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Biomedical subjects

G Schiffman

Publications and source records attributed to G Schiffman.

At least 145 records · Page 8Linked to original sources

Experimental otitis media after nasal inoculation of Streptococcus pneumoniae and influenza A virus in chinchillas.

Otitis media developed in 67% of chinchillas inoculated intranasally with type 7 Streptococcus pneumoniae and influenza A virus. Only 4% of chinchillas inoculated with influenza alone and 21% of chinchillas inoculated with S. pneumoniae alone developed otitis media. Among the chinchillas that developed otitis media after inoculation with both pneumococcus and influenza, 73% of the affected ears contained effusion, and 27% of the affected ears showed tympanic membrane inflammation without middle ear effusion obtained on paracentesis. Although a majority of the ears with effusion yielded S. pneumoniae on culture, one-third of the effusions were sterile for aerobic bacteria. This model resembles conditions accompanying otitis media in humans and suggests that respiratory viral infection contributes significantly to the pathogenesis of acute otitis media.

Animals↗

Pneumococcal capsular polysaccharide vaccination in adult chronic hemodialysis patients.

PCP vaccine was administered to 21 adult hemodialysis patients and 25 control patients with no renal nor hepatic dysfunction. Antibody concentrations measured by the RIA technique were lower in the hemodialysis than in the control patients in both prevaccination sera and specimens obtained 3 to 4 weeks following vaccination. However, 6 months after vaccination, RIA GMACs in hemodialysis and control subjects were more nearly alike. OTs against Streptococcus pneumoniae, types 1 and 3, were measured in paired sera from vaccine recipients. Opsonic activity against S. pneumoniae, type I, was detected as frequently in the 3 to 4 week postvaccine sera of the dialysis as in those of control patients. However, there was a poor correlation between OTs and RIA-ACs against this organism. There was good correlation between OT and RIA-AC against type 3 pneumococci in 3 to 4 week postvaccine sera, and significantly more control patients had opsonic activity detectable in these specimens. No clinical S. pneumoniae infections have been observed in vaccine recipients. However, continued follow-up will be necessary to document the degree to which hemodialysis patients are protected by pneumococcal vaccines and the relationship between protection and antibody concentration or OTs.

Antibodies, Bacterial↗

Immunodeterminant specificity of human immunity to type III group B streptococcus.

The type III polysaccharides of group B Streptococcus in its native state chemically consists of glucose, galactose, glucosamine, and sialic acid. The core of this polysaccharide lacks sialic acid and precipitates with type III antiserum to give a partial identity with the precipitate between the native antigen and this serum. The core determinant is immunochemically similar to the capsular polysaccharide of type XIV Streptococcus pneumoniae, while the native type III group B streptococcal polysaccharide does not cross-react with type XIV pneumococcal antiserum. In human sera, it is antibody directed to the native antigen which correlates very highly with opsonic immunity (r = 0.94) while a poorer correlation exists between antibody to the core antigen and opsonins (r = 0.51 P less than 0.001). In natural infections, as association exists between low levels of maternal antibody to the native antigen and risk of disease in the infant. This association is not true for antibody to the core structure, where both infected infants and their mothers have much higher levels of antibody to the core than the native antigens. Infected infants are also more likely to respond to infection by developing antibody to the native antigen. Immunization of 12 adults with multivalent pneumococcal polysaccharide induced significantly better antibody response to the core antigen than to the native, and this vaccine induced opsonic activity in only one recipient. Immunization of adults with type III group B streptococcal antigens induced antibody to the native determinant which correlated with opsonic activity. Therefore, it would appear that native group B streptococcal polysaccharides will provide the best candidate antigens for immunization.

Antibodies, Bacterial↗

A controlled study of pneumococcal polysaccharide vaccine in systemic lupus erythematosus.

The immunogenicity and potential for disease modification of pneumococcal polysaccharide vaccine in systemic lupus erythematosus were evaluated in a controlled, double-blind study. Forty patients were randomly chosen to receive an intramuscular injection of either vaccine or placebo. Changes in mean antibody concentrations (nanograms antibody nitrogen per milliliter serum) to 12 type-specific pneumococcal capsular antigens from prevaccination to one month after vaccination were 177 to 1045 in the vaccine (P less than 0.001) and 164 to 153 in the placebo-treated patients. In the month after vaccination, neither vaccine nor placebo-treated patients had a significant change in lupus disease activity as assessed by a composite clinical, laboratory, and serologic index. We conclude that patients with systemic lupus erythematosus can be successfully immunized with pneumococcal vaccine without detectable alterations of the underlying disease.

Adolescent↗

Experimental otitis media in chinchillas following nasal colonization with type 7F Streptococcus pneumoniae: prevention after vaccination with pneumococcal capsular polysaccharide.

Chinchillas were colonized intranasally with type 7F Streptococcus pneumoniae, and pneumococcal otitis media developed in greater than 50% of the animals during the first week after negative middle ear pressure (-25 mm Hg) was briefly applied. Twenty-three chinchillas were vaccinated subcutaneously with the capsular polysaccharde of type 7F S. pneumoniae to determine whether vaccination could prevent the development of experimental otitis media. Following vaccination, 14 animals seroconverted with at least a twofold rise in serum antibody concentration; nine animals that were vaccinated did not seroconvert. All of 23 vaccinated animals and 42 of 42 unvaccinated control animals became colonized after intranasal inoculation with pneumococci. Only one (7%) of the vaccinated seroconverting animals developed pneumococcal otitis media, whereas 26 (62%) of the control animals developed middle ear infection with type 7F pneumococci. Four (44%) of nine vaccinated nonseroconverting animals developed pneumococcal otitis media. Protection was associated with high levels of serum antibody prior to intranasal inoculation. Higher antibody levels were found in sterile middle ear effusions than in S. pneumoniae-infected effusions. Vaccination with type 7F pneumococcal capsular polysaccharide significantly reduced the incidence of pneumococcal otitis media following intranasal inoculation of type 7F S. pneumoniae in chinchillas.

Animals↗

Comparative immunogenicity of group 6 pneumococcal type 6A(6) and type 6B(26) capsular polysaccharides.

The comparative immunogenicity of the two cross-reacting group 6 pneumococcal capsular polysaccharides, type 6A(6) and type 6B(26), was studied with hyperimmune rabbit typing antisera and with sera from adult volunteers injected with polyvalent pneumococcal vaccines containing either 50 mug of type 6A (U.S. designation, type 6) or 50 mug each of type 6A and type 6B (U.S. designation, type 26) polysaccharides. Both group 6 polysaccharides were linear copolymers composed of 1 mol each of d-galactose, d-glucose, l-rhamnose, and d-ribitol phosphate. They differed only in that type 6A had a rhammopyranosyl-(1 --> 3)-d-ribitol bond and the type 6B had a rhamnopyranosyl-(1 --> 4)-d-ribitol bond. Quantitative precipitation and absorption analyses with rabbit hyperimmune antisera induced by simultaneous injection with type 6A and type 6B organisms revealed extensive cross-reactions between the two group 6 polysaccharides. There was less, although still quite extensive, cross-reactivity between the two group 6 polysaccharides examined with antisera from rabbits injected with only one of the group 6 pneumococci. In a radioimmunoassay, using (14)C internally labeled type 6A or type 6B polysaccharide antigens, there was no difference in the serum antibody level to either type of volunteer injected with polyvalent pneumococcal vaccines containing type 6A or both type 6A and type 6B polysaccharides. These studies indicate that the structural similarity of the pneumococcal group 6 polysaccharides confers extensive cross-reactivity with hyperimmune typing antisera prepared with whole organisms or after injection of purified polysaccharides in adult volunteers. With our current polysaccharides, it appears that a polyvalent pneumococcal vaccine formulation that contains only type 6A will serve to induce the maximum amount of serum antibodies to both group 6 organisms.

Adult↗

Response of patients with Hodgkin's disease to pneumococcal vaccine.

Postsplenectomy, 41 patients previously treated for Hodgkin's disease were given pneumococcal vaccine, and type-specific antibody levels were measured before and after immunization. Postimmunization antibody levels in patients with Hodgkin's disease were significantly lower than those in normal control subjects for 10 of the 12 serotypes measured. Mean postimmunization antibody level for patients (587 +/- 427 ng of antibody nitrogen/mL) was much lower than that for control subjects (1787 +/- 694). Antibody levels tended to increase with time from therapy for Hodgkin's disease, and several patients who had not received therapy for more than 3 years had normal responses to immunization. Despite vaccination, one patient developed pneumococcal meningitis and another, pneumococcal bacteremia. Both infected patients had low postimmunization mean antibody levels (282 and 137 ng/mL, respectively). Postsplenectomy sepsis in patients with Hodgkin's disease is related to a humoral immune deficiency probably induced by radiation and chemotherapy, and this immune deficiency persists for several years.

Adolescent↗

Pneumococcal infections after human bone-marrow transplantation.

Seven of 26 long-term survivors (greater than 7 months post-transplant) of bone-marrow transplantation developed penicillin-sensitive pneumococcal infections more than 7 months after transplantation. One patient had two infections. Six of eight infections were associated with pneumococcal bacteremia, and Streptococcus pneumoniae type 6A was isolated in three cases. Two infections were fatal. All patients had normal nematopoietic function, and none was receiving immunosuppressive therapy. The development of pneumococcal infection was significantly associated with males and with abnormally low or high serum IGG and IgM levels but not with graft-versus-host disease. Serum opsonic activity for S. pneumoniae type 6A was decreased in six of the seven patients when compared to normal pooled serum in an in-vitro bactericidal assay. Four of the six patients with impaired opsonic activity had low serum antibody levels for S. pneumoniae type 6A capsular polysaccharide, while the other two patients had low serum CH100 complement activity. Bone-marrow transplant recipients have an increased susceptibility to pneumococcal infections and should be evaluated for prophylactic penicillin or pneumococcal vaccination.

Adolescent↗

Effect of splenectomy on the immune response of BALB/c mice bearing an immunoglobulin M plasmacytoma (TEPC-183).

Mice bearing TEPC-183, an immunoglobulin M(kappa)-secreting plasmacytoma, exhibit severe suppression of their immune responses to both thymus-dependent and thymus-independent antigens, 2,4-dinitrophenyl, and the type 3 pneumococcal polysaccharide SSS-III. This immunosuppression is not lifted by splenectomy of the tumor-bearing mice or prevented by removal of the spleen prior to tumor injection. On the contrary, splenectomy either before or after tumor implantation further accentuates the immunosuppressed state of tumor bearers and even depresses the immune response of normal mice. A secondary immune response of normal mice 34 to 51 days after splenectomy is still reduced. Thus, spleen cells may play a dual role. While splenectomy may remove a source of suppressor cells in tumor-bearing mice, it also eliminates a major source of antibody-producing cells and results in reduced immune responses of normal and TEPC-183-bearing mice. These findings have clinical relevance since splenectomy is used as a therapeutic and diagnostic procedure in neoplastic lymphoproliferative disorders.

Animals↗

Impaired antibody response to pneumococcal vaccine after treatment for Hodgkin's disease.

To determine if a normal antibody response can develop after therapy for Hodgkin's disease, we immunized 53 patients and 10 normal controls with dodecavalent pneumococcal vaccine. Antibody concentrations three weeks after immunization (geometric mean of 11 serotypes) were 1566 ng of protein nitrogen per milliliter in controls, 963 ng per milliliter after subtotal radiation (P less than 0.05 compared to controls), 658 ng per milliliter after chemotherapy (P less than 0.05), 377 ng per milliliter after subtotal radiation plus chemotherapy (P less than 0.01) and 283 ng per milliliter after total nodal radiation plus chemotherapy (P less 0.001). Low levels of antibody before immunization correlated with a poor response (r = +0.73, P less than 0.001). The ability to respond to immunization improved significantly but did not return to normal as long as four years after combined therapy. The antibody response to pneumococcal vaccine is profoundly impaired in patients who have received intensive treatment for Hodgkin's disease: the ability of this vaccine to protect them from overwhelming postsplenectomy infections remains in doubt.

Adolescent↗

Immune response after splenectomy.

The immune response to intravenously administered bacteriophage phiX 174 and subcutaneously administered tridecavalent pneumococcal polysaccharide vaccine was studied in 31 patients with anatomical or functional asplenia. Antibody responses to primary immunisation with phiX 174 were significantly decreased while clearance was normal. Secondary responses were quantitatively normal; however, production of antibody did not switch from IgM to IgG as seen in controls. All groups of asplenic patients accept those patients with Hodgkin's disease demonstrated significant seroconversions in response to pneumococcal polysaccharide antigens. One patient with Hodgkin's disease, treated with local irradiation only, demonstrated normal responses to pneumococcal capsular antigens. 10 of the 12 capsular antigens for which antibody was measured stimulated threefold increases in antibody in the 26 asplenic patients without Hodgkin's disease, which is similar to that observed in controls. Since the majority of cases of overwhelming postsplenectomy infection are caused by Streptococcus pneumoniae, all patients with either anatomical or functional asplenia should receive pneumococcal polysaccharide vaccine.

Adolescent↗

Antibody response to capsular polysaccharide vaccine of Streptococcus pneumoniae in patients with nephrotic syndrome.

Twenty-three normal subjects and 19 patients with nephrotic syndrome were vaccinated with tridecavalent pneumococcal capsular polysaccharide vaccine of Streptococcus pneumoniae. The antibody response of the nephrotic patients to pneumococcal capsular antigens was equal to that of the control subjects. These findings indicate that patients with nephrotic syndrome, despite hypogammaglobulinemia, can mount an adequate antibody response to pneumococcal polysaccharides and that there is no evidence of suppressor thymus-derived (T) cells of dysfunctioning bone marrow-derived (B) cells in these patients.

Adolescent↗