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Biomedical subjects

P Anderson

Publications and source records attributed to P Anderson.

At least 487 records · Page 27Linked to original sources
PubMed1977

Antibody of polyribophate of Haemophilus influenzae type b in infants and children: effect of immunization with polyribophosphate.

Antibody to polyribophosphate, the capsular polysaccharide of Haemophilus influenzae type b, was measured in healthy ambulatory children by a radioactive antigen-binding assay. Titers fell from birth through nine months of age, then increased until six years, when they plateaued. Antibody activity was not correlated with the child's sex, ethnic status, or area of residence. Doses of 0.2-50 microgram of polyribophosphate given as single or booster doses had similar effects on antibody activity. Of 368 doses given to infants two to six months of age, 7% produced a significant antibody response; of 95 doses given to infants seven to 12 months old, 17% produced a response. The geometric mean titers of antibody resulting from immunization with polyribophosphate given at various times in relation to diphtheria-pertussistetanus vaccine did not differ significantly from one another or from titers observed in infants given only the latter vaccine. These data indicate that purified polyribophosphate will not provoke humoral immunity in young infants against H. influenzae type b and that it should no longer be considered as a candidate vaccine for this purpose.

Age Factors↗
PubMed1977

Immunogenicity in weanling rabbits of a polyribophosphate complex from Haemophilus influenzae type b.

Polyribophosphate (PRP), the capsular polysaccharide of Haemophilus influenzae type b, is more effectively immunogenic when it is associated with the bacterium than when it is in the purified form that is being tested as a vaccine for humans. In an effort to analyze this difference, we isolated from H. influenzae type b a high-molecular-weight, soluble complex, in which PRP appears to be combined with protein (about 7% protein). The pyrogenicity and limulus lysate gelation activity of the complex suggest that a small amount of lipopolysaccharide also is present. The protein was resolved into five polypeptides by electrophoresis in polyacrylamide gel containing sodium dodecyl sulfate. In weanling rabbits, which do not respond to purified PRP, the complex induces high titers of antibody of PRP, in an anamnestic pattern. Bactericidal antibody to other bacterial components was also elicited. Equilibrium density gradient centrifugation of the complex indicated that most of the immunogenicity of PRP resides in the least dense fractions, which are high in protein, low in polysaccharide, and active in the limulus lysate test; denser fractions that react strongly with limulus lysate but are poor in protein were much less immunogenic.

Animals↗
PubMed1977

Isolation of the capsular polysaccharide from culture supernatant of Haemophilus influenzae type b.

The capsular polysaccharide (CP) of Haemophilus influenzae type b is known to be spontaneously released from the cells in culture. The CP is precipitable from culture supernatant by the cationic detergent hexadecyltrimethylammonium. Most of the nucleic acid and some of the protein, but almost none of the endotoxin, in the supernatant are co-precipitated. Extraction of the precipitate with progressively stronger NaCl solutions separates nucleic acid and protein from the CP and also effects a molecular size fractionation. Residual endotoxin and protein can be reduced by extraction with cold phenol and ultracentrifugation. The resulting preparation has ribose, ribitol, and phosphate as principal components and contains less than 1% other sugars, protein, or nucleic acid; it elutes on Sepharose 2B as a symmetrical peak with Kav 0.51.

Chemical Precipitation↗
PubMed1976

Synthesis and release of polyribophosphate by Haemophilus influenzae type b in vitro.

Polyribophosphate, the capsular polysaccharide antigen of Haemophilus influenzae type b, can be assayed in crude bacterial extracts by a combination of immunoprecipitation, hot-acid extraction, and colorimetry. In vitro, the antigen is synthesized during growth and, in well-buffered media, in early stationary phase as well. It is shed from the cell throughout the course of synthesis, and at 37 C almost all the extractable antigen has been released spontaneously within several hours after synthesis. Various strains are similar in extent of synthesis and gross composition of the antigen; however, strains differ in the rate of release during exponential phase. The antigen is released as (or as part of) a very large structure, although under certain culture conditions much smaller antigenic units are found.

Antigens, Bacterial↗
PubMed1976

The paradox of Hemophilus infuenzae type B bacteremia in the presence of serum bactericidal activity.

We investigated the role of serum bactericidal activity in Hemophiplus influenzae type b infections in infants with meningitis and in a rat model. In infected infants, 13/22 admission sera had bactericidal activity against the infecting strain, and bacteremia was as frequent in those with bactericidal activity (54%) as those without (56%). The coexistence of bactericidal activity and bacteremia was reproduced and studied in experimentally infected weanling rats. Serum from such rats kills in vitro 95% of conventionally broth-grown bacteria within 10 min, but does not kill organisms obtained from the infected animals. Thus bactericidal activity as conventionally determined for H. influenzae b may have no relevance in vivo, Incubation of broth-grown bacteria in normal rat serum for 30 min at 37 degrees C produces a resistance like that of in vivo organisms. This phenotypic conversion depends on factors that are of molecular weight less than 1,000, stable to 100 degrees C, but destroyed by ashing. When injected intravenously into nonimmune animals, broth-grown bacteria are quickly cleared, while serum-preincubated bacteria are not. The latter, however, are cleared when injected into bacteremic rats (half-life 30 min). Bacteremia in the rats may persist despite this capacity for clearance because bacteria are entering the blood from extravascular fluids, which contain greater than 90% of the total bacterial burden.

Animals↗
PubMed1975

Two generators of hippocampal theta activity in rabbits.

Spontaneous and hypothalamically induced theta activity was studied in rabbits lightly anaesthetized with urethane or urethane-chloralose. Well-developed theta activity was found over a large area of the dorsal part of the hippocampal formation, roughly corresponding to the CA1 field. Cross-correlation analysis between a stationary and a moving electrode showed that a large sheet of tissue oscillated in remarkable synchrony. This region was at least 8 mm along the longitudinal axis of the hippocampus and 6 mm in a plane transverse to this axis, thus comprising the whole of the rostro-caudal extension of the CA1 region. For technical reasons the temporal half was not explored. Depth recordings showed two foci of theta activity, one in the basal part of CA1 (stratum oriens) and a second, separate region with considerably larger amplitudes in the dentate region, having its maximum in the molecular layer. Due to the folded nature of the dentate fascia, an electrode often recorded two maxima corresponding to its upper and lower blades. Wave form analysis showed that the dentrate and CA1 rhythmic activity was roughly 180 degrees out of phase. The dentate theta activity remained in conditions where the CA1 theta activity was absent, either spontaneously or due to experimental interference. Systematic micro-electrode tracking showed absence of theta activity in the CA3 region. Nor was convincing theta activity found in the subiculum, parasubiculum, presubiculum or entohinal areas.

Animals↗
PubMed1975

Selective localization of histamine to electron dense granules in antigen-challenged sensitized rat mast cells and to similar granules isolated from sonicated mast cells. An electron microscope autoradiographic study.

The subcellular localization of histamine was studied in sensitized rat mast cells following antigen challenge and in granules obtained from sonicated cells, using an electron microscope autoradiographic technique. The mast cells were furnished with labelled histamine by incubation in 3-H-histidine. The silver grain distribution (reflecting the radioactive histamine) was highly non-random. The highest silver grain densities occured over homogeneous, electron dense (normal) granules and moderately electron dense granules. Swollen, less electron dense ("changed") granules with a reticular appearance and devoid of a limiting membrane had the lowest density of all subcellular structures studied and were therefore probably almost free of histamine. There was a good correlation between the percentage of electron dense granules, the histamine content and the silver grain density insaline-washed granule fractions isolated after sonication of mast cells for different times. These results support the hypothesis that histamine release occurs during the sequential exocytosis of storage granules, and during the sonication of mast cells, probably as a cation exchange between the amine, which is ionically bound to the heparin-protein complex of the granule matrix, and cations from the extracellular fluid. The exchanges will occur as soon as the perigranular membrane becomes premeable to water and cations.

Albumins↗
PubMed1975

Circulating polyribophosphate in Hemophilus influenzae, type b meningitis. Correlation with clinical course and antibody response.

In systemic infections caused by Hemophilus influenzae, type b, the capsular polysaccharide, polyribophosphate, is released into the circulation. Polyribophosphate was quantitated in serial serum and cerebrospinal fluid samples from 45 children with H. influenzae, type b meningitis by means of a radiolabeled antigen-binding inhibition assay. Polyribophosphate was regularly found in acute serum and cerebrospinal fluid samples and could be detected in unbound form for periods of 1-30 days after initiation of effective therapy. Complexes of polyribophosphate dissociable with acid and pepsin were detected in serum samples from 17 patients, in one case for a period of 145 days after hospitalization. Polyribophosphate levels and patterns of clearance were studied in relation to hospital course and antibody response. Patients with prolonged antigenemia had protracted fevers and severe neurological symptoms during hospitalization, frequently with focal complications.Antipolyribophosphate antibody responses were detected during the first 100 days of convalescence by radioimmunoassay in 79% of the patients studied, including 60% of the children 1 yr or less in age. The intensity of antibody response although clearly related to the age of the patient, was more reliably predicted by the efficiency of antigen clearance. Antibody responses were uniformly of low magnitude in patients with prolonged antigenemia, irrespective of age. Paients who failed to develop antibody to polyribophosphate after meningitis also exhibited impaired antigen clearance. These studies suggest that mechanisms necessary for clearance of polyribophosphate may influence the development and intensity of the humoral immune response and raise the possibility of developmental deficiencies in the clearance system in infants and children.

Age Factors↗
PubMed1975

Antibody responses to a combination vaccine against Haemophilus influenzae type b, diphtheria, pertussis, and tetanus.

Forty-one children were studied in order to provide information on antibody responses to H. influenzae type b polyribophosphate (PRP), given in combination with diphtheria-pertussis-tetanus vaccine (DPT). When PRP was administered alone, 9 of 15 children demonstrated fourfold or greater increases in titres of anti-PRP antibody. In contrast, in the group receiving a combination vaccine consisting of DPT and PRP only 1 of 13 children showed a similar rise in anti-PRP antibody. It was concluded that, in the population studied, the combination vaccine was less effective than PRP alone. The reasons for this difference and its potential significance are discussed.

Antibody Formation↗