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Biomedical subjects

Y Chung

Publications and source records attributed to Y Chung.

At least 19 recordsLinked to original sources

1H NMR observation of redox potential in liver.

1H NMR spectral editing techniques can select the distinct signals of lactate, pyruvate, beta-hydroxybutyrate, and acetoacetate and provide a unique way to monitor the biochemical processes in vivo. These metabolite levels reflect the near-equilibrium dehydrogenase activity and therefore the cellular redox state. The quantitative comparison between the 1H NMR and biochemical assay data is in excellent agreement. Lactate/pyruvate and beta-hydroxybutyrate/acetoacetate ratios, obtained from normalized 1H NMR spectra, respond directly to changes in the cytosolic and mitochondrial redox states. Because NMR is noninvasive, our results set the groundwork for implementing these techniques to observe tissue redox states in vivo.

3-Hydroxybutyric Acid

Phase I study of continuous-infusion soluble CD4 as a single agent and in combination with oral dideoxyinosine therapy in children with symptomatic human immunodeficiency virus infection.

To determine the safety and pharmacokinetics of recombinant soluble CD4 (sCD4) administered by continuous intravenous infusion to children with symptomatic human immunodeficiency virus type 1 infection, we conducted a phase I study at the National Cancer Institute. Three dose levels of sCD4 were evaluated: 100, 300, and 1000 micrograms/kg per day. After an initial 12 weeks of treatment with sCD4 alone, dideoxyinosine at a dose of 90 mg/m2 every 8 hours was added and subjects were observed for an additional 12 weeks. Combination therapy was continued in patients in whom it was well tolerated. In addition to toxicity and pharmacokinetic monitoring, surrogate markers of antiviral activity were evaluated. Eleven children were enrolled in the study. During the 12 weeks of treatment with sCD4 alone, and during subsequent sCD4 plus dideoxyinosine combination therapy, no significant toxic reaction attributable to sCD4 or dideoxyinosine was encountered. Low-level anti-CD4 antibodies developed in two patients. Steady-state sCD4 levels increased proportionately at higher doses. The CD4 cell counts and serum p24 antigen levels did not provide evidence of antiviral activity. We conclude that sCD4 was well tolerated at doses up to 1000 micrograms/kg per day when administered by continuous intravenous infusion; however, evidence of in vivo antiviral activity was not observed in this study.

Acquired Immunodeficiency Syndrome

Injection sites utilized for DPT immunizations in infants.

The purpose of this investigation was to determine the site utilized by nurses for administering Diphtheria and Tetanus Toxoids and Pertussis (DPT) injections to infants under 7 months of age. Twenty-six of the 28 agencies identified in a metropolitan area as administering DPT injections chose to participate in the study. Those individuals administering DPT injections in the agencies completed a questionnaire with a return rate of 69% (n = 55). Forty-four participants indicated that they used the anterolateral thigh, the recommended site, 100% of the time. The participants in the study administered a total of 1,453 DPT injections per month. Eighty-seven percent of those injections were administered in the anterolateral thigh, 3.6% were given in the deltoid, 5.1% were given in the dorsal gluteal, and 4% were given in the ventrogluteal. The estimated proportion of DPT injections administered at the correct site was 84.65% which is much lower than the critical value 94.06% for alpha = .05 (p less than .00001).

Diphtheria-Tetanus-Pertussis Vaccine

Leg pain in the rural Iowa 65+ population. Prevalence, related factors, and association with functional status.

Research tabulating the existence and effects of pain and related factors in the elderly is lacking, in spite of the continued growth of the aged population. Leg pain, in particular, may interfere with activities and interpersonal interactions. This study of 3,097 rural elderly examines the prevalence of complaints of leg pain and related factors in a geographically-defined population. Findings indicate that leg pain is clearly a common experience which impacts daily activities of the elderly.

Age Factors

Ferret tracheal epithelial cells grown in vitro are resistant to lethal injury by activated neutrophils.

Airway inflammation is often accompanied by accumulation of polymorphonuclear leukocytes (PMN) as well as epithelial sloughing. To determine whether PMN contribute to epithelial damage in inflammatory states, we examined the interaction of PMN and tracheal epithelial cells in culture. Ferret tracheal epithelial (FTE) cells were grown in primary culture on collagen-coated multiwell dishes. Confluent monolayers were loaded with [51Cr]O4 and exposed to resting and activated neutrophils. There was no significant increase in cell death as assessed by [51Cr]O4 release over 8 h of exposure, at effector (PMN)-to-target cell (epithelial cell) ratios up to 90:1, whether PMN were activated by maximal activating concentrations of phorbol myristate acetate or formylmethionylleucylphenylalanine with or without cytochalasin B. This result was confirmed by using a [3H]leucine release assay as well as by uptake of a supravital dye. However, exposure of FTE cells to activated PMN for 4 h resulted in separation of adjacent cells and formation of gaps in the monolayer, without significant detachment of epithelial cells from the dish. Gap formation was prevented by alpha 1-antitrypsin, N-methoxysuccinyl-Ala-Ala-Pro-Val-chloromethylketone, or 10% serum, was mimicked by PMN elastase (24 micrograms/ml), but not by hydrogen peroxide in concentrations up to 10 mM, or superoxide generated by xanthine/xanthine oxidase, and was reversible within 24 h of removal of elastase and exposure to fresh medium. We conclude that activated PMN do not kill FTE cells in culture. However, disruption of the epithelial cell monolayer probably by a proteolytic mechanism can result from exposure to activated PMN and may allow alteration of the epithelial barrier during airway inflammation.

Animals

Receptor-mediated cAMP production in adult and infant ferret tracheal epithelium.

Tracheal epithelial cells obtained from adult and infant ferrets were grown in primary culture in vitro. Cells from adult animals grew readily, and many ciliated cells were observed in the cultures. Successful cultures were derived from infant animals, but cell number in infant and adult cultures began to decrease after 6 d. Receptor-mediated activation of adenylate cyclase was determined by incubating monolayers of adult or neonatal cells with beta-adrenergic agonists, prostaglandin E2 (PGE2) and vasoactive intestinal peptide and measuring cAMP production. beta-adrenergic agonists and PGE2, but not vasoactive intestinal peptide, stimulated production of cAMP in both cell types. The 50% effective concentration for isoproterenol and PGE2 in neonatal ferret tracheal epithelial (NFTE) cells was nearly 10-fold more than for adult ferret tracheal epithelial (FTE) cells, but maximal agonist-stimulated cAMP production was significantly different between the cell types only for PGE2. Radioligand binding studies were performed using the beta-adrenergic antagonist [125I]iodocyanopindolol on membrane particulates from confluent monolayers and freshly isolated FTE cells. Binding of iodocyanopindolol was saturable, stereoselective, and of high affinity (binding affinity = 26.1 +/- 6.6 pmol/L, adult; 16.5 +/- 5.7 pmol/L, NFTE). Competition studies with the specific beta 2-adrenergic receptor antagonist, ICI 118 551 revealed a predominance of beta 2-adrenergic receptors on both adult FTE and NFTE cells. Receptor density was significantly higher in adult FTE compared with NFTE cells (48.2 +/- 9.1, 18.1 +/- 1.5 fmol/mg, respectively). Basal adenylate cyclase activity was significantly lower in neonatal cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenylyl Cyclases

Human immunodeficiency virus causes mononuclear phagocyte dysfunction.

There is compelling clinical evidence for dysfunction of the mononuclear phagocyte system in patients with AIDS, which is believed due in part to loss of T-cell cooperativity. The direct consequences of human immunodeficiency virus infection on macrophage function are unknown. To address this question we infected normal human macrophages in vitro with a monocytotropic strain of human immunodeficiency virus and performed assays to quantify their extra- and intracellular killing ability. Human immunodeficiency virus-infected macrophages were significantly less effective than control cells in mediating antibody-dependent cell-mediated cytotoxicity against leukemic cell targets and intracellular killing of Candida pseudotropicalis. The functional defects were profound, related temporarily to active virus production by the macrophages, and could not be overcome by granulocyte-macrophage colony-stimulating factor. Treatment of macrophages with 3'-azido-3'-deoxythymidine (AZT) 6 days after infection caused a marked decrease in virus production and prevented development of the intracellular killing functional defect. The results suggest that early antiviral therapy may be useful in preventing or mitigating some virus-induced mononuclear phagocyte dysfunction.

Antibody-Dependent Cell Cytotoxicity

Foreign body epithelioid granuloma after cosmetic eyebrow tattooing.

We describe two patients with epithelioid granulomatous inflammation on the eyebrows after undergoing cosmetic eyebrow tattooing. We tried to analyze the causative elements from biopsy specimens and tattoo inks with x-ray microanalysis. We suggest that granuloma caused by cosmetic eyebrow tattooing is a complication worthy of mention.

Adult

13C NMR studies of glycogen turnover in the perfused rat liver.

To assess whether hepatic glycogen is actively turning over under conditions which promote net glycogen synthesis we perfused livers from 24-h fasted rats with 20 mM D-[1-13C]glucose, 10 mM L-[3-13C]alanine, 10 mM L-[3-13C]lactate, and 1 microM insulin for 90 min followed by a 75-min "chase" period with perfusate of the same composition containing either 13C-enriched or unlabeled substrates. The peak height of the C-1 resonance of the glucosyl subunits in glycogen was monitored, in real time, using 13C NMR techniques. During the initial 90 min the peak height of the C-1 resonance of glycogen increased at almost a constant rate reflecting a near linear increase in net glycogen synthesis, which persisted for a further 75 min if 13C-enriched substrates were present during the "chase" period. However, when the perfusate was switched to the unenriched substrates, the peak height of the C-1 resonance of glycogen declined in a nearly linear manner reflecting active glycogenolysis during a time of net glycogen synthesis. By comparing the slopes of the curve describing the time course of the net [1-13C] glucose incorporation into glycogen with the rate of net loss of 13C label from the C-1 resonance of glycogen during the "chase" period we estimated the relative rate of glycogen breakdown to be 60% of the net glycogen synthetic rate. Whether this same phenomenon occurs to such an appreciable extent in vivo remains to be determined.

Alanine

Lex and Ley antigen expression in human pancreatic cancer.

Carbohydrate antigens are useful markers for the serological detection of pancreatic cancer. However, data concerning the expression of structurally well-defined carbohydrate antigens in normal and malignant pancreatic tissue is quite limited. The Lex and Leg antigens are closely related carbohydrate antigens synthesized on type 2 blood group oligosaccharide side chains of glycolipids and glycoproteins. Monoclonal antibodies anti-SSEA-1 and AH6 recognize "simple" Lex and Ley epitopes, respectively, regardless of the length of the carrier carbohydrate. Other monoclonal antibodies recognize Lex (FH4), sialyl Lex (FH6, IB9) or Ley (KH1, CC-1, CC-2) carried only by elongated type 2 side chains with or without internal alpha 1,3 fucosyl substitution. The present comparative immunohistochemical study used tissues of normal pancreas, chronic pancreatitis, and pancreatic cancer to determine the normal expression of Lex and Ley antigens in the pancreas and to elucidate any cancer-associated alterations. Lex-related antigens were not expressed in normal pancreas, expressed in only 10-20% of chronic pancreatitis tissues, but expressed in 50-70% of pancreatic cancer tissues. The frequency of Lex-related antigen expression in pancreatic cancer tissues was lowest in poorly differentiated cancers. Within a given specimen, at least three or all four of the Lex recognizing monoclonal antibodies were simultaneously expressed. Unlike Lex antigens, Ley-related antigens were expressed in 32-77% of specimens of normal pancreas, with similar frequencies in specimens of chronic pancreatitis and pancreatic cancer. In normal pancreas, simple Ley was expressed by both ductal and acinar cells, but extended Ley antigens were expressed only by acinar cells. In pancreatic cancer, extended Ley antigen expression was found in less than 10% of poorly differentiated tumors. Coexpression among the Ley-related antigens was less common than with the Lex-related antigens. Also in cancer specimens, simple Lex and simple Lex antigens were often concordantly expressed, whereas extended Lex and extended Ley antigen expression was often discordant. Hyperplastic ducts and ductules associated with pancreatic cancer expressed Lex-related antigens more frequently than morphologically similar lesions associated with chronic pancreatitis. These results demonstrate that Lex-related antigens are cancer-associated determinants in the human pancreas. The discrepant expression between Lex and Ley antigens in these tissues implies altered regulation of fucosyltransferase activity associated with the malignant state.

Antibodies, Monoclonal

Evaluation of serum pancreatic enzymes, carbohydrate antigen 19-9, and carcinoembryonic antigen in various pancreatic diseases.

Comparative studies of pancreatic enzymes carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA) were performed in various pancreatic disease. In acute pancreatitis as well as during acute exacerbation of chronic pancreatitis, all pancreatic enzymes were abnormally high. In chronic pancreatitis, they did not have any diagnostic sensitivity for pancreatic insufficiency. In pancreatic carcinoma, serum elastase levels may have a diagnostic value compared with other pancreatic enzymes. In studies of CEA and CA 19-9, both tumor markers were within normal range in benign pancreatitis but 27.7% of CEA and 30.7% of CA 19-9 in acute pancreatitis were above normal. In pancreatic carcinoma, although most of these patients had advanced disease, both tumor markers were extremely high and 61% for CEA and 71% for CA 19-9 were above normal. In patients with resected pancreatic carcinoma, serum CEA was slightly higher than normal CA 19-9 was much higher than normal. The sensitivity of CEA and CA 19-9 in this group were 33 and 77.7%, respectively. The results indicate that the CA 19-9 assay is a useful adjunct in the diagnosis of pancreatic carcinoma, possibly in the resectable stage especially combined measurement of serum elastase and CEA.

Adolescent

Rapid test for assay of ozone sensitivity in Escherichia coli.

A rapid test devised for assay of ozone sensitivity in Escherichia coli is described. The detection of new mutants, either more resistant or more sensitive than wild type strain to ozone, and the genetic analysis of ozone recombinants are now possible. Results confirm that ozone resistance is probably involved with DNA repair mechanism; and show that ozone and ultraviolet light inhibit the cell division capacity of lon mutant in a similar way.

Bacteriological Techniques