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Biomedical subjects

C C Chang

Publications and source records attributed to C C Chang.

At least 559 records · Page 31Linked to original sources
PubMed1985

Localization of the human MHC-linked complement genes between HLA-B and HLA-DR by using HLA mutant cell lines.

A C4 cDNA clone has been used to localize the C4 genes within the human major histocompatibility complex (MHC). The clone, pC4AL1, detects a DNA polymorphism of the C4 genes in Southern blot hybridization experiments and established the genotype of a lymphoblastoid cell line, LCL 721, as heterozygous for the C4 DNA patterns. Subclones of LCL 721 that had gamma-ray-induced lesions of the MHC were analyzed with pC4AL1. Loss or retention of chromosome-specific C4 DNA patterns relative to the loss or retention of other MHC genes on the same chromosome was assessed. This permitted the mapping of the C4 genes, and the other MHC-linked complement genes, between the HLA-DR and HLA-B loci.

Cell Line↗
PubMed1985

Effect of inhibition of polyamine biosynthesis by DL-alpha-difluoromethylornithine on the growth and melanogenesis of B16 melanoma in vitro and in vivo.

The objective of the present study was to investigate the effect of polyamine depletion by alpha-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ornithine decarboxylase, on the growth and differentiation of B16 melanoma cells grown in culture and also as solid tumors in mice. Polyamine depletion by DFMO (2.5 mM) resulted in a complete inhibition of cell growth in culture and a 90% inhibition of viability of melanoma cells as determined by clonogenic assay at the end of 7 days after DFMO treatment. These results indicate that polyamine depletion induced by DFMO is cytotoxic to B16 melanoma cells in culture. Furthermore a 2- to 5-fold increase in tyrosinase activity and 10-fold accumulation of melanine were observed in polyamine depleted cells compared to control cultures. These effects of DFMO could easily be reversed by the addition of putrescine simultaneously with DFMO. Administration of different doses of DFMO in drinking water to B16 melanoma tumor bearing mice also resulted in an increase in tyrosinase activity and a dose dependent inhibition (86-90%) of tumor growth. Although one cannot rule out the possibility of induction of differentiated phenotype as a result of antiproliferative activity of DFMO, the data presented indicate that the unique sensitivity of melanoma to DFMO may be due to a combination of cell growth inhibition and concomitant induction of differentiation upon polyamine depletion. The results of the present study indicate that polyamines play an important role in growth and differentiation of melanoma and also provide an example of inhibition of tumor cell growth by induction of cellular differentiation.

Animals↗
PubMed1984

Imaging of human tumor xenografts in nude mice with radiolabeled monoclonal antibodies. Limitations of specificity due to nonspecific uptake of antibody.

To determine if in vivo binding specificities of monoclonal antibodies to tumor nodules would reflect in vitro antibody specificities as determined by radioimmunoassay, two monoclonal antibodies were selected for imaging of human tumor xenografts in nude mice. By in vitro radioimmunoassay, antibody 436 binds to the M20 melanoma cell line, but not to the P3 carcinoma cell line; antibody 44 binds to P3 but not to M20. Both antibodies are IgG1 isotypes. Nude mice bearing an M20 melanoma in one flank and a P3 carcinoma in the other were injected intravenously with 5 to 25 micrograms of each antibody labeled with either I-125 or I-131; in separate animals the labels were reversed. Animals were imaged daily with a scintillation camera equipped with a pinhole collimator. On day 6 the animals were sacrificed, and binding of the antibodies to the tumors and normal tissue were compared. Antibody 436 had up to a two-fold binding advantage in vivo for the melanoma, whereas antibody 44 had up to a two-fold binding advantage for the carcinoma, thus confirming the in vitro specificities of each. However, imaging on day 4 and computer analysis of percent radioactivity in the tumors showed that tumor images were related directly to tumor size and relatively uninfluenced by antibody specificity. Thus, even though antibody specificity can be demonstrated by differential tissue counting, imaging of tumor deposits appears to involve a nonspecific phenomenon that is largely dependent upon tumor weight.

Animals↗
PubMed1984

Serum from outdated human platelet concentrates: an alternative supplement for tissue (fibroblast) culture media.

Fetal calf serum (FCS) is used as a component of the media for cells grown in culture. However, the high cost of FCS has stimulated a search for a possible alternative. Approximately 10% of human platelet concentrates prepared for clinical transfusions are outdated. Sera prepared from platelet concentrates were compared with FCS and calf serum (CS) as a media supplement. A similar number of fibroblast (NSF-791) colonies grew in media supplemented with the three different sera. However, colonies grown in the presence of human platelet serum (HPS) were larger than those grown in media containing CS and FCS. Hence, serum prepared from outdated human platelet concentrates may be substituted for fetal calf serum as a cell culture nutrient, for fibroblasts.

Blood Physiological Phenomena↗
PubMed1984

Inhibition of metabolic cooperation in Chinese hamster V79 cells by various organic solvents and simple compounds.

Gap-junctional intercellular communication is a biological process implicated in the regulation of cell proliferation and differentiation. Metabolic cooperation between 6-thioguanine-sensitive and resistant Chinese hamster cells, in vitro, has been used as a means to detect chemicals which can inhibit this form of intercellular communication. To further characterize this in vitro system as a potential screening assay for potential teratogens, tumor promoters and reproductive toxicants, a series of common solvents as well as other chemicals representing eight different functional groups, i.e., alcohols with straight or side chains, glycols, ketones, esters, ethers, phenols, aldehydes, amines and amino compounds and oxygen-heterocyclic compounds, were tested for their ability to inhibit colony-formation and to inhibit metabolic cooperation. A wide range of effects were observed which suggested a structure/activity relationship between a chemical's ability to inhibit gap junction-mediated intercellular communication and the cytotoxicity of a chemical. Possible mechanisms affecting the modulation of gap junctional communication by these chemicals are discussed.

Animals↗
PubMed1984

Evidence for mutagenic repair in V79 cell mutant with aphidicolin-resistant DNA polymerase-alpha.

An aphidicolin-resistant ( aphr ) mutant of Chinese hamster V79 cells, aphr -4-2, is shown to be slow-growing, sensitive to ultraviolet (UV) irradiation, hypermutable for spontaneous and UV-induced mutations, and known to contain an aphr mutant DNA polymerase-alpha, with a 10-fold reduction in the Km for dCTP but not for dATP. We show here that the mutant had a normal repair replication measured by unscheduled DNA synthesis assay. The mutant was specifically sensitive and hypermutable to UV and N-methyl-N'-nitro-N-nitrosoguanidine, but it had normal sensitivity to ionizing radiation and dimethyl sulfate. Unlike the V79 (wt) cells, the mutant exhibited further enhancement in the already elevated mutability following UV and conditioned medium treatment. The mutant characteristic is explained by the presence of an error-prone long-patch excision repair synthesis. The association in the mutant properties--an aphr DNA polymerase-alpha, UV sensitivity, and hypermutability to UV-induced mutation--provides the genetic evidence that DNA polymerase-alpha is likely to be involved in UV-induced DNA repair synthesis.

Animals↗
PubMed1984

Presynaptic effects of snake venom toxins which have phospholipase A2 activity (beta-bungarotoxin, taipoxin, crotoxin).

The presynaptic effects of beta-bungarotoxin, crotoxin and taipoxin were studied in the mouse phrenic nerve-diaphragm preparation (27 degrees C). The phospholipase A2 activity, assayed by pH-stat titration, was reduced to 4-10% at 27 degrees C compared with that at 37 degrees C. The late neuromuscular blocking activity was also reduced by more than three fold for all toxins. In contrast, the early biphasic response to the toxins, i.e. immediate depression followed by facilitation, was not delayed. The evoked quantal release of acetylcholine was enhanced by all toxins at low Ca2+-concentrations during the phase of facilitation, without an increase of the maximal release. At the late phase of treatment with beta-bungarotoxin and taipoxin, the curve relating the quantal contents of endplate potentials with Ca2+-concentration was shifted parallel to the right at low Ca2+, but marked depression of the maximal release occurred at high Ca2+. When diaminopyridine was added at the time of the late phase block by beta-bungarotoxin, the quantal release could still be enhanced at low Ca2+-concentrations, even beyond control; however, the maximal release was not simultaneously restored. It is concluded that the late phase block, but not the early biphasic response, is due to an enzymatic action and the release mechanism is abolished when the hydrolysis of membrane phospholipids proceeds to a certain critical level.

Acetylcholine↗
PubMed1984

Homozygous deletions that simultaneously eliminate expressions of class I and class II antigens of EBV-transformed B-lymphoblastoid cells. I. Reduced proliferative responses of autologous and allogeneic T cells to mutant cells that have decreased expression of class II antigens.

Mutant human B-lymphoblastoid cell lines, 721.174 and 721.180, that have greatly reduced expressions of known class I and class II HLA antigens were produced by two cycles of gamma-ray mutagenesis followed by selection for HLA antigen loss. Residual binding of monoclonal antibodies directed against class II antigens was negligible except for 10% residual binding of SB-binding antibody ILR1. However, deletion of SB was functionally complete as indicated by failure of the mutants to stimulate proliferation of SB-primed lymphocytes. Residual binding of monoclonal antibodies directed against class I "framework" determinants was reduced by 90-95%. However, the binding of monoclonal antibodies directed against beta 2-microglobulin and against the A2 epitope recognized by monoclonal antibody BB 7.2 was about 20% of normal. The identities of the residual class I-like antigens are unknown. The mutants retained full expression of the EBV-induced EBVCS antigen. Mutants 721.174 and 721.180 have lost most, but definitely not all, of their capacity to stimulate primary allogeneic and autologous lymphoproliferative responses. Therefore, the mutants still express antigens other than those that are presently known to stimulate lymphocyte proliferation. By means of studies of the present sort, and in future studies on expression of transferred HLA genes, mutants 721.174 and 721.180 promise to be useful in molecular and functional analysis of MHC-region-encoded gene products and their genetic regulation.

Antibodies, Monoclonal↗
PubMed1984

Inhibition of intercellular communication in cultures of Chinese hamster V79 cells by 2,4-dichlorophenoxyacetic acid and 2,4,5-trichlorophenoxyacetic acid.

Using the Chinese hamster V79 in vitro cell system designed to measure intercellular communication, 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and several mixtures of these compounds were tested for their ability to inhibit this biological process. The ability of these chemicals to inhibit colony-forming ability of these cells was tested prior to the studies to measure intercellular communication. 2,4-D was less cytotoxic than 2,4,5-T. Both 2,4,5-T and 2,4-D were able to inhibit intercellular communication at their respective noncytotoxic dose ranges. Various mixtures of both chemicals were also able to inhibit intercellular communication, showing some kind of additivity. No-effect levels were also noted in the intercellular communication assay. These results were interpreted as being consistent with the hypothesis that these compounds might be teratogenic by their ability to inhibit intercellular communication during development.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1984

Biosynthesis of ketomycin.

The antibiotic ketomycin is formed from shikimic acid via chorismic acid and prephenic acid. Phenylalanine and 2',5'-dihydrophenylalanine are not intermediates in the biosynthesis. Degradation of ketomycin derived from [1,6-14C]shikimic acid showed that prephenic acid is converted into ketomycin with stereospecific discrimination between the two enantiotopic edges of the ring, the pro-S-R edge giving rise to the C-2', C-3' side of the cyclohexene ring of ketomycin.

Anti-Bacterial Agents↗
PubMed1984

Potentiation between neostigmine and 3,4-diaminopyridine in antagonizing the neuromuscular block induced by D-tubocurarine.

The antagonisms to the d-tubocurarine-induced neuromuscular blockade by neostigmine and 3,4-diaminopyridine (DAP) were studied quantitatively in the isolated phrenic nerve-diaphragm preparation of mice in vitro and in lethality of mice in vivo by assaying concentrations of d-tubocurarine needed to produce 70% block of indirect muscle contraction and LD50, respectively. The "antagonist efficacies", defined as the ratio of d-tubocurarine concentration (dose) after pretreatment with antagonistic agents over that of control, were 1.87, 2.24 and 14.7, respectively, for neostigmine, DAP and both agents combined when the stimulus pulses were at 0.1 Hz. Under 50 Hz train stimulation, the antagonist efficacies were lower, being 1.85, 1.64 and 5.33, respectively. For the lethality to d-tubocurarine, the values were still lower, being only 1.21, 1.33 and 1.84, respectively. The synergism between neostigmine and DAP, as evident from the marked increase of antagonist efficacy in vitro, is more than expected from the possible interaction of the major pharmacological actions of these two agents.

4-Aminopyridine↗
PubMed1984

Effect of clonidine on neuromuscular transmission and the nicotinic acetylcholine receptor.

The effects of clonidine on neuromuscular transmission were investigated in the mouse phrenic nerve-diaphragms and chicken biventer cervicis. Clonidine inhibited the indirect twitch response dose-dependently and reversibly without an effect on the direct response of the muscles to electrical stimulation and KCl. This effect was antagonized effectively by diaminopyridine but not by yohimbine, phentolamine or physostigmine. The quantal content was not affected although the amplitudes of end-plate potential (epp) and spontaneous miniature epp (mepp) were markedly depressed. Clonidine also decreased the slope of the ACh dose-response curve and maximal response in denervated mouse diaphragms as well as the carbachol response in the chinck muscle. In the latter, ACh response was not depressed by clonidine probably because of its inherent anticholinesterase activity. Clonidine facilitated the fading of ACh-contracture either in mouse or chick muscle. It is concluded that clonidine impairs the neuromuscular transmission by a noncompetitive blockade of ACh receptors, most likely affecting the ACh channel but not the recognition site of the ACh receptor. Its inhibitory effect is not mediated by alpha 2-adrenoceptor, suggesting that there is no alpha 2-adrenoceptor on the motor nerve terminal to modulate the transmitter release.

Acetylcholinesterase↗
PubMed1984

Adaptive and nonadaptive consequences of chemical inhibition of intercellular communication.

Intercellular communication is a fundamental process in multicellular organisms developed to orchestrate homeostatic control of mitotic and differentiation processes in pre- and postmitotic cells. Endogenous and exogenous chemicals can, via a series of mechanisms, interfere with intercellular communication between and within various tissues. The responses to the inhibition of non-gap-junctional and gap-junctional communication can be either adaptive or nonadaptive depending on the mitigating circumstances. The inhibition of gap-junctional communication appears to be one of the sequelae of a membrane-triggered response to many natural and man-made pharmacological chemicals. The biological consequences of inhibited intercellular communication might include teratogenesis (embryo or fetal toxicity), tumor promotion, reproductive toxicology, and neuroendocrine-related disorders.

Adaptation, Physiological↗