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Biomedical subjects

G Schiffman

Publications and source records attributed to G Schiffman.

At least 109 records · Page 6Linked to original sources

Function of the replanted spleen in dogs.

The function of replanted splenic fragments was studied by comparing three groups of five dogs each, one group with intact spleens; one, post-splenectomy; and one with splenic replantation. Fifteen fragments were implanted into the omentum. Howell-Jolly bodies appeared after splenectomy but cleared in the replanted group after several months. I125-tagged attenuated pneumococcal clearance studies showed a significant difference between control and replanted group compared with the splenectomized group. The increase of pneumococcal antibody titers after vaccination differed significantly between the splenectomized and the replanted group. All replanted fragments were viable and showed growth over a 2-year period. These studies demonstrate that omental replantation of the canine spleen leads to the maintenance of certain functional splenic parameters comparable to the normal spleen which are significantly different from the splenectomized animal.

Animals↗

Bone marrow transplantation in the Wiskott-Aldrich syndrome. Complete hematological and immunological reconstitution.

A 21-month-old boy with the Wiskott-Aldrich syndrome conditioned with cyclophosphamide and dimethyl myleran received bone marrow from an HLA-matched sibling. Complete hematological chimerism was achieved. During the first 3 months after transplantation, in vitro B cell function, measured by a direct plaque assay, was abnormal, T cell helper activity impaired, and suppressor T cell function was excessive. These abnormalities resolved gradually over 16 months. Antibody responses to the T-dependent antigen, bacteriophage phi X174, were initially low, then became normal; antibody responses to keyhole limpet hemocyanin (KLH) and to 4 of 12 type-specific pneumococcal polysaccharide antigens were adequate when studied 9 months after transplantation. The clinical response was excellent: the patient has been free of infection, no longer has a bleeding tendency, and has shown normal growth and development.

Antibody Formation↗

Antibody response to vaccination with pneumococcal capsular polysaccharides in splenectomized children.

In 67 splenectomized children vaccinated with a 14-valent pneumococcal capsular polysaccharide vaccine an antibody fold increase above 2 from pre- to postvaccination samples was found in 60% of all single type antibody determinations performed. The vaccine may only afford protection against 55% of those serotypes that cause serious infections in children, assuming a protective antibody level of 300 ng antibody N/ml. Our results indicate a somewhat reduced antibody response to pneumococcal vaccine in splenectomized children and suggest that pneumococcal vaccination may not be relied upon as the only kind of prophylaxis against pneumococcal infection in this patient group.

Adolescent↗

Cross-immunogenicity of pneumococcal group 9 capsular polysaccharides in adult volunteers.

Group 9 organisms (types 9N, 9A, 9L, and 9V) account for about 3 to 4% of pneumococcal disease isolates throughout the world. Types 9N and 9V comprise about 90% of the group 9 disease isolates. Type 9N is more common than type 9V in adults, and type 9V predominates in infants and children. In the United States there have been eight reported cases due to group 9 pneumococci in individuals previously vaccinated; six were type 9V and two were type 9N. To ascertain the cross-immunogenicity of group 9 polysaccharides, volunteers were injected with vaccines of monovalent types 9N, 9A, 9V, or 9L, or bivalent (9N and 9A) or trivalent (9N, 9A, and 9V) polysaccharide vaccines. Monovalent types 9N, 9V, and 9L each stimulated a 5.8- to 7.5-fold geometric mean rise, and at least 80% of the volunteers responded with a twofold or greater homologous antibody rise. Type 9V induced a 5.8-fold geometric mean rise, but only 66% of the volunteers responded with a twofold or greater homologous antibody rise. Type 9N induced only a 2.1-fold geometric increase, and only 54% of the volunteers responded with a twofold or greater rise in anti 9V antibodies. Types 9L and 9A were the most cross-immunogenic. The trivalent preparation (9N, 9A, and 9V) gave the highest geometric mean titer and seroconversion rate to each of the group 9 polysaccharides. These results suggest that the polyvalent pneumococcal vaccine with its type 9N does not induce a satisfactory anti-type 9V response and should contain additional components in order to achieve greater protection against group 9 organisms.

Adult↗

Antibody responses in adult volunteers to pneumococcal polysaccharide types 19F and 19A administered singly and in combination.

The immunogenicity of the two major group 19 pneumococcal polysaccharides, types 19F and 19A, was studied in human volunteers. Antibody responses after vaccination with either 50 micrograms of type 19F polysaccharide, 50 micrograms of type 19A polysaccharide, or 25 micrograms of both polysaccharides premixed in a single injection revealed that the combined vaccine was immunogenic for both types, but that the optimal immunogen for each was the homologous polysaccharide. We concluded that vaccination with type 19F polysaccharide antigen, included in the current pneumococcal vaccine, does not induce a satisfactory heteroimmunogenic response to type 19A.

Antibodies, Bacterial↗

The presence of sialic acid on two related bacterial polysaccharides determines the site of the primary immune response and the effect of complement depletion on the response in mice.

We have examined the antibody responses in mice to two structurally similar antigens: the capsular polysaccharide of type 3 group B streptococci (sssGBS 3) and the capsular polysaccharide of type 14 pneumococci (sssPn 14), which differ only in the presence of a terminal sialic acid on the side chain of the former. The cells that produce antibody to the nonsialated antigen (sssPn 14) reside in the spleen, whereas the cells that produce antibody to the sialated antigen (sssGBS 3) do not. Cobra venom factor treatment of the mice before immunization abrogates the antibody response to the nonsialated antigen, but does not affect the response to the sialated antigen.

Animals↗

Serum antibody response to pneumococcal vaccine in children with nephrotic syndrome.

Children with nephrotic syndrome are susceptible to serious pneumococcal disease and may be immunodeficient on the basis of abnormal humoral immune responses to natural antigens or immunoglobulin loss during relapse. As part of an ongoing study to evaluate pneumococcal anticapsular antibody concentration and immunologic competence, 27 steroid-responsive and six steroid-resistant patients with nephrotic syndrome, and 12 age-matched control subjects, were vaccinated with polyvalent pneumococcal vaccine. Antibody responders were defined as patients with at least a twofold increase in antibody after vaccination as well as an antibody concentration greater than 200 ng of anticapsular antibody nitrogen per milliliter (ngN/ml) after vaccination. Pneumococcal antibody concentrations before and after vaccination were significantly depressed in steroid-resistant patients when compared with control subjects (P less than .002) and with the steroid-responsive nephrotic syndrome group (P less then .001). Steroid-responsive nephrotic children who were not receiving corticosteroid therapy at the time of vaccination had significantly higher antibody concentrations to five pneumococcal types before vaccination and to seven types after vaccination compared with control subjects (P less than .05). Fewer steroid-responsive patients receiving corticosteroids achieved antibody concentrations greater than or equal to 200 ngN/ml against type 19F compared with patients not receiving steroids or with control subjects (P less than .05). These results suggest that pneumococcal vaccine is immunogenic in children with steroid-responsive nephrotic syndrome and may protect these patients from disease due to pneumococcal types contained in the vaccine.

Adolescent↗

Effect of anesthesia and splenectomy on antibody response to pneumococcal polysaccharide immunization.

Whether anesthesia-induced immunosuppression and postsplenectomy decreased antibody response are important in the timing of postsplenectomy pneumococcal vaccination was tested in 57 inbred 150 to 175 gm Fischer 344 rats immunized three weeks preoperatively (Group 1), immediately after anesthesia (Group II), and three weeks postoperatively (Group III). Groups IV and V were not immunized. All rats had splenectomy and one hour of 1 per cent halothane anesthesia. After intraperitoneal immunization of the rats with 5 mu g of Type III pneumococcal polysaccharide, weekly serum antibody levels were determined by radioimmunoassay. Six weeks postoperatively, Groups I through IV received an intravenous LD50 dose of Type III pneumococcus; Group V was challenged one week after operation. Survival was assessed every 12 hours for one week. Antibody responses among the groups were statistically equal, except on day 4 and day 26 postimmunization. On day 4, Group I had higher levels than Groups II and III (P less than .05), showing the spleen's role in early antibody production, and on day 26, Group I had much lower levels than Group II (P less than .05), indicating a short-term depressive effect of anesthesia and operation on ongoing antibody formation. Survival was equal among Groups I through IV. Survival in Group V was poorer than in Group IV (P less than 0.5), probably indicating that nonsplenic sites had acquired an enhanced ability to clear pneumococcus. The study shows, therefore, that anesthesia and splenectomy do not affect the timing of pneumococcal vaccination postsplenectomy.

Anesthesia, Inhalation↗

Polyvalent pneumococcal immunization of patients with plasma cell dyscrasias.

Thirteen patients with plasma cell dyscrasias and 27 healthy adults were immunized with polyvalent pneumococcal vaccine. Antibody responses were determined by radioimmunoassay. Patients with plasma cell disorders had significantly lower preimmunization and postimmunization antibody titers compared with those of the controls (P-0.01 abd 0.008, respectively). Even though the overall response in myeloma patients was poor, occasional rises in antibody titers occurred. Immunizing myeloma patients with the pneumococcal vaccine is recommended.

Aged↗

Recurrent pneumococcal otitis media in the chinchilla. A longitudinal study.

To define the relative importance of the local and systemic immune mechanisms in otitis media, middle ear infections were induced in 47 chinchillas by unilateral intrabullar inoculation of Streptococcus pneumoniae type 6A. Bacterial challenges were repeated ipsilaterally or contralaterally several times during the five-month course of the study. The middle ear condition was assessed with the use of otomicroscopy, tympanometry, and direct inspection and culture through a bullar opening. Pneumococcal 6A antibodies were assayed periodically in the serum and middle ear effusions. The concentration levels of serum antibodies did not correlate with the course of otitis media, and antibiotics did not protect either the ipsilateral or contralateral ear from infection. There was a minimal number of bacteria that rendered the middle ear resistant to subsequent infection. This resistance was a local phenomenon and occurred only when the middle ear had previously been exposed to the same bacteria.

Animals↗

Pneumococcal vaccination in patients with chronic renal disease and renal allograft recipients.

Polyvalent pneumococcal vaccine was administered to 7 patients with chronic renal failure, 14 patients on chronic hemodialysis, 14 splenectomized and 11 nonsplenectomized renal allograft recipients, and 14 normal adults. Ninety-three percent of normal subjects had at least a twofold rise in serum antibody concentration after vaccination, with a geometric mean antibody concentration after vaccination greater than 200 ng N/ml. The response to vaccination in hemodialysis patients was similar to that in normal persons. Renal failure patients showed impaired antibody synthesis in response to the vaccine, with 43% achieving at least a twofold rise in antibody concentration. Allograft recipients had a lower antibody concentration before as well as after vaccination, and among splenectomized recipients the prevaccination antibody concentration was directly related to the interval between transplantation and antibody determination. But, 80% of allograft recipients achieved a twofold rise in antibody concentration after vaccination. The response to pneumococcal vaccine was quantitatively similar for splenectomized and nonsplenectomized allograft recipients.

Adolescent↗

Antibody response to pneumococcal vaccine in patients with multiple myeloma.

Patients with multiple myeloma and Waldenström's macroglobulinemia respond poorly to antigenic stimuli and may not be protected by pneumococcal vaccine. Thirty-seven patients and 10 controls received 14-valent pneumococcal capsular polysaccharide vaccine. The patients had lower (P less than 0.01) titers of antibody to 11 of the 12 antigens assayed before vaccination and to 10 of 12 antigens (P less than 0.01) after vaccination than did controls, but the ratios of antibody titers before vaccination to those after vaccination were remarkably similar. A poorer antibody response was observed in patients receiving multiagent chemotherapy than in those receiving chemotherapy with alkylating agents (P less than 0.01 for six of the antigens). That these patients did respond to the vaccine (although titers of antibody after vaccination were significantly lower than those in controls) suggests that patients with multiple myeloma or macroglobulinemia may benefit from pneumococcal vaccine.

Aged↗

Epidemiologic studies of Streptococcus pneumoniae in infants: antibody response to nasopharyngeal carriage of types 3, 19, and 23.

The relationship between nasopharyngeal carriage of Streptococcus pneumoniae types 3, 19, and 23 and the development of homotypic serum antibody was examined in 17 infants followed prospectively from birth. Serially drawn sera from these children and single serum samples from 18 normal adolescents were assayed for opsonizing antibody using reduction of nitroblue tetrazolium to measure phagocytosis of killed whole pneumococci. Selected sera were also tested for quantitative antibody level by a radioimmunoassay, which correlated quite well with the nitroblue tetrazolium assay. All but one of the adolescents had antibody to type 19, and all 18 had antibody to type 23. None of the 12 infants tested for antibody to type 19 pneumococci showed evidence of an antibody response. Two of 10 infants responded to type 23 pneumococci, as did two of three infants tested to type 3 pneumococci.

Antibodies, Bacterial↗

Serum antibody and opsonic responses after immunization with pneumococcal vaccine in kidney transplant recipients and controls.

We immunized 31 renal transplant patients and 6 control subjects with a pneumococcal vaccine containing 14 capsular polysaccharides. Antibody levels to Streptococcus pneumoniae types 3 and 6A were measured by a radioimmunoassay, and opsonic activity to S. pneumoniae types 3 and 6B was determined by using a luminol-enhanced chemiluminescence phagocytic assay on serum samples obtained before and 1 month after immunization. There was a 10.2-fold and a 2.9-fold increase in antibody to S. pneumoniae type 3 (P less than 0.005) and type 6A (P less than 0.01), respectively, but only a 1.3-fold (P greater than 0.05) and 1.1-fold (P greater than 0.05) increase in opsonic activity. For S. pneumoniae type 3, changes in opsonic activity correlated well with antibody concentration (P less than 0.05). However, for S. pneumoniae type 6, these two tests correlated poorly (P greater than 0.05). This poor correlation suggests that concentrations of antibody to type 6A polysaccharide which are achieved after immunization may not be opsonically active in vitro against S. pneumoniae type 6B.

Antibodies, Bacterial↗

Pneumococcal immunization in adult diabetics.

The antibody responses of 102 adult insulin-treated diabetics who received 14-valent pneumococcal polysaccharide vaccine were measured. Grand mean preimmunization antibody levels were similar for diabetics, 255 ng protein N/ml, and controls, 234 ng protein N/ml. Postimmunization, the values in the diabetics, 1009 ng protein N/ml, and 834 ng protein N/ml in 48 healthy controls, were not significantly different. The height of antibody response in the diabetic group did not correlate with age, sex, duration of diabetes, insulin dose, concentration of glycosylated hemoglobin, fasting or 2-h postprandial glucose concentrations, or the presence of retinopathy. Side effects were minimal and occurred in 26%. Antibody response to pneumococcal polysaccharide vaccine is not impaired in adult diabetics. Pneumococcal immunization is safe and may reduce the frequency of pneumonia and its complications in the diabetic population.

Adult↗