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Biomedical subjects

G Schiffman

Publications and source records attributed to G Schiffman.

At least 163 records · Page 9Linked to original sources
PubMed1978

Modification of otitis media following vaccination with the capsular polysaccharide of Streptococcus pneumoniae in chinchillas.

An animal model was used to determine whether vaccination with the capsular polysaccharide of Streptococcus pneumoniae could alter the development of experimental otitis media induced by the same type of S. pneumoniae as the vaccine. Following vaccination with the capsular polysaccharide of S. pneumoniae type 7, 36(63%) of 57 chinchillas seroconverted with at least a 100% increase in concentration of antibody in serum which remained elevated for at least six weeks. The middle ears of 23 chinchillas that were vaccinated and seroconverted, 13 that were vaccinated and did not seroconvert, and 47 that were not vaccinated were inoculated with S. pneumoniae type 7. Vaccinated animals that seroconverted developed otitis media as readily as nonseroconverting and unvaccinated animals but had fewer pneumococci in their middle ears, a lower incidence of bacteremia, and lower mortality rates during the first week after inoculation of bacteria. Animals that did not seroconvert showed no evidence of modification of their middle ear infections. These results indicate that type 7 pneumococcal capsular polysaccharide vaccine is antigenic for the chinchilla and modifies experimental otitis media due to type 7 S. pneumoniae.

Animals↗
PubMed1977

Temperature-sensitive mutants of Streptococcus pneumoniae. I. Preparation and characterization in vitro of temperature-sensitive mutants of type I S. pneumoniae.

After exposure of type I Streptococcus pneumoniae to nitrosoguanidine, 13 temperature-sensitive (ts) mutants were selected that were restricted in capacity to form colonies on blood agar at 38 C. Whereas colony formation by the type I parent (ts+) was unaffected by a temperature of as high as 39 C, the ts mutants exhibited a spectrum of temperature sensitivity in which colony formation was inhibited significantly at 36 C, 37 C, 38 C, or 39 C. Growth of ts mutants at 38 C in broth was reduced or delayed relative to that of ts organisms under identical conditions. In general, there was a direct correlation between degree of temperature sensitivity and genetic stability. Mutants grown at a permissive temperature resembled the ts+ type I parent in colonial morphology and properties of alpha-hemolysis, bile solubility, optochin sensitivity, and antibiotic sensitivity. Moreover, in vitro studies indicated that the mutants retained capsules of immunochemically reactive type I capsular polysaccharide.

Bile↗
PubMed1977

Immunologic studies in pneumococcal disease.

Many patients die from pneumococcal disease despite the availability of effective antimicrobial agents. Immunologic studies including detection, typing, and quantitation of serum pneumococcal capsular polysaccharide (PCP) antigen by counterimmunoelectrophoresis (CIE), quantitation of PCP antibody by radioimmunoassay (RIA), and quantitation of serum complement components C3, C4, and C3PA and serum immunoglobulins IgG, IgM, and IgA by the radial immunodiffusion technique of Mancini were performed with the sera of 18 patients. Five patients died (group I), and 13 survived (group II) pneumococcal infection. Both groups were comparable in age, underlying disease, and leukopenia on admission. All patients of group I and 10 of 13 (77%) of group II patients were bacteremic. Two patients in each group had an extrapulmonary focus infection. PCP antigen was detected in the sera of all group I and nine of 13 group II patients. PCP antigen levels were larger than or equal to 15 microng/ml in four of five group I and two of 13 group II patients (p = 0.022). Levels of antibody to PCP exceeded 100 ng/ml of antibody nitrogen (AbN) in 10 of 12 group II and one of five group I patients (p = 0.027) during the course of illness. All group I patients and three of 12 group II patients had decreased levels of one or more complement components on admission (p less than 0.01). One or more complement components remained decreased until death in four group I patients but returned to normal or elevated levels in all group II patients. No difference in serum immunoglobulin concentrations were found.

Adult↗
PubMed1976

The role of the capsular polysaccharide in the activation of the alternative pathway by the pneumococcus.

Previous studies have shown that when pneumococci are incubated in normal, nonimmune serum, they activate the alternative pathway and opsonically active C3b is fixed to the surface of the organism. Other studies have demonstrated that C3-dependent opsonization via the alternative pathway plays a significant role in the nonimmune host's defense against the pneumococcus. The present studies concern the role of the capsular polysaccharide in initiating the activation of the alternative pathway by the pneumococcus. Some pneumococcal capsular polysaccharide types, but not all, are able to activate the alternative pathway. Soluble purified capsular polysaccharide types 1, 4 and 25 activate the alternative pathway, whereas types 2, 3, 14, and 19 do not. Since the capsular polysaccharides exist in their native form attached to the pneumococcal surface, selected capsular polysaccharides were also tested for their ability to activate the alternative pathway when attached to a particulate carrier, sheep erythrocytes. Capsular polysaccharide types 2 and 3 failed to activate the alternative pathway when attached to sheep erythrocytes, paralleling the results obtained when these capsular polysaccharides were in solution. In contrast, the type 25 capsular polysaccharide not only activated the alternative pathway when attached to sheep erythrocytes, as it had when in solution, but it also initiated alternative pathway-mediated lysis of the erythrocytes. The capsular polysaccharide is not required for the activation of the alternative pathway by the pneumococcus. Although all types of encapsulated pneumococci are able to activate the alternative pathway, not all the purified capsular polysaccharide types are able to do so. In addition, a nonencapsulated pneumococcus, derived originally from a type 2 organism, activates the alternative pathway as well as a fully encapsulated type 2 pneumococcus.

Cell Wall↗
PubMed1971

Capsulation of pneumococcus with soluble cell wall-like polysaccharide. II. Nonidentity of cell wall and soluble cell wall-like polysaccharides derived from the same and from different pneumococcal strains.

Methods are described for the separation of the C or cell wall polysaccharide from the C(s) or soluble C-like capsular polysaccharide of C(s) pneumococcal strains. Immunologic analysis has shown that both the C and C(s) polysaccharides of a variety of pneumococcal strains are heterogeneous and that the dissimilarities appear to reside in the mucopeptide portion of the molecule or in the region of its attachment to the teichoic acid moiety of the molecule rather than in the teichoic acid fraction. Differences of the type described have been observed in the C polysaccharides of wild-type capsulated strains of several types, in those of independently isolated noncapsulated variants derived from a single strain of a given capsular type, and in the C and C(s) polysaccharides of spontaneous mutant or transformed strains of pneumococci producing capsules of C(s) polysaccharide.

Animals↗
PubMed1970

Some biological properties of Pneumococcus type 37 and the chemistry of its capsular polysaccharide.

Pneumococcus Type 37, like pneumococcus Type 3, is characterized by the production of large mucoid colonies on the surface of solid media and by its very large capsule. It differs from the highly virulent pneumococcus Type 3 in that it is only slightly virulent for mice and rats and is isolated infrequently from man. A study of the behavior of pneumococcus Type 37 in systems comparable to those used in the study of pneumococcus Type 3 and an examination of the chemical structure of the capsule of pneumococcus Type 37 are described. The capsular polysaccharide of pneumococcus Type 37 is a viscous, optically inactive polymer composed of 95% hexose. Glucose is obtained in 88% yield upon acid hydrolysis. Periodate oxidation studies and the behavior of the polysaccharide on acid hydrolysis suggest that the molecule consists of a core of repeating units of 1,3 glucosyl-glucose to which short chains of glucose are attached at frequent intervals. Isolation of a disaccharide, the properties of which are identical with those of sophorose (beta1 --> 2 glucosyl-glucose), and of a trisaccharide are described. A tentative structure for the capsular polysaccharide of pneumococcus Type 37 is proposed.

Glucose↗
PubMed1968

Capsulation of pneumococcus with soluble C-like (Cs) polysaccharide. I. Biological and genetic properties of Cs pneumococcal strains.

Capsulated mutants of pneumococcus producing a capsule of soluble polysaccharide related immunologically to the C or cell wall polysaccharide of pneumococcus have been isolated from several noncapsulated variants of this organism. The capsular material of these strains reacts with antisera both to homologous strains and to noncapsulated strains of pneumococcus and with human C-reactive protein. C-reactive protein has been shown to give a positive capsular precipitin or Quellung reaction with C(s) pneumococcal variants and to agglutinate them. The genetic locus which determines the production of C(s) polysaccharide is situated in a region of the pneumococcal chromosome distinct from that controlling normal capsular polysaccharide synthesis. Binary and ternary capsulated pneumococci, one of the capsular components of which is C(s) polysaccharide, have been isolated following DNA-mediated transformation.

Agglutination Tests↗
PubMedDate not supplied

Immune responses to pneumococcal polysaccharide antigens: a comparison of the murine model and the response in humans.

The immune response to pneumococcal polysaccharide antigens has been studied both in mice and, to a lesser extent, in humans. Although there are differences in the immune responses of these two organisms, several major points of similarity have emerged. In both cases the role of the spleen is of importance in mounting an immune response. In both species the presence of certain malignancies causes profound immunosuppression, and treatment of malignancies with radiation and/or cytotoxic drugs results in severe impairment of the host's ability to respond to an immunogenic stimulus and to continue biosynthesis of the specific antibody.

Animals↗
PubMedDate not supplied

Clinical studies of pneumococcal vaccines in infants. II. Efficacy and effect on nasopharyngeal carriage.

Two polyvalent pneumococcal polysaccharide vaccines were evaluated in about 200 infants. Vaccination did not affect nasopharyngeal carriage of pneumococci nor was titer of type-specific antibody, as determined by radioimmunoassay, predictive of subsequent carriage of individual types. Otitis media occurred with equal frequency in vaccinated and in control children. One of four episodes of documented pneumococcal bacteremia occurred after vaccination and was caused by a type contained in the vaccine. No indication of either an efficacious or detrimental effect of pneumococcal polysaccharide vaccines administered to infants was seen in this study.

Antibodies, Bacterial↗
PubMedDate not supplied

Response to pneumococcal vaccine among children with Hodgkin's disease.

Nineteen children with Hodgkin's disease were immuized with dodecavalent pneumococcal vaccine; the efficacy of vaccination, the duration of response, and the significance of the time of immunization in relation to splenectomy and subsequent irradiation and chemotherapy were investigated. Eight children were immunized before splenectomy, and 11 were immunized after splenectomy, irradiation, and chemotherapy. All children were irradiated, and all but two received chemotherapy with MOPP (nitrogen mustard, vincristine sulfate, procarbazine, and prednisone). Sera were assayed for antibodies to the 12 polysaccharide types in the vaccine. The group of children immunized before splenectomy had a significant antibody response to 67% of the antigens tested, whereas the group immunized after splenectomy responded to 40% of the antigens (P less than 0.0001). The duration of response was variable. Pneumococcal vaccine was more likely to provoke an immunologic response if administered before splenectomy than if administered after splenectomy, irradiation, and chemotherapy; however, the response was not uniform. A response to one antigen did not necessarily imply a response to other antigens. In the absence of a readily available assay to determine a protective antibody response, one cannot rely on the vaccine as the sole means of preventing pneumococcal infections in asplenic children with Hodgkin's disease.

Adolescent↗
PubMedDate not supplied

Immunization of immunosuppressed patients with pneumococcal polysaccharide vaccine.

The antibody response after immunization with capsular polysaccharides of Streptococcus pneumoniae of patients with Hodgkin's disease or with carcinoma of the head and neck was studied. Patients with Hodgkin's disease who were immunized prior to the institution of immunosuppressive therapy were capable of responding to each of the pneumococcal polysaccharides evaluated. The level of antibody achieved by the patients is lower than that of normal control subjects. Nevertheless, absolute values were in the range that would be expected to result in protection. The duration of antibody response was not evaluated. Patients with carcinoma of the head and neck did not demonstrate a significant increase in antibody levels after vaccination, which was done at the time of radiation therapy. Two years after immunization antibody levels were lower with recovery at three years. However, these changes were not statistically significant. Decreased levels of antibody to pneumococcal polysaccharide types not present in the vaccine were observed. Studies of patients with carcinoma of the heat and neck demonstrated that radiation therapy has a profound immunosuppressive effect on antibody levels. More selective immunosuppressive therapy and/or an increase in the immunogenicity of the polysaccharides in the vaccine are required for protection of patients with malignancy.

Adolescent↗
PubMedDate not supplied

Serum antibody responses of high-risk children and adults to vaccination with capsular polysaccharides of Streptococcus pneumoniae.

Pneumococcal antibody was measured in the sera of splenectomized children, children with neprotic syndrome, adult with chronic renal failure, adults maintained on hemodialysis, adult recipients of renal allografts, and normal children and adults before and after vaccination with a polyvalent vaccine against Streptococcus pneumoniae. The medical conditions of these patients are associated with increased morbidity and mortality due to pneumococcal disease. Nonimmunosuppressed splenectomized children, children with steroid-responsive nephrotic syndrome, and adults maintained on hemodialysis had normal concentrations of antibody in serum and normal antibody responses to pneumococcal vaccine. Children with steroid-resistant nephrotic syndrome and adult recipients of renal allografts had low concentrations of antibody in serum before and after vaccination but showed an antibody increase after vaccination. During the first year after vaccination of the splenectomized patients, serum antibody concentrations declined linearly by 24%-32% from the peak antibody level. These results suggest that immunization with pneumococcal polysaccharides may reduce the indicence of pneumococcal disease in some high-risk patients but not in others.

Adolescent↗
PubMedDate not supplied

Chemistry and immunochemistry of the pneumococcal polysaccharide vaccine with special reference to cross-reactions and immunologic factors.

This review summarizes data on the cross-reactions observed among the subtypes of Streptococcus pneumoniae. Types 6A and 6B; 19F, 19A, 19B, and 19C; 18F, 18A, 18B, and 18C; and 23F, 23A, and 23B were examined with use of radioimmunoassay for measurement of inhibition of binding; the cross-reactions are discussed in terms of the known chemical structures of the antigens involved. Cross-reactions observed with use of rabbit antisera proved to be an unreliable guide to the responses observed thus far in humans. Cross-reactions of pneumococcal capsular polysaccharide antigens with other bacterial antigens are mentioned. These cross-reactions are analyzed with the idea of maximizing the effectiveness of the pneumococcal vaccine. Immunologic factors that may determine the quality and/or quantity of the immune response to immunization are discussed. These factors include antigenic competition and influence of preimmunization levels of antibody. Antigenic competition, although not a major concern with the present vaccine, may determine the upper limit of the number of capsular types that can be present in a single vaccine. The preimmunization level of antibody may determine the specificity of the antibody produced after vaccination.

Animals↗