Search PubMed⌕ Search

Biomedical subjects

G Schiffman

Publications and source records attributed to G Schiffman.

At least 73 records · Page 4Linked to original sources
PubMed1985

Pneumococcal vaccination in children with acute lymphocytic leukemia.

Sixty-three children with ALL in CCR and treated according to a standard therapy protocol were immunized with the 14-valent pneumococcal vaccine. Forty-six children were vaccinated 1, 3, or 6 months following initial induction remission; 15 were vaccinated 4-6 weeks following successful completion of 30 months of antileukemia therapy; and two were vaccinated at the time of diagnosis. Response to the vaccine was suboptimal and by the 6-month follow-up there were only two serotypes for which more than half the patients tested had greater than or equal to 300 ng antibodies N/ml.

Adolescent↗
PubMed1985

Response to immunization after partial and total splenectomy.

Survival after infection from Streptococcus pneumoniae in both animals and man is influenced by the amount of splenic tissue. We investigated the effect of differences in splenic weight upon the antibody response to immunization and the effect of immunization upon survival after pneumococcal challenge. Young Sprague-Dawley rats had either sham operation, hemisplenectomy, splenectomy with splenic autotransplantation, or total splenectomy. Nine weeks later, rats were immunized with a heat- and formalin-killed type-specific pneumococcal vaccine. Antibody response measured by radioimmunoassay was similar in all operative groups and was significantly higher than in nonimmune rats (P less than 0.01). Splenic weight was less after hemisplenectomy or autotransplantation than in sham-operated animals (P less than 0.01). Immunization improved survival after live pneumococcal challenge in rats that had autotransplantation and total splenectomy (P less than 0.001). Our results demonstrate that splenic weight does not affect the antibody response to pneumococcal immunization in rats. Immunization improves survival after bacterial challenge in susceptible animals and minimizes the detrimental effect of reduction in splenic mass.

Animals↗
PubMed1985

Comparison of an enzyme-linked immunosorbent assay with radioimmunoassay for the measurement of pneumococcal capsular polysaccharide antibodies.

An enzyme-linked immunosorbent assay (ELISA) has been developed to measure antibodies against pneumococcal polysaccharides of the IgA, IgG and IgM isotypes. Antibodies against pneumococcal polysaccharide types 1, 3, 6A, 8 and 9N were measured by ELISA and radioimmunoassay. Similar antibody responses were observed when comparing both assays. The study included 39 persons at high risk of developing pneumococcal infection and 13 healthy adults. Within 1 month after immunization IgM was the principle isotype. After 1 month, IgG was the principle isotype. Very low levels of IgA were detected in the post-immunization serum. The ELISA procedure described can be used to study the immune response to pneumococcal vaccines.

Adolescent↗
PubMed1985

A new 23 valent pneumococcal vaccine: immunogenicity and reactogenicity in adults.

A 23 valent pneumococcal vaccine containing 25 micrograms of each polysaccharide was administered to 30 healthy adults. Adverse reactions were always mild, consisting only of local pain and erythema in most subjects. Pre- and four weeks post-vaccination sera were analysed by radioimmunoassay. Geometric mean titre (GMT) ratios were between 2.3 and 14.3 (overall mean X 5.7) according to type. A level of 300 ng of antibody N/ml, the supposedly protective level, was achieved in at least 86.6% of the subjects for all the serotypes.

Adult↗
PubMed1985

Correlation of serum opsonins with in vitro phagocytosis of Streptococcus pneumoniae.

C-reactive protein (CRP), an acute-phase reactant which binds to phosphocholine (PC) in the pneumococcal cell wall, and anti-PC antibodies are protective against experimental pneumococcal bacteremia in mice. To determine the relative opsonic capacities of CRP and anti-PC compared with those of antibodies against pneumococcal capsular polysaccharides (anti-PCP), we correlated in vitro opsonic activity for serotype 7F Streptococcus pneumoniae with concentrations of CRP, anti-PC, and anti-type 7F PCP in human sera from 10 normal subjects and 38 patients with sickle cell (SS) disease, a high-risk group for pneumococcal infection. Opsonic activity, measured by a radiolabeled bacterial uptake assay, correlated with anti-PCP levels but not with CRP or anti-PC in both the normal subjects and patients with SS disease. Addition of CRP to normal sera did not increase opsonic activity for serotypes 4 and 7F S. pneumoniae, although it did so for serotype 27, a nonpathogenic strain unique for having PC in its capsule. CRP and anti-PC were not effective opsonins when they bound to the pneumococcal cell wall rather than the capsule. The protective effects of CRP or anti-PC against these serotypes may be produced by means other than complement-dependent opsonization.

Adult↗
PubMed1985

Correlation between G2m(n) immunoglobulin allotype and human antibody response and susceptibility to polysaccharide encapsulated bacteria.

To determine whether genetic factors influence the human antibody response to polysaccharides, we correlated Ig allotypes with the concentrations of antibody to 14 bacterial capsular antigens in 130 actively immunized Caucasian adults. The 88 individuals possessing G2m(n), an allotype antigen of IgG2 subclass heavy chains, had significantly higher postimmunization antibody levels to Haemophilus influenzae type b (Hib) and 8 of 11 pneumococcal types (P less than 0.05) than the 42 lacking this antigen. For Hib, pneumococcus type 14, and meningococcus group C, an increased response was observed in IgG class but not in IgM or IgA classes of antibody. The G2m(n) positive individuals also had higher preimmunization antibody levels to most polysaccharide antigens. Total IgG2 concentrations were correlated with the mean postimmunization antibody concentrations to pneumococci (P = 0.005), but this correlation was independent of G2m(n) by multiple regression analysis. To determine if the lack of G2m(n) was associated with increased susceptibility to infection, we compared the frequencies of various Ig allotypes in 98 children infected with Hib and 98 matched controls. Caucasian children with Hib infections other than epiglottitis were significantly more likely to lack the G2m(n) allotype than controls (P less than 0.05). G2m(n) negative Caucasian children less than or equal to 18 mo old have a 5.1-fold higher risk of nonepiglottitic Hib infections than G2m(n) positive children (P less than 0.01). We conclude that allotypic variants of the gamma-2 heavy chain genes, or genes in linkage equilibrium with them, exert a regulatory influence on the caucasian antibody response to a variety of immunologically distinct bacterial polysaccharide antigens. Young Caucasian children of the low responder phenotype, i.e., those lacking the G2m(n) allotype, are genetically predisposed to Hib and perhaps other bacterial infections.

Adult↗
PubMed1985

Pneumococcal immunization in patients with systemic lupus erythematosus treated with immunosuppressives.

Immunogenicity of 14 valent pneumococcal vaccine was evaluated in a placebo controlled, double blind, randomized study involving 77 patients with systemic lupus erythematosus (SLE). Antibodies to 12 type specific capsular antigens were measured prior to and one and 6 months post injection. In 17 patients treated with prednisone plus cyclophosphamide and/or azathioprine, mean body concentrations (ng antibody nitrogen/ml serum) increased from 528 to 1328 and 852, respectively, in vaccinated patients compared to 307, 308 and 344 following placebo. In 60 patients not receiving immunosuppressives, mean antibody concentrations were 355, 1361 and 920 post vaccine and 401, 473 and 377 post placebo. Our study demonstrates that antibody responses to pneumococcal vaccine in SLE patients is unaffected by these immunosuppressive agents.

Adolescent↗
PubMed1984

B-cell immunodeficiency in acquired immune deficiency syndrome.

To investigate B-cell function in acquired immune deficiency syndrome (AIDS), we immunized a group of patients with AIDS with pneumococcal polysaccharide (tetradecavalent) and protein (keyhole-limpet hemocyanin) antigens. Antibody responses were determined three to four weeks after immunization. Compared with controls, patients with AIDS had significantly lower geometric mean antibody levels to polysaccharide before and after immunization. Levels before and after immunization were frequently below a level thought to correlate with protection. Patients with AIDS also had a significant reduction in their primary antibody response to the protein antigens. The results of these studies indicate that AIDS is associated with an acquired B-cell as well as T-cell immunodeficiency. It is suggested that future studies should consider the evaluation of passive antibody in the prevention of infection and/or prevention of progressive immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1984

A comparison of antibody concentration measured by mouse protection assay and radioimmunoassay in sera from patients at high risk of developing pneumococcal disease.

The radioimmunoassay (RIA) of pneumococcal capsular polysaccharide antibodies is dependent on the association of radiolabeled antigen and pneumococcal antibody. However, it is not known whether the ability of the antibody to complex with antigen correlates with in vivo protection against infection. A method for evaluating protective ability of antibody vis-à-vis binding ability is to passively transfer a measured quantity of antibody into recipient mice followed by a lethal challenge with virulent pneumococci. Protection against a fatal outcome is then correlated with the amount of antibody (as measured by RIA) passively transferred. This comparison of quantitation by RIA and biological protection in mice was performed on 30 sera from humans. The sera were obtained from vaccinated healthy persons and vaccinated persons at high risk of developing pneumococcal infection, including people with nephrotic syndrome, chronic obstructive pulmonary disease and various forms of cancer. The results of these studies indicate that antibody as measured by RIA correlates with protective antibody against pneumococcal infection. These studies were conducted on pneumococcal serotype 3.

Adolescent↗
PubMed1984

Decline of serum antibody in splenectomized children after vaccination with pneumococcal capsular polysaccharides.

Asplenic persons are at increased risk of overwhelming sepsis caused by Streptococcus pneumoniae. Vaccination with polyvalent pneumococcal polysaccharide has been shown to stimulate a nearly normal antibody response in these individuals, indicating that active vaccination might prevent pneumococcal disease in this population. To obtain information on the duration of protective levels of pneumococcal antibody, 33 asplenic children were vaccinated and antibody levels were measured at intervals for up to 4 1/2 years after vaccination. Significant antibody decline was observed in children who had undergone splenectomy because of trauma, but antibody decline was not observed in children whose spleens had been removed because of hereditary spherocytosis. There was a highly significant difference in rates of antibody decline among the 12 antibody serotypes measured: types 1, 4, 6A, 7F, 8, 19F, and 23F showed the greatest decline. Based on measured rates of antibody decline, subprotective antibody levels (antibody nitrogen less than 300 ng/ml) for types 7F, 8, and 19F would be reached 1 to 2 years after vaccination; type 6A never reached the protective level; and antibodies against the remaining eight types either were within the protective range initially or did not show significant decline. Asplenic children may benefit from revaccination with certain antigen types (7F, 8, and 19F) 1 to 2 years after initial vaccination.

Adolescent↗
PubMed1984

Preparation of human hyperimmune globulin to Haemophilus influenzae b, Streptococcus pneumoniae, and Neisseria meningitidis.

As a first step in exploring the feasibility of passive antibody prophylaxis and therapy of serious infections caused by common encapsulated bacteria, we have immunized healthy adults with Haemophilus influenzae type b vaccine, 14-valent pneumococcal vaccine, and meningococcal group A and C vaccine; collected plasma by repeated pheresis; and purified a hyperimmune globulin termed bacterial polysaccharide immune globulin by the cold-ethanol fractionation method of Cohn and Oncley. Specific antibacterial antibody concentrations were measured in individual donors before and after immunization. In addition, antibody concentrations were measured in plasma pools prepared from immunized donors and from unimmunized controls and in the immunoglobulin-containing Cohn-Oncley fractions II and III derived from the respective plasma pools. A comparison of Cohn-Oncley fractions II, which contain primarily immunoglobulin G and which are used therapeutically as immune globulin, revealed that antibody to H. influenzae type b was enriched 15.3-fold and that antibody to meningococcal serogroups and pneumococcal types was enriched a mean of 4.4-fold (range, 1.2- to 9.9-fold). Enrichment of antibacterial antibody in Cohn fraction III, which contains substantial amounts of immunoglobulin M and immunoglobulin A in addition to immunoglobulin G, closely paralleled that in fraction II. Only antibodies to pneumococcal types 1 and 7 were increased disproportionately in fraction III. Based on the clinical experience that conventional immune serum globulin at a dose of 100 mg/kg protects agammaglobulinemic patients for ca. 1 month, we estimate that bacterial polysaccharide immune globulin, in similar dosage, will provide protection from systemic H. influenzae type b infection for 4 to 6 months and from pneumococcal and meningococcal infections for 3 to 4 months.

Antibodies, Bacterial↗
PubMed1984

Persistence of protective pneumococcal antibody following vaccination in patients with the nephrotic syndrome.

We have determined the level of persisting pneumococcal antibody in a group of nephrotic children vaccinated by us 5 years ago. Of the 19 vaccinated children, 2 have died and 1 has moved away. Sera from the remaining 16 patients were examined by radioimmunoassay to determine the antibody response to 11 of the 14 types contained in the polyvalent pneumococcal vaccine. The lowest protective level of geometric mean titre (GMT) of antibody in our laboratory is 300 ng antibody nitrogen per millilitre. 56% (9/16) of the patients showed adequate GMT 5 years after vaccination. All 9 patients had minimal change nephrotic syndrome. 44% (7/16) of the children had a GMT less than 300 ng antibody nitrogen per millilitre. 3 of these patients had focal sclerosis, 3 had membranoproliferative glomerulonephritis, and 1 patient had IgM nephropathy. Of these 7 patients, 1 with the lowest GMT (23 ng antibody nitrogen per millilitre) developed pneumococcal peritonitis. During this same period, in 20 other unvaccinated nephrotic patients followed continuously from 1976 to 1981, 7 cases of pneumococcal peritonitis occurred (p less than 0.05). Additionally, 1 unvaccinated child died of pneumococcal sepsis. Our study indicates that patients with minimal change nephrotic syndrome continue to maintain adequate amounts of antibody, but those with disease other than minimal change nephrotic syndrome are unable to maintain an adequate level of antibody.

Adolescent↗
PubMed1984

Streptococcus pneumoniae infections and bacteremia in patients with acquired immune deficiency syndrome, with report of a pneumococcal vaccine failure.

Five patients had Streptococcus pneumoniae infections among the 35 hospitalized with acquired immune deficiency syndrome (AIDS) at the New York Veterans Administration Medical Center between January 1, 1982, and June 30, 1983. Three of these patients had pneumococcal bacteremia and 2 had pneumonia without bacteremia. Twenty-seven bacteremic S. pneumoniae infections occurred among 5,143 patients without AIDS admitted to the Medical Service of this hospital during the same period. Thus, pneumococcal bacteremia was more likely to occur in patients with AIDS than in the general hospitalized population (x2 = 26, p = less than 0.001). Two of the bacteremic infections were caused by S. pneumoniae type 4. One of these occurred in a patient who had been inoculated with the 14 valent pneumococcal vaccine 5 months earlier. There were no significant differences in concentrations of radioimmunoassay antibody to type 4 pneumococcal polysaccharide in sequential serum samples collected from this patient, and opsonic titers to this organism were not detected. It is concluded that pneumococcal infections are very common among patients with AIDS, and may not be prevented by active immunoprophylaxis.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Reactivity and antibody responses of volunteers given two or three doses of pneumococcal vaccine.

Pneumococcal antibody responses and adverse reactions were assessed in 12 healthy volunteers who received either two (10 volunteers) or three (2 volunteers) doses of pneumococcal polysaccharide vaccines at 1 or 2 year intervals. The volunteers were given hexavalent (types 1, 3, 4, 7F, 8, 12F) octavalent (types 14, 19F added) nonavalent (type 5 added), and tridecavalent (types 6A, 6B, 9N, 18C, 23F added; type 5 removed) pneumococcal vaccines. Local and systemic reactions following any of the vaccines, either first, second, or third doses, were low, and these were mild; fever did not occur. Twelve volunteers received types 1, 3, 4, 7F, 8, and 12F in two doses of vaccine, and four volunteers received types 14 and 19F in two doses of vaccine. Primary immunization induced significant antibody rises to these antigens in most volunteers, but a second dose of vaccine did not further increase antibody levels to the same antigens; when it also contained new antigens, antibody rises usually developed to these antigens. Although the data are limited to detailed studies of only 12 persons, the results suggest that additional studies of this issue would seem appropriate.

Adult↗
PubMed1984

Use of total lymphoid irradiation (TLI) in studies of the T cell-dependence of autoantibody production in rheumatoid arthritis.

The effect of total lymphoid irradiation (TLI) on T cell-dependent and -independent humoral immune responses was studied in patients with intractable rheumatoid arthritis (RA). The serum levels of several autoantibodies and of antibodies to diphtheria (DT) and tetanus (TT) toxoids and to pneumococcal polysaccharide (PPS; 12 antigenic types) were studied before and after TLI. In addition, the patients were given a booster injection of DT and TT and a single injection of pneumococcal vaccine after radiotherapy. Antibody levels to DT and TT decreased about twofold after TLI and did not rise significantly (p greater than 0.05) after a booster injection. However, there was no reduction in antibody levels to PPS after TLI, and a significant rise in titers was observed after a single vaccination (p less than 0.01). The serum levels of rheumatoid factor (RF), anti-nuclear antibody (ANA), and granulocyte associated IgG rose slightly after TLI. Thus, the autoantibodies and antibodies to polysaccharides appear to be relatively independent of helper T cell function, which is markedly reduced after TLI. On the other hand, antibodies to protein antigens such as DT and TT appear to be more closely dependent upon T helper function in man, as has been reported in rodents. The findings suggest that T cell-independent autoantibody responses alone do not maintain the joint disease activity in RA, because improvement in joint disease after TLI has been reported.

Antibody Formation↗
PubMed1984

Subpopulations of antibodies to phosphocholine in human serum.

We investigated the heterogeneity of anti-phosphocholine (PC) antibodies present in human serum taken from individuals before and after immunization with a multivalent pneumococcal vaccine. The fine specificity of IgM, IgG, and IgA anti-PC antibodies was determined in an ELISA by using phosphocholine or p-nitrophenyl phosphocholine (NPPC) to inhibit binding of antibody to PC-histone. We identified two populations specific for PC that differed in their binding properties. One population is inhibited by NPPC much better than by PC and is most evident in IgG antibodies. The second population has similar avidity for PC and NPPC and is consistently associated with the IgM and IgA isotypes as well as with IgG. The IgG antibodies in both populations were predominantly of the IgG2 subclass. Both populations were found in serum samples taken before immunization with pneumococcal vaccine, suggesting that they had been stimulated through prior environmental contacts with PC-containing antigens. Previously, we found populations with similar fine specificity patterns in the murine response to PC. The two murine antibody populations have been shown to derive from different immunoglobulin variable region genes. The presence of comparable antibody populations in the human suggests the possibility that these two fine specificity families have been conserved in evolution.

Animals↗
PubMed1984

Specific antibody response after in vivo antigenic stimulation in systemic lupus erythematosus.

Several in vitro studies have demonstrated a polyclonal B cell response to antigenic stimulation in patients with systemic lupus erythematosus (SLE). To determine if this polyclonal response occurs in vivo, 18 patients with SLE were antigenically stimulated with the pneumococcal vaccine Pneumovax . Mean antibody response to immunization was the same in SLE and normal control subjects. Although elevated antibody levels to several viruses were present in SLE subjects preimmunization, these levels did not change postimmunization. Total immunoglobulin levels, immune complex levels, and antiblood group B antibody levels did not change in SLE patients after immunization. Antiblood group A titers rose in both SLE patients and normals due to a media contaminant in the Pneumovax . Thus, SLE patients appear to have a specific antibody response to antigenic stimulation with pneumococcal polysaccharide. Polyclonal activation as seen in vitro in SLE may be more restricted in vivo.

Adult↗