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R E Morris

Publications and source records attributed to R E Morris.

At least 181 records · Page 10Linked to original sources

Rapamycin: FK506's fraternal twin or distant cousin?

Rapamycin (RPM) is the latest in a series of new bacterial-derived immunosuppressants. Here, Randall Morris compares and contrasts the mechanism of action and immune-modulating potential of RPM with the structurally-similar FK506.

Animals↗

The importance of the spleen for the immunosuppressive action of cyclosporine in transplantation.

The spleen plays an important role in the response of the recipient's immune system to a primarily vascularized graft and cyclosporine treatment is known to alter this response. To investigate the interaction between the splenic immune response and CsA's immunosuppressive actions more thoroughly, Lewis recipients of Brown-Norway heterotopic heart grafts were treated i.p. daily with normal saline or with CsA doses of 0.75, 1.5, or 3.0 mg/kg/day from day 1 through day 50 or until rejection. Rats treated with 3 mg/kg were splenectomized intraoperatively (i.o.) or not splenectomized. Rats in subgroups of the other treatment groups were splenectomized i.o., on day 5, not splenectomized, or the recipient's spleen cells were reinfused after i.o. splenectomy. In non-CsA-treated rats, i.o. splenectomy (median survival time, [MST] = 11 days) and day 5 splenectomy (MST = 11 days) prolonged graft survival minimally in comparison with nonsplenectomized animals (MST = 7 days). Reinfusion of the spleen cells reversed this effect (MST = 7 days). Most interestingly, the immunosuppressive efficacy of 1.5 mg/kg of CsA (MST = 91 days) was reduced by day 5 splenectomy (MST = 24 days) and completely abolished by i.o. splenectomy (MST = 11 days). Spleen cell reinfusion partially restored the effect of CsA treatment (MST = 88 days). Since splenectomy resulted in a complete abrogation of the immunosuppressive efficacy of 1.5 mg/kg CsA, our results support the hypothesis that certain spleen cells augment immunosuppression by CsA. These findings provide additional evidence that the immune system's own regulation of its antigraft response can be an important component of the overall suppression of rejection that is associated with the use of certain immunosuppressive drugs.

Animals↗

Mouse liver contains a Pseudomonas aeruginosa exotoxin A-binding protein.

The opportunistic pathogen Pseudomonas aeruginosa produces several potential virulence factors, including the ADP-ribosylating toxin, exotoxin A (PE). Studies using a burned mouse model have shown that PE consistently inhibits protein synthesis and depletes elongation factor 2 in mouse liver and variably in other organs. One reason for toxin sensitivity could be the presence of a PE receptor on the surface of cells. Therefore we examined detergent extracts of mouse tissues for the presence of toxin-binding proteins. Proteins which specifically bind PE were present in extracts from liver, kidney, lung, spleen, and heart. Because liver appears to be a prominent target for the toxin in a burned animal, we choose to isolate the PE-binding protein from mouse liver and compare this protein to the recently characterized toxin-binding protein from toxin-sensitive mouse LM fibroblasts. The toxin-binding proteins from both sources have a molecular mass of approximately 350 kDa, share similar protease digestion profiles, and are glycosylated. However the glycosylation patterns for the two species are quite different. Both glycoproteins bind toxin with high avidity. The toxin-binding moiety is located, at least in part, on the plasma membrane and thus could represent the receptor involved in internalization of toxin molecules responsible for cell death.

ADP Ribose Transferases↗

Gold enhancement of gold-labeled probes: gold-intensified staining technique (GIST).

In this report we present a staining method in which gold chloride is used to enhance the size of gold colloids. We show the utility of this technique when used in conjunction with small gold colloids, i.e., 5 nm, 4 nm, and 2.6 nm. Post-embedding staining of epoxy-embedded, gold-labeled mouse LM fibroblasts showed that staining with 0.1% gold chloride facilitated the visualization of the smallest gold colloids.

Animals↗

Immunoregulatory role of transforming growth factor beta (TGF-beta) in development of killer cells: comparison of active and latent TGF-beta 1.

Using recombinant DNA technology, we have generated Chinese hamster ovary (CHO) cell lines that synthesize latent transforming growth factor beta 1 (TGF-beta 1) to study immune regulation by TGF-beta 1. In vitro, latent TGF-beta 1 synthesized by transfectants or added exogenously as a purified complex after activation inhibited CTL generation to a similar extent as seen with acid-activated recombinant human (rHu) TGF-beta 1. In vivo, serum from nu/nu mice bearing CHO/TGF-beta 1 tumors contained significant levels of latent TGF-beta 1 in addition to depressed natural killer (NK) activity in spleens which paralleled that seen in C3H/HeJ mice treated with acid-activated rHuTGF-beta 1. rHuTGF-beta 1 treatment of mice receiving heart allografts resulted in significant enhancement of organ graft survival. Because of possible regulated tissue-specific activation, administration of latent rather than active TGF-beta may provide a better route to deliver this powerful immunosuppressive agent in vivo.

Animals↗

Human immunodeficiency virus: quantifying the risk of transmission of HIV to dental health care workers.

The potential for the increased risk of transmission of HIV (Human Immunodeficiency Virus) from patients to dental health care workers (DHCWs) in the workplace is examined. Based on published and hypothetical risk estimates, the authors conclude that in certain world communities with high prevalence rates of HIV infection (e.g. Central Africa), the potential yearly incidence rate and cumulative long-term incidence rate of HIV transmission in the dental workplace could place these workers in a high risk subgroup similar to that of homosexuals. Reported high levels of noncompliance with infection control procedures in the dental care workplace in the United States by these workers suggests the potential for increased risk in communities with high prevalence rates of this disease. Present and past educational efforts toward protection of the DHCW in the United States may be considered inadequate, and even more so when these educational efforts are applied in the world community. Additional efforts should be made by the public health community to alert and educate DHCWs worldwide to the potential for increased HIV transmission in the workplace.

Acquired Immunodeficiency Syndrome↗

The transforming growth factor-betas. A new family of immunoregulatory molecules.

Within the past three years there has been a rapid expansion in our knowledge of the role TGF-beta mediates in regulating immune responses in vitro. Whether the TGF-beta will be clinically useful to suppress immune responses to transplanted organs or autoimmune responses is unknown. However, now that highly purified quantities of TGF-beta are available through recombinant DNA technologies, questions concerning the in vivo immunosuppressive activities of TGF-beta can be answered.

Animals↗