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Biomedical subjects

R P Cleveland

Publications and source records attributed to R P Cleveland.

35 records · Page 2Linked to original sources
PubMed1991

Differences in HLA-B27 positive and negative patients with ankylosing spondylitis: study of clinical disease activity and concentrations of serum IgA, C reactive protein, and haptoglobin.

To find out whether disease activity and B27 status were associated with serum concentrations of IgA, C reactive protein (CRP), and haptoglobin in ankylosing spondylitis (AS) multivariate analysis of variance was used to study 101 patients with AS whose disease was clinically classified as active or inactive, and who were HLA-B27 typed. It was found that B27 and disease activity do interact significantly to affect the serum concentrations of IgA, CRP, and haptoglobin. When the 77 B27+ patients were examined, however, it was found that disease activity was significantly associated with serum concentrations IgA. In contrast, in the 24 B27- patients concentrations of serum IgA were significantly associated with disease activity, but not. These results emphasise the known difference between B27+ and B27- AS and suggest different pathogenic mechanisms in the two forms of AS.

C-Reactive Protein↗
PubMed1989

Immunodeficiency in patients with hemophilia: an underlying deficiency and lack of correlation with factor replacement therapy or exposure to human immunodeficiency virus.

Nineteen patients with hemophilia, five of whom were classified as untreated, were immunologically evaluated by the measurement of cell surface markers, natural killer cell activity, mitogenic responses, polyclonal immunoglobulin production, and serologic evidence of human immunodeficiency virus infection. No correlations were found between human immunodeficiency virus infection and immune abnormalities, or between patients who did or did not receive factor therapy, although the abnormalities were more profound in those who received treatment. An intrinsic B cell abnormality in patients with hemophilia is suggested.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Development of a leukocytopenic baby guinea pig model with azathioprine and cyclophosphamide.

Immunosuppressive agents were given to baby guinea pigs to develop a leukocytopenic baby guinea pig model. Azathioprine in different doses, and cyclophosamide and methylprednisolone combinations did not result in predictable leukocytopenia without significant mortality. A combination of azathioprine 20 mg and cyclophosphamide 20 mg administered once daily for 5 days to 42 baby guinea pigs resulted in a mean white blood cell count of 2531/mm3 +/- 1198 (a reduction of 3931 +/- 1413 from pretreatment values). The mean counts for polymorphonuclear leukocytes and lymphocytes on day 6 were 398/mm3 and 2035/mm3, respectively. Only 7% mortality was seen in these animals. This model can be utilized to study a variety of bacterial and viral infections in "immunocompromised hosts".

Animals↗
PubMed1988

"Immunoregulatory effects of cimetidine: inhibition of suppressor cell effector function in vivo".

The effects of cimetidine upon suppressor cell effector function in a well-studied murine model of contact hypersensitivity were examined. Intravenous inoculation of BALB/c mice with DNP-coupled syngeneic spleen cells induced the production of DNP-specific suppressor cells which was demonstrated by a reduction in ear swelling after contact sensitization with 1-fluoro-2, 4-dinitrobenzene (DNFB) following transfer of spleen and lymph node cells to naive syngeneic recipients. Cimetidine treatment of mice who had also received suppressor cells eliminated the manifestation of suppressor cell activity as measured by the development of normal immunologic response following contact sensitization with DNFB. While all the groups receiving cimetidine showed restoration of delayed hypersensitivity, the maximum effect was seen when 50 mg/kg of cimetidine was administered on Day 5 (day of challenge). These results indicate that, in addition to its previously described inhibitory role in suppressor cell induction, cimetidine is also capable of inhibiting suppressor cell effector function. The involvement of histamine in both these processes in vivo is also suggested.

Animals↗
PubMed1988

Interferon inhibition of IL-2-mediated lymphocyte proliferation.

Interleukin-2 (IL-2) combined with hybrid human alpha interferon (IFN-alpha A/D) mediates enhanced tumor regression compared with either agent alone. To elucidate the underlying mechanism of interaction of IL-2, with its known ability to induce expansion of T lymphocytes, and IFN-alpha A/D, with its antiproliferative activity, we studied splenocytes from normal and tumor-bearing C57BL/6 mice in 5-day cultures and measured proliferation by means of a standard 4-hour 3H-thymidine incorporation assay. Potent inhibition of IL-2-induced proliferation (usually greater than 90%) resulted from high concentrations of IFN (100 to 1000 U/ml). Splenocytes from both tumor-bearing and normal mice, cultured alone or with mitomycin-treated syngeneic tumor, MCA106, exhibited similar patterns of inhibition. Unexpectedly, allostimulation with DBA/2 (H-2d) stimulators and C57BL/6 (H-2b) responders showed enhanced proliferation, most pronounced at lower IFN concentrations. Time course of IFN action revealed minimal duration of exposure necessary for inhibition to be less than 24 hours. Microfluorometric cell analysis showed the striking increase in Thy-1+ cells (55% to 96%) induced by IL-2 with parallel increase in Lyt2+ cells but almost complete disappearance of L3T4+ cells. IFN reduced IL-2-induced increase in Lyt-2+ cells (61% to 31%). These results emphasize the complexity of IL-2 and IFN interaction and the potential for dose-related antagonistic effects. This may be important in the clinical use of this combination.

Animals↗
PubMed1987

Enhancement of anti-sheep erythrocyte plaque-forming cell levels by cimetidine in vivo.

Previous studies demonstrated an immunomodulatory role for cimetidine in contact sensitivity responses in vivo. The present experiments have examined the effects of cimetidine upon in vivo antibody production. When given intravenously, cimetidine treatment consistently resulted in enhanced numbers of IgM plaque-forming cells (PFC) following immunization with sheep erythrocytes. This enhancement was dependent upon both the dose and timing of cimetidine administration. In timing experiments, maximal enhancement of PFC levels was obtained when cimetidine was given at the time of or within three days following immunization. Treatment with cimetidine four days after immunization or one day before assay led to a slight decline in PFC level. In contrast, intraperitoneal treatment with cimetidine has little effect upon the anti-sheep erythrocyte PFC level regardless of dose or timing. Overall, these results indicate that cimetidine may be capable of modulating PFC development in vivo. This modulation, however, depends critically upon dose, timing, and route of cimetidine administration.

Animals↗
PubMed1986

Induction of T-cell proliferation and enhancement of NK activity by supernatants from Con A-stimulated human peripheral blood mononuclear cells: a new lymphokine.

Supernatants from human peripheral blood mononuclear cells activated by Con A contain a factor(s) that stimulates blastogenic activity of normal human peripheral blood mononuclear cells. This Con A supernatant (CAS) contains stimulatory activity for E-rosette positive lymphocytes (T cells) and requires adherent cells for stimulation of T-cell proliferation. CAS does not contain detectable amounts of IL-2 as determined by its inability to support CTLL cell growth. Nor does it contain IL-1 or interferon. Examination of functional activity of lymphocytes stimulated for 3 days by CAS revealed that NK activity is augmented. This supernate does not appear to have any direct effect on B-cell function, although it induces suppression of polyclonal PWM stimulation of immunoglobulins. Thus, CAS appears to contain a new cytokine with immunomodulating potential.

Cell Division↗
PubMed1986

Inhibition of suppressor cell function by cimetidine in a murine model.

Immunomodulatory effects of cimetidine, an H2 histamine receptor antagonist, have been reported in humans and animals. To define these effects more clearly, the action of cimetidine on suppressor cell function was studied utilizing a murine model of contact hypersensitivity. Intravenous inoculation of BALB/c mice with DNP-coupled syngeneic spleen cells induced the production of DNP-specific suppressor cells which could easily be demonstrated by a reduction in ear swelling after contact sensitization with 1-fluoro-2,4-dinitrobenzene (DNFB) following transfer of spleen and lymph node cells to naive syngeneic recipients. Cimetidine treatment of animals in which suppressor cells were induced resulted in an inability of these mice to transfer cellular suppression as measured by development of a normal immunologic response in the recipient mice. The effect of cimetidine was both dose and time related. While all groups receiving cimetidine showed some loss of suppressor cell function, the maximum effect (up to 100% inhibition) was seen when 50 mg/kg of cimetidine was administered intraperitoneally 2 days before or on the day of suppressor cell induction. Some restoration also occurred when cimetidine was given after the day of induction. It has been shown that suppressor cells possess histamine receptors which may be involved in suppressor cell activation. The results indicate that cimetidine may inhibit the functioning of these receptors.

Animals↗
PubMed1983

T-cell responses induced by the parenteral injection of antigen-modified syngeneic cells. II. Mechanisms, specificity, and cellular analysis of 2,4,6-trinitrophenol (TNP)-specific cytolytic response priming by intravenous versus subcutaneous injection with TNP-modified syngeneic cells.

We have examined the underlying mechanisms accounting for the enhanced in vitro TNP-specific cytotoxic T-lymphocyte (CTL) response following the parenteral injection of syngeneic hapten-modified lymphoid cells. Augmented CTL activity noted following parenteral injection (iv vs sc) of 2,4,6-trinitrophenol-modified syngeneic spleen cells (TNP-SC) is most apparent when limiting numbers of TNP-modified stimulator cells are used in the in vitro sensitization phase. Enhanced CTL responses seen following sc and iv priming is due to distinct mechanisms. Spleen and lymph node (LN) cells from sc primed mice were found to contain significant levels of radioresistant helper activity upon coculture with either viable normal spleen cells in bulk culture or with thymocytes as the source of precursor CTLs in a limiting dilution assay. The helper activity was found to be mediated by a Lyt 1+2- T cells. In addition, Lyt 2-depleted spleen and LN cells from sc primed BALB/c mice could restore the ability of tolerant spleen cells from 2,4,6-trinitrobenzenesulfonic acid (TNBS)-injected BALB/c mice to generate TNP-specific CTLs. Conversely, Lyt 2-depleted spleen and LN cells from iv primed mice provided no measurable helper activity either in bulk culture or in the limiting dilution assay and did not restore the ability of TNBS-tolerant BALB/c spleen cells to generate TNP-specific CTLs. CTL priming via the iv route was found to be completely antigen specific as iv injection of either 2,4-dinitrophenol (DNP)- or fluorescein isothiocyanatel (FITC)-modified cells caused no enhanced CTL activity. Priming via the sc route exhibited a unique specificity pattern as it was shown that sc injection of both TNP-SC and DNP-SC, but not FITC-SC, resulted in enhanced TNP-specific CTL responses. CTL T-helper (Th)-cell induction via the sc route was correlated with (1) the presence of H-2 I region determinants on the inducer cells as the sc injection of TNP-modified erythrocytes led to no enhanced CTL responses or CTL Th activity (while iv injection of TNP-erythrocytes did lead to enhanced CTL responses without detectable helper activity) and (2) the detection of both hapten-specific T-cell proliferation and Interleukin 2 (IL-2) production upon restimulation in culture. We conclude that the sc injection of TNP-SC leads preferentially to an increase of specific Lyt 1+ helper activity, while iv injection leads preferentially to an apparent expansion of Lyt 2+ prelytic effector CTLs.

Animals↗
PubMed1983

Role of complement in murine corneal infection caused by Pseudomonas aeruginosa.

The role of complement components C3 and C5 was examined in murine corneal infection induced by Pseudomonas aeruginosa. DBA/2 and Swiss-Webster mice are naturally resistant to experimental P. aeruginosa corneal infection. Mice of these two strains are able to restore a clear cornea within 4-6 weeks following Pseudomonas corneal challenge and are genetically deficient in the fifth component of complement. In contrast, ocular infection of congenic C5-deficient B10.D2o/Sn or normocomplementemic B10.D2n/Sn mice results in an identical pattern of susceptibility in which corneal perforation and phthisis bulbi occur. Taken together, these results indicate that C5 plays little or no role in susceptibility or resistance to Pseudomonas eye infection. In contrast, depletion of C3 in normally resistant DBA/2 mice using cobra venom factor (CoVF) diminishes the ability of these mice to restore a clear cornea following Pseudomonas infection. A single inoculation of CoVF, 24 hours prior to ocular challenge, is as effective in altering the response of DBA/2 mice as is continuous depletion of C3 during the course of infection using multiple inoculations of CoVF. Mice that are unable to clear Pseudomonas ocular infection following CoVF treatment regain this ability when the contralateral eye is infected after recovery of normal levels of C3. Depletion of C3 by CoVF treatment of DBA/2 mice, which had previously restored a clear cornea following Pseudomonas eye infection, again renders these mice susceptible.

Animals↗
PubMed1982

Peripheral T lymphocytes from rheumatoid arthritis patients recognize determinants on light chains and/or Fab fragments of immunoglobulin G.

Peripheral blood T lymphocytes from 29 of 31 patients with rheumatoid arthritis incorporated significant quantities of thymidine when cultured with pooled human immunoglobulin G (IgG). In contrast to the observation of general reactivity to pooled Igg, responses to pooled IgM were rare (3 of 26 patients). None of 11 controls responded to either IgG or IgM. Response to IgG is maximal on day 6 of culture and is dependent on concentration of IgG. The responding cells recognize determinants on monoclonal light chains and/or Fab fragments. Response to light chains follows one of three patterns: preferential response to lambda chains, preferential response to kappa chains, and essentially equal response to either kappa of lambda chains.

Arthritis, Rheumatoid↗