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Biomedical subjects

J Hyun

Publications and source records attributed to J Hyun.

At least 19 recordsLinked to original sources

Potentiation of cholecystokinin and secretin-induced pancreatic exocrine secretion by endogenous insulin in humans.

To investigate the effects of endogenous insulin on pancreatic exocrine secretion in humans, we evaluated the pure pancreatic juice obtained by endoscopic cannulation of the main pancreatic duct in 21 healthy subjects (14 men and seven women). Samples of pancreatic juices were collected after intravenous injection of either glucose (50%, 40 ml), secretin (0.25 CU/kg), and cholecystokinin-8 (CCK) (40 ng/kg), or a combination of glucose, secretin, and CCK in six 5-min periods. The responses of plasma glucose, insulin, and C-peptide to intravenous administration of glucose were measured. After infusion of glucose, the plasma insulin and C-peptide levels were significantly increased and remained at high levels during 30-min experiments, intravenous administration of secretin and CCK resulted in significant increases of pancreatic secretion including volume, bicarbonate, and protein output. When glucose was simultaneously administered with secretin and CCK, pancreatic secretion was significantly increased, more than the effects achieved by the secretin and CCK. However, glucose alone did not increase basal pancreatic secretion. These observations suggest that endogenous insulin intensifies pancreatic secretion stimulated by secretin and CCK in humans.

Adult

The reductive metabolism of nitric oxide in hepatocytes: possible interaction with thiols.

Nitric oxide (NO) is both an endogenously generated species and the active species released from a variety of important drugs. Due to its endogenous generation and use as a therapeutic agent, the metabolism and fate of NO is of interest and concern. To date, most attention regarding the metabolism and fate of NO has been paid to its oxidized metabolites. Due to the reducing environment of cells, we considered that NO may also undergo reductive metabolism as well. Therefore, we have examined the reductive metabolism of NO by hepatocytes. Generation of nitrous oxide (N(2)O) was used as an indication of NO reduction. Indeed, we observed that NO could be reduced to N(2)O by the cytosolic fraction of hepatocytes. The N(2)O production was partially inhibited by the thiol modifying agent, N-ethylmaleimide and thiol consumption was observed during N(2)O formation. Thus, our results indicate that NO reduction is feasible and likely occurs via a thiol-dependent process.

Anaerobiosis

Reaction between S-nitrosothiols and thiols: generation of nitroxyl (HNO) and subsequent chemistry.

S-Nitrosothiols have been implicated to play key roles in a variety of physiological processes. The potential physiological importance of S-nitrosothiols prompted us to examine their reaction with thiols. We find that S-nitrosothiols can react with thiols to generate nitroxyl (HNO) and the corresponding disulfide. Further reaction of HNO with the remaining S-nitrosothiol and thiol results in the generation of other species including NO, sulfinamide, and hydroxylamine. Mechanisms are proposed that rationalize the observed products.

Aerobiosis

The protective effect of tetrahydrobiopterin on the nitric oxide-mediated inhibition of purified nitric oxide synthase.

The nitric oxide synthases (NOS) are a class of enzymes responsible for the generation of NO via an oxygen and NADPH dependent oxidation of the amino acid arginine. These enzymes are ironheme proteins which contain FAD and FMN and, enigmatically, require tetrahydrobiopterin (BH4). NOS has recently been shown to be subject to inhibition by its product, NO. Preliminary data by us indicate that a possible role for BH4 is to prevent and/or reverse the NO-mediated inhibition of NOS. The objective of this study was to elucidate the mechanism by which BH4 protects NOS against NO inhibition. Protection of NOS from NO inhibition was observed by both BH4 and the BH4 regeneration system, dihydropteridine reductase (DHPR)/NADH. NO, rather than an oxidation product, appears to be the inhibitory species. Protection by BH4 is not likely due to a simple chemical reaction between BH4 and NO or its oxidation product, NO2. The results are consistent with a protective mechanism by which BH4 may act as a nonstoichiometric reducing agent for a redox active enzyme component, such as the ironheme, to prevent NO ligation.

Amino Acid Oxidoreductases

The role of thiols in the apparent activation of rat brain nitric oxide synthase (NOS).

The role of thiols on the activation and/or stabilization of rat brain nitric oxide synthase (NOS) has been investigated. It was found that thiols are not necessary for stabilizing or protecting the protein during purification but are required during enzyme turnover for maximum activity. In the complete absence of thiols but with added tetrahydrobiopterin, the enzyme retained a low basal activity. Thiol addition to a thiol-deplete preparation of the enzyme resulted in a 4 to 7-fold increase in activity when measured after 15 min. High concentrations of dihydropteridine reductase also caused an apparent activation of NOS and was capable of replacing thiols. The data presented is consistent with a cofactor role for thiols. The possibility that they serve as reducing agents for the regeneration of tetrahydrobiopterin from dihydrobiopterins is discussed.

Animals

Aging of the human crystalline lens and anterior segment.

Changes in the unaccommodated human crystalline lens were characterized as a function of subject age for 100 normal emmetropes over the age range 18-70 yr by Scheimpflug slit-lamp photography. With increasing age, the lens becomes thicker sagittally, but since the distance from the cornea to the posterior lens surface remains unchanged, this indicates that the center of lens mass moves anteriorly and the anterior chamber becomes shallower. Sagittal nuclear thickness is independent of age, but both anterior and posterior cortical thicknesses increase with age, shifting the location of the nucleus and the central sulcus in the anterior direction. The amount of light scattered by the lens at high angles, as represented by normalized and integrated lens densities from the digitized images, increases with increasing age in an exponential fashion. Similar relationships to age are observed for the major anterior zone of discontinuity (maximum density) and the central sulcus (minimum density). The relationships of these results to accommodation and presbyopia are discussed.

Accommodation, Ocular

Captopril-induced hypersensitivity lung disease. An immune-complex-mediated phenomenon.

Captopril has not yet been included in the list of drugs causing hypersensitivity lung disease. We report a patient with hypertension, congestive heart failure, and chronic renal failure who, when rechallenged with captopril, developed upper lung field infiltrates associated with productive cough and striking peripheral eosinophilia. Gallium scan, transbronchial biopsy histologic findings, and direct immunofluorescent study were consistent with an immune-complex-mediated hypersensitivity reaction. There was no other etiology discovered for the patient's eosinophilia, nor was there evidence for an infectious etiology to explain his presentation.

Aged

Increased viability and differentiation of normal and dystrophic striated muscle in vitro.

Primary cultures of muscle from normal (line 412) and dystrophic (line 413) chick embryos were exposed to corticosterone-21-acetate (C-21-A) or sodium ibuprofen (Motrin) for 28 d after myotube formation. Ibuprofen (0.5 to 500 micrograms/ml) or C-21-A (0.4 to 40 micrograms/ml)-treated cultures were fixed and assessed semiquantitatively using phase microscopy. On this basis, ibuprofen (50 micrograms/ml) and C-21-A (40 micrograms/ml) seemed to be effective in maintaining both normal and dystrophic muscle cultures. Using ibuprofen and C-21-A at these concentrations, experiments were repeated and analyzed quantitatively. Ibuprofen maintained culture viability (up to 68% more myotubes than untreated controls) but had no significant effect on the number of striated cells. C-21-A effectively maintained culture viability (up to 73% increase) and strongly promoted the formation of striated cells in these cultures (up to a sixfold increase). Both normal and dystrophic cultures were affected similarly by these agents, but the dystrophic cultures showed more consistent if not more extensive improvements in the parameters examined here. Thus, it seems that ibuprofen and C-21-A may affect both normal and dystrophic muscle directly to maintain survival and even promote differentiation.

Animals

Acute interstitial nephritis. A case characterized by increase in serum IgG, IgM, and IgE concentrations. Eosinophilia, and IgE deposition in renal tubules.

A case of acute interstitial nephritis with a distinct immunopathologic pattern was seen. The relevant findings included elevated levels of serum IgG, IgM, and IgE; persistent eosinophilia; prominent granular and electron-dense depositions of IgE and C3 in renal tubules, as demonstrated by direct immunofluorescent and electron microscopic procedures; persistent failure to demonstrate anti-basement membrane antibodies (both glomerular and tubular); and hypocomplementemia. The findings in our case suggest a type of acute interstitial nephritis with a somewhat different clinical outlook. In this respect, serial assays of complement components and IgE in serum and kidney tissue and determinations of circulating anti-basement membrane antibodies (both glomerular and tubular) may be of particular importance.

Acute Disease