Alternate-day cyclosporine. Allograft and antibody immunosuppression.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
G Schiffman
Publications and source records attributed to G Schiffman.
Immunoregulatory role of the spleen in antibody responses to pneumococcal polysaccharide antigens.
Antibody responses to two structurally different pneumococcal polysaccharides, type 3 (SIII) and type 14 (SXIV), were examined in intact and splenectomized (Sx) A/J mice to determine whether the role of the spleen in immune responses to these antigens varies with respect to the dosage, the antigenic structure, or the interval between immunization and assay. Antibody responses to SIII and SXIV, measured over a 4-week period by radioimmunoassay, differed in antigenic load requirements, kinetics, and extent of dependence upon the spleen. Intact mice given 50 or 100 ng of SIII produced peak antibody responses on day 5, which tapered off by days 14 and 21. Intact mice given SXIV required doses 100 times greater than those of SIII to stimulate high levels of antibody response; antibody responses increased on day 5 and remained elevated through day 28. In Sx mice given 50 or 100 ng of SIII, the peak antibody response on day 5 was obliterated, but extrasplenic sources produced low levels of antibody which peaked by day 14. In Sx mice given SXIV, all anti-SXIV responses were abrogated regardless of the dose or day of assay. Differences between the anti-SIII and anti-SXIV responses in dependence upon the spleen were probably due to structural differences between the two antigens and to the localization of each to different sites in the reticuloendothelial system. These results attest to the importance of the spleen in antibacterial resistance. They show that, even in the presence of extrasplenic antibody synthesis, the spleen is required for early antibody production, the timing of which is critical for the effective clearance of bacteria.
Animals↗
Effect of cocaine on the immune response and host resistance in BALB/c mice.
This study focuses on the effect of varying regimens of cocaine administration on three parameters of the immune response: antibody production, resistance to infection by Streptococcus pneumoniae following immunization, and resistance to tumors. The effect of cocaine on antibody production of female and male BALB/c mice was investigated to both a T-independent (pneumococcal polysaccharide type III [SSS-III]) and a T-dependent antigen (the 2,4-dinitrophenyl ligand [DNP]). It was found that high doses of cocaine injected 3 times/day prior to SSS-III resulted in a small rise in antibody levels in male mice. Low doses given for 4 days prior to or subsequent to SSS-III injection had no effect on the antibody response nor on the susceptibility to infection by live S. pneumoniae. High dosages of cocaine administered 3-5 times/day had no effect on the anti-DNP immune response of male mice but resulted in an almost 2-fold increase of anti-DNP plaque-forming cells in female mice.
Animals↗
Pneumococcal infection and immunologic response to pneumococcal vaccine in chronic obstructive pulmonary disease. A pilot study.
We assessed the importance of Streptococcus pneumoniae and immunologic response to 14-valent pneumococcal vaccine in a randomized (saline placebo or vaccine) double-blind pilot study involving 103 patients with chronic obstructive pulmonary disease (COPD). Antibody titers, the flora of the sputum, respiratory infections or pneumonias, and deaths were monitored. The patients' antibody titers before immunization were higher than healthy control subjects. Titers rose normally in those vaccinated but declined more rapidly. Differences between the group receiving placebo and vaccine were not significant at 12 and 24 months. The incidence of pneumonia was high before and after vaccine (47/1,000 vs 41/1,000 patient-years). Nonpneumococcal causes predominated (73 percent of pneumonias; 83.4 percent of lethal pneumonias). Isolates from sputum were predominantly nonvaccine types (50 to 62.5 percent). Twenty-seven patients died; pneumonia occurred in six (one pneumococcal in a vaccinated patient) as a terminal complication of other diseases. Thus, although pneumonia occurred frequently in these patients with COPD and contributed to mortality in 22 percent (six) of the 27 deaths, the predominance of nonpneumococcal causes and the data on antibodies and sputum suggest that pneumococcal vaccine may not be as beneficial for patients with COPD as was hoped. More observations are needed.
Adult↗
Inhibition of suppressor-cell activity by cyclophosphamide in patients with malignant melanoma.
Twenty patients with malignant melanoma were treated with cyclophosphamide (100, 300 or 500 mg/m2 i.v.) in pilot studies to determine whether such treatment affected suppressor-cell activity. Delayed hypersensitivity to dinitrochlorobenzene and other recall antigens, the serological response to primary immunization with pneumococcal or influenza virus antigens, and the serological response to melanoma antigens were found to be normal and were not changed by cyclophosphamide (Cy) treatment. In vitro assays for production of antibodies against sheep red blood cell (SRBC) antigens, reactivity in the mixed lymphocyte culture reaction, and induction of suppressor cells by Concanavalin-A (Con-A) yielded abnormal results as a consequence of increased suppressor-cell activity in eleven, three, and nine patients, but no concordance was seen between results with the three assays prior to treatment. After treatment with Cy, the results of these tests became normal in seven, three, and seven of the patients with previously abnormal results, independent of the dose given. Examining all patients as a group, a statistically significant effect was seen after treatment with Cy on days 14 and 21 in the assay for the production of antibodies against SRBC, and days 7, 14, 21, 28, and 35 in the assay for Con-A-induced suppressor cells. The decrease in suppressor-cell activity was largely restricted to patients who showed increased suppressor-cell activity prior to treatment with Cy. Our results suggest that increased suppressor-cell activity in patients with malignant melanoma does not affect immune reactions generally but is selective, and that the anti-suppressor-cell effect of Cy is restricted to reactions with increased suppressor-cell activity to start. Based on these results, attempts at increasing the immune response to melanoma antigen vaccines administered between 7 and 35 days after treatment with Cy seem justified.
Antibody Formation↗
Tamarin model of pneumococcal bacteremia.
Tamarins (Saguinus labiatus) were utilized to study host defenses against pneumococcal bacteremia. Tamarins had a poor antibody response to immunization with varying doses of pneumococcal capsular polysaccharide (PCP) vaccine (2 of 15 positive) or to infection with serotype 7F Streptococcus pneumoniae (2 of 14 positive). Tamarins were protected against challenge with a lethal dose of serotype 7F S. pneumoniae if the bacteria were preopsonized with human immune globulin intravenous or if the tamarins were injected with the immune globulin 30 min before challenge. There was minimal protection utilizing a mouse monoclonal anti-type 7F PCP antibody.
Animals↗
Low-dose azathioprine is synergistic with low-dose cyclosporine in rabbit skin allograft survival.
Explore the source record for details and available documents.
Animals↗
Efficacy of pneumococcal vaccine in high-risk patients. Results of a Veterans Administration Cooperative Study.
We conducted a randomized, double-blind, placebo-controlled trial to test the efficacy of the 14-valent pneumococcal capsular polysaccharide vaccine in 2295 high-risk patients (patients with one or more of the following: age above 55 years and the presence of chronic cardiac, pulmonary, renal, or hepatic disease, alcoholism, or diabetes mellitus). Seventy-one episodes of proved or probable pneumococcal pneumonia or bronchitis occurred among 63 of the patients (27 placebo recipients and 36 vaccine recipients). Vaccine-serotype Streptococcus pneumoniae strains were recovered in association with 11 infections in the placebo group and 14 infections in the vaccine group. Pneumococcal infections occurred most frequently among patients with chronic pulmonary, cardiac, or renal diseases. Among vaccine recipients who subsequently had vaccine-type pneumonia or bronchitis, the majority did not make or sustain serum antibodies against their infecting organism in concentrations that were twice as high as the base-line values, or more than 400 ng of antibody nitrogen per milliliter, although their base-line levels were higher than those in subjects in whom infection did not develop. We were unable to demonstrate any efficacy of the pneumococcal vaccine in preventing pneumonia or bronchitis in this population. Our data suggest that chronically ill patients, who are most susceptible to infection, may have an impaired immune response to the pneumococcal vaccine.
Antibodies, Bacterial↗
Effect of total lymphoid irradiation on levels of serum autoantibodies in systemic lupus erythematosus and in rheumatoid arthritis.
The effects of total lymphoid irradiation (TLI) on serum levels of autoantibodies, and of antibodies to diphtheria toxoid, tetanus toxoid, and pneumococcal polysaccharide in patients with lupus nephritis were compared with those previously observed in rheumatoid arthritis (RA) patients. Baseline levels of antibodies to diphtheria toxoid and tetanus toxoid decreased significantly after TLI in patients with lupus and RA, but antibody levels to pneumococcal polysaccharide remained unchanged. After TLI, the levels of antinuclear and anti-DNA antibodies were reduced significantly in lupus, but levels of rheumatoid factor, antinuclear, and antigranulocyte antibodies all tended to increase in RA.
Arthritis, Rheumatoid↗
Decline of vaccine-induced antipneumococcal antibody in children with nephrotic syndrome.
Twenty-five children with steroid-responsive idiopathic nephrotic syndrome were studied for persistence of antipneumococcal capsular polysaccharide antibody during relapse of their disease and at 1, 6, and 12 months after vaccination with the 14-valent pneumococcal vaccine. Nonrelapsers (group I) were compared to those who had at least one relapse but whose sera were obtained during remission (group II). Group II had a more rapid decline in total anticapsular antibody per month than group I (5.3% v 2.4%). Analysis by individual anticapsular types showed that differences between groups approached significance only for type 4 (P = .07). Rates of decline of antibody against pneumococcal capsular polysaccharide varied among types. One year after vaccination, 50% of patients had less than 300 ngAbN/mL against types 4, 6A, 7F, 8, and 19F. Sera obtained from seven patients during relapse had geometric mean antibody concentrations less than 300 ngAbN/mL against those same types; two of these types have been reported to cause disease in vaccinated patients with nephrosis. Decline of antibody against pneumococcal capsular polysaccharide following vaccination varies by capsular type. Type-specific analysis should be used when monitoring serum antibody levels in these patients after vaccination.
Adolescent↗
Quantitative and qualitative analyses of serum antibodies elicited in adults by Haemophilus influenzae type b and pneumococcus type 6A capsular polysaccharide-tetanus toxoid conjugates.
Covalent binding to immunogenic proteins increases the immunogenicity of the capsular polysaccharides of Haemophilus influenzae type b (Hib) and pneumococcus type 6A (Pn6A). Conjugates composed of Hib, Pn6A, or the cross-reacting Escherichia coli K100 covalently bound to tetanus toxoid (TT) were injected into young adult volunteers. Local reactions were common and were probably due to Arthus reactivity mediated by the preexisting antibodies reacting with the TT component of the conjugates. Fever occurred in about 10% of the volunteers after the first injection; no volunteers had fever after the second injection. Similar levels of Hib or Pn6A antibodies were elicited by either 50- or 100-micrograms doses or by concurrent injection of two different conjugates (Hib-TT and Pn6A-TT or Hib-TT and K100-TT). The Hib-TT elicited about a 180-fold increase in Hib antibodies, and the Pn6A-TT conjugate elicited about an 8-fold increase in Pn6A antibodies after one injection. Booster reactions were not elicited in adults; similar levels of antibodies in the five experimental groups suggested that the responses elicited by the conjugates were maximal. A one-way cross-reaction was noted as Pn6A conjugates elicited rises of Hib antibodies in 13 of 20 volunteers; only 4 of 59 volunteers immunized with Hib-TT had increases in Pn6A antibodies. The preimmunization Hib antibodies were composed of immunoglobulin M (IgM), IgA, and IgG. The postimmunization sera showed an increase in all three isotypes; the elevation of the IgG was the highest of the three isotypes. Conjugate-induced antibodies to both the polysaccharide and TT exerted biological activities that have been correlated with immunity. Adsorption of the Hib-TT onto aluminium hydroxide resulted in higher levels and an earlier Hib antibody response in infant rhesus. These results encourage the evaluation of Hib and Pn6A conjugates in human children and infants.
Adjuvants, Immunologic↗
Pneumococcal vaccine immunization of patients with renal impairment.
The immunogenicity of the polyvalent pneumococcal vaccine was studied in renal allograft recipients and dialysis patients. There was no significant overall difference in the antibody response of the allograft recipients compared to control subjects at 1 month following immunization. Chronic hemodialysis patients had significantly lower postvaccination antibody levels for 6 of 12 serotypes. Better graft function in the allograft recipients correlated positively with higher antibody levels. Azathioprine and prednisone in dosages employed had no consistent effect on antibody response. No deterioration of renal function ascribable to the vaccine was observed. Patients were sampled at 1, 2, and 3 1/2 years following immunization. Geometric mean titers (GMT) were calculated for all the serotypes per group for each time of sampling. There was a significant decrease with time in antibody GMTs for all the groups (P less than 0.01). Chronic hemodialysis patients had significantly lower GMTs than control subjects and allograft recipients at 1, 2, and 3 1/2 years postimmunization (P less than 0.05). The 3 1/2 years postimmunization antibody levels were very low in dialysis patients, suggesting that reimmunization of these patients may be required.
Adult↗
Bacterial pneumonia in patients with the acquired immunodeficiency syndrome.
Eighteen episodes of community-acquired bacterial pneumonia were diagnosed in 13 patients among 336 with the acquired immunodeficiency syndrome (AIDS) cared for at Memorial Sloan-Kettering Cancer Center since 1979. Bacterial pathogens isolated in 16 of 18 episodes were Haemophilus influenzae in 8, Streptococcus pneumoniae in 6, group B streptococcus in 1, and Branhamella catarrhalis in 1. Eight episodes were presumed Pneumocystis carinii pneumonia until cultures obtained at bronchoscopy confirmed a bacterial cause. Specific antibacterial therapy was curative in 16 of 18 episodes; 2 patients died. Given an estimated yearly incidence of pneumococcal pneumonia in the general population of 2.6/1000, 1.09 cases were expected in our patients with AIDS; we saw 6 (p = 0.001), for an attack rate of 17.9/1000. Bacteria associated with B-cell defects should be anticipated when formulating empiric antibiotic therapy, pending a definitive diagnosis, for pulmonary infiltrates in patients with AIDS.
Acquired Immunodeficiency Syndrome↗
Antibody response to pretreatment immunization and post-treatment boosting with bacterial polysaccharide vaccines in patients with Hodgkin's disease.
Overwhelming sepsis is a serious complication of staging splenectomy in Hodgkin's disease. To define an optimal immunization strategy, 51 patients received 14-valent pneumococcal, Haemophilus influenzae type b, and meningococcal group C vaccines before therapy and 2 to 12 months after completion of therapy. Natural antibody levels to bacterial polysaccharide antigens and the response to immunization were normal or only minimally impaired in patients with Hodgkin's disease compared with findings in healthy adults. The antibody response was not affected by the timing of immunization relative to splenectomy but was frequently impaired if chemotherapy was begun less than 10 days after immunization. Both post-immunization and "natural" antibody declines were significantly greater in patients with Hodgkin's disease than in healthy adults; the magnitude of the decline was related to the intensity of therapy. A spontaneous rebound in antibody concentrations was not seen during the 12 months after treatment. Booster immunizations of all three vaccines given during this period also failed to elicit an antibody increase.
Adolescent↗
Revaccination of renal transplant and hemodialysis recipients with pneumococcal vaccine.
Two years after pneumococcal vaccine was given to patients on a university renal transplant and hemodialysis service, vaccine failures began to occur. Serologic studies showed a threefold decrease in antibody levels during this period, from 913 ng of antibody nitrogen per milliliter to 315 ng/mL. The decrease was greater in patients undergoing hemodialysis than in renal transplant recipients (879 to 215 ng/mL vs 932 to 385 ng/mL). The lowest antibody levels were to types 4, 6A, and 19F. Patients were revaccinated, without serious reactions, and pneumococcal infections decreased as they had after the original vaccination program. After revaccination, there was a twofold increase in antibody levels (315 to 602 ng/mL), but the levels did not reach those seen after primary vaccination. The increase was greater in hemodialysis than in renal transplant recipients (215 to 757 ng/mL vs 385 to 536 ng/mL). This experience indicates that pneumococcal vaccines may be effective in patients undergoing hemodialysis and in asplenic renal transplant recipients, but these groups will require revaccination sooner than normal subjects to maintain immunity.
Antibodies, Bacterial↗
Revaccination with polyvalent pneumococcal vaccine in children with sickle cell anemia.
To determine if revaccination improves levels of antibodies to pneumococcal polysaccharide types 6A, 14, and 19, 86 subjects with sickle cell anemia between 4 and 23 years old were given a booster injection of a polyvalent pneumococcal vaccine 37 to 53 months after primary immunization. Most subjects had mild local reactions similar to those seen after primary immunization. Only two subjects, both young adults, had severe local and systemic reactions. The percentages of subjects with protective antibody levels to types 6A, 14, and 19 increased from 74%, 44%, and 79% respectively before boosting, to 92%, 66%, and 92% respectively after boosting. Revaccination of children and young adults with sickle cell anemia appears to result in increased protective levels of antibody, and is associated with a low prevalence of severe reactions.
Adolescent↗
Pneumococcal polysaccharide antibody levels in patients with term and preterm pregnancies.
Serum antibody levels against 12 serotypes of pneumococcal polysaccharide were assessed in pregnant women as well as in cord bloods of their infants. Twelve women were evaluated during the first trimester, second trimester, and in labor at term, and eight women were assessed in the first trimester and in preterm labor. Antibody levels significantly decreased from the first trimester to delivery both in patients with term (339 versus 281 ng AbN/mL; P less than .001), and preterm (448 versus 299 ng AbN/mL; P less than .001) deliveries. There was no significant difference in mean antibody levels or their rate of decline between term and preterm pregnancies.
Adult↗
Maternal-fetal transfer of pneumococcal capsular polysaccharide antibodies.
Maternal-fetal transfer of IgG antibodies is an important host defense for newborns, who have an increased incidence of bacterial infections. To study the transfer of specific pneumococcal capsular polysaccharide (PPS) antibodies, we measured the concentrations, in 30 paired maternal and cord serum samples, of IgG and IgM by radial immunodiffusion, of serotype 7F Streptococcus pneumoniae PPS antibodies by radioimmunoassay and enzyme immunoassay, and of opsonic activity to that organism by a radiolabeled bacterial uptake assay. Cord serum had significantly greater total IgG, yet significantly less type 7F PPS IgG antibodies and opsonic activity than maternal serum. Cord serum had low concentrations of total IgM and no IgM type 7F-specific antibodies. Reduced transport of specific IgG antibodies and absent transfer of IgM may contribute to the susceptibility of newborns to bacterial infection.
Antibodies, Bacterial↗