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C Chen

Publications and source records attributed to C Chen.

At least 1,189 records · Page 66Linked to original sources
PubMed1988

Histometric investigations of the effect of cyclosporin A on the testicular tissue of rats.

The effect of cyclosporin A (CsA) on rat testes was assessed in Lewis rats which were given 10 mg/kg of CsA im per day. The rats were divided into 13 subgroups, and 1 subgroup was sacrificed each month. The rat testes were measured and examined for histometrical and morphological changes in comparison to controls. Histometrical analysis included testicular cross-sectional surface area, tubular density, tubular diameter, and the amounts of testicular germinal epithelium, lumen, and interstitial tissue. In the parameters examined, there were no overall differences between CsA-treated animals and controls. CsA does not affect rat testicular tissue.

Age Factors↗
PubMed1988

Subunit interactions within the T-cell antigen receptor: clues from the study of partial complexes.

The T-cell antigen receptor is a multisubunit complex composed of seven transmembrane chains (alpha beta gamma delta epsilon zeta 2). Subunit interactions within this complex were defined by analyzing the subunit composition of partial complexes. These partial complexes were observed in mutant and tumor T cells that fail to synthesize one or more of the receptor chains or in fibroblasts transfected with genes encoding T-cell antigen receptor chains. In addition, partial complexes were generated by immunoprecipitation with antibodies that cause selective dissociation of T-cell antigen receptor chains. The alpha and beta chains were found to form a disulfide-linked dimer in the absence of any of the other chains. The gamma, delta, and epsilon chains were also efficiently associated in the absence of a complete heterodimer. Complexes composed only of delta epsilon or gamma epsilon could be observed. Both these dimers, as well as the gamma delta epsilon trimer, could form stable complexes with alpha beta, even in the absence of zeta 2. The zeta 2 dimer could bind directly to alpha beta. In the absence of a complete clonotypic heterodimer, zeta 2 was not stably associated with gamma delta epsilon. These observations suggest a model in which alpha beta interacts directly with the gamma delta epsilon trimer and zeta 2, with less-direct interaction between the latter two.

Animals↗
PubMed1988

Selective degradation of T cell antigen receptor chains retained in a pre-Golgi compartment.

We have examined the fate of newly synthesized T cell antigen receptor (TCR) subunits in a T cell hybridoma deficient in expression of the clonotypic beta chain. Synthesis and assembly of the remaining chains proceed normally but surface expression of TCR chains is undetectable in these cells. A variety of biochemical and morphological techniques has been used to show that the TCR chains in these cells fail to be transported to any of the Golgi cisternae. Instead, they are retained in a pre-Golgi compartment which is either part of or closely related to the endoplasmic reticulum. The CD3-delta chain is degraded by a non-lysosomal process that is inhibited at temperatures at or below 27 degrees C. By contrast, the remaining chains (CD3-epsilon, CD3-gamma, and zeta) are very stable over 7 h. We propose possible mechanisms that may explain the differential fate of TCR chains retained in a pre-Golgi compartment.

Animals↗
PubMed1988

Primary structure of the cytochrome P450 lanosterol 14 alpha-demethylase gene from Candida tropicalis.

We report the nucleotide sequence of the gene and flanking DNA for the cytochrome P450 lanosterol 14 alpha-demethylase (14DM) from the yeast Candida tropicalis ATCC750. An open reading frame (ORF) of 528 codons encoding a 60.9-kD protein is identified. This ORF includes a characteristic heme-binding domain, HR2, common to all P450 proteins. This protein and the 14DM from Saccharomyces cerevisiae share 66.5% identical and 23.1% conservatively replaced amino acids in a 516-amino-acid alignment, and thus are orthologous forms of the P450LIA1 gene. Conversely, C. tropicalis 14DM shares relatively little sequence similarity with P450alk, the predominant P450 protein present when this organism is grown on n-alkanes. Sequence information of these three yeast P450s will be useful for structure-function analyses in the future.

Base Sequence↗
PubMed1988

Nephrotoxicity of cyclosporine A and cyclosporine G in a rat model.

Cyclosporine G (CsG) like cyclosporine A (CsA) is a cyclic endecapeptide where the alpha-amino butyric acid residue in position 2 is replaced by norvaline. We studied the effects of both drugs on renal function in a nontransplant rat model to avoid the additional variable of rejection. Age- and weight-matched pairs of male Sprague-Dawley rats were treated subcutaneously for 21 days with a daily dose of 25 mg/kg bw of either powdered CsA or CsG dissolved in 1 ml of olive oil. A control group (C) received olive oil only. Blood pressure (BP) and creatinine (Cr) were measured on days 0, 7, 14, and 21. On day 22, animals were weighed, anesthetized, and glomerular filtration rate (GFR) and renal plasma flow (RPF) were measured using c14 inulin and 3H paraAminohippuric acid, respectively. Renal plasma flow and glomerular filtration rate were unaltered in CsG-treated animals compared to controls but significantly reduced in CsA-treated animals. Histologically, vacuolization and microcalcification were seen in significantly greater frequency among the CsA-treated animals. CsG with lesser nephrotoxic potential may prove to be of use in maintenance of therapy of transplants as well as selected autoimmune disorders.

Animals↗
PubMed1988

Regulation of Hermissenda K+ channels by cytoplasmic and membrane-associated C-kinase.

Pharmacologic activation of endogenous protein kinase C (PKC) together with elevation of the intracellular Ca2+ level was previously shown to cause reduction of two voltage-dependent K+ currents (IA and ICa2+-K+) across the soma membrane of the type B photoreceptor within the eye of the mollusc Hermissenda crassicornis. Similar effects were also found to persist for days after acquisition of a classically conditioned response. Also, the state of phosphorylation of a low-molecular-weight protein was changed only within the eyes of conditioned Hermissenda. To examine the role of PKC in causing K+ current changes as well as changes of phosphorylation during conditioning (and possibly other physiologic contexts), we studied here the effects of endogenous PKC activation and exogenous PKC injection on phosphorylation and K+ channel function. Several phosphoproteins (20, 25, 56, and 165 kilodaltons) showed differences in phosphorylation in response to PKC activators applied to intact nervous systems or to isolated eyes. Specific differences were observed for membrane and cytosolic fractions in response to both the phorbol ester 12-deoxyphorbol 13-isobutyrate 20-acetate (DPBA) or exogenous PKC in the presence of Ca2+ and phosphatidylserine/diacylglycerol. Type B cells pretreated with DPBA responded to PKC injection with a persistent reduction of K+ currents. In the absence of DPBA, PKC injection also caused K+ current reduction only following Ca2+ loading conditions. However, the direct effect of PKC injection in the absence of DPBA was only to increase ICa2+-K+. According to a proposed model, the amplitude of the K+ currents would depend on the steady-state balance of effects mediated by PKC within the cytoplasm and membrane-associated PKC. The model further specifies that the effects on K+ currents of cytoplasmic PKC require an intervening proteolytic step. Such a model predicts that increasing the concentration of cytoplasmic protease, e.g., with trypsin, will increase K+ currents, whereas blocking endogenous protease, e.g., with leupeptin, will decrease K+ currents. These effects should be opposed by preexposure of the cells to DPBA. Furthermore, prior injection of leupeptin should block or reverse the effects of subsequent injection of PKC into the type B cell. All of these predictions were confirmed by results reported here. Taken together, the results of this and previous studies suggest that PKC regulation of membrane excitability critically depends on its cellular locus. The implications of such function for long-term physiologic transformations are discussed.

Animals↗
PubMed1988

In vitro activity of pyronaridine against field isolates and reference clones of Plasmodium falciparum.

Pyronaridine, a 9-substituted 1-aza-acridine, was assayed for in vitro activity against clinical and field isolates as well as characterized clones of Plasmodium falciparum. The in vitro antimalarial activity of pyronaridine was compared to activities of standard antimalarials against multidrug-resistant isolates of P. falciparum from eastern and northern Thailand using an assay based on the inhibition of schizont maturation. Isolates from eastern Thailand (n = 30) were susceptible to pyronaridine (IC50 8.40 nM), mefloquine (IC50 6.97 nM), and amodiaquine (IC50 12.7 nM) and resistant to chloroquine (IC50 361 nM), quinine (IC50 388 nM), and pyrimethamine (IC50 11,800 nM). The isolates from northern Thailand (n = 7) showed no statistical difference in susceptibility to pyronaridine (IC50 10.1 nM), amodiaquine (IC50 7.29 nM), and mefloquine (IC50 5.48 nM); however, isolates were significantly more susceptible to chloroquine (IC50 167 nM), quinine (IC50 248 nM), and pyrimethamine (IC50 1,980 nM). These data suggest a lack of cross-resistance between pyronaridine and either chloroquine, quinine, or pyrimethamine. Using the same assay system the in vitro activity of pyronaridine was evaluated against isolates from treatment failures of mefloquine or enpiroline from eastern Thailand. The IC50 values for mefloquine against five recrudescent isolates were significantly higher (IC50 16.4 nM) than the field isolates collected from the same region (IC50 6.97 nM); however, there was no significant difference in the pyronaridine susceptibility between the isolates from the field study (IC50 8.89 nM) and the isolates from the treatment failures (IC50 8.40 nM). These observations suggest a lack of cross-resistance to mefloquine following treatment failure with either mefloquine or enpiroline.(ABSTRACT TRUNCATED AT 250 WORDS)

Amodiaquine↗
PubMed1987

Covalent attachment of an alkylamine prevents the B to Z transition in poly(dG-dC).

Covalent complexes of n-butylamine and double-stranded poly(dG-dC) were prepared by coupling the amine to exocyclic amino groups of guanine bases with CH2O. Neither the absorption spectrum above 230 nm nor the s020,w of the complexes in low to moderate ionic strength solvents, freed of excess unreacted reagents, differs significantly from that of unreacted poly(dG-dC) or a control which had been exposed only to CH2O. In contrast, the CD spectra are profoundly altered. The minimum at 252 nm becomes more negative, and the rotational strength of the positive band above 260 nm is reduced as a linear function of the extent of amine attachment. At 0.22 mol of amine per mole of nucleotide, the transformation is similar to that observed by others in poly(dG-dC) when complexed to core histones in reconstituted core particles or in concentrated LiCl solvents at temperatures below the B----Z transition. Sedimentation studies reveal that these changes in the circular dichroism (CD) spectra reflect secondary structural effects rather than the formation of aggregates or psi type structures. Raman spectra reveal, however, that these secondary structural changes must occur within the B family as the amine complex retains B backbone geometry. The conformation produced by the attachment of the amine is probably a higher winding angle (overwound) B variant.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkylation↗
PubMed1987

Functionally distinct agretopic and epitopic sites. Analysis of the dominant T cell determinant of moth and pigeon cytochromes c with the use of synthetic peptide antigens.

The dominant T cell determinant on moth and pigeon cytochromes c in B10.A (E beta k:E alpha k) mice is located in the C-terminal portion of the protein, contained within residues 93-103 or 93-104. Thirty-seven antigen analogs, containing single amino acid substitutions at positions 98, 99, 101, 102, 103, and 104, were synthesized. The effects of the substitutions on in vitro antigenicity and in vivo immunogenicity were determined. Functional assays with T cell clones identified residues 99, 101, 102, and 103 as critical, based on their effect on antigenic potency. Peptides containing substitutions at residues 99, 101, and 102 were capable of eliciting unique clones upon immunization of B10.A mice. This was consistent with the identification of these residues as part of the epitope, the site on the antigen that interacts with the T cell receptor. Immunization with peptides substituted at residue 103, however, failed to elicit clones with unique specificity for the immunogen. When these peptides were tested for their ability to stimulate the T cell clones with antigen-presenting cells from B10.A(5R) mice expressing the E beta b:E alpha k Ia molecule, a consistent change in the relative antigenic potency was observed with 50% of the peptides. The effect of the Ia molecule on the antigenic potency ruled out the possibility that residue 103 nonspecifically affected antigen uptake or processing and identified residue 103 as part of the agretope, the site that interacts with the Ia molecule. The locations of the agretope and the epitope on this antigenic determinant appear to be fixed, even in the presence of large numbers of amino acid substitutions. However, some substitutions were found to affect both the agretope and the epitope, placing limits on the functional independence of the two sites. The results are discussed in terms of the trimolecular complex model of T cell activation and the implications of these data for antigen-Ia molecule interactions.

Amino Acid Sequence↗