestine decreased with increasing distance from the pancreatic duct. These observations support the concept that "intestinal" cholesterol esterase is of pancreatic origin. This enzyme is localized within the cells as opposed to the absorptive surface.

Animals↗