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Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 433 records · Page 24Linked to original sources
PubMed1990

Sonographic presentation in autoimmune thyroiditis.

We used real-time ultrasonography to examine 60 patients with autoimmune thyroiditis, then correlated the ultrasonic pictures with thyroid function, thyroid autoantibodies and fine needle aspiration cytology. In these 60 patients, 45 (75%) showed diffuse goiter, 6 (10%) showed multinodular goiter, and 9 (15%) had a solitary thyroid nodule sonographically. One of the 9 patients with a solitary nodule was a case of autoimmune thyroiditis combined with papillary carcinoma. The echogenicity of the thyroid was more than, the same as, or less than that of the adjacent muscles in 17, 22, and 21 patients, respectively. The groups were classified as hyperechoic, isoechoic, and hypoechoic, respectively. The mean serum T4 level was significantly lower in the hypoechoic group than in the hyperechoic or isoechoic groups (p less than 0.01 and p less than 0.05, respectively), and the incidence of hypothyroidism was significantly higher in the hypoechoic group than in the hyperechoic or isoechoic groups (p less than 0.001 and p less than 0.005, respectively). In addition, high titers of the antithyroid microsomal antibody (greater than or equal to 1280) were present more frequently in the hypoechoic group than in the hyperechoic or isoechoic groups (p less than 0.01 and p less than 0.05, respectively). There was no significant correlation between the cytomorphology and echogenicity of the thyroid in these cases. We conclude that sonography has two major uses in evaluating autoimmune thyroiditis: First, it is useful in excluding the coexistence of thyroid nodules; and second, marked hypoechogenicity of the thyroid implies an active cytotoxic autoimmune process and possibly a hypothyroid state.

Humans↗
PubMed1990

Immunochemical characterization of alpha-bungarotoxin detoxified with glutaraldehyde.

Modification of alpha-bungarotoxin (alpha-BuTX) with glutaraldehyde (GA), a bifunctional reagent, resulted in the formation of crosslinked derivatives. The intramolecular linked monomeric derivative as well as dimeric and higher molecular weight derivatives arising from intermolecular reactions were separated by gel filtration. The dimer and polymers were completely detoxified and the monomer lost nearly all of its lethal toxicity as well as binding activity to the nicotinic acetylcholine receptor. However, all the modified derivatives retained relatively high antigenic activity towards the antibody against native toxin. Antisera prepared by immunization with the unfractionated modified products of alpha-BuTX contained considerable amounts of a non-precipitating antibody, but much less of a precipitating antibody to alpha-BuTX, while they had the same capacity as that of anti-alpha-BuTX for neutralizing the lethal toxicity of alpha-BuTX. Furthermore, the antisera could be obtained in only half period required for anti-alpha-BuTX sera so that the detoxified GA-alpha-BuTX is an useful immunogen for the production of antibody to alpha-BuTX.

Animals↗
PubMed1990

Modulation of intercellular communication during radiation and chemical carcinogenesis.

Carcinogenesis is a multistep process, involving the irreversible conversion of a stem cell to a terminal-differentiation-resistant cell ("initiation"), followed by the clonal expansion of this cell ("promotion") and by the acquisition of other genetic alterations leading to malignancy ("progression"). The initiation and progression steps seem to be facilitated by mutagenesis. Promotion has been associated with agents and conditions that cause mitogenesis. Gap junctional intercellular communication, a fundamental biological process regulating cell growth and differentiation, has been postulated to play a major role in carcinogenesis. The hypothesis is supported by the fact that many cancer cells have some dysfunction in gap junctional intercellular communication, many tumor-promoting chemicals and several oncogenes (i.e., ras, src, mos, neu, but not myc) reduce gap junctional intercellular communication, and several growth factors (i.e., EGF, TGF-beta, bovine pituitary extract) inhibit gap junction function. This integrative concept postulates that chemical promoters, oncogenes coding for growth factors, receptors, or transmembrane signaling elements, and growth factors can isolate an initiated cell from the suppressing influence of surrounding normal cells by down-regulating the transfer of ions and small molecules through gap junctions.

Animals↗
PubMed1990

[A study of changes in the ratio of collagen types in skin after long-term treatment with topical glucocorticoids].

The topical glucocorticoids, widely used in the treatment of a variety of skin disorders, usually induce skin atrophy after long-term administration. In this study, the skin from a 30-year-old female patient was used, and the changes in the ratio of collagen types in atrophic skin derived from the treatment with glucocorticoid were investigated in comparison with that of normal human skin. By transmission electron microscopy, the collagen fibrils in the papillary dermis of normal skin were loose and fine, their diameters ranging from 30 to 40 nm; while those in the atrophic skin appeared tightly compact, their diameters increasing to 50-60 nm. The collagen chains, alpha 1 (I), alpha 2 and alpha 2 (III), from peptic digest of skin were separated by interrupted gel electrophoresis. The ratios of collagen type III to type I as calculated from the normal skins of a 21- and a 39-week fetus and a 36-year-old human were 49.45, 45.51 and 43.65%, respectively, while that of the atrophic skin was 12.89%. Therefore, the persistent treatment of skin with topical glucocorticoids results in a decrease in the ratio of collagen type III to type I.

Administration, Topical↗
PubMed1990

Gap junctional intercellular communication (GJIC) in rat glioma cells--characterizations to detect inhibitors of metabolic cooperation.

Gap junctional intercellular communication (GJIC) as measured by metabolic cooperation was examined in a rat glioma cell line P98F47. X-ray induced mutants of P98F47 cells were grown in 6-thioguanine selective medium (6TG medium) to separate 6TG-resistant HGPRT- mutant cells (6TGr). By co-culturing 200 6TGr cells with varied high densities of the wild type 6TG-sensitive cells (6TGs), it was found that the recovery of 6TGr cells depended on the density of 6TGs cells. Higher densities of 6TGs cells reduced the recovery of 6TGr cells. These results demonstrate the ability of P98F47 cells to perform metabolic cooperation which is indicative of GJIC. When metabolic cooperation was inhibited, increased recovery of 6TGr cells was observed. Presented results also demonstrate metabolic cooperation between P98F47 glioma cells and normal rat glial cells. Effect of tumor promoting chemicals on metabolic cooperation of P98F47 cells was studied. 3H-uridine nucleotide autoradiography technique was used to confirm the above observations. The results suggest that these cells may provide the basis for an in vitro assay specially to study brain tumor promoters and neurotoxins.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1990

Relation between macrophage infiltrates and peritumoral edema.

Peritumoral edema is one of the most serious complications of intracranial neoplasms. However, the exact pathogenesis of peritumoral edema is still unknown. To explore the role of macrophages and LTs in brain tumors, we examined macrophage infiltrates in the brain tumors by immunohistological method using anti-Leu M3 monoclonal antibody and measured tissue LTC4 and LTD4 by HPLC with ODS column and UV spectrophotometer in the wavelength of 280 nm. Nine of 14 gliomas, 10 of 14 meningiomas, and all six metastatic brain tumors had macrophage infiltrates. The correlation was good between macrophage infiltration and peritumoral edema detected on CT. In many cases with peritumoral edema, LTC4 was detected. In most cases without peritumoral edema and many cases with preoperative steroid treatment, LTC4 was not detected. These data suggest that macrophages and LTs may play an important role in the formation of peritumoral edema.

Adrenal Cortex Hormones↗
PubMed1990

Effect of dexamethasone on neurotransmitter amines in a rat glioma model.

Vasogenic brain edema was produced by transplantation of rat glioma C6 cells into rat brain. Using this model, we measured neurotransmitter concentrations and water content of regional brain tissue. In the tumor-implanted controls, monoamine neurotransmitters in the hypothalamus, cortex, and striatum significantly decreased. When treated with DEX, these monoamines tended to return to the levels of the sham-operated controls. Additionally, DEX markedly lowered tumoral monoamines. In the nonsurgical animals, DEX significantly increased norepinephrine but not DA. Regardless of treating with DEX or not, water content showed no changes in the hypothalamus and striatum in the tumor-implanted animals. However, the increase in water content in the cortex was significant, and this increase could be reduced by DEX to the levels of controls. Water content of tumor tissue could also be markedly reduced by DEX. In the nonsurgical animals, there were no changes in water content between DEX-treated and nontreated animals. In conclusion, brain edema produced by the brain tumor may reduce noradrenergic and dopaminergic activities. This is more likely due to compression anoxia caused by the tumor mass, glial hydrops, and edema fluid. It is presumed that the effect of DEX is due to reduction of water content of the tumor and peritumoral white matter as well as by increasing noradrenergic activity.

Animals↗
PubMed1989

Comparison of phosphatidylethanolamine and phosphatidylcholine vesicles produced by treating cholate-phospholipid micelles with cholestyramine.

We have previously reported the preparation and characterization of unilamellar phosphatidylcholine vesicles from cholate-phospholipid micelles treated with the bile-salt sequestrant cholestyramine (Ventimiglia, J.B., Levesque, M.C., and Chang, T.Y. (1986) Anal. Biochem. 157, 323-330). We now describe a slightly modified procedure for forming unilamellar vesicles consisting of phosphatidylethanolamine, and the characterization of the resultant vesicles by gel exclusion chromatography. In contrast to phosphatidylcholine vesicles, the formation of phosphatidylethanolamine vesicles is highly pH dependent; pH 9.2 is superior to pH 8.1 or pH 7.1. Via the dialysis step, the final pH of the vesicles could be altered to be at 8.1 or at 7.1, although decreasing the pH from 9.2 resulted in the loss of approx. 20% of the total lipid as large aggregates. Residual cholate was still present in the resultant vesicles after cholestyramine treatment; the low levels of cholate, removable by dialysis, was found to stabilize the phosphatidylethanolamine vesicles formed at pH 8.1. These results suggest that the majority of the amino groups of the phosphatidylethanolamine molecules should either be in the deprotonated form, or be neutralized and/or restricted by the anionic cholate monomers in order to facilitate the vesicle formation. Phosphatidylethanolamine vesicles were found to be much more permeable to small ions than phosphatidylcholine vesicles. The incorporation of phosphatidylserine, but not phosphatidylinositol, into the phosphatidylethanolamine vesicles at 10% resulted in decreased permeability of the bilayer against the cobalt ion influx, suggesting cooperative and complementary packing of phosphatidylethanolamine and phosphatidylserine molecules within the bilayer.

Cholestyramine Resin↗
PubMed1989

Antagonism by tubocurarine and verapamil of the regenerative acetylcholine release from mouse motor nerve.

The role of presynaptic acetylcholine receptors and Ca2+ channels in the regenerative acetylcholine release was studied in the cut muscle preparation of mouse phrenic nerve hemidiaphragm. The regenerative release shown as a prolonged endplate depolarization was evoked by stimulation of the nerve with a train of pulse at 75-300 Hz when acetylcholinesterase activity was depressed with neostigmine or by lowering temperature. Tubocurarine, cobratoxin, verapamil, diltiazem and nifedipine at low concentrations, which had a negligible effect on the endplate potential, shortened the duration of regenerative depolarization while leaving the amplitude unaffected. In contrast, Mn2+ at concentrations that markedly reduced the amplitude of single endplate potentials caused little suppression of the regenerative depolarization though intensive stimulation was needed to trigger the response. On the other hand, atropine inhibited the regenerative depolarization only at high concentrations which also depressed endplate potentials. These results indicate that the mechanism for evoking the regenerative release involves the activation of acetylcholine receptors and Ca2+ channels which are sensitive to tubocurarine and Ca2+ channel blockers. The Ca2+ channel concerned, however, appears to differ from that involved in the normal quantal release of acetylcholine.

Acetylcholine↗
PubMed1989

Potential role of the human Ha-ras oncogene in the inhibition of gap junctional intercellular communication.

The modulation of gap junctional intercellular communication (GJIC) plays an important role during tumor promotion. Several tumor-promoting agents are known to inhibit this form of cellular coupling. In addition, tumor cells and cells expressing certain oncogenic products have been shown to exhibit inhibited or reduced GJIC. The Ha-ras oncogene is expressed in a wide variety of human tumors from different tissues. Its p21 product is a membrane-bound polypeptide, the function of which is not fully characterized. We tested the effects of the expression of the human c-Ha-ras-1 oncogene, derived from the EJ/T4 bladder carcinoma cell line, on the ability of the Chinese hamster V79 cells to conduct gap junctional communication. The junctional competence was studied by two different methods, the scrape-loading/dye transfer technique and the metabolic cooperation assay. The results indicate a strong correlation between the expression of p21 ras protein and the inhibition of gap junctional function. Assuming that reversible inhibition of intercellular communication plays a role during tumor promotion and stable inhibition during the tumor progression phase of carcinogenesis, our data suggest that, while chemical tumor promoters and the ras oncogenes might work by different biochemical mechanisms, they both affect a critical cellular function; namely, GJIC.

Animals↗
PubMed1989

Synergistic inhibition of metabolic cooperation by oleic acid or 12-0-tetradecanoylphorbol-13-acetate and dichlorodiphenyltrichlorethane (DDT) in Chinese hamster V79 cells: implication of a role for protein kinase C in the regulation of gap junctional intercellular communication.

The effects of TPA and/or DDT and oleic acid and/or DDT on gap junction-mediated intercellular communication (i.e. metabolic cooperation) between Chinese hamster V79 cells was examined. Addition of TPA, DDT or oleic acid alone to cocultures of 6-thioguanine-resistant (6-TGR) and 6-thioguanine-sensitive (6-TGS) V79 cells significantly increased the recovery of 6-TGR cells indicating inhibition of metabolic cooperation. In the presence of TPA and DDT or oleic acid and DDT the observed recovery of 6-TGR cells was significantly greater than the expected (calculated) additive 6-TGR cell recovery. No synergistic increases in 6-TGR cell recovery were observed when co-cultures of V79 cells were exposed to dieldrin and DDT. These results indicate that TPA and DDT or oleic acid and DDT can act synergistically to inhibit metabolic cooperation. These data suggest a role for protein kinase C in the regulation of gap junction-mediated intercellular communication.

Animals↗
PubMed1989

Establishment of a human glioma cell line bearing a homogeneously staining chromosomal region and releasing alpha- and beta-type transforming growth factors.

A human glioma cell line (YKG1), which was positively identified for glial fibrillary acidic (GFA) and S-100 proteins, was established from a surgical specimen of a patient with glioblastoma. Chromosome analysis of the cells revealed a homogeneously staining region (HSR) on a marker chromosome. The assay for transforming growth factors (TGFs) in the conditioned medium of the cell line revealed that it contained high levels of alpha- and beta-type TGFs, which might regulate the growth of glioblastoma and influence on the peritumoral tissues.

Cell Line↗
PubMed1989

Preparation and characterization of monoclonal antibody specific for alpha-bungarotoxin and localization of the epitope.

We prepared a monoclonal antibody (mAb) specific for alpha-bungarotoxin (alpha-BuTX) which can neutralize the lethal toxicity of the toxin and inhibit the binding of [3H]-alpha-BuTX to the nicotinic acetylcholine receptor. The radiolabelled toxin has a high affinity for the mAb. alpha-BuTX was digested with acid protease A and the resulting peptide fragments were isolated by reverse-phase HPLC. The epitope recognized by the mAb has been localized on the basis of competition radioimmunoassay between [3H]-alpha-BuTX and the peptide fragments of alpha-BuTX towards the antibody. The epitope specific for the mAb may be located in the second loop of alpha-BuTX, probably involving residues 34-41.

Amino Acid Sequence↗
PubMed1989

Stem cell theory of carcinogenesis.

Our present understanding of the carcinogenic process, involving complex interactions of genetic, developmental, sex, dietary and environmental factors during the multistage initiation/promotion/progression process of carcinogenesis, would lead us to reject simplistic non-biologically based risk assessment models. This understanding, plus recent results of the National Toxicology Bioassay program and of the studies of short-term tests for genotoxicity, has challenged the primary paradigm of 'carcinogens as mutagens' which governs our current risk assessment models. The concepts of the stem cell theory of cancer, of oncogenes/tumor suppressor genes, of gap junctional intercellular communication, and of mutagenic and epigenetic mechanisms must be integrated into a biologically-based model of the multistage nature of carcinogenesis. Current understanding of the complex interactions during this process prevents us from believing that a simple and accurate, biologically-based risk assessment model will be developed soon, if ever.

Animals↗
PubMed1989

The degeneration and regeneration of cutaneous nerves in experimental flaps in rats.

The cutaneous nerves in pedicled flaps lifted from rats backs were studied by electron microscopy for eight weeks. On the rat back, the paniculus carnosus is supplied by cutaneous nerves from C7-8 and T1 and anastomosed with the cutaneous branch of the spinal nerves (T2 to L5), located deeper under the flap. The cutaneous nerves showed degeneration immediately after the flap was raised; four days later, unmyelinated nerve fibers had disappeared. Regeneration was observed at the seventh day. Regenerated axons of the new fibers were presumed to have originated from the few nerves placed centrally and peripherally at the base of flap, through nerve anastomoses.

Animals↗
PubMed1989

Isolation of Chinese hamster ovary cell lines expressing human acyl-coenzyme A/cholesterol acyltransferase activity.

We have previously reported the isolation of Chinese hamster ovary cell mutants deficient in acylcoenzyme A/cholesterol acyltransferase (ACAT) activity (Cadigan, K. M., J. G. Heider, and T. Y. Chang. 1988, J. Biol. Chem. 263:274-282). We now describe a procedure for isolating cells from these mutants that have regained the ability to synthesize cholesterol esters. The protocol uses the fluorescent stain Nile red, which is specific for neutral lipids such as cholesterol ester. After ACAT mutant populations were subjected to chemical mutagenesis or transfected with human fibroblast whole genomic DNA, two revertants and one primary transformant were isolated by virtue of their higher fluorescent intensities using flow cytofluorimetry. Both the revertants and transformant have regained large amounts of intracellular cholesterol ester and ACAT activity. However, heat inactivation experiments revealed that the enzyme activity of the transformant had heat stability properties identical to that of human fibroblasts, while the ACAT activities of the revertants were similar to that of other Chinese hamster ovary cell lines. These results suggest that the molecular lesion in the ACAT mutants resides in the structural gene for the enzyme, and the transformant has corrected this defect by acquiring and stably expressing a human gene encoding the ACAT polypeptide. Secondary transformants were isolated by transfection of ACAT mutant cells with primary transformant genomic DNA. Genomic Southern analysis of the secondary transformants using a probe specific for human DNA revealed several distinct restriction fragments common to all the transformants which most likely comprise part or all of the human ACAT gene. The cell lines described here should facilitate the cloning of the gene encoding the human ACAT enzyme.

Animals↗