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Biomedical subjects

C B Christian

Publications and source records attributed to C B Christian.

8 recordsLinked to original sources
PubMed1993

Papillomas and carcinomas in transgenic rabbits carrying EJ-ras DNA and cottontail rabbit papillomavirus DNA.

Two transgenic rabbits (TRI and TRIII) that carried cottontail rabbit papillomavirus (CRPV) DNA alone were identified; another (TRII) carried both CRPV DNA and EJ-ras. TRI and TRIII developed extensive skin papillomas at about 1 month of age, and transcripts of CRPV DNA were detectable only in skin and/or papillomas. TRII developed extensive squamous carcinomas of the skin at a very early age. Transcription of both CRPV DNA and EJ-ras was found in the skin cancers. Thus, the tissue specificity of CRPV DNA expression in transgenic rabbits was the same as in virion-infected animals. The expression of EJ-ras could be dependent on the expression of certain CRPV genes and may be a critical cofactor of CRPV DNA in the progression of carcinomas.

Animals↗
PubMed1992

Preclinical system for evaluating topical podofilox treatment of papillomas: dose-response and duration of growth prior to treatment.

The objective of the present study was to assess the utility of Shope rabbit papillomas as an animal model system for studying topical podofilox treatment and to evaluate dose-response relations and influence of duration of papilloma growth prior to treatment. New Zealand White rabbits received inoculations of cottontail rabbit papillomavirus (CRPV) virions of two dilutions at four sites total on the dorsum. Two papillomas on the left side were treated with podofilox (Oclassen Pharmaceuticals, Inc., San Rafael, CA). The drug was given topically twice each day, 5 d per week, for 21 d. We evaluated the effects of drug dose and the duration of papilloma growth prior to treatment. Results indicated that treatment beginning on day 28 with both 0.5 and 2.5% (w/v) podofilox inhibited papilloma growth, but 5.0% was more effective. In a separate experiment, papillomas were treated at 7, 21, or 60 d after virus inoculation. At 7 d, the untreated lesions were latent (not visible). At 21 d after infection, they were about 2.5 mm in diameter. At 60 d, papillomas were about 25 mm. Treatment with 5.0% podofilox beginning on any of those days strongly inhibited papilloma growth. Neither Southern blots nor PCR detected CRPV DNA in cured sites of previous virus infection. Antibody production to CRPV virion was not affected by drug treatment. 5.0% podofilox irritated normal skin adjacent to papillomas as evidenced by inflammation, induration, and superficial erosion. However, healing was satisfactory and no scarring resulted. We concluded that the Shope papilloma was a good model system for studying podofilox treatment because the lesions responded to drug across a broad range of drug concentrations and papilloma sizes.

Administration, Topical↗
PubMed1985

Interleukin-2 restores the depressed allogeneic cell-mediated lympholysis and natural killer cell activity in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is characterized by a variety of profound T-cell abnormalities among which are decreased cytotoxic capacity measured by allogeneic cell-mediated lympholysis (CML), natural killer cell (NK) activity, and decreased lymphokine production. In a group of 13 patients with active SLE, allogeneic CML, tested by a 4-hr 51Cr-release assay, was 18.2 +/- 2.7% while in the group of normal individuals CML was 41.2 +/- 2.7%. If optimal doses of affinity-purified interleukin-2 (IL-2) were present during the mixed lymphocyte culture, the CML of SLE patients was increased to normal levels (40.4 +/- 4.0%). In contrast, interferon-alpha (IFN-alpha) increased (but not significantly) the levels of CML. Mixed lymphocyte reaction, tested by tritiated thymidine incorporation, was also decreased in the group of patients (14,820 +/- 815 cpm vs 28,972 +/- 5880 cpm in normals) and it was increased to normal levels if IL-2, but not IFN-alpha was added to the cultures. NK activity was decreased in the group of patients tested by 51Cr-release assay, harvested at 6 and 18 hr. IL-2 increased the NK activity up to normal levels, while IFN-alpha was only partially efficacious. These results demonstrate that IL-2, but not IFN-alpha, can potentiate or even fully restore the deficient cytotoxic effector function of peripheral mononuclear cells in patients with SLE.

Cytotoxicity, Immunologic↗
PubMed1985

Current status of coronary artery bypass grafting for coronary artery atherosclerosis.

Coronary artery bypass grafting has now undergone 18 years of proven benefit in the treatment of myocardial ischemic disease. The technique of CABG has been further extended to other situations in which myocardial blood supply is threatened, such as cardiac trauma, aneurysms of coronary arteries, and congenital lesions. The emphasis in choosing CABG over medical therapy in 1985 should be preservation of myocardium at jeopardy of infarction as well as relief of angina. Proximal stenoses in vessels subserving viable muscle that is ischemic at rest or with minimal exercise should be treated with reperfusion by angioplasty or CABG to prevent further injury. After infarction occurs and ventricular function is impaired, CABG is also necessary to preserve remaining myocardium at jeopardy. Such an aggressive approach seems warranted with today's excellent surgical results. Long-term results have also improved, as more attention has been paid to saphenous vein graft preparation, use of mammary artery grafts, complete revascularization, use of antiplatelet agents, control of spasm, and identification of hypercoagulable states that may require sodium warfarin (Coumadin). Angioplasty of vein grafts and distal anastomoses also appears promising to help extend the results of initial CABG. Figure 1 is our recommended approach for the treatment of coronary atherosclerosis.

Angina Pectoris↗
PubMed1983

Induction of monocytic suppression after stimulation of peripheral human mononuclear cells with staphylococcal protein A and Staphylococcus aureus.

Staphylococcal protein-A (SPA) and Staphylococcus aureus are known to be polyclonal human B-cell activators. It was noted that they induced plaque-forming-cell (PFC) responses lower than those induced by pokeweed mitogen (PWM) and the possibility of early triggering of a suppressor cell was investigated in the present series of experiments. Peripheral mononuclear cells (MNC) were passed through Sephadex G-10 columns to eliminate monocytes. The PFC responses to SPA and S. aureus were thereby increased. PWM-driven PFC responses are suppressed by the simultaneous presence of SPA in a dose-related way, if present in the early phases of the cultures. MNC precultured with SPA or S. aureus have the ability to suppress the PFC response of autologous MNC to PWM. Interestingly this suppressor cell activity was radiation resistant and could not be abrogated by treatment with anti-T-cell monoclonal antibody plus complement. The above experiments clearly demonstrate that the observed low PFC responses of MNC after stimulation with SPA and S. aureus are due to the induction of suppressor cells by these stimulants. The suppressor cells are apparently of monocytic origin.

Antibody-Producing Cells↗
PubMed1982

Concanavalin-induced suppressor cells: characterization on the basis of corticosteroid and radiation sensitivity.

Experiments were performed to examine whether the concanavalin A (Con A)- induced suppressor cells of several in vitro T- and B-lymphocyte functions constitute a functionally unique cell population. This study included simultaneous studies of three different assays of suppression of T- and B-lymphocyte functions. We found that Con-A-induced suppressor cells which inhibit the allogeneic mixed lymphocyte reaction (MLR) and the pokeweed mitogen-induced, plaque-forming cell (PEC) response are radiation sensitive at doses greater than 1000 rad, but corticosteroid resistant, while those suppressing allogeneic cell-mediated lympholysis (CML) are both radiation and corticosteroid resistant. These studies indicate either that Con-A-induced suppressor cells include heterogeneous populations which are differentially sensitive to corticosteroids and radiation, or that functionally distinct suppressor mechanisms are variably sensitive to these agents.

Adult↗
PubMed1976

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