Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the agents associated with acute lower respiratory infection in young children, we studied 102 hospitalized children less than 5 years old using culture and serology for viruses and Chlamydia trachomatis, fluorescent antibody testing for pertussis and respiratory syncytial virus, blood cultures and counterimmunoelectrophoresis of nasopharyngeal secretions and urine for pneumococcal and Haemophilus influenzae type b antigens. At least one agent was detected in 87 children and multiple agents were found in 33. Viruses were detected 80 times; respiratory syncytial virus was most common (61 cases) and was detected as often by fluorescent antibody testing as by culture. C. trachomatis was detected in 10 children; all were less than 4 months old and 9 had mixed infections. Bacteria were detected 32 times, were usually pneumococcus (23) or H. influenzae (5) and were detected more often by counterimmunoelectrophoresis than by blood culture. Compared with children yielding only C. trachomatis or viruses, those with bacteria were significantly more likely to have fever, a band count over 2000/mm3 and radiographic consolidation. In this study acute lower respiratory infection was associated commonly with viruses, often with multiple pathogens but not with C. trachomatis after 4 months of age.
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PMID:Pathogens associated with acute lower respiratory tract infection in young children. 670 Nov 1

In addition to Ipa proteins and IcsA, which are involved in entry into epithelial cells and intercellular spread, respectively, Shigella secretes a 110 kDa protein, designated SepA. We report the identification, cloning, and nucleotide sequence determination of the sepA gene, analysis of SepA secretion, and construction and characterization of a sepA mutant. The sepA gene is carried by the virulence plasmid and codes for a 150 kDa precursor. Upon secretion, which does not involve accessory proteins encoded by the virulence plasmid, the precursor is converted to a mature protein of 110 kDa by two cleavages removing an N-terminal signal sequence and a C-terminal fragment. Extensive similarities were detected between the sequence of the first 500 residues of mature SepA and the N-terminal region of IgA1 proteases from Neisseria gonorrhoeae and Haemophilus influenzae, the Tsh haemagglutinin of an avian pathogenic Escherichia coli, and the Hap protein involved in adhesion and penetration of H. influenzae. The C-terminal domain of the SepA precursor, which is not present in the secreted protein, exhibits sequence similarity with pertactin of Bordetella pertussis and the ring-forming protein of Helicobacter mustelae. Construction and phenotypic characterization of a sepA mutant indicated that SepA is required neither for entry into cultured epithelial cells nor for intercellular dissemination. However, in the rabbit ligated ileal loop model, the sepA mutant exhibited an attenuated virulence, which suggests that SepA might play a role in tissue invasion.
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PMID:SepA, the major extracellular protein of Shigella flexneri: autonomous secretion and involvement in tissue invasion. 747 98

A murine monoclonal antibody, MAHI 3 (immunoglobulin G2b), that is broadly reactive with Haemophilus influenzae lipopolysaccharides (LPSs) but nonreactive with all enterobacterial LPSs tested was generated by fusing mouse myeloma cells with spleen cells of BALB/c mice immunized with azide-killed H. influenzae RM.7004. MAHI 3 bound to all H. influenzae, all other human Haemophilus spp., all Bordetella pertussis and Bordetella parapertussis, and all Aeromonas spp. tested but not to any Neisseria or Moraxella catarrhalis strains, as determined by enzyme immunoassay, colony dot immunoblotting, and immunoblotting. In an inhibition enzyme immunoassay, MAHI 3 reacted with all 45 H. influenzae LPSs tested but not with the LPS from the rough mutant I69 Rd-/b+, which has only 3-deoxy-D-manno-octulosonic acid (P) [Kdo(P)] and lipid A. The antibody was not inhibited by H. influenzae lipid A or lipid-free polysaccharide isolated after mild acid hydrolysis. Only native LPSs show positive inhibitory activity, indicating that part of lipid A is involved in the binding of MAHI 3. From the results, it is indicated that the structural element recognized by MAHI 3 is Hep alpha 1-->2Hep alpha 1-->3Hep alpha 1-->Kdo together with part of lipid A, including the phosphate.
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PMID:The tetrasaccharide L-alpha-D-heptose1-->2-L-alpha-D-heptose1--> 3-L-alpha-D-heptose1-->(3-deoxy-D-manno-octulosonic acid) and phosphate in lipid A define the conserved epitope in Haemophilus lipopolysaccharides recognized by a monoclonal antibody. 754 87

Bacteriological, pharmacokinetic and clinical studies on SY5555 dry syrup (powder which is dissolved before use), a new penem antibiotic for oral use, were performed. The following results were obtained. 1. Antibacterial activities. MICs of SY5555, clavulanic acid/amoxicillin (CVA/AMPC), cefotiam (CTM), cefpodoxime (CPDX), cefaclor (CCL) and cefdinir (CFDN) were determined against clinically isolated Staphylococcus aureus, coagulase negative staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli and Enterobacter cloacae at a dose of 10(6) CFU/ml. MICs of SY5555 against S. aureus, CNS, S. pneumoniae, S. pyogenes, H. influenzae, M. catarrhalis, E. coli and E. cloacae were 0.2, 0.2, 0.2, < or = 0.025, 0.78, 0.2, 0.78 and 3.13 micrograms/ml, respectively, showing excellent antibacterial effects on these pathogens. Although the effects of SY 5555 against H. influenzae and E. coli were slightly inferior to those of CPDX and CFDN, the drug showed the most excellent antibacterial effect on other strains as compared with the control drugs. 2. Absorption and excretion In this study, plasma concentrations and urinary recovery rates were examined after administration of SY5555 at doses of 5 and 10 mg/kg (potency) after meals. With both 5 and 10 mg/kg doses, peak plasma concentrations were reached 1 hour after administration, at 0.25-2.61 micrograms/ml (mean 1.47 micrograms/ml) and 1.08-2.17 micrograms/ml (mean 1.74 micrograms/ml), respectively. The plasma levels rapidly decreased to 0.06-0.19 micrograms/ml (0.12 micrograms/ml) and 0.0503-0.0637 micrograms/ml) after 6 hours. The half-lives 1.12 hours in the 5 mg/kg group and 1.0 hour in the 10 mg/kg group. The urinary recovery rates were determined in the first 8 hours after administration in the 5 mg/kg and 6 hours in the 10 mg/kg group, and the values were as low as 1.05-12.3% and 1.6-4.33%, respectively. 3. Clinical results The clinical responses were examined in a total of 73 cases including 4 acute pneumonia, 13 acute bronchitis, 11 tonsillitis, 3 pharyngitis, 12 scarlet fever, 2 pertussis, 6 urinary tract infection, 6 otitis media, 7 lymphadenitis, 2 staphylococcal scalded skin syndrome, 2 phlegmon, 4 impetigo and 1 purulent parotitis. The treatment was effective or better in 66 of 70 cases with an efficacy rate of 94.3% (3 undeterminable cases were excluded). Bacteriological effects were examined during the clinical course for detected or suspected pathogens found before administration of SY5555. The effects were determined in 50 cases including 7 cases of polymicrobacterial infections, 57 strains in total. Eight strains, however, persisted, hence the overall eradication rate was 86.0%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Bacteriological, pharmacokinetic and clinical studies of SY5555 dry syrup in the pediatric field]. 769 46

We previously reported the cloning and sequencing of genes designated hmw1 and hmw2 from a prototype nontypeable Haemophilus influenzae strain. The genes encode proteins which are related to filamentous hemagglutinin of Bordetella pertussis and promote attachment of the nontypeable H. influenzae strain to human epithelial cells (J. W. St. Geme III, S. Falkow, and S. J. Barenkamp, Proc. Natl. Acad. Sci. USA 90:2875-2879, 1993). Subcloning studies suggested that correct processing of these high-molecular-weight proteins required the products of additional downstream genes. In the present study we analyzed the 3'-flanking regions of the hmw1A and hmw2A structural genes and found that both genes are flanked by two additional downstream open reading frames (ORFs), designated B and C, respectively. The B ORFs are 1,635 bp long. Their derived amino acid sequences are 99% identical and demonstrate similarity to the derived amino acid sequences of two genes that encode proteins required for secretion and activation of hemolysins of Proteus mirabilis and Serratia marcescens. The C ORFs are 1,950 bp long, and their derived amino acid sequences are 96% identical. In Escherichia coli transformants, interruption of the hmw1C or both the hmw1B and hmw1C genes resulted in defective processing of the hmw1A structural gene product and loss of the ability of the transformants to adhere to human epithelial cells. The precise interactions of the proteins encoded by these gene clusters are yet to be defined, but their elucidation may further our understanding of the biology of nontypeable H. influenzae bacteria and the interaction of these organisms with the human host.
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PMID:Genes encoding high-molecular-weight adhesion proteins of nontypeable Haemophilus influenzae are part of gene clusters. 803 3

Because inactivated poliovirus vaccine (IPV) and Haemophilus influenzae b vaccine are advised in many programs and may be incorporated further in other programs, we undertook a study to determine whether the administration of a tetravalent preparation of diphtheria-tetanus-pertussis-IPV mixed in one syringe with tetanus-conjugate H. influenzae b vaccine (DTP-IPV-PRPT) is associated with increased reactogenicity or interference with immunogenicity of individual vaccine components. In a placebo-controlled, double blind study, a total of 161 infants were enrolled (80 DTP-IPV-PRPT and 81 DTP-IPV-placebo). Vaccine was administered at 2, 4 and 6 months of age. Oral poliovirus vaccine was added at 7 months of age and a booster of oral poliovirus vaccine and DTP-IPV was also administered at 12 months of age, according to the policy in Israel. Local and systemic side effects were similar in both groups except for irritability after the second dose and use of acetaminophen which we observed slightly but significantly more often in the DTP-IPV-PRPT recipients. After the third dose the geometric mean titers of anti-polyribosyl-ribitol phosphate antibodies were 3.7 and 0.05 micrograms/ml in the PRPT and placebo groups, respectively (P < 0.001). Higher tetanus antitoxin titers were observed among recipients of DPT-IPV-placebo (1.1 IU/ml vs. 0.7 IU/ml, P = 0.003). A similar trend was found for pertussis agglutinin titers (93.4 vs. 65.4, P = 0.054). No difference was observed for anti-diphtheria toxoid and poliovirus 1, 2, and 3.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety and immunogenicity in young infants of Haemophilus b-tetanus protein conjugate vaccine, mixed in the same syringe with diphtheria-tetanus-pertussis-enhanced inactivated poliovirus vaccine. 807 16

The molecular basis for direct bacteria-macrophage interactions that distinguishes nontypeable (NT) Haemophilus influenzae from type b organisms is not known. Because of similarities between filamentous hemagglutinin (FHA) adhesin of Bordetella pertussis and high-molecular-weight (HMW) proteins commonly expressed by NT H. influenzae, the role that HMW proteins play in determining NT H. influenzae-macrophage interactions was assessed. In tests with genetically engineered organisms, HMW protein-expressing bacteria bound significantly better than isogenic HMW protein-deficient bacteria to macrophages. HMW protein-dependent binding to macrophages is trypsin-sensitive, is independent of divalent cations, does not occur via the leukocyte integrin CD11b/CD18, and is not affected by galactose-containing carbohydrates. Organisms bound via HMW proteins remain largely extracellular and viable. Like FHA of Bordetella organisms, HMW proteins mediate binding of NT H. influenzae to macrophages. However, unlike the interaction determined by FHA, this interaction is characteristically one of adhesion and requires additional serum opsonization for efficient killing of bacteria by macrophages.
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PMID:High-molecular-weight surface-exposed proteins of Haemophilus influenzae mediate binding to macrophages. 810 76

Structural analysis of the human immunoglobulin repertoire holds promise for determining the basis of variable region gene usage in response to a variety of auto and exogenous antigens. Here we report the nucleotide sequences of the heavy and light chain variable regions expressed by three human monoclonal antibodies specific for two clinically relevant bacterial pathogens, Bordetella pertussis and Haemophilus influenzae type b. The cell lines were derived by in vitro stimulation of lymphocytes from spleen or tonsillar tissue, respectively, and bind to different antigens from the two organisms. The single B. pertussis antibody is of the IgM lambda isotype and utilizes the single VH6 gene segment in combination with a V lambda 2 gene and demonstrates limited somatic mutation, yet is highly indicative of an antigen-driven immune response. One H. influenzae antibody is of the IgG2 lambda isotype and expresses a VH3 gene segment with a V lambda 1 gene, while the second cell line produces an IgG3 lambda antibody expressing a combination of VH2/V lambda 3. Both molecules show evidence of somatic mutation. The D gene segments of the heavy chains vary in length and display limited sequence homology with known germline D segments. As demonstrated previously, JH4 predominates (two JH4 and one JH3) and all three utilize the J lambda 3 gene segment. In addition, we have isolated and sequenced a number of germline VH2 gene segments in an attempt to better understand the nature of the VH2 germline repertoire. In addition to contributing to the understanding of the human antibody repertoire, such clinically relevant molecules may prove to be a source of passive immunotherapy for those at risk to developing disease.
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PMID:Molecular characterization of human antibodies to bacterial antigens: utilization of the less frequently expressed VH2 and VH6 heavy chain variable region gene families. 824 31

Bacteriological, pharmacokinetic and clinical studies on cefditoren pivoxil (CDTR-PI, ME 1207) in granules, a new oral cephalosporin, were performed in the field of pediatrics. The results are summarized below. 1. Antibacterial activities: Antibacterial activities of CDTR were studied against Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Haemophilus parainfluenzae and Branhamella catarrhalis in comparison with those of cefteram (CFTM), cefixime (CFIX), cefaclor (CCL), cefpodoxime (CPDX) and cefotiam (CTM). MIC80's of CDTR against S. aureus, S. pneumoniae, S. pyogenes, H. influenzae, H. parainfluenzae and B. catarrhalis were 1.56, 0.39, < or = 0.025, < or = 0.025, 0.05 and 0.20 micrograms/ml, respectively. These results showed that CDTR has high antibacterial activities against these organisms. 2. Absorption and excretion: Serum concentrations and urinary recovery rates of CDTR-PI (administered in granules) were determined. Upon single oral doses of 3 mg/kg and 6 mg/kg, the peak serum concentrations were 0.5-2.45 micrograms/ml at 2 to 4 hours and 1.79-4.05 micrograms/ml at 1 to 4 hours, respectively, and T 1/2 was 1.07-9.67 hours and 0.99-3.00 hours, respectively. At 8 hours after dosing, serum concentrations were 0-0.87 micrograms/ml with a dose of 3 mg/kg and 0.27-0.73 micrograms/ml with 6 mg/kg. These values indicated that the drug has a dose-dependent pharmacokinetic behavior. Urinary recovery rates in the first 8 hours were 12.9-34.2% with a dose of 3 mg/kg and 11.8-26.9% with 6 mg/kg. 3. Clinical study: Clinical efficacies were examined in a total of 81 cases consisting of 20 cases of acute bronchitis, 13 of acute pneumonia, 21 of tonsillitis, 5 of pharyngitis, 7 of scarlet fever, 2 each of impetigo, otitis media and purulent cervical lymphadenitis, 1 of pertussis and 8 of UTI. The clinical efficacy rate was 97.5% (79/81), and bacteriological eradication rate was 100% (76/76). As for side effects, 2 cases of watery stools and 1 case of minor elevation of GPT were observed.
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PMID:[Bacteriological, pharmacokinetic and clinical studies of cefditoren pivoxil in the pediatric field]. 837 96

Nontypable Haemophilus influenzae are Gram-negative bacilli that represent a common cause of human disease. These organisms initiate infection by colonizing the upper respiratory tract. Despite the essential role of colonization, the bacterial determinants of this process remain poorly defined. We recently identified a family of surface-exposed high-molecular-weight proteins of nontypable H. influenzae that are related to filamentous hemagglutinin, a critical adherence factor of Bordetella pertussis. The genes encoding the two such high-molecular-weight proteins (HMW-1 and HMW-2) expressed by a prototypic nontypable H. influenzae strain have now been cloned and sequenced. In this study we examined the role of the HMWs in adherence to human epithelial cells. We found that loss of expression of HMW-1 by the prototypic strain and a HMW-1-like protein in a heterologous nontypable H. influenzae strain markedly decreased the capacity to adhere. The absence of expression of both HMW-1 and HMW-2 in the prototypic strain or their homologs in the second strain was associated with a further decrease in adherence. Expression of either HMW-1 or HMW-2 in nonadherent laboratory strains of Escherichia coli resulted in acquisition of the adherence phenotype. These results indicate that both HMW-1 and HMW-2 and the homologous proteins from a second strain can mediate attachment. We speculate that these proteins and the related proteins in other nontypable H. influenzae isolates are important colonization factors.
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PMID:High-molecular-weight proteins of nontypable Haemophilus influenzae mediate attachment to human epithelial cells. 846 2


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