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

The P6 outer membrane protein is a highly conserved molecule which is present on the surface of all strains of Haemophilus influenzae. Sixty strains of nontypeable H. influenzae which caused invasive disease or colonized the female urogenital tract were studied with monoclonal antibodies 7F3 and 4G4, which recognize different surface-exposed epitopes on the P6 molecule. All 60 strains expressed the epitope recognized by 4G4, whereas 47 of 60 strains expressed the epitope recognized by antibody 7F3. The 7F3-nonreactive strains were all biotype 4 and were recovered from the blood of neonates or postpartum women or from the female urogenital tract. The P6 genes from two 7F3-nonreactive strains were cloned, and the nucleotide sequences were determined. Analysis of amino acid sequences, immunoassays with synthetic peptides, and site-directed mutation of the P6 gene indicate that the epitope recognized by antibody 7F3 is conformational and that the sequence Asp-Ile-Thr is critical in maintaining the conformation of the epitope. We conclude that the unusually virulent clone family of biotype 4 strains of nontypeable H. influenzae express a variant P6 molecule which has an alteration in a highly conserved surface-exposed epitope.
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PMID:Neonatal, urogenital isolates of biotype 4 nontypeable Haemophilus influenzae express a variant P6 outer membrane protein molecule. 137 3

Bacteriological and clinical studies on cefodizime (CDZM, THR-221), a new cephem developed by Hoechst AG and Roussel Uclaf, were carried out and the results are summarized below: 1. Against Gram-positive bacteria, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, antibacterial activities of CDZM were similar to those of cefotaxime (CTX), cefazolin, cefotiam and piperacillin. Against Escherichia coli, Klebsiella pneumoniae and Serratia sp., antibacterial activities of CDZM were similar to that of CTX, and superior to those of other tested antibiotics. Especially against Haemophilus influenzae and Branhamella catarrhalis, it showed an excellent antibacterial activity. 2. Although the clinical efficacy was poor in 1 patient with sepsis caused by Salmonella marcescens and in another with cervical lymphadenitis, in 5 patients with upper respiratory tract infection, 4 patients with bronchitis, 6 patients with bronchopneumonia, 18 patients with pneumonia, 5 patients with urinary tract infection and 1 patient with enteritis, the clinical efficacy was excellent or good and the efficacy rate was 95.1% (39/41) including excellent efficacies in 25 cases. 3. Bacteriologically, all identified causative bacteria were eradicated except for 1 case of Salmonella sp., thus the eradication rate was 97.4% (38/39). Especially S. pneumoniae in 10 cases, H. influenzae in 12 cases and B. catarrhalis in 3 cases were eradicated totally. 4. Adverse reactions were studied in 46 cases, and digestive symptoms were observed in 9 cases (diarrhea 5 cases, loose stools 4 cases). Eruption and vascular pain were observed in 1 case each. As digestive symptoms in 9 cases were mild, the treatment were not suspended. In laboratory test values, elevation of GOT, elevation of GPT, elevation of bilirubin, and eosinophilia were observed in 1 case each. Influences on blood coagulation parameters were studied. No change was observed between the beginning and the end of the treatment. From above results, we have concluded that CDZM is a useful and safe antibiotic in pediatrics, administered at a daily dose of 20 mg/kg divided into 3 or 4 doses and administered intravenously.
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PMID:[Bacteriological and clinical studies of cefodizime in pediatrics]. 188 Sep 19

The amino acid sequence T-P-P-T-P-S-P-S is tandemly duplicated in the heavy chain of human immunoglobulin A1 (IgA1), the major antibody in secretions. The bacterial pathogen Streptococcus sanguis, a precursor to dental caries and a cause of bacterial endocarditis, yields IgA protease that cleaves only the Pro-Thr peptide bond in the left duplication, while the type 2 IgA proteases of the genital pathogen Neisseria gonorrhoeae and the respiratory pathogen Haemophilus influenzae cleave only the P-T bond in the right half. We have sequenced the entire S. sanguis iga gene cloned into Escherichia coli. A segment consisting of 20 amino acids tandemly repeated 10 times, of unknown function, occurs near the amino-terminal end of the enzyme encoded in E. coli. Identification of a predicted zinc-binding region in the S. sanguis enzyme and the demonstration that mutations in this region result in production of a catalytically inactive protein support the idea that the enzyme is a metalloprotease. The N. gonorrhoeae and H. influenzae enzymes were earlier shown to be serine-type proteases, while the Bacteroides melaninogenicus IgA protease was shown to be a cysteine-type enzyme. The streptococcal IgA protease amino acid sequence has no significant homology with either of the two previously determined IgA protease sequences, that of type 2 N. gonorrhoeae and type 1 H. influenzae. The differences in both structure and mechanism among these functionally analogous enzymes underscore their role in the infectious process and offer some prospect of therapeutic intervention.
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PMID:Analysis of the immunoglobulin A protease gene of Streptococcus sanguis. 198 65

Cefodizime (THR-221, CDZM), a new cephalosporin antibiotic, was evaluated for its safety and efficacy in 27 children with various bacterial infections. The episodes of infections included pneumonia (6 cases), bronchopneumonia (11 cases), lung abscess (1 case), acute pharyngitis (2 cases), cervical lymphadenitis (1 case), infected cephalohematoma (1 case), urinary tract infection (1 case), sepsis (2 cases) and purulent meningitis (2 cases). CDZM was effective in all but one, and its efficacy rate was 96.3%. The main etiologic pathogens were Staphylococcus aureus, Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Streptococcus agalactiae, Escherichia coli, Citrobacter freundii and Branhamella catarrhalis. The elimination rate was 92.3%. As adverse reactions or abnormalities, diarrhea was encountered in 4 cases. A slight elevation of serum transaminases or eosinophils was observed in 4 cases. The serum half-life was approximately 1.8-1.9 hours in children after intravenous bolus injections. Concentrations of CDZM in cerebrospinal fluids were well above MIC values of CDZM against those organisms responsible for the infections. The data suggest that CDZM is a safe and effective antibiotic when used in children with bacterial infections including purulent meningitis.
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PMID:[Clinical and pharmacokinetic study on cefodizime, a new cephalosporin antibiotic, in the pediatric infections]. 279 54

1. Absorption and elimination Serum and urinary levels of cefodizime (CDZM, THR-221) were determined in 7 children with ages ranging from 3 to 12 years after a intravenous bolus injection of the drug at 20 mg/kg. The average serum level of the drug was 119.27 +/- 13.83 micrograms/ml at 30 minutes, then decreased gradually with a half-life of 2.01 +/- 0.25 hours to 10.56 +/- 2.93 micrograms/ml at 6 hours. The average urinary elimination rate was 77.34 +/- 12.60%. 2. Clinical study CDZM was given to the following 39 patients with ages ranging from 2 months to 15 years and clinical efficacy, bacteriological response and adverse reactions were evaluated. The treated cases were 2 cases of acute purulent tonsillitis, 30 cases of acute pneumonia, 1 case of acute purulent otitis media and 2 cases of acute urinary tract infections. Clinical efficacies were excellent in 29 cases, good in 5 cases and poor in 1 with an efficacy rate of 97.1%. Organisms presumed to be pathogens included 3 strains of Streptococcus pneumoniae, 1 beta-Streptococcus, 1 Staphylococcus epidermidis, 9 Haemophilus influenzae (1 beta-lactamase producing strain and 8 non-producing strains) and 1 Enterococcus faecalis. The last one was decreased and the others were eradicated with an eradication rate of 93.3% for all strains. Adverse reactions occurred in no patients. Abnormal changes in laboratory test values involved only 1 case each of elevated GOT, elevated GOT and GPT, eosinophilia and thrombocytosis. Based on the above-mentioned result and features of this drug, it was confirmed that this drug showed an excellent usefulness in the treatment of infections in childhood. It may be also effective in the management of infections under immunosuppression.
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PMID:[Experimental and clinical studies on cefodizime in pediatrics]. 279 56

Cefodizime (THR-221, CDZM), a new parenteral cephalosporin, was evaluated for its efficacy and safety in 20 children with bacterial infections (Table 1), and the following results were obtained. 1. CDZM was administered in 3 or 4 divided doses at daily dosages ranging from 54.5 to 84.2 mg/kg administered by 30 minutes drip infusion or intravenous injection to 20 patients (7 cases of acute tonsillitis, 6 cases of pneumonia, 2 cases each of bronchitis and suppurative cervical lymphadenitis, and 1 case each of acute pharyngitis, acute enteritis and furunculosis) and the following clinical results were obtained: excellent, 7 cases; good, 11 cases; fair, 2 cases. The overall efficacy rate was 90% (Table 4). 2. MICs of CDZM against 15 strains of isolated organisms are shown in Table 2. MICs against all 7 strains of Haemophilus influenzae were less than 0.025 micrograms/ml. MIC against 1 out of 5 strains of Streptococcus pneumoniae was 0.05 micrograms/ml and those against 2 strains were 0.10 micrograms/ml and against the other 2 were 0.20 micrograms/ml. MICs against 3 strains of Staphylococcus aureus were 1.56, 25 and higher than 100 micrograms/ml, respectively. 3. No clinical adverse reaction was observed in any of the 20 patients. Eosinophilia was observed in 2 cases. A slight elevation of S-GOT was found in 1 patient (case No. 8) and moderate elevation of S-GOT and S-GPT in another (case No. 18) (Table 4). In case No. 18, the S-GOT and S-GPT activity improved after the administration of the drug was stopped.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Clinical evaluation of cefodizime in children]. 279 59

Cefodizime (CDZM, THR-221), a new cephem antibiotic, was investigated for its clinical efficacy and pharmacokinetics in children. The results obtained are summarized as follows. 1. Antimicrobial activities Antimicrobial activities of CDZM against clinically isolated organisms were determined. MICs of CDZM against 1 strain each of Streptococcus pneumoniae, Escherichia coli and Klebsiella pneumoniae were 0.05 micrograms/ml to 0.10 micrograms/ml. Especially, MIC against all 6 strains of Haemophilus influenzae was less than or equal to 0.024 micrograms/ml. This MIC value was lower than those of other antibiotics such as cefotaxime, cefotiam, cefazolin, piperacillin. 2. Pharmacokinetics CDZM was given to 1 case at a dose of 20 mg/kg by a 60-minute intravenous drip infusion. The peak value of serum concentration of CDZM was 207.80 micrograms/ml at the end of the infusion. The half-life was 2.15 hours. The mean urinary excretion rate was 68.5% in the first 4 hours, 79.2% in 6 hours and 76.5% in 8 hours after the 30-minute drip infusion. 3. Clinical efficacy CDZM was given to a total of 27 patients, 13 with pneumonia, 1 with bronchitis, 2 with acute pharyngitis, 1 with purulent tonsillitis, 5 with urinary tract infection, 1 each with retrograde cholangitis, acute enteritis, pericementitis, phlegmon and inguinal lymphadenitis. Overall clinical efficacies were excellent in 5 cases, good in 17 and the efficacy rate was 81%. Bacteriological effects were investigated in 13 cases and the eradication rate was 85%. No adverse reactions were observed in any case. As abnormal laboratory findings, elevated GOT, GPT, A1-P, LAP and gamma-GTP, were noted in 1 out of the 28 cases examined.
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PMID:[Clinical and pharmacokinetic evaluation of cefodizime in children]. 279 60

Cefodizime (THR-221, CDZM), a newly developed injectable cephem antibiotic, was injected intravenously to 13 cases of pediatric infections. Patients received the drug at a dose level of approximately 20 mg/kg x 3 times daily. The results obtained are summarized as follows. 1. Clinical efficacy was excellent in 4 patients, good in 6 and poor in 0 for 10 cases (2 phlegmon, 1 periproctal abscess, 5 pneumonia and 2 bronchitis) except 3 Mycoplasma pneumonia. 2. Three strains of pathogens were followed for their changes (Streptococcus pyogenes in 1 phlegmon, Klebsiella pneumoniae in periproctal abscess and Haemophilus influenzae in 1 bronchitis) and they were found to have been eliminated. 3. No adverse reactions occurred. Abnormal changes in laboratory test data found were 2 cases of eosinophilia, 1 cash each of increased GOT and GPT, and thrombocytosis, but none of them was severe.
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PMID:[Clinical experience with cefodizime on pediatric infections]. 279 61

Clinical studies were performed on cefodizime (THR-221, CDZM), a new cephem antibiotic as described below. CDZM was administered to 13 patients in dose levels ranging from 55 to 96 mg/kg/day t.i.d. for 3-7 days (5.5 days on average). These patients included 8 with pneumonia, 2 with tonsillitis, 1 each with bronchitis, phlegmon and urinary tract infection. The overall efficacy rate was 92.3%, i.e., efficacy was excellent in 8, good in 4 and poor in 1. Bacteriological efficacy was 83.3%, i.e., 5 strains of bacteria (Streptococcus pneumoniae 1, Haemophilus influenzae 3, Haemophilus parainfluenzae 1) were eradicated and 1 was unchanged (Enterobacter cloacae, MIC greater than 100 micrograms/ml). Clinical side effect was not observed during the treatment. Laboratory abnormalities were observed in 2 cases, i.e., a slight elevation of GPT and a mild eosinophilia. The above results suggest that CDZM is a useful antibiotic for treating pediatric bacterial infections.
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PMID:[Clinical experience with cefodizime in bacterial infection of children]. 279 62

Employing a combination of chemical and spectroscopic techniques, the structure of the Haemophilus influenzae type d capsular polysaccharide was found to be leads to 4)-beta-D-GlcNAc-(1 leads to 3)-beta-D-ManNAcA-(1 leads to. L-Alanine, L-serine, and L-threonine, in the molar ratios of approximately 1.0:1.0:0.3, were linked to C-6 of the D-mannosyluronic residue as amides; the (serine + alanine + threonine) to ManNAcA ratio was approximately 0.95:1.0. Removal of the amino acids by mild hydrolysis with sodium hydroxide resulted in a material that was cross-reactive with the native, type d polymer. The base-treated, type d polysaccharide was not observed to cross-react with either the H. influenzae type e or Escherichia coli K7 capsular polysaccharide, both of which are structurally similar to type d.
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PMID:Structural and immunological studies of the Haemophilus influenzae type d capsular polysaccharide. 679 29


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