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Biomedical subjects

M Y Chang

Publications and source records attributed to M Y Chang.

At least 91 records · Page 5Linked to original sources

In vitro fertilization, gamete intrafallopian transfer and combined IVF-GIFT results: three-year experience at Chang Gung Memorial Hospital.

A review is presented summarizing the IVF-ET, GIFT and combined IVF-ET-GIFT experienced at Chang Gung Memorial Hospital. Since the building of an aseptic dust free laboratory next to the operation room, the clinical pregnancy rate has been 12.2% per embryo transfer in IVF-ET, 16.7% in the GIFT program and 30.0% in the combined IVF-GIFT program. The overall clinical pregnancy rate was 14.9%. The overall pregnancy rate appeared to be independent of the causes of infertility, be it tubal factor, endometriosis or unexplained infertility. It was lower in couples with male factor or combined factors. The different regimens for follicular stimulation were hMG-hCG, clomiphene-hMG-hCG and FSH-hMG-hCG. No one regimen showed a better pregnancy rate than the others. The methods of oocyte retrieval were laparascopy, laparotomy, transbladder ultrasound-guided, and transvaginal ultrasound-guided retrieval. There were 4.53 oocytes retrieved pertreatment cycle. The transvaginal ultrasoundguided oocyte retrieval has greatly simplified the procedures in the IVF-ET program. The patient selection was important not only for the indications but also for the methods of IVF-ET, GIET and combined IVF-GIFT.

Evaluation Studies as Topic↗

Precolumn derivatization for improved detection in liquid chromatography-photolysis-electrochemistry.

Precolumn, homogeneous chemical derivatization with Sanger's reagent (2,4-dinitrofluorobenzene) is utilized to improve the chromatographic and detection properties of amino alcohols and amino acids. The 2,4-dinitrophenyl derivatives are separated using reversed-phase liquid chromatography and are detected using the hybrid photolysis-electrochemical (hv-EC) detector in tandem with UV absorbance detection. Following optimization of reaction, chromatographic, and detection variables, the derivatization-detection approach provides limits of detection in the low parts-per-billion range, with a linearity of roughly three orders of magnitude. Selectivity is based on retention times as well as dual electrode response ratios and a "lamp on/off" responsiveness criterion unique to the hv-EC detector. The method is applied to the determination of serine in beer.

Amino Acids↗

Further studies of the riboflavin-binding immunoglobulin IgGGar. Resolution into fractions of different riboflavin content and aspects of reassembly.

A previously described human immunoglobulin with unusual flavin-binding activity, IgGGar [Farhangi, M., & Osserman, E. F. (1976) N. Engl. J. Med. 294, 177], is further characterized. The protein can be fractionated into two subpopulations, one of which is nearly completely saturated with riboflavin and one in which the binding sites are largely vacant. Possible differences between these fractions and/or their binding sites are explored. While electrophoretically distinct, the IgGGar-riboflavin complexes possess a basic similarity in the binding sites of both fractions as evidenced by spectroscopic examination. However, an important difference exists in that added riboflavin equilibrates reversibly with the vacant sites of native IgGGar, while the riboflavin in the occupied sites is essentially irreversibly bound. The tight association may be due to an in vivo combination of riboflavin with protein of different conformation than occurs in vitro, such as an incompletely assembled or folded tetramer. Accordingly, in vitro renaturation was examined. Studies of renaturation revealed that the reduced interchain disulfides within a tetramer reoxidize smoothly, although inter-heavy-chain bonds form less readily than inter-heavy-light-chain disulfides. Renaturation of IgGGar, unlike previously studied IgG molecules, does not proceed under conditions in which the protein structure had previously been significantly disrupted. The assembly defect is localized in the inability of the denatured heavy chain to refold into a stable species capable of combining with the light chain.

Binding Sites↗

Further studies on the riboflavin-binding immunoglobulin IgGGar. Equilibrium and kinetic aspects of the interaction.

The subpopulation of flavin-binding protein IgGGar which differ with respect to the degree of saturation with riboflavin [Chang, M. Y., Friedman, F. K., Beychok, S., Shyong, J. S., & Osserman, E. F. (1981) Biochemistry (preceding paper in this issue) are characterized in terms of hapten binding activity. Riboflavin fluorescence is used as a sensitive probe of the rate and extent of complex formation. The vacant sites on native IgGGar reversibly bind up to a total of 2 equiv of riboflavin/mol of protein. Kinetic and equilibrium measurements yield an affinity constant of (1.7 +/- 0.1) x 10(9) M-1. This value is the highest found to date for a hapten-monoclonal antibody system and is a consequence of an unusually low dissociation rate for the complex. The system exhibits maximal binding efficiency between pH 6 and 8, van't Hoff analysis of binding yields delta H = -15 kcal mol-1 and delta S = -9.5 cal deg-1 mol-1. The occupied sites on native IgGGar irreversibly bind riboflavin under normal reaction conditions. Irreversible denaturation of protein with urea affects the release of riboflavin. The dissociation mechanism is complex and is partially characterized.

Binding Sites↗

Furosemide compared with hydrochlorothiazide. Long-term treatment of hypertension.

In a double-blind crossover study, the effectiveness of furosemide, 40 mg twice daily, was compared with hydrochlorothiazide, 50 mg twice daily, in hypertensive patients. Both hydrochlorothiazide and furosemide significantly reduced blood pressure (BP) during three months of therapy. However, the fall in BP was consistently greater with hydrochlorothiazide than with furosemide, although the difference was significant only with respect to systolic BP. The somewhat greater antihypertensive effectiveness of hydrochlorothiazide may be related to its longer action permitting a more continuous diuretic effect and, hence, maintenance of reduced extracellular fluid volume throughout the 24-hour period.

Blood Pressure↗

Kinetics of interaction of heavy and light chains in immunoglobulins. Use of a sulfhydryl-specific light chain fluorescent probe.

The fluorescent probe N-(iodoacetylaminoethyl)-8-naphthylamine-1-sulfonic acid (1,8-I-AEDANS) reacts stoichiometrically with the COOH-terminal cysteine residue of a human immunoglobulin light (L) chain. The absorption and fluorescence spectral properties of the L-AEDANS product and the environmental sensitivity of the fluorescence suggest the utility of L-AEDANS in the study of the subtle conformational changes accompanying interactions between light chain and other proteins or ligands. Its applicability to the problem of immunoglobulin assembly is illustrated by the association of L-AEDANS with heavy chain dimers, which results in an enhancement of fluorescence. The data indicate that L-AEDANS binds to kinetically equivalent, noninteracting sites with an apparent second order rate constant of 6 X 10(6) liters mol(-1) s(-1) at 20 degrees, pH 7.5.

Dansyl Compounds↗

Fatal infectious mononucleosis. Association with liver necrosis and herpes-like virus particles.

A 20-year-old woman died of infectious mononucleosis associated with extensive hepatic necrosis with herpes-type inclusions within nuclei of remaining liver cells. Electron microscopical examination of these liver cells showed intranuclear and occasional intracytoplasmic herpes-like virus. This case supports the concept that a herpes-like virus, or a structurally closely related agent, is the etiological agent of infectious mononucleosis.

Adult↗

Second trimester maternal serum hCG level in an Asian population: normal reference values by ultrasound dating.

OBJECTIVE: To establish normative data of maternal serum chorionic gonadotropin (hCG) during the second trimester in an Asian population. METHODS: We measured the maternal serum hCG levels in 17,955 normal singleton pregnancies between 15 and 21 weeks of gestation. The gestation age was estimated by measurement of fetal biparietal distance (BPD) in all cases. Median values of hCG at various gestational weeks were calculated and the values of hCG were converted to multiple of median (MoM). The incidences of low MoM value and high MoM value were also calculated. RESULTS: The mean and median values of hCG were 57,153 mIU/ml and 50,120 mIU/ml, respectively, at 15 weeks of gestation and then decreased to 30,898 mIU/ml and 26,226 mIU/ml, respectively, at 21 weeks. We found 8.6% and 9.4% of normal singleton pregnancies have hCG MoM values >2.0 MoM and <0.5 MoM, respectively. CONCLUSIONS: Our report provides a normal reference data of second trimester maternal hCG levels by ultrasound dating in an Asian population.

Chorionic Gonadotropin↗

The evaluation of adenoviral p53-mediated bystander effect in gene therapy of cancer.

Because many tumors have mutated p53, one potential strategy proposed for cancer gene therapy is the introduction of the wild-type p53 gene into tumor cells. One puzzling aspect of this approach is that currently available gene transfer protocols result in a small percentage of tumor cells being transduced in vivo, thus implicating a "bystander effect" to achieve therapeutic efficacy. Because bystander effects in the context of p53-mediated gene therapy have not been well characterized, we evaluated the role of in vitro and in vivo bystander effects of adenovirally delivered p53 (AdWTp53). Using human tumor cell lines that did not express p53 protein but were infectible with adenovirus and showed sensitivity to p53-mediated apoptosis, we were unable to demonstrate an AdWTp53-mediated in vitro bystander effect, despite seeing strong bystander effects when cells were infected with an adenovirus containing the suicide gene herpes simplex virus thymidine kinase and treated with ganciclovir. In contrast, in vivo flank mixing studies using one of these cell lines showed a weak but significant p53-mediated bystander effect (a 40% inhibition of tumor growth). This bystander effect translated into a small survival advantage in an established intraperitoneal tumor model when tumor burden was low at the time of viral instillation. The survival advantage was lost, however, when tumor burden was increased. This study indicates that treatment of human tumors using AdWTp53 may be possible; however, because of the weak bystander effect in vivo, effective treatment will likely require a large percentage of tumor cells to be transduced.

Adenoviridae↗

Preparation of antihemophilic factor and fibronectin from human plasma cryoprecipitate.

Starting with human plasma cryoprecipitate, fibronectin was separated from antihemophilic factor (AHF) by fractional precipitation under mild conditions resulting in excellent recovery of AHF in the supernatant solution of the cryoprecipitate. Separation of fibronectin enabled accelerated sterile filtration of the supernatant solution containing AHF even after three- to fourfold concentration (by ultrafiltration) to desired potency. The sterile AHF concentrate, dispensed at 1000 u per vial and lyophilized, was completely dissolved within 3 minutes upon addition of 30 ml of pure water. The expected increment in circulating factor VIII and its hemostatic effects were found following intravenous infusion into factor VIII-deficient patients. Yield of AHF of five successive batches, each starting with the cryoprecipitate from some 12,000 units of fresh-frozen plasma, averaged 51 percent. The fibronectin precipitate was purified by affinity on insolubilized gelatin with chaotropic elution at pH 5.5 followed by removal of the chaotrope by diafiltration. Thermal denaturation of adventitious fibrinogen resulted in electrophoretically pure fibronectin which, following lyophilization and reconstitution with pure water, retained biological properties in an in vitro assay designed to reflect opsonic activity. The yield of fibronectin for seven successive batches, each starting with the cryoprecipitate from some 900 units of fresh-frozen plasma, averaged 10 percent.

Blood Transfusion↗

Short-term small-dose intravenous iron trial to detect functional iron deficiency in dialysis patients.

BACKGROUND/AIM: Management of renal anemia in end-stage renal disease requires careful evaluation of the iron status before and in particular during erythropoietin treatment. However, there is no simple and practical iron index accurately predictive of functional iron deficiency in these patients till now. The purpose of this prospective study, therefore, is to evaluate whether a short course of low-dose intravenous iron challenge can detect functional iron deficiency in hemodialysis patients. METHODS: Twenty-four patients with baseline serum ferritin levels between 100 and 500 ng/ml were treated with intravenous saccharated ferric oxide, 960 mg over 24 hemodialysis treatments, and the hemoglobin level was checked every week. RESULTS: Patients whose hemoglobin value increased at least by 1 g/dl within the 8-week period were classified as having functional iron deficiency or as responders (n = 26; 81.2%). All other subjects were classified as having adequate iron levels or as nonresponders (n = 6; 18.8%). There were no significant differences in age, sex, dialysis years, Kt/V, dialyzers, hemoglobin, and basal and final transferrin saturation and ferritin between responders and nonresponders. In addition, there were no iron indices with acceptable levels of sensitivity and specificity. On the contrary, the cutoff value of increments of hemoglobin of at least 0.2 g/dl after a 2-week intravenous iron trial had a sensitivity of 96.2% and a specificity of 100% in all patients (n = 32) and a sensitivity of 100% and a specificity of 100% after patients with transferrin saturation <20% were excluded (n = 24). These values had the greatest utility of the tests studied in this work. CONCLUSION: A 240-mg intravenous iron challenge during a 2-week period may be a simple, accurate, and straightforward method to detect a functional iron deficiency status in hemodialysis patients undergoing erythropoietin therapy.

Adult↗