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P J Staples

Publications and source records attributed to P J Staples.

13 recordsLinked to original sources
PubMed1985

Effects of penicillamine on serum immunoglobulins and immune complex-reactive material in primary biliary cirrhosis.

Although penicillamine is used in the treatment of primary biliary cirrhosis, its mechanism of action in this disease is unknown. As an immunologic action had been attributed to the drug, we investigated whether penicillamine might alter serum immunoglobulin levels or immune complex-reactive material in patients with primary biliary cirrhosis. Immunoglobulin levels and immune complex reactivity were measured and clinical tests were performed in 53 consecutive patients entering a double-blind randomized trial of 750 mg vs. 250 mg of penicillamine. Measurement of immune complex reactivity was determined by laser nephelometry, 125I-C1q binding, and Raji cell assays. Immune complex reactivity was detected by at least one assay in 75% of patients tested before treatment. Sixty-two percent were positive in the C1q assay, 28% in the Raji cell assay, and 39% by nephelometry. After therapy with either dose, we found no change in immune complex-reactive material by any assay. Concentrations of immunoglobulins G and M fell (p less than 0.05) after 12 mo of therapy. Concentrations of immunoglobulin A decreased (p less than 0.05) only in the high-dose group. Correlation was not consistent between results of immune complex assays and clinical liver tests. Although immunoglobulin levels fell during penicillamine therapy, no decrease in immune complex-reactive material was detected. The effect of penicillamine in primary biliary cirrhosis is not mediated through alteration of immune complex-reactive material.

Antigen-Antibody Complex↗
PubMed1970

Induction of immunologic tolerance in older New Zealand mice repopulated with young spleen, bone marrow, or thymus.

Newborn, 7-9 day, and 16-18 day old NZB and B/W mice were, unlike older New Zealand mice, rendered tolerant to single doses of 8-10 mg of soluble BGG. After challenge, this tolerance was of short duration and escape occurred rapidly. Age-matched and similarly treated C3H, Balb/c and C57Bl mice did not escape from tolerance. Partial tolerance could be maintained by repeated injections of BGG. Biofiltration ruled out hyperphagocytosis as an explanation for this resistance to tolerance. Tolerance could be induced in older B/W mice if they were thymectomized, irradiated, and repopulated with young (12-15 day), but not old (2-3 month), spleen or bone marrow cells. Old bone marrow cells gave a non-tolerant response even when combined with young thymic grafts. Young bone marrow gave a tolerant response which was followed by the expected rapid escape only if a young thymus graft was also present. Escape was retarded if old thymus, or old irradiated thymus, was combined with young bone marrow. These results are best explained by abnormalities of both lymphoid precursors and thymic regulation.

Aging↗
PubMed1969

Rapid loss of tolerance induced in weanling NZB and B-W F1 mice.

Young adult mice (30 to 43 days old) of autoimmune NZB and BIW F(1) strains failed to develop immunologic tolerance when treated with ultracentrifuged bovine gamma globulin and then challenged 12 days later. By contrast, weanling NZB and B/ W F(1) mice (18 to 25 days) as well as weanling C3H mice (16 to 19 days) became tolerant and had no serum antibody 12 days after challenge. The C3H mice remained unresponsive, but NZB and B! W F(1) mice produced antibody between days 27 and 41. The rapid loss of previously established tolerance to foreign antigens could have its parallel in the loss of tolerance to autoantigens with subsequent development of lupus nephritis and Coombs' positive hemolytic anemia in these animals.

Anemia, Hemolytic, Autoimmune↗
PubMed1969

Relative inability to induce tolerance in adult NZB and NZB-NZW F1 mice.

Immunologic tolerance to ultracentrifuged bovine gamma globulin could not be induced in 6-wk old NZB or B/W mice, but developed readily in C3H, NZW, and C57Bl mice. NZB and B/W mice, as well as Balb/c mice, failed to become tolerant to ultracentrifuged human gamma globulin. The NZB and B/W mice also showed higher antibody titers to a standard antigenic challenge. This immunologic hyperreactivity and lack of experimental tolerance may be related to the lack of self-tolerance, autoimmunity, and lymphomas that develop in these mice at a later age.

Animals↗
PubMed1966

Role of the thymus in tolerance. 3. Tolerance to bovine gamma globulin after direct injection of antigen into the shielded thymus of irradiated rats.

Rats subjected to high doses of whole-body irradiation, with simultaneous shielding of the thymus or spleen, recovered at 3 wk the ability to develop delayed sensitization and to form hemagglutinating and precipitating antibody following foot-pad injection of BgammaG in complete adjuvant. Injection of BgammaG into the shielded thymus immediately after irradiation, in amounts between 20 gammag and 40 mg, inhibited these response to later challenge partially or completely. A comparable effect on immune responses to BgammaG was not seen after injection of heterologous antigen (Ea) intrathymically, BgammaG intraperitoneally, or BgammaG into the shielded spleen. However high doses (20 or 40 mg) of antigen given by the latter routes resulted in some diminution of later response. Arthus reactivity recovered partially in the spleen-shielded group and was readily suppressed by intrasplenic administration of antigen.

Animals↗
PubMedDate not supplied

Elevated circulating immune complexes in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is a syndrome of unknown etiology characterized by an association with inflammatory bowel disease in 50% or more cases. Since altered immunity, including circulating immune complexes, has been implicated in the pathogenesis of inflammatory bowel disease, we postulated that humoral immune mechanisms might also be important in the development of PSC. Therefore, as an initial step in testing this hypothesis, we examined sera of patients with PSC for the presence of circulating immune complexes by two independent methods: C1q binding and Raji cell assays. Twenty-four patients with PSC, 16 of whom had coexisting chronic ulcerative colitis, were prospectively selected by predefined biochemical, histologic, and radiographic criteria. Sixteen patients with inflammatory bowel disease and normal liver tests as well as six patients with extrahepatic biliary obstruction served as disease controls. Sera were positive for circulating immune complexes by at least one method in 80% (16/20) of patients with PSC; 70% (14/20 were positive by the Raji cell assay, 58% (14/24) by the C1q binding assay, and 45% (9/20) by both methods. Levels of circulating immune complexes by each assay were higher in sera from patients with PSC than in sera from healthy controls or patients with inflammatory bowel disease alone (p less than 0.01). There were no differences in the levels of circulating immune complexes or in the frequency of positive tests in PSC patients with or without associated inflammatory bowel disease. In addition, there was no difference between the Raji cell binding of sera from six patients with extrahepatic biliary obstruction and six healthy controls tested concurrently. These data are consistent with the hypothesis that immunologic mechanisms may be important in the pathogenesis of PSC.

Antigen-Antibody Complex↗