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Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 451 records · Page 25Linked to original sources

Altered regulation of intercellular communication by epidermal growth factor, transforming growth factor-beta and peptide hormones in normal human keratinocytes.

Since many chemical tumor promoters and some oncogenes have been shown to inhibit gap junction-mediated intercellular communication, the effect of various growth factors on gap junctional intercellular communication on normal human keratinocytes was examined. In order to measure the effect of the growth factors on gap junctional communication, the scrape loading/dye transfer technique was used on human keratinocytes grown in a serum-free medium in vitro. At 24 h after treatment epidermal growth factor (10 ng/ml), transforming growth factor-beta (1 ng/ml), whole bovine pituitary extract (70 micrograms/ml) and 12-O-tetradecanoylphorbol-13-acetate (TPA) (100 ng/ml) inhibited intercellular communication. Treatment of these cells with transforming growth factor-beta (1 ng/ml) induced morphological changes in some of the cells and brought about selective intercellular communication within and between the nonaltered and altered cells. Epidermal growth factor and whole bovine pituitary extract, significantly enhanced [3H]thymidine uptake and also stimulated cellular proliferation under the experimental conditions used to inhibit intercellular communication. Both transforming growth factor-beta and TPA markedly inhibited [3H]thymidine uptake and induced differentiation of some of these cells. In order to study the possible mechanism by which the growth factors might inhibit intercellular communication, the effect of the growth factors on protein kinase C activation and alterations of intracellular free calcium was investigated. The results indicated that neither protein kinase C nor an increase in [Ca2+]i were involved in the modulation of gap junctional communication by epidermal growth factor or transforming growth factor-beta. The study suggests that in the human keratinocytes inhibition of intercellular communication may be involved (i) in the action of growth factors such as epidermal growth factor during cellular proliferation and (ii) in the differentiation of primary keratinocytes by transforming growth factor-beta.

Calcium↗

Use of geographutoxin II (mu-conotoxin) for the study of neuromuscular transmission in mouse.

1. Endplate potentials (e.p.ps) were investigated in the presence of geographutoxin II (GTXII) in the mouse phrenic nerve diaphragm preparation. This toxin preferentially blocks muscle Na+ channels which allows the study of e.p.ps in the absence of nicotinic receptor antagonists or substances to depress acetylcholine release. 2. GTXII abolished muscle action potentials and antagonized the depolarization of the muscle membrane produced by the crotamine-induced opening of Na+ channels. 3. E.p.ps as large as 19-25 mV were observed after 2-4 micrograms ml-1 GTXII. These concentrations of GTXII did not cause discernible changes of resting membrane potential and frequency and amplitude of miniature e.p.ps. 4. Lower concentrations (1-2 micrograms ml-1) of GTXII caused incomplete blockade of the muscle Na+ channel resulting in exaggerated 'e.p.ps', while higher concentrations of GTXII (8 micrograms ml-1) abolished e.p.ps by a prejunctional effect. 5. Trains of e.p.ps on repetitive stimulation after GTXII neither ran down, as in tubocurarine-treated preparations, nor facilitated, as in low Ca2+ and/or high Mg2+-treated preparations, and were indistinguishable from those of untreated cut muscle preparation. 6. In cut muscle preparations, GTXII did not affect the rise and decay times, amplitude or rundown of e.p.ps. 7. It is concluded that GTXII is a useful agent for studying neuromuscular transmission. This method provides e.p.ps which are neither attenuated nor modified because manipulations that alter transmitter release and postjunctional receptor responses are avoided.

Animals↗

Selective antagonism to succinylcholine-induced depolarization by alpha-bungarotoxin with respect to the mode of action of depolarizing agents.

1. The interactions of alpha-bungarotoxin or tubocurarine with the neuromuscular block and endplate depolarization induced by succinylcholine (SCh) in the phrenic nerve-diaphragm preparation of mice were studied in order to elucidate the role of depolarization by SCh in the neuromuscular blockade. 2. The SCh concentrations required to depress the indirect twitch response by 20% and the evoked endplate potential in cut muscle preparations by 80% were 10 microm and 6 microM, respectively, while only 2 microM SCh was needed to induce maximal endplate depolarization from -80 mV to about -60 mV. 3. SCh blocked the neuromuscular transmission synergistically with either alpha-bungarotoxin or tubocurarine. There was an initial partial reversal of the neuromuscular inhibition caused by tubocurarine, but not that by alpha-bungarotoxin. 4. alpha-Bungarotoxin (0.025 microM) antagonized SCh (10 microM)-induced depolarization more effectively than it depressed miniature endplate potentials and the antagonism was insurmountable by increasing SCh concentration. By contrast, tubocurarine preferentially depressed miniature endplate potentials and antagonized SCh-depolarization competitively. 5. The above difference was attributed to the irreversible nature of alpha-bungarotoxin binding to acetylcholine receptors, to the slow diffusion of the toxin molecule into the synaptic cleft and thus to the more rapid binding with perijunctional receptors compared with junctional ones. 6. It is concluded that the sustained depolarization of the endplate by SCh results largely from an action on the perijunctional receptor in mice and, unlike cats, the neuromuscular block by SCh is not due to the depolarization per se but rather to a direct attenuation of endplate potential.

Animals↗

Comparison of Corynebacterium parvum and Bordetella pertussis with Freund's complete adjuvant as immunopotentiators for beta-human chorionic gonadotropin linked to an atoxic fragment of tetanus toxin.

Corynebacterium parvum and Bordetella pertussis were compared with Freund's complete adjuvant (FCA) for their abilities to potentiate the immune response to haptenic beta-human chorionic gonadotropin covalently coupled to an atoxic 54,000-molecular-weight fragment of tetanus toxin (beta-hCG-TTII). The ability of each adjuvant to enhance production of antibodies to hCG in rabbits was measured by 125I-hCG radioimmunoassay. At sera dilutions of 1:10,000, analysis of variance for the 8-week postimmunization course showed that the mean 125I-hCG binding capacities of the C. parvum group was significantly greater overall than the B. pertussis group (P = .0002) and that the FCA-treated group had the greatest binding capacity overall (P less than .018). The mean binding capacities at 1:40,000 dilution again showed the FCA-treated group to have significantly higher anti-hCG titers overall (P less than .0015), with C. parvum potentiating a greater overall antibody response than B. pertussis (P = .001). These results indicate that FCA is the most efficacious of the three tested adjuvants in potentiating antibody production to the hapten component of beta-hCG-TTII. C. parvum was also effective at promoting an anti-beta-hCG response, although not to the same degree as FCA. B. pertussis had only minimal potentiating effect compared to FCA or C. parvum.

Adjuvants, Immunologic↗

In situ pyrimidine dimer determination by laser cytometry.

By using antiserum against pyrimidine dimers and argon-laser imaging microspectrofluorometry, we established a new method to determine UV-induced pyrimidine dimers and their repair in individual human cells. The method was sensitive enough to determine dimers induced by UV dose as low as 2 J/m2. Normal human cells repaired 50 and 60% of total damage within 8 and 24 h after UV irradiation (20 J/m2), but Xeroderma pigmentosum cells (complementation group A) were unable to repair any within the same period. Therefore, the method proved to be a quick, easy, sensitive and accurate means to determine pyrimidine dimers in situ.

DNA Repair↗

Altered imino diacid synthesis and transcription in crown gall tumors with transposon Tn5 insertions in the 3' end of the octopine synthase gene.

Octopine synthase encoded by the T-DNA (transferred DNA) locus ocs synthesizes N2-(D-1-carboxyethyl)-L-amino acids in octopine-type crown gall tumors. So far, derivatives of only basic amino acids have been isolated. We have detected a glutamine derivative and called it heliopine. Tumors induced by several Ti plasmids with transposon Tn5 insertions in the 3' end of ocs still synthesized small quantities of N2-(1-carboxyethyl)-arginine and N2-(1-carboxyethyl)-glutamine. In addition, N2-(1,3-dicarboxypropyl)-asparagine, which is absent in wild-type octopine tumors, was detected in these tumors. These three imino diacids (octopine, heliopine, and asparaginopine, respectively, or their isomers) were undetectable in tumors induced by Ti plasmids harboring deletions of the ocs gene. Poly(A)+ RNAs which hybridize to the ocs sequence can also be detected in the ocs::Tn5 tumors; these RNAs, however, were heterogeneous in size and shorter in length than the normal ocs mRNA. These results indicate that mutant ocs products synthesize imino diacids in these ocs::Tn5 tumors.

Amino Acid Oxidoreductases↗

Nicardipine inhibits axon conduction but causes dual changes of acetylcholine release in the mouse motor nerve.

The effects of nicardipine, a dihydropyridine Ca2(+)-channel antagonist, on neuromuscular transmission and impulse-evoked release of acetylcholine were compared with those of nifedipine. In the isolated mouse phrenic nerve diaphragm, nicardipine (50 microM), but not nifedipine (100 microM), induced neuromuscular block, fade of tetanic contraction, and dropout or all-or-none block of end-plate potentials. Nicardipine had no significant effect on the resting membrane potential and the amplitude of miniature end-plate potentials but increased the frequency and caused the appearance of large size miniature potentials. The quantal contents of evoked end-plate potentials were increased. In the presence of tubocurarine, however, nicardipine depressed the amplitude of end-plate potentials. The compound nerve action potential was also decreased. It is concluded that nicardipine blocks neuromuscular transmission by acting on Na+ channels and inhibits axonal conduction. Nicardipine appeared to affect the evoked release of acetylcholine by dual mechanisms, i.e., an enhancement presumably by an agonist action on Ca2+ channels, like Bay K 8644 and nifedipine, and inhibition by an effect on Na+ channels, like verapamil and diltiazem. In contrast with its inactivity on the amplitude of miniature end-plate potentials, depolarization of the end plate in response to succinylcholine was greatly depressed. The contractile response of baby chick biventer cervicis muscle to exogenous acetylcholine was noncompetitively antagonized by nicardipine (10 microM), but was unaffected by nifedipine (30 microM). These results may implicate that nicardipine blocks the postsynaptic acetylcholine receptor channel by enhancing receptor desensitization or by a use-dependent effect.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Neurotransmitter amines in brain edema of a rat glioma model.

The effect of vasogenic brain edema on amine neurotransmitter concentrations was studied in rats bearing transplanted glioma C6 brain tumors. In comparison with sham-operated and nonoperated controls, the tumor-implanted animals showed significant decreases in both dopamine (DA) and norepinephrine (NE) in the hypothalamus, cortex, and striatum. Treatment with dexamethasone (DEX) tended to restore these monoamines to the levels measured in sham-operated controls. In the nonoperated controls, DEX significantly increased NE but not DA. In tumor-bearing rats there was no increase in hypothalamic or striatal water content, and DEX had no effect on the water content of these structures. However, there was a significant increase in the cortical water content, which was reduced by DEX to the control levels. The water content within the tumor was also significantly decreased by DEX. In the nonoperated controls, there was no difference in water content between DEX-treated and nontreated animals. These findings suggest that tumor-induced brain edema reduces noradrenergic and dopaminergic activities. DEX administration resulted in normalization of the water content in edematous regions and of the DA and NE concentrations, and brought about marked symptomatic improvement.

Animals↗

Serum prolactin and growth hormone response to thyrotropin-releasing hormone in patients with pituitary adenomas.

The dynamics of growth hormone (GH) and prolactin (PRL) secretion in response to intravenous 400 micrograms thyrotropin-releasing hormone (TRH) in 13 untreated patients with pituitary adenomas (6 women, 7 men; ages 20-64 years; 8 patients with acromegaly, 3 prolactinomas and 2 non-functional adenomas) were correlated with the results of immunohistochemical studies of GH and PRL in the adenoma cells. The basal serum GH concentrations were abnormally high in 6 and normal in 2 cases of acromegaly. In 5 of 6 acromegalic patients with pure GH-containing adenomas, TRH stimulated GH release by less than 100%. One patient with acromegaly and pancreatic islet cell carcinoma had the maximum increment for GH by 303%. TRH stimulated GH release by more than 100% in 2 acromegalic patients with mixed GH/PRL-containing adenomas. In 3 patients with prolactinoma and in 2 patients with non-functional adenoma the basal GH levels were 0.5 mU/L or undetectable and there was no GH response to TRH. The peak serum PRL levels after TRH were less than 100 ng/ml in 6 acromegalic patients with pure GH-containing tumors and in 2 patients with non-functioning pituitary tumors, and were more than 230 ng/ml in 3 patients with prolactinoma and in 2 acromegalic patients with mixed GH/PRL-containing tumors. It is suggested that the TRH test may help clinically in establishing the diagnosis of prolactinoma, pure GH-secreting tumors and mixed GH/PRL-containing tumors.

Adenoma↗

Deficient erythrocyte membrane Gs alpha activity and resistance to trophic hormones of multiple endocrine organs in two cases of pseudohypoparathyroidism.

Patients with pseudohypoparathyroidism (PHPT) have been shown to have deficient cell membrane stimulatory GTP-binding regulatory protein activity (Gs activity) and other defects, which cause renal resistance to parathyroid hormone (PTH). Those patients also have a higher incidence of deficiency of other endocrine axes. To investigate the mechanisms of this syndrome on 2 patients, we measured erythrocytic ghost Gs activity by ADP-ribosylation method, which showed low and low normal levels for the 2 patients who were from the same family, suggesting type Ia of this syndrome. While basal T3, T4 and TSH were compatible with mild primary hypothyroidism in both patients, a TRH test showed exaggerated TSH responses. The estrogen, progesterone and testosterone levels were low and LH and FSH responses were marginally high, indicating gonadal resistance to gonadotropins. ACTH levels were also elevated and ACTH response to CRH was exaggerated in one patient, suggesting additional primary adrenal insufficiency. This finding indicates that systemic endocrine tests are essential for the management of PHPT patients who may have a deficiency of multiple endocrine axes subclinically.

Adolescent↗

Zinc phosphide ingestion: a case report and review.

We present the case of a patient who attempted suicide by ingestion of the rodenticide zinc phosphide. Zinc phosphide manifests its immediate toxicity through production of phosphine gas. Signs and symptoms of toxicity include nausea, vomiting, dyspnea, and changes in mental status; immediate death results from pulmonary edema. Delayed effects are secondary to the absorption of phosphide, affecting primarily the liver, heart and kidneys. Delayed deaths are related to a direct cardiotoxicity. Treatment is mainly symptomatic and supportive; aggressive airway management and circulatory support are critical to a successful outcome.

Adult↗

An unusual case presentation: pericardial tamponade complicating central venous catheter.

The use of central venous catheters in very low birthweight infants to provide adequate calories for growth is an integral part of the care of the high-risk neonate. The use of surgically placed Broviac catheters has been associated with infectious and mechanical complications. Recently, there has been increasing use of silastic central venous catheters inserted through a peripheral vein and advanced to the right atrium. These catheters have a reported low rate of complications. However, we report a case of a very low birthweight infant in whom a peripherally inserted silastic catheter perforated the wall of the right atrial appendage and led to fatal pericardial tamponade. This is a very rare but nearly always fatal complication. It is potentially avoidable by careful placement of the tip of the central venous catheter, so that it is not impinging on a wall of the heart. Serial venograms may be useful to reconfirm the position of the catheter.

Cardiac Tamponade↗

Association of HLA-DR tissue types with Graves' disease in Taiwan.

To determine the association of HLA-DR tissue types and Graves' disease (GD) in Chinese residing in Taiwan, we studied HLA-DR antigens on 93 unrelated patients with Graves' disease, and 106 normal persons (N). The prevalence of DR2 (GD: 40.9%, N: 21.7%, pc = 0.028 where pc is the Fisher's probability times the numbers of antigens considered), DR9 (GD: 29%, N: 13.2%, pc = 0.048), DQw1 (GD: 58.1%, N: 39.6%, pc less than 0.003) and DRw53 (GD: 58.1%, N: 41.5%, pc less than 0.002) were significantly increased in patients with Graves' disease, while the prevalence was decreased significantly for DR3 (GD: 16.1%, N: 33.0%, pc = 0.031) and DRw52 (GD: 58.1%, N: 76.4%, pc = 0.01). When the combinations of DR2, DR3 and DR9 were compared with other HLA-DR antigens, DR3 remained less prevalent in GD; DR2/9 heterozygotes were strongly associated with GD; while neither DR2 nor DR9 remained significantly associated with GD when DR2/9 heterozygotes were removed from each. When we separated the patients into subgroups according to the onset of clinical symptoms occurring by the age of 35 years, there was no significant difference in the frequencies of HLA-DR antigens in those two subgroups. Patients with or without exophthalmos, antimicrosomal antibody or antithyroglobulin antibody had similar distribution of HLA-DR types. Our data suggested that in our area DR2 and DR9 played additive roles in the susceptibility of Graves' disease.

Adolescent↗

Anaplastic thyroid carcinoma: review of 24 cases, with emphasis on cytodiagnosis and leukocytosis.

Twenty-four cases of anaplastic thyroid carcinoma seen in the National Taiwan University Hospital from 1980 to 1988 were reviewed. The median age was 61.5 years. The ratio of men to women was 1:1.4. A preceding history of long-standing goiter could be obtained in 14 patients (58.3%) with a median duration of 20 years. Twenty patients (83.3%) presented with a rapid-growing neck mass with a median duration of 1.3 months. Nine out of 19 patients (47.4%) had white blood cell (WBC) counts over 10,000/microliters, which were closely related to the presence of fever (p less than 0.02). Serial follow-up showed that WBC and platelets gradually increased but red blood cells and hemoglobin decreased. Fever was noted at the time of diagnosis in 8 out of 24 patients (33.3%), and was closely related to the presence of abundant neutrophils in the cytologic smears of thyroid aspirates (p less than 0.01). Fever was not due to bacterial infection. Three out of 10 patients (30.0%) had calcification in the thyroid shown on neck X ray, and 7 out of 18 patients (38.9%) had lung metastasis shown on chest X ray. The ultrasonographic images of thyroid anaplastic carcinoma done in 6 patients were heterogeneous and hypoechoic. Fine-needle aspiration cytology was done in 20 patients. Anaplastic thyroid carcinoma was easily diagnosed in 18 patients (90.0%). One was misdiagnosed as acute thyroiditis. Another one was diagnosed as papillary carcinoma cytologically, which combined with anaplastic carcinoma shown on histology. The median survival was 2.2 months, ranging from 0.2 to 25.3 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Determination of protein concentration in human saliva].

Seven colorimetric methods (Biuret, Lowry, a modified Lowry technique using bicinchoninic acid, Coomassie brilliant blue G (CBBG) dye-binding in phosphoric acid, perchloric acid or hydrochloric acid, and bromophenol blue dye-binding) were evaluated for determination of protein concentration in human whole saliva. Using bovine serum albumin (BSA), mucin, and thyroglobulin as protein standards to calculate salivary protein concentration gave different results among the assays used and even with the different standards of the same method. Among the seven methods used, the CBBG dye-binding assay in hydrochloric acid appeared to provide the most accurate estimation of protein concentration in human saliva. Using BSA as a standard, the mean values of human salivary proteins from 39 healthy individuals ranged from 0.72 to 2.45 mg/ml. The optimum conditions for the CBBG dye-binding assay in hydrochloric acid are: (1) the absorbance at 595 nm was measured between 15 to 30 minutes after addition of reagent. (2) the optimum concentration of dye in hydrochloric acid was 0.06-0.12% (w/v) for the assay. (3) the dye reagent was stable within one month.

Colorimetry↗

Isolation of antigenically reactive peptide fragments and localization of antigenic regions of alpha-bungarotoxin.

alpha-Bungarotoxin was digested with acid protease A and the resulting peptide fragments were isolated by reverse-phase HPLC. The antigenic activity of the peptide fragments were examined by competitive solid phase radioimmunoassay and the probably sequences were assigned. The two antigenic regions are likely located around the residues 34-41 and 68-74 of alpha-bungarotoxin, and the other two may be within the residues 3-26 and 45-67, respectively. Radioimmunoassay revealed a maximum number of four antigenic determinants of alpha-bungarotoxin that can simultaneously be occupied by antibody.

Amino Acid Sequence↗

Biosynthesis of monoterpenes. Enantioselectivity in the enzymatic cyclization of (+)- and (-)-linalyl pyrophosphate to (+)- and (-)-pinene and (+)- and (-)-camphene.

Cyclase I from Salvia officinalis leaf catalyzes the conversion of geranyl pyrophosphate to the stereo-chemically related bicyclic monoterpenes (+)-alpha-pinene and (+)-camphene and to lesser quantities of monocyclic and acyclic olefins, whereas cyclase II from this plant tissue converts the same acyclic precursor to (-)-alpha-pinene, (-)-beta-pinene and (-)-camphene as well as to lesser amounts of monocyclics and acyclics. These antipodal cyclizations are considered to proceed by the initial isomerization of the substrate to the respective bound tertiary allylic intermediates (-)-(3R)- and (+)-(3S)-linalyl pyrophosphate. [(3R)-8,9-14C,(3RS)-1E-3H]Linalyl pyrophosphate (3H:14C = 5.14) was tested as a substrate with both cyclases to determine the configuration of the cyclizing intermediate. This substrate with cyclase I yielded alpha-pinene and camphene with 3H:14C ratios of 3.1 and 4.2, respectively, indicating preferential, but not exclusive, utilization of the (3R)-enantiomer. With cyclase II, the doubly labeled substrate gave bicyclic olefins with 3H:14C ratios of from 13 to 20, indicating preferential, but not exclusive, utilization of the (3S)-enantiomer in this case. (3R)- and (3S)-[1Z-3H]linalyl pyrophosphate were separately compared to the achiral precursors [1-3H]geranyl pyrophosphate and [1-3H]neryl pyrophosphate (cis-isomer) as substrates for the cyclizations. With cyclase I, geranyl, neryl, and (3R)-linalyl pyrophosphate gave rise exclusively to (+)-alpha-pinene and (+)-camphene, whereas (3S)-linayl pyrophosphate produced, at relatively low rates, the (-)-isomers. With cyclase II, geranyl, neryl, and (3S)-linalyl pyrophosphate yielded exclusively the (-)-isomer series, whereas (3R)-linalyl pyrophosphate afforded the (+)-isomers at low rates. These results are entirely consistent with the predicted stereochemistries and additionally revealed the unusual ability of these enzymes to catalyze antipodal cyclizations when presented with the unnatural linalyl enantiomer.

Acyclic Monoterpenes↗