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Biomedical subjects

S Chang

Publications and source records attributed to S Chang.

At least 307 records · Page 17Linked to original sources
PubMed1990

Neurite outgrowth promoting activity of G4 and its inhibition by monoclonal antibodies.

The chick G4 molecule is a cell surface glycoprotein which is a member of the L1/NILE/NgCAM/8D9 group of neural cell adhesion molecules. Polyclonal antisera against G4 have been shown to decrease sympathetic neurite outgrowth on sympathetic axons and to de-bundle retinal axons growing on a tectal membrane substrate. We have extended the specificity of these results by showing that a panel of monoclonal antibodies against G4 is also effective in reducing sympathetic neurite outgrowth on sympathetic axons. Furthermore, purified G4 adsorbed onto an inert substrate promotes extensive neurite outgrowth. Monoclonal antibodies to G4 completely inhibit the activity of purified G4. These data show that G4 is a cell surface neurite outgrowth promoting molecule, a function which was first suggested by antibody perturbation experiments and now is confirmed directly.

Adrenergic Fibers↗
PubMed1990

Limiting concentrations of activated mononucleotides necessary for poly(C)-directed elongation of oligoguanylates.

Selected imidazolide-activated nucleotides have been subjected to hydrolysis under conditions similar to those that favor their template-directed oligomerization. Rate constants of hydrolysis of the P-N bond in guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) and in guanosine 5'-monophosphate imidazolide (ImpG), kh, have been determined in the presence/absence of magnesium ion as a function of temperature and polycytidylate [poly(C)] concentration. Using the rate constant of hydrolysis of 2-MeImpG and the rate constant of elongation, i.e., the reaction of an oligoguanylate with 2-MeImpG in the presence of poly(C) acting as template, the limiting concentration of 2-MeImpG necessary for oligonucleotide elongation to compete with hydrolysis can be calculated. The limiting concentration is defined as the initial concentration of monomer that results in its equal consumption by hydrolysis and by elongation. These limiting concentrations of 2-MeImpG are found to be 1.7 mM at 37 degrees C and 0.36 mM at 1 degrees C. Boundary conditions in the form of limiting concentration of activated nucleotide may be used to evaluate a prebiotic model for chemical synthesis of biopolymers. For instance, the limiting concentration of monomer can be used as a basis of comparison among catalytic, but nonenzymatic, RNA-type systems. We also determined the rate constant of dimerization of 2-MeImpG, k2 = 0.45 +/- 0.06 M-1 h-1 in the absence of poly(C), and 0.45 +/- 0.06 less than or equal to k2 less than or equal to 0.97 +/- 0.13 M-1 h-1 in its presence at 37 degrees C and pH 7.95.(ABSTRACT TRUNCATED AT 250 WORDS)

Guanosine Monophosphate↗
PubMed1990

Shuttling of the autoantigen La between nucleus and cell surface after uv irradiation of human keratinocytes.

During the past years we have established that the nuclear autoantigen La shuttles between the nucleus and the cytoplasm in tumor cells after inhibition of transcription or virus infection. We reinvestigated this shuttling using primary human keratinocytes from both healthy donors and patients with xeroderma pigmentosum. Ultraviolet irradiation resulted in both an inhibition of transcription and a translocation of La protein from the nucleus to the cytoplasm. After a prolonged inhibition of transcription La protein relocated into the nucleus and assembled with nuclear storage regions. The uv-induced shuttling included a translocation to the cell surface, where La protein colocalized with epidermal growth factor receptors.

Autoantigens↗
PubMed1990

Processing of refractory meteorite inclusions (CAIs) in parent-body atmospheres.

The refractory meteorite inclusions known as CAIs (calcium-aluminum rich inclusions) display melted rims that were produced by thermal events of only a few seconds duration. We show that gas dynamic deceleration in a temporary atmosphere around an accreting parent body, produced by gas release during accretion, could provide a regime of sufficiently high gas density and small scale height to achieve partial melting of the CAIs. In addition, the presence of dust in the atmosphere would increase the gradient of pressure with height (i.e., effectively reduce the scale height), lower the rate of blowoff (thus keeping more gas around the body), as well as allow dust particles to become trapped in the partially melted material as is observed in some cases. Thus, CAIs may be regarded as probes of a primitive atmosphere by virtue of the thermal and mineralogical alteration that occurred upon their passage through the atmosphere.

Aluminum↗
PubMed1990

On the mechanism by which an ACAT inhibitor (CL 277,082) influences plasma lipoproteins in the rat.

CL 277,082 is an inhibitor of acyl-CoA: cholesterol acyltransferase (ACAT). The effects of this drug on lipoprotein metabolism have been examined in cholesterol-fed rats. An optimal dose of drug incorporated into the diet (0.1% w/w) for 7 days reduced plasma cholesterol by 48% and plasma triglycerides by 72%. The decrease in plasma cholesterol was due to a reduction in triglyceride-rich lipoproteins and in HDL cholesterol. There was a significant 72% reduction in intestinal ACAT activity, accompanied by a 41% reduction in hepatic cholesterol content. There was a smaller 21% reduction in hepatic ACAT activity. Hepatic HMG-CoA reductase activity increased 3-fold. HDL binding activity by liver membranes was not altered significantly. The decrease in plasma cholesterol with this ACAT inhibitor is most likely due to decreased absorption of dietary cholesterol resulting from inhibition of intestinal ACAT.

Analysis of Variance↗
PubMed1990

Anatomic distribution of pancreatic endocrine tumors.

Pancreatic endocrine tumors are grouped together by their common histologic, cytochemical, and ultrastructural features. Although useful conceptually, this paradigm has been unable to predict the anatomic location of different tumor types. Successful surgical excision of these tumors would be facilitated by an improved understanding of their anatomic distribution. Based on the available data, a bimodal distribution of pancreatic endocrine tumors was identified. Cluster 1 (gastrinomas, pancreatic polypeptide (PP)-secreting tumors, somatostatinomas) had 75% of tumors to the right of the superior mesenteric artery, whereas cluster 2 (insulinoma, glucagonoma) had 75% of tumors to the left of the superior mesenteric artery (p less than 0.05). This distribution is similar to that distribution predicted based on the volume density of the corresponding islet cells for insulinoma, glucagonoma, and PP-secreting tumors, but not for somatostatinoma. These findings suggest that pancreatic endocrine tumors are derived from similar cytologic precursors as pancreatic islet cells, and their distribution may be a consequence of embryologic development from either the ventral (cluster 1) or dorsal (cluster 2) pancreatic buds.

Adenoma, Islet Cell↗
PubMed1990

Effect of weight cycling on susceptibility to dietary obesity.

Weight cycling, defined as repeated episodes of weight loss followed by weight regain, has been suggested to make rats more energy efficient and produce a state of energy balance favoring accumulation of excess body fat. In addition, weight cycling may favor accumulation of fat in central vs. peripheral adipose depots. In the present study, we gave two groups of female Wistar rats ad libitum access to an obesity-producing high-fat diet (60% of calories from fat). Both groups had previously eaten a low-fat stock diet, but one group had been subjected to three bouts of weight cycling. Rats that were previously weight cycled gained less body weight and body fat when given the high-fat diet than did controls. The lower rate of weight gain was due to a lesser increase in food intake, since daily energy expenditure was significantly lower in previously cycled rats than in controls. In summary, weight cycling does not appear to predispose rats to becoming obese on a high-calorie diet and apparently produces some effect on food intake that reduces, at least in the short run, weight gain on the high-calorie diet.

Adipose Tissue↗
PubMed1990

Metabolic differences between obesity-prone and obesity-resistant rats.

We compared, across several physiological variables, rats most and least susceptible to develop obesity when given a high-fat diet. After 4 wk of eating a high-fat diet (60% of calories from fat), rats in the upper (obesity prone, OP) and lower (obesity resistant, OR) quartiles for weight gain were further studied. OP rats ate significantly more than OR rats, but this did not completely explain differences in their susceptibility to dietary obesity. No differences in 24-h energy expenditure were found between groups. OR rats had a significantly lower 24-h respiratory quotient, indicative of a greater relative proportion of fat oxidation and lower plasma levels of free fatty acids (FFA) than OP rats. Thus the ability to avoid dietary obesity produced by a high-fat diet may depend on an ability to increase fat oxidation in response to increased fat intake. Insulin sensitivity, measured by a euglycemic insulin clamp, was significantly higher in OR than OP rats. We cannot determine from these data whether insulin resistance developed as a consequence of elevated FFA levels or whether the ability to oxidize FFA declined as a result of development of insulin resistance. In summary, we propose that rats able to resist becoming obese on a high-fat diet have the ability to adjust the composition of fuel oxidized to the fuel composition of the diet with a minimum increase in body fat. The specific mechanisms by which this occurs are unknown but may be related to effects of diet on insulin sensitivity.

Animals↗
PubMed1990

Arachidonic acid causes cyclooxygenase-dependent and -independent pulmonary vasodilation.

In this study we examined the action of arachidonic acid in the isolated rat lung perfused with a cell- and protein-free physiological salt solution. When pulmonary vascular tone was elevated by hypoxia, bolus injection of a large dose of arachidonic acid (75 micrograms) caused transient vasoconstriction followed by vasodilation. When arachidonic acid (100 micrograms) was injected during normoxia and at base-line perfusion pressure (low vascular tone) or when vascular tone was elevated by KCl, arachidonic acid (50 micrograms) caused only vasoconstriction. Doses less than 7.5 micrograms caused vasodilation only when injected during hypoxic vasoconstriction and subsequent blunting of either angiotensin II- or hypoxia-induced pulmonary vasoconstriction. The higher doses of arachidonic acid (7.5 and 75 micrograms), but not the lower doses (7.5-750 ng), caused increases in effluent 6-ketoprostaglandin F1 alpha, thromboxane B2, and prostaglandin E2 and F2 alpha. 6-Ketoprostaglandin F1 alpha was the major cyclooxygenase product. Meclofenamate (10(-5) M) blocked the increased metabolite synthesis over the entire dose range of arachidonic acid tested (7.5 ng-75 micrograms). Because vasodilation immediately after arachidonic acid was cyclooxygenase-independent, we investigated whether this effect was due to the unsaturated fatty acid properties of arachidonic acid and compared its action with that of oleic acid and docosahexaenoic acid. Because neither compound mimicked the vasodilation observed with arachidonic acid, we concluded that the cyclooxygenase-independent action of arachidonic acid could not be explained by unsaturated fatty acid properties per se. Because 1-aminobenzotriazole, a cytochrome P-450 inhibitor, partially inhibited the immediate arachidonic acid-induced pulmonary vasodilation, we concluded that cytochrome P-450-dependent metabolites can account for some of the cyclooxygenase-independent vasodilation of arachidonic acid.

Animals↗
PubMed1990

The effects of adrenergic blockade on lipoproteins using the rat as an experimental model.

Adrenergic blocking drugs are known to have adverse effects on lipids and lipoproteins in man, although the mechanisms underlying these effects are unclear. In order to see whether the rat might be a suitable model to explore this issue, adrenergic blockers having differing properties with respect to receptor interaction were administered to rats orally over seven days, followed by measurement of plasma lipids and lipoproteins. Total plasma cholesterol was not significantly influenced by any of the drugs used, while triglycerides were reduced by 20% and 31% respectively with pindolol and prazosin. With respect to changes in HDL cholesterol, it was found that: (a) HDL cholesterol was significantly reduced by 8% during combined beta 1, beta 2 blockade with propranolol; (b) HDL cholesterol was not significantly changed during selective beta 1 blockade using atenolol, or during combined beta 1, beta 2 blockade and partial beta 2 stimulation using pindolol; and (c) HDL cholesterol was significantly increased during combined beta 1 blockade and beta 2 stimulation using celiprolol by 12%, or during alpha 1 blockade with prazosin by 8%. It appears that beta 2 receptor exposure or stimulation may be one of the key points in the interaction between adrenergic blockade and lipoprotein metabolism.

Adrenergic beta-Antagonists↗
PubMed1990

Fibroblast behavior at aqueous interfaces with perfluorocarbon, silicone, and fluorosilicone liquids.

Perfluorocarbon, silicone, and fluorosilicone liquids with potential for use as vitreous substitutes in the management of complex retinal detachment were evaluated for surface reactivity by assessing the behavior of anchorage-dependent fibroblasts plated at the phase boundary between these compounds and culture medium. Low-viscosity perfluorcarbons were alumina-treated to remove polar impurities. On perfluorodecalin, perfluorodimethylcyclohexane, perfluorotrimethylcyclohexane, perfluoroethylcyclohexane, perfluorooctane, perfluoroperhydrophenanthrene, perfluoromethyladamantane, perfluorodimethyladamantane, the highly viscous perfluoropolyether liquids Krytox TLF7067 and 6354, and dimethylsiloxane liquids of a variety of viscosities, most cells did not attach; the few that did attach exhibited minimal spreading behavior and did not achieve the flattened spindle-shape morphology which is a prerequisite to normal proliferative activity. Conversely, on perfluoromethyldecaline, perfluorofluorene, perfluorotributylamine, the perfluoropolyether K-6 hexamer, trifluoropropylmethylsiloxane (fluorosilicone), and diphenyldimethylsiloxane, some cells became fusiform-shaped and exhibited proliferation, the extent of which varied with the compound. The association of alumina treatment of perfluorocarbon liquids with a reduction in cell growth was indicative of a relationship between the presence of residual hydrogen-containing impurities and the capacity for cellular attachment and growth. This correlation was demonstrated also in experiments in which cell attachment and growth was facilitated by the addition of hydrogen-rich monohydroperfluorooctane to alumina-treated perfluorooctane. In conclusion, evidence for the presence of surface active impurities in liquid vitreous substitute materials can be obtained by observing the behavior of attachment-dependent cells plated at the boundary between these compounds and culture medium.

Aluminum Oxide↗
PubMed1989

Purified perforin induces target cell lysis but not DNA fragmentation.

Rapid and extensive target cell DNA fragmentation is a unique characteristic of CTL-mediated killing. We studied the role of the granule pore-forming protein (PFP/perforin/cytolysin) of CTL in mediating lysis and DNA fragmentation of target cells. Perforin was isolated from murine CTL by sequential application of perforin-enriched granule fractions to four chromatographic columns: DEAE-Sepharose, Q-Sepharose, Polyanion SI, and Superose 12. Purified perforin was eluted as a single band of 70 kD in SDS-PAGE. While purified perforin produced potent lysis of a variety of target cells tested, it did not induce any measurable amount of DNA fragmentation. In parallel experiments, intact CTL produced marked DNA fragmentation of the same target cell populations. Our results suggest that perforin alone is not responsible for the DNA fragmentation observed during CTL-mediated killing and that other, as yet unknown, mediators or mechanisms are likely to be involved in the induction of target cell nuclear damage.

Animals↗
PubMed1989

Giant retinal tears. Surgical techniques and results using perfluorocarbon liquids.

Three low-viscosity perfluorocarbon liquids provided an intraoperative tool during vitrectomy to manage giant retinal tears. These clear fluids have a high specific gravity (1.8 to 1.9) and are immiscible with water. In six eyes, the giant tear was less than 180 degrees; in 11 eyes, it was 180 degrees or greater. In all eyes, the tear was unfolded and the retina was flattened while the patient was supine. The perfluorocarbon liquid was aspirated and replaced by air-perfluorocarbon gas mixtures (16 eyes) or silicone oil (one eye) at the end of the operation. The retina was reattached in 16 eyes (94%), with a minimum follow-up period of 6 months. In five eyes (29%), the retina was reattached without scleral buckling. Residual droplets of perfluorocarbon liquid were observed in four patients. These new materials complement present surgical techniques for managing giant retinal tears.

Air↗
PubMed1989

Novel poly-substituted aryl acridinium esters and their use in immunoassay.

A new series of stable acridinium ester conjugates have been developed for use as non-isotopic labels in immunoassay. They have proved to be a flexible alternative to radioimmunoassay. We present data showing the successful development of immunoassays in sandwich, competitive and receptor formats. In addition, hydrophilic acridinium ester analogues have been synthesized, encapsulated in liposomes, and utilized as labels in immunoassay. The potential of this technology is discussed.

Acridines↗
PubMed1989

Isotopic characteristics of simulated meteoritic organic matter: 1--Kerogen-like material.

Carbonaceous residues from a variety of laboratory syntheses yield release patterns for C and H isotopes during stepwise combustion that fail to mimic the striking patterns characteristic of meteoritic kerogen-like residues that otherwise superficially resemble them. It seems likely that the meteoritic material comprises a complex mixture of substances having different origins and/or synthesis conditions.

Carbon↗