Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fifteen children with previous invasive Haemophilus influenzae type b disease were immunized with a Hemophilus-diphtheria toxin mutant protein conjugate vaccine. Serologic responses were compared with those of 31 newly immunized children without previous invasive H influenzae type b disease. Mean levels of antibody to polyribosylribitol phosphate among study children younger than 18 months were 0.086 mg/L before immunization, 0.737 mg/L after first immunization, and 4.453 mg/L after second immunization. In contrast, the comparable mean polyribosylribitol phosphate antibody levels among control children younger than 18 months were 0.107, 3.580, and 63.502 mg/L. A similar pattern of results was found among children aged 18 months or older. Although children with previous invasive H influenzae type b disease do not respond as vigorously to conjugate vaccine as do previously healthy controls, the response is sufficient to justify routine immunization of such children.
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PMID:Immunization after invasive Haemophilus influenzae type b disease. Serologic response to a conjugate vaccine. 278 56

Vaccines consisting of oligosaccharide (OS) derived from Haemophilus influenzae type b capsular polysaccharide and conjugated to carrier proteins had been shown capable of eliciting memory-type capsular polysaccharide of H. influenza type b antibody responses in human infants, but the structural variables governing immunogenicity were not defined. Here a series of conjugates were made with the diphtheria protein CRM197 and with uniterminally coupled OS haptens that varied in chain length, exposed terminal residue, or multiplicity of loading as defined by ribose/protein ratio. Adults were given a single injection, 1-yr-old infants were given a two-injection sequence, and capsular polysaccharide of H. influenzae type b antibody responses were assessed by radioantigen binding. Vaccines C-4r, C-6r, and C-12r, in which ribitol-ended OS of mean length 4, 6, or 12 repeat units were coupled at low hapten loading, were about equally immunogenic (geometric means 2 to 5 micrograms/ml in infants, 5 to 9 micrograms/ml in adults). Vaccine C7p was made with a higher loading of OS having mean length 7 repeat units and having mainly phosphate monoester at the exposed termini Vaccine C-7R was made from a portion of C-7p by enzymatic removal of most of the terminal phosphates. Compared to the C-4r, C-6r, and C-12r series, vaccines C-7p and C-7R induced geometric means about 10-fold higher in adults and 20-fold higher in infants. Thus OS chain length (in the range studied) and exposed terminus are less critical variables in this system than the extent of hapten loading.
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PMID:Effect of oligosaccharide chain length, exposed terminal group, and hapten loading on the antibody response of human adults and infants to vaccines consisting of Haemophilus influenzae type b capsular antigen unterminally coupled to the diphtheria protein CRM197. 278 64

Fifty-seven children ages 1 month to 12 years hospitalized because of community-acquired pneumonia were compared with age-matched controls who had acute asthma without pneumonia to test the value of rapid bacterial antigen detection and clinical and radiographic criteria for diagnosis of bacterial pneumonia. Bacterial pneumonia, defined on the basis of positive cultures of blood or pleural fluid, was diagnosed in 4 children (7%), 1 of whom also had viral pneumonia. Viral pneumonia, defined as a positive nasopharyngeal sample or positive serology, was diagnosed in 20 children (35%). Serum and concentrated urine were tested by latex agglutination (Wellcogen) for Haemophilus influenzae type b and pneumococcal antigens and by countercurrent immunoelectrophoresis for pneumococcal antigens. Pneumococcal antigen could not be detected in serum or urine from 3 children with culture-proved pneumococcal pneumonia, indicating poor sensitivity of the tests. In contrast apparent H. influenzae type b antigenuria was detected by latex agglutination in 4 of 40 children with pneumonia but also in 5 of 57 controls, and a sensitive enzyme-linked immunosorbent assay for polyribosyl ribitol (PRP) phosphate antigen showed that all 9 cases were false positives. The specificity of H. influenzae type b antigen detection was thus poor. Children with viral and bacterial pneumonia could not be distinguished by radiographic or clinical criteria (symptoms, fever) or by total or differential white blood cell counts, serum C-reactive protein or nasal or serum interferon levels. It is not possible to distinguish reliably childhood viral from bacterial pneumonia clinically or by rapid diagnostic tests.
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PMID:Problems in determining the etiology of community-acquired childhood pneumonia. 278 61

A Haemophilus influenzae type b (Hib) capsular polysaccharide (polyribosylribitol phosphate, PRP)/diphtheria toxoid (D) conjugate vaccine was given to 71 infants. The level of anti-PRP antibody believed to predict long-term protection, 1.0 microgram/ml, was reached in 50% of the infants who were vaccinated at 3, 5, and 7 months, and in 57% of the infants who received PRP-D at 7 and 9 months of age. A lower level of antibody, 0.15 micrograms/ml, which has been associated with protection at the time of assay, was reached in 92% and 87% of the two groups. Thus, the seroresponse was dependent upon both the frequency of immunisation and age of the infant. Comparison of these results with previous experience with PRP immunisation in Finland showed that PRP-D induced substantial antibody rises at an earlier age than did PRP.
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PMID:Antibody levels achieved in infants by course of Haemophilus influenzae type B polysaccharide/diphtheria toxoid conjugate vaccine. 286 Mar 87

The outer membrane (OM) component(s) from Bordetella pertussis which potentiated the antigenicity of purified Haemophilus influenzae type b capsular polysaccharide, polyribosyl ribitol phosphate (PRP), has been isolated and partially characterized. The OM was isolated from spheroplasting medium by precipitating at pH 5.0; fractionation was carried out by dissolving the crude OM in Triton X-100 followed by selective precipitation of OM in 50% ethanol. Further purification of OM was accomplished by DEAE-Sepharose 6BCL and Sephacryl S-300 chromatography. The biochemical composition and protein profiles on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of various OM preparations have been examined. Combined vaccines consisting of OM components and PRP were given to young Sprague-Dawley rats, and the serum antibody to PRP was measured by an [3H]PRP binding assay. The purified OM containing mainly a 30,000-dalton protein, but not purified lipopolysaccharide or leukocytosis-promoting toxin, exhibited strong enhancement of PRP immunogenicity.
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PMID:Isolation of the outer membrane components of Bordetella pertussis which enhance the immunogenicity of Haemophilus influenzae type b capsular polysaccharide polyribosyl ribitol phosphate. 286 92

The 2':3'-cyclic nucleotide phosphodiesterase:3'-nucleotidase of Haemophilus influenzae was purified from a periplasmic preparation by affinity chromatographic techniques. The enzyme-catalysed hydrolysis of 2':3'-cyclic AMP to adenosine without accumulation of the intermediate substrate 3'-AMP was demonstrated by high performance liquid chromatography. Competitive inhibition of the enzyme by a variety of nucleosides and mononucleotides indicated the presence of either purine or pyrimidine bases to be essential for selective interactions with the enzyme, and confirmed the need for a 3'-position phosphate for the functioning of mononucleotides as substrates for the enzyme. The enzyme had a molecular weight of 79 000, was stable at low temperatures and was thermally denatured at temperatures above 50 degrees C.
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PMID:Studies of the 2':3'-cyclic nucleotide phosphodiesterase of Haemophilus influenzae. 299 67

The mechanism(s) by which the lipopolysaccharide (LPS) of Haemophilus influenzae type b may contribute to the virulence of this organism is unclear. Purified LPS of Haemophilus influenzae type b or phosphate buffered saline was administered intranasally to infant rats prior to the intranasal instillation of approximately 2-20 x 10(6) cfu of Hib two or three times per day for three consecutive days. The preadministration of 2.0 micrograms Hib LPS resulted in a significantly greater incidence of bacteremia (P = 0.0006) than PBS 30 min after the completion of the intranasal inoculation. Four days following completion of intranasal Hib inoculation the incidence of bacteremia was greater (P = 0.017) in the animals pretreated with LPS at 2.0 micrograms compared to the PBS pretreated animals. Preadministration of 0.2 micrograms LPS had no effect on the incidence of bacteremia or meningitis. There were no differences in the histology of the nasal cavities or turbinates of infant rats inoculated intranasally only with LPS or PBS. There were no differences in the frequency or density of bacteremia following intranasal administration of LPS from either Hib or E. coli. Although the mechanism is unknown, our findings suggest that the LPS of Hib may contribute to the ability of H. influenzae type b to invade the nasal mucosa in this infant rat model.
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PMID:Contribution of Haemophilus influenzae type b lipopolysaccharide to pathogenesis of infection. 307 63

Human antibodies specific, for polyribosyl-ribitol-phosphate (PRP), the capsular polysaccharide of Hemophilus influenzae b, were studied using idiotypic analysis. Antisera were prepared against purified F(ab')2 anti-PRP from two unrelated adults, H.H. and P.T. After repeated absorption with IgG myeloma proteins and with PRP-absorbed normal human Ig and donor Ig, anti-idiotypic (anti-Id) sera were obtained that specifically reacted with anti-PRP antibodies. Anti-IdHH and anti-IdPT reciprocally crossreacted with H.H. and P.T. anti-PRP antibodies and F(ab')2 fragments, and also reacted with the serum anti-PRP antibodies from three additional adults unrelated to P.T. and H.H. Both anti-Id sera partially inhibited anti-PRP paratopes but not anti-tetanus toxoid paratopes. PRP did not inhibit anti-Id recognition of shared or crossreactive idiotypic (CRI) determinants. Naturally occurring and PRP immunization-induced anti-PRP antibodies expressed CRI. While CRI titer increased after immunization, the increase was usually less than the rise in total anti-PRP antibody. Quantitative differences in CRI expression were also apparent between natural and immunization-induced H.H. and P.T. anti-PRP antibodies as shown by their differential inhibitability by anti-Id. Our data demonstrate that anti-PRP antibodies from five unrelated adults express CRI determinants that are probably distant from the PRP combining site. Naturally occurring and immunization-induced anti-PRP antibodies share CRI and therefore appear to be clonally related, although immunization apparently induces the expression CRI-negative antibodies as well. These results, taken with previous studies showing restricted and identical anti-PRP isoelectric focusing spectrotypes in unrelated adults, suggest that some PRP-specific V domains are structurally conserved and probably germ-line encoded.
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PMID:Expression of crossreactive idiotypes by human antibodies specific for the capsular polysaccharide of Hemophilus influenzae B. 325 99

Human neutrophils contain large amounts of a neutral serine protease, human neutrophil elastase (HNE), which has been implicated as a mediator of acute and chronic lung injury. We found that this enzyme is effectively inhibited, at physiological ionic strength, by several synthetic non-base-paired polyribonucleotides. Among the most active of these is polyguanylic acid (poly G). Inhibitory activity is greatest with high-molecular-weight poly G fractions, but poly G fractions even as low as 60K Mr (app) are effective. Both amidolysis of synthetic elastase substrates, such as succinyl-ala-ala-ala-p-nitroanilide, and proteolysis of elastin are blocked. Poly G inhibits elastin proteolysis even when subsequently added to mixtures of elastin and HNE that have first been preincubated together for 10 min. Under these conditions, polyribosylribitol phosphate, a polyanion derived from Haemophilus influenzae capsular polysaccharide, is not inhibitory. Complex formation between HNE and poly G is dependent on ionic rather than covalent interactions, since it is blocked by 0.6 M NaCl but not by inactivation of the enzyme's catalytic-site serine residue with diisopropylfluorophosphate. However, nonspecific ionic interactions alone cannot explain complex formation, since pancreatic elastase and cathepsin G, an even more basic serine protease from human neutrophils, do not form complexes with poly G, even at low ionic strength. Moreover, in the presence of the amphiphiles taurocholic acid and glycocholic acid, HNE is much less effectively blocked by poly G. Peptide chloromethyl ketone-inactivate HNE (which has its extended substrate-binding pocket occupied by the peptidyl inactivator) also fails to form complexes with poly G. These results indicate that HNE may utilize both hydrophobic and ionic binding sites to couple with poly G, and suggest that these sites may be close to or within the extended substrate-binding pocket of the enzyme.
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PMID:Inhibition of human neutrophil elastase by polyguanylic acid and other synthetic RNA homopolymers. 325 33

To determine the in vitro and in vivo activity of human antibody induced by different Haemophilus influenzae type b (Hib) vaccines, pooled human antisera obtained from adults immunized with either polyribosyl ribitol phosphate (PRP) or PRP-conjugated with diphtheria toxoid (PRP-D) vaccines were evaluated for opsonic and protective activity against Hib. In vitro, opsonophagocytic studies revealed that PRP-D induced antisera were approximately 2.5-fold more effective than PRP-induced antisera in supporting neutrophil-mediated killing of an Hib strain. In vivo studies using the infant rat model or Hib disease revealed that the decay of PRP antibody was similar with PRP or PRP-D induced antisera in unchallenged rats. However, in infant rats challenged with Hib, the PRP induced antibody decayed more rapidly than the PRP-D induced antibody as shown by significantly shorter half-life of the former. The protective efficacy was significantly greater with the PRP-D induced antisera than with the PRP induced antisera. This finding was shown by the significantly lower incidence of bacteraemia and the 5-fold lower dose of antibody required for 50% protection against bacteraemia in rats receiving the PRP-D induced antisera. The findings suggest that antibody to PRP induced by PRP-D vaccine is more opsonic and protective against Hib, and also decays more slowly in infant rats challenged with Hib than does antibody induced by PRP vaccine. Further studies are needed to elucidate the reason(s) for this difference in functional activity and in half-life of PRP antibody induced by PRP or by PRP-D vaccines.
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PMID:Functional activities of human antibody induced by the capsular polysaccharide or polysaccharide-conjugate vaccines against Haemophilus influenzae type b. 325 59


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