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Biomedical subjects

D Sun

Publications and source records attributed to D Sun.

At least 397 records · Page 22Linked to original sources

Functional heterogeneity among CD4+ encephalitogenic T cells in recruitment of CD8+ T cells in experimental autoimmune encephalomyelitis.

Inoculation of Lewis rats with live or attenuated (irradiated or paraformaldehyde-fixed) CD4+ encephalitogenic T cells (S1 line) protects the recipients from transferred experimental autoimmune encephalomyelitis (tEAE) induced by S1 cells. A CD8+ T lymphocyte population specifically activated against the EAE-inducing S1 cells can be readily isolated from the lymphoid organs of pretreated animals. We show, in the present study, that encephalitogenic T cell lines derived from Lewis rats differ in their ability to induce resistance against tEAE in vivo and to stimulate CD8+ cell proliferation in vitro. We also demonstrate that the S19 line of encephalitogenic T cells, in combination with myelin basic protein (MBP), can stimulate CD8+ cell proliferation in vitro. The CD8+ cells generated in this way strongly suppress MBP-specific T cell proliferation in vitro. This combined effect of T cells and MBP was also evident in vivo. Neither S19 cells nor MBP alone induced resistance against S19-mediated tEAE, rather coinjection of these cells and MBP was required. Our results suggest that resistance to EAE is mediated by distinct populations of encephalitogenic T cells that activate Ts cells through different mechanisms. In some instances, both autoreactive T cells and their relevant autoantigen(s) may be needed to activate Ts cells in vivo.

Animals↗

Inhibitors of adenosine catabolism improve recovery of dog myocardium after ischemia.

The effects of inhibitors of adenosine catabolism on contractile function and metabolites were assessed during 15 minutes of ischemia followed by 30 minutes of reperfusion in the open-chest dog heart. As compared to sham treatment, pretreatment with erythro-9-(2-hydroxy-3-nonyl)adenine (EHNA) and dipyridamole (DP) protected contractile function during ischemia, and improved recovery of high energy phosphate content and contractile function during reperfusion following ischemia. Testing EHNA and DP in a free-radical generating system indicated both compounds have some scavenging ability, suggesting the effect of EHNA + DP may not be on adenosine nucleotide metabolism alone. Comparison of end diastolic segment lengths to contractile function indicated the results were not affected by changes in preload resulting from peripheral vasodilation.

Adenine↗

Inhibition of HIV replication by liposomal encapsulated amphotericin B.

This report shows the potential of using a liposomal encapsulated preparation of amphotericin B (a polyene macrolide antibiotic) for the in vitro inhibition of HIV. There was no significant difference between the effective doses of the free form of drug when compared to the liposomal encapsulated preparation in inhibiting the growth of HIV. Virus expression was suppressed at a concentration of 5-10 micrograms/ml of the drugs. The liposomal preparation showed greatly reduced cytotoxicity in experiments using cultures of murine leukocytes. These results show the potential usefulness of liposomal encapsulated drugs in the treatment of patients with AIDS or AIDS related complex.

Acquired Immunodeficiency Syndrome↗

Inhibition of human immunodeficiency virus in early infected and chronically infected cells by antisense oligodeoxynucleotides and their phosphorothioate analogues.

Antisense oligodeoxynucleotides, both the phosphorothioate analogues and unmodified oligomers of the same sequence, inhibit replication and expression of human immunodeficiency virus already growing in tissue cultures of MOLT-3 cells with much greater efficacy than do mismatched ("random") oligomers and homooligomers of the same length and with the same internucleotide modification. This preferential inhibitory effect is elicited in as short a time as 4-24 hr postinfection. Likewise, antisense oligomers exhibit greater inhibitory effects on human immunodeficiency virus in chronically infected cells than do mismatched oligomers and homooligomers. Phosphorothioate antisene oligomers are up to 100 times more potent than unmodified oligomers of the same sequence in these inhibitory assays. These results, in major respects, confirm and extend those recently published by Matsukura et al. [Matsukura, M., Zon, G., Shinozuka, K., Robert-Guroff, M., Shimada, T., Stein, C. A., Mitsuza, H., Wong-Staal, F., Cohen, J. S. & Broder, S. (1989) Proc. Natl. Acad. Sci. USA 86, 4244-4248]. They also point out the importance of computer analysis of sequences though to be random but that in reality contain significant areas of likely hybridization, either to the viral genome or to the complementary DNA strand synthesized from it. They thus reinforce the concept that specific base pairing is a crucial feature of oligonucleotide inhibition of human immunodeficiency virus.

Antiviral Agents↗

Evidence for an additional temporal class of gene expression in the forespore compartment of sporulating Bacillus subtilis.

We present evidence indicating that the previously studied, sporulation-induced gene 0.3 kb, which encodes a stable RNA present at late developmental stages, is transcribed in the forespore chamber of sporulating cells of Bacillus subtilis. Compartmentalized gene expression was demonstrated on the basis of subcellular fractionation experiments in which severalfold-higher levels of 0.3 kb-directed beta-galactosidase specific activity were observed in forespore extracts than in extracts from the mother cell and dependence studies in which 0.3 kb transcription was found to be blocked in mutants bearing mutations in spoIIIA, spoIIIE, and spoIIIG, genes which are known to govern forespore gene expression. Also, 0.3 kb transcription could be switched on during growth in cells in which transcription of the forespore regulatory gene spoIIIG was engineered to be activated in response to the lac inducer IPTG (isopropyl-beta-D-thiogalactopyranoside). Although it is transcribed in the forespore, 0.3 kb is switched on at a later developmental stage than other previously studied forespore-expressed genes, and hence it appears to be representative of an additional temporal class of compartmentalized gene expression.

Bacillus subtilis↗

Inactivation of human immunodeficiency virus (HIV) by ionizing radiation in body fluids and serological evidence.

A method to use ionizing radiation to inactivate HIV (Human Immunodeficiency Virus) in human body fluids was studied in an effort to reduce the risk of accidental infection to forensic science laboratory workers. Experiments conducted indicate that an X-ray absorbed dose of 25 krad was required to completely inactivate HIV. This does not alter forensically important constituents such as enzymes and proteins in body fluids. This method of inactivation of HIV cannot be used on body fluids which will be subjected to deoxyribonucleic acid (DNA) typing.

Acquired Immunodeficiency Syndrome↗

Conservation of the D-mannose-adhesion protein among type 1 fimbriated members of the family Enterobacteriaceae.

A variety of genera and species of the family Enterobacteriaceae bear surface fimbriae that enable them to bind to D-mannose residues on eukaryotic cells. Until recently, it was thought that the D-mannose binding site was located in the major structural subunit (FimA), of relative molecular mass (Mr) 17,000 (17 K), of these organelles in Escherichia coli. New evidence indicates that this binding site resides instead in a minor protein Mr 28-31 K (FimH) located at the tips and at long intervals along the length of the fimbriae, and is reminiscent of the minor tip adhesion proteins of pyelonephritis-associated pili (Pap) and S fimbriae. In contrast to the antigenic heterogeneity of the major FimA subunit, the antigenic structure of FimH is conserved among different strains of E. coli. Here, we report an even broader conservation of this minor adhesion protein extending to other genera and species of type 1 fimbriated Enterobacteriaceae. Our results may have implications for the development of broadly protective vaccines against Gram-negative bacillary infections in animals and perhaps in man.

Antibodies, Monoclonal↗

Suppression of experimentally induced autoimmune encephalomyelitis by cytolytic T-T cell interactions.

Down-regulatory phenomena have been described in several experimental models of tissue-specific, T-cell-mediated autoimmunity. For example, resistance to active induction of experimental autoimmune encephalomyelitis (EAE) can be induced by pretreating animals with non-pathogenic inocula of autoantigen or effector cells. Moreover, animals that have recovered from one EAE episode are resistant to subsequent induction of EAE. In some models, resistance to EAE has been transferred with immune cells to naive recipients. These experiments, which were based on transfers of unseparated immune cell populations, are difficult to interpret. Immune suppression circuits are known to be complex and involve various distinct cellular subsets. To further complicate the issue, resistance to EAE can be transferred not only by suppressor cells, but also by encephalitogenic effector cells injected in 'subclinical' doses. We describe now the isolation of homogeneous T lymphocyte lines from the spleens of Lewis rats that had recovered from T-cell-mediated EAE (tEAE) caused by the MBP-specific T cell line S1. These spleen-derived T line cells express the CD8 phenotype and specifically respond to determinants on the inducing S1 line, but not to the autoantigen MBP. Furthermore, the anti-S1 cells selectively lyse the encephalitogenic S1 T line in vitro and efficiently neutralize their encephalitogenic capacity in vivo.

Animals↗

Regulatory circuits in autoimmunity: recruitment of counter-regulatory CD8+ T cells by encephalitogenic CD4+ T line cells.

In this study, pretreatment of Lewis rats with a syngeneic encephalitogenic T cell line (S1) was found to be able to constantly induce resistance to the subsequent induction of transferred experimental autoimmune encephalomyelitis (tEAE). This treatment was capable of protecting recipient animals for at least 2-4 months. Here we show an enhanced suppressor T(anti-S1) cell activity, which can be readily detected in the lymphoid organs of animals which recovered from S1-induced tEAE, or from rats pretreated with attenuated (irradiated, fixative treated or water-lysed) S1 cells. Anti-S1 cells, which uniformly express the CD8 phenotype, were selectively stimulated to grow and expand into lines by confronting primed lymphoid cells with irradiated S1 cells in culture. The proliferative response of anti-S1 cells was independent of myelin basic protein and antigen-presenting cells, and the responses against unrelated encephalitogenic T cell lines were minimal. It was also found that none of the monoclonal antibodies tested (including CD8 and MHC class I antigen-specific antibodies) was able to block S1/anti-S1 interactions. These cells are functionally suppressive to the proliferation of S1 cells in vitro, are specifically cytolytic directed against the EAE-inducing S1 cells and are able to antagonize encephalitogenic capacity of S1 cells in vivo. In vivo elimination of the CD8+ T subset from Lewis rats, using a combined treatment of thymectomy and OX-8 antibody injection before the initial cell transfer, totally blocked the induction of resistance. Our experiments document that induction of functionally active suppressor T cells is responsible for the induced resistance observed in tEAE.

Animals↗

A Mobile Oocyte Incubation Unit (MOIU): a device for improvement of the gamete intrafallopian transfer (GIFT) program.

Forty couples with infertility due to various causes were selected for the gamete intrafallopian transfer (GIFT) program at our hospital. When the first 21 couples (Group A) had been treated in the program, the rate of pregnancy achieved was 23.8%, which did not seem satisfactory. This might have been caused by the distance between the embryo laboratory and the operating room. To eliminate this defect, a Mobile Oocyte Incubation Unit (MOIU) was designed. This is actually a compact laboratory that can be placed in the operating room. After the MOIU was utilized, the rate of pregnancy for the following 19 couples (Group B) increased to 42.1%. The MOIU has helped improve the performance of the GIFT program by increasing the stability of the pH value of the culture medium (Chetkowski R, et al.: J Vitro Fert Embryo Transfer 1985;2:207), lessening the exposure of the gametes to air and room temperature, and most importantly, shortening the time required for a GIFT procedure from 45-100 to 15-30 min. We expect that the MOIU will eventually become an integral part of the standard equipment for the GIFT program and make the program more successful and reliable in the treatment of infertility.

Adult↗

Scintillation counting of 14C-labeled soluble and insoluble compounds in plant tissue.

A method is described for the liquid scintillation counting of 14C in plant tissues. Samples are fixed, in the scintillation vial, in a solution of ethanol and acetic acid (3:1) and decolorized with commercial bleach before the addition of scintillation liquid. The method was compared to other techniques of tissue oxidation or digestion and found to be equally effective at least with thin tissue samples. The technique is simple, rapid, and inexpensive and does not result in loss of 14C.

Carbon Radioisotopes↗

Dual biological activity of apurinic acid on human lymphocytes: induction of interferon-gamma and protection from human immunodeficiency virus infection in vitro.

The chemically modified DNA, apurinic acid (APA), is cytotoxic for human lymphocytes at concentrations above 100 micrograms/ml. At low concentrations (0.05-1 micrograms/ml) APA acts as an inducer interferon gamma (IFN-gamma) in lymphocytes in vitro; the maximum interferon titer of 50 units/ml was reached at 0.4 micrograms/ml. When added to the cells in combination with phytohemagglutinin A (PHA), APA displays a significant synergistic interferon-inducing ability; the maximum titer of 940 units/ml was obtained with 10 micrograms/ml of APA and 6.25 micrograms/ml of PHA. APA also proved to be an effective inhibitor of human immunodeficiency virus (HIV-1) replication in H9 cells. At a concentration of 10 micrograms/ml, APA causes a 49% inhibition of virus growth, while 20 micrograms/ml of APA are required to inhibit expression of HIV-1 p17 and p24 gag proteins by 60%. The mechanism of anti HIV-1 activity of APA likely occurs at the level of viral reverse transcriptase. This enzyme is inhibited by APA in a noncompetitive way with a Ki of 0.39 microM, while the cellular DNA polymerases alpha, beta and gamma are 140- to 300-fold less sensitive to APA.

Apurinic Acid↗

Inhibition of human immunodeficiency virus replication by antisense oligodeoxynucleotides.

Twenty different target sites within human immunodeficiency virus (HIV) RNA were selected for studies of inhibition of HIV replication by antisense oligonucleotides. Target sites were selected based on their potential capacity to block recognition functions during viral replication. Antisense oligomers complementary to sites within or near the sequence repeated at the ends of retrovirus RNA (R region) and to certain splice sites were most effective. The effect of antisense oligomer length on inhibiting virus replication was also investigated, and preliminary toxicity studies in mice show that these compounds are toxic only at high levels. The results indicate potential usefulness for these oligomers in the treatment of patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex either alone or in combination with other drugs.

Animals↗

Influence of berberine sulfate on synthesis and expression of Pap fimbrial adhesin in uropathogenic Escherichia coli.

We investigated the influence of berberine sulfate, an ancient Chinese antibiotic, upon the adhesion of uropathogenic Escherichia coli to erythrocytes and epithelial cells. Although berberine sulfate in increasing concentrations had no effect on bacterial growth or on the synthesis of major outer membrane proteins of the E. coli organisms, it increasingly blocked adhesion. The decreased adhesion was accompanied by a reduction in the synthesis of fimbrial subunits and in the expression of assembled fimbriae. These results suggest that the anti-infectious activity of berberine sulfate in E. coli-induced urinary tract infections may be mediated by the selective suppression of the synthesis and assembly of fimbriae by uropathogenic organisms.

Adhesins, Escherichia coli↗

Berberine sulfate blocks adherence of Streptococcus pyogenes to epithelial cells, fibronectin, and hexadecane.

Berberine sulfate is an alkaloid extracted from the roots and bark of various plants and possesses antibacterial, antifungal, and antiprotozoal activities. Most studies have focused on the bacteriostatic or bactericidal activities of this compound. In this study, we report that berberine sulfate is bacteriostatic for streptococci and that sub-MICs of berberine blocked the adherence of streptococci to host cells, immobilized fibronectin, and hexadecane. Concentrations of berberine below its MIC caused an eightfold increase in release of lipoteichoic acid from the streptococci. Higher concentrations of berberine directly interfered with the adherence of streptococci to host cells either by preventing the complexing of lipoteichoic acid with fibronectin or by dissolution of such complexes once they were formed. Thus, berberine sulfate interferes with the adherence of group A streptococci by two distinct mechanisms: one by releasing the adhesin lipoteichoic acid from the streptococcal cell surface and another by directly preventing or dissolving lipoteichoic acid-fibronectin complexes.

Alkanes↗