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Biomedical subjects

N Talal

Publications and source records attributed to N Talal.

At least 235 records · Page 13Linked to original sources
PubMed1978

Levamisole maintains cyclophsophamide-induced remission in murine lupus erythematosus.

Antibodies to DNA in 14 month old male NZB/W F1 mice were markedly decreased after 4 weeks of cyclophosphamide therapy. A group of these mice and untreated controls subsequently received levamisole for 12 weeks. Antibodies to DNA returned to pretreatment levels within 8 weeks in animals receiving only cyclophosphamide, whereas levamisole treatment after cyclophosphamide delayed the reappearance of these antibodies. Glomerular immunoglobulin deposition and the degree of lymphocytic tissue infiltrate were decreased in animals receiving cyclophosphamide followed by levamisole as compared with non-treated control animals or those receiving cyclophosphamide or levamisole alone. In vitro T-cell mitogen reactivity was inversely correlated with the final DNA antibody titres of individual mice, suggesting a relationship between decreased autoantibody production and augmented cellular immunity. We discuss possible mechanisms by which levamisole may delay the reappearance of autoantibodies and decrease the histological evidence of lupus nephritis when given to New Zealand mice first treated with cyclophosphamide.

Animals↗
PubMed1978

Lipopolysaccharide induction of IgM antibodies to polyadenylic acid in normal mice.

Lipopolysaccharide (LPS) is able to induce autoantibodies reversibly in normal mice. Single or multiple doses of LPS induced a rapid and dose-dependent rise in antibodies to Poly A from 113 ng to 590 ng/ml serum as determined by Millipore filter radioimmunoassay. The response peaked at day 3 and was over by day 21. No response was seen if the LPS was chemically inactivated or injected into genetically nonresponsive mice. Antibodies were specific for Poly A and were not induced by T cell mitogens. Sucrose gradient ultracentrifugation demonstrated only IgM antibody. Neonatal thymectomy altered neither the immunoglobulin class nor quantity of antibody. Neonatal splenectomy did not affect antibody class but reduced the amount produced. No free Poly A could be detected in circulation after LPS stimulation. These findings suggest that normal mice have B lymphocytes capable of limited and reversible autoantibody production.

Animals↗
PubMed1978

Natural history of murine lupus. Modulation by sex hormones.

Pathologic and immunologic features of the spontaneous autoimmune disease of NZB and NZB/NZW F1 (B/W) mice resemble human SLE in three major respects: formation of antibodies to nucleic acids, deposition of immune complexes containing DNA in the kidney, and earlier onset of severe disease in females. Genetic, viral, and hormonal factors are involved in a pathogenetic mechanism that is manifest primarily as a disturbance in immunologic regulation. Recent studies on the sequential development of IgM and then IgG antibodies to DNA and RNA suggest that the thymus, spleen, and gonads exert important regulatory influences. We have found that sex hormones modulate the expression of autoimmunity in B/W mice, with androgens suppressing and estrogens accelerating disease. The hormones may act by restoring immunologic control.

Androgens↗
PubMed1978

beta-Estradiol reduces natural killer cells in mice.

beta-estradiol was administered to mice continuously by diffusion from a silastic tube that was implanted subcutaneously at 4 weeks of age. Four to 6 weeks of estrogen administration caused a substantial reduction in natural killer cell activity in the spleens from mice of either sex. Androgen (5alpha-dihydrotestosterone) did not. Castration of male or female mice did not affect natural killing and did not alter the effect of beta-estradiol. Estradiol did not affect natural killing in vitro and the loss of natural killing was not due to a soluble or a cellular suppressor of natural killing. The effects of estradiol were not dependent on the thymus, since estradiol reduced natural killing in mice that had been neonatally thymectomized. After removal of the estrogen implant, natural killing recovered over a period of 8 weeks. The loss of natural killing may reflect a loss of bone marrow secondary to estrogen-induced osteosclerosis.

Animals↗
PubMed1977

Immune complexes in hepatitis B antigen-associated periarteritis nodosa. Detection by antibody-dependent cell-mediated cytotoxicity and the Raji cell assay.

A subpopulation of peripheral blood lymphocytes with the ability to lyse target cells coated with specific antibody (antibody-dependent cell-mediated cytotoxicity, ADCC) was serially studied in a patient with hepatitis B antigen-associated periarteritis nodosa. The effector lymphocytes possess FC and complement receptors but do not require complement for functional activity. We found that the patient's ADCC was decreased during periods of disease activity and was almost normal during remission. The patient's serum could block ADCC in normal lymphocytes, and the blocking ability correlated with the concentration of immune complexes as determined by the Raji cell assay (a radioimmunoassay using complement receptors on human cultured lymphoblastoid cells). The concentration of immune complexes and the ADCC blocking ability of ther serum both correlated with disease activity. Serum from five other patients with active vasculitis was found to contain significant amounts of immune complexes and was able to block normal ADCC. It appears that the ADCC assay can be used to detect the presence of circulating immune complexes and to monitor disease activity in periarteritis nodosa.

Adult↗
PubMed1977

Androgenic hormones modulate autoantibody responses and improve survival in murine lupus.

Antibodies to native DNA and to polyadenylic acid (Poly A) occur spontaneously and undergo a regulated switch from IgM to IgG during the course of autoimmune disease in NZB/NZW F(1) (B/W) mice. B/W females have higher titers and earlier commitment to 7S antibodies to DNA and Poly A, whereas B/W males bind DNA and Poly A primarily by 19S antibodies. We have performed castration experiments to determine the effects of sex hormones on this switch from IgM to IgG.NZB/NZW F(1) (B/W) mice were either castrated or subjected to sham surgery at 2 wk of age and studied for immunoglobulin class of antibodies to nucleic acids at 4, 6, and 7 mo post-surgery. Prepubertal castration of males caused premature death in 60% of mice. Castrated males had a significant decline in their serum testosterone concentration, an increase in DNA and Poly A binding, and an accelerated switch from 19S to 7S antibodies to nucleic acids. Castrated females had no change in mortality. However, castrated females given maintained androgen treatment had a decreased mortality compared to castrated females receiving estrogen (14 vs. 94%). The anticipated switch to 7S antibodies to Poly A was almost eliminated in castrated females. These results suggest that sex hormones modulate immunologic regulation and that androgenic hormones are protective in murine lupus.

Androgens↗
PubMed1977

Antigen induced alterations in splenic prostaglandin and cyclic nucleotide levels in NZB mice.

Studies were undertaken in order to determine if NZB mice injected with sheep erythrocyte antigens would respond by showing elevated splenic prostaglandin and cyclic nucleotide levels similar to that observed in normal mice. The results show that young NZB mice can respond to sheep erythrocytes by yielding increased levels of splenic PGF2alpha and cAMP. However, because of increased basal levels of PGF2alpha and cAMP, the net increase observed is lower than that observed with normal mice. In old NZB mice exhibiting signs of disease (splenomegaly) and in which defects in immune competence are known to occur, the injection of SRBC results in in no increase in splenic PGF2alpha levels and a decrease in cAMP levels. These animals also have greatly elevated basal levels of PGF2alpha, cAMP, and cGMP. It is concluded that the cellular immune defect in NZB mice is reflected by their faulty metabolic responses to sRBC. Also, the altered basal levels of PG and cyclic nucleotides may be related to the altered cellular immune competence. The latter conclusion is supported by the reduced capacity of spleen cells from young NZB mice to respond to PGE by increasing cAMP levels and by the lack of an effect of inhibitors of PG synthesis on the immune response to sRBC in both young and old NZB mouse spleen cell cultures.

Aging↗
PubMed1977

Immunological regulation of spontaneous antibodies to DNA and RNA. II. Sequential switch from IgM to IgG in NZB/NZW F1 mice.

Serial serum samples from NZB/NZW F1 mice were studied by sucrose density gradient ultracentrifugation and filter radioimmunoassay for the immunoglobulin class of antibodies to double-stranded DNA and single-stranded RNA (Poly A). These antibodies occur spontaneously during the course of an autoimmune disease resembling systemic lupus erythematosus. Study of serum samples at 2-week intervals showed the sequential appearance of 19S followed by 7S anti-nucleic acid antibodies, an earlier commitment to 7S antibodies in female compared to male mice, and an independent and unrelated switching mechanism (19S-7S) for antibodies to DNA and Poly A. The more severe disease in female mice is correlated with an earlier appearance of 7S anti-DNA antibodies. This sequential and ordered appearance of antibodies to nucleic acids is discussed in relation to possible immunologic regulatory mechanisms.

Animals↗
PubMed1977

Lymphocytes binding polyriboadenylic acid and synthesizing antibodies to nucleic acids in autoimmune and normal mice.

Splenic lymphocytes from both normal and autoimmune mice bind significant quantities of polyriboadenylic acid (poly rA) when incubated with radiolabeled poly rA for 40 min at 37 degrees C. This poly rA binding is specifically inhibited by an excess of nonradioactive poly rA and by anti-mouse immunoglobulin. Poly rA binding is decreased by exposing spleen cells to Pronase and is restored by subsequent culture for 18 to 72 hr. Poly rA-binding activity is associated more with bone marrow-derived than with thymus-derived lymphocytes. These results suggest the presence of autoantigen-binding lymphocytes in normal as well as autoimmune mice. Furthermore, spleen cells from normal and autoimmune mice cultured for 72 hr synthesize and secrete antibodies to poly rA and DNA. These antibodies can be recovered from the culture supernatants by a solid immunoadsorbent technique and antibody immunoprecipitation. The synthesis of antibodies to nucleic acids by normal spleen cells suggests that autoreactive lymphocytes may be released from normal immunoregulatory control during in vitro culture conditions.

Animals↗
PubMed1977

Effects of neonatal thymectomy and splenectomy on survival and regulation of autoantibody formation in NZB/NZW F1 mice.

NZW F1 (B/W) mice were subjected to sham surgery or neonatal thymectomy and/or splenectomy and studied for immunoglobulin class of antibodies to double-stranded DNA and polyadenylic acid (Poly A) at 4 to 13 months of age. These antibodies occur spontaneously during the course of autoimmune disease in B/W mice. Sera were fractionated by sucrose density gradient ultracentrifugation and assayed for antibodies by a filter radioimmunoassay method. IgM was recovered in the 19S region and IgG in the 7S region as demonstrated by immunodiffusion. In sham-operated controls, at all ages studied, anti-DNA antibodies were both IgM and IgG, with the former predominating in males, and the latter in females. In both sexes, anti-Poly A antibodies were primarily IgM in young mice. There was a sequential switch from IgM to either enhanced or new IgG production in the following sequence: female anti-DNA and anti-Poly A (6 months), male anti-DNA (9 months), and male anti-Poly A (11 months). Both thymectomy and splenectomy caused earlier death in male mice, whereas females lived significantly longer after thymectomy. Neonatal thymectomy in males caused a premature switch from IgM to IgG antibodies to DNA, but it had a transient effect in females. Thymectomy almost completely prevented the late switch to IgG antibodies to Poly A in both sexes. By contrast, splenectomy promoted the formation of IgG antibodies to Poly A in male mice. These results suggest that the newborn B/W thymus and spleen contain regulatory cells and/or factors exerting different controlling influences on spontaneous antibodies to DNA and Poly A. Male B/W mice appear to be under the regulatory influence of suppressor cells, whereas the predominant regulation in female B/W mice appears to be a helper effect.

Age Factors↗