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)

Haemophilus influenzae Rd and its derivatives are mutated either not at all or to only a very small extent by ultraviolet (UV) radiation, X-rays, methyl methanesulfonate, and nitrogen mustard, though they are readily mutated by such agents as N-methyl-N'-nitro-N-nitrosoguanidine, ethyl methanesulfonate, and nitrosocarbaryl. In these respects H. influenzae Rd resembles the lexA mutants of Escherichia coli that lack the SOS or reclex UV-inducible error-prone repair system. This similarity is further brought out by the observation that chloramphenicol has little or no effect on post-replication repair after UV irradiation. In E. coli, chloramphenicol has been reported to considerably inhibit post-replication repair in the wild type but not in the lexA mutant. Earlier work has suggested that most or all the mutations induced in H. influenzae by NC result from error-prone repair. Combined treatment with NC and either X-rays or UV shows that the NC error-prone repair system does not produce mutations from the lesions induced by these radiations even while it is producing them from its own lesions. It is concluded that the NC error-prone repair system or systems and the reclex error-prone system are different.
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PMID:Evidence that UV-inducible error-prone repair is absent in Haemophilus influenzae Rd, with a discussion of the relation to error-prone repair of alkylating-agent damage. 30 10

Cefamandole, a new cephalosporin antibiotic, has greater activity against common pathogens, including Escherichia coli, Haemophilus influenzae, and Proteus (including indole-positive strains), than available cephalosporin drugs. We have evaluated the safety and pharmacokinetics of this drug in 30 infants and children. Blood levels and urinary excretion of the drug were similar to those previously found in adults. The only side effects were mild and transient elevation of serum glutamic oxalacetic transaminase in 12 patients and of blood urea nitrogen in 1 patient in whom serum creatinine remained normal and unchanged.
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PMID:Pharmacokinetics and safety of cefamandole in infants and children. 57 Mar 72

After almost forty years of its introduction, erythromycin will not be the exclusive member of the macrolide group of antibiotic agents, but a new generation of its derivatives which surpass it in pharmacological properties and clinical efficacy will also be available. Clarithromycin, a 14-membered derivative, has shown acid stability, longer half-life, lower protein binding and higher lung tissue penetration. Its exceedingly high activity against erythromycin-susceptible gram-positive cocci, Mycoplasma pneumoniae, and Legionella pneumophila makes it and important alternative choice in the therapy of respiratory tract infections. Also, it has shown high activity against Chlamydia trachomatis, and high urinary clearance of this unmetabolized molecule, important properties which would render it a special role in the treatment of genitourinary tract infections. Azithromycin, a 15-membered derivative has shown enhanced basicity (due to the nitrogen atom in its lactone ring), longer half-life and lower protein bindings. Its exceptional activity against Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Ureaplasma urealyticum and gram-negative bacteria, and its high concentration in tonsillar, pulmonary, prostatic and female reproductive tract tissues, assigns it an honorific place among the macrolides in the therapy against respiratory tract and genitourinary tract infections. Its role against T. gondii deserves further study, but points out this agent as a promise against this parasite.
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PMID:The new macrolides: expanding the ways in antibiotic treatment. 150 85

Pneumococcus vaccine, injected alone or mixed with diphtheria-tetanus toxoid-pertussis, did not elicit significant concentrations of pneumococcus type 6 antibodies in 2- to 5-year-old sickle cell anemia patients (n = 22). Reinjection 5 months later failed to elicit a booster response to pneumococcus type 6. We then injected conjugates of pneumococcus type 6B and of Haemophilus influenzae type b (Hib), each bound to tetanus toxoid (TT), alternatively at monthly intervals into sickle cell anemia patients of the same age group (n = 25); most received 3 injections of each vaccine. Pneumococcus vaccine was administered to 19 patients and Hib to 1 at approximately 1 year of age. Blood samples were taken before each and approximately 6 months after the last injection. Infrequent and minimal local reactions and only 6 episodes of fever (3%) occurred after injection of the conjugates. Pneumococcus type 6B-TT elicited a rise in the geometric mean concentration of pneumococcus type 6 antibodies (Ab) from 104 ng of antibody nitrogen (AbN)/ml in preimmunization sera to 385 ng of AbN/ml after the first injection (P less than 0.01). There were further increases after the 2 subsequent injections; 6 months after the third injection, the mean concentration was 940 ng of AbN/ml and 15 of 16 (94%) had greater than 300 ng of AbN/ml. Hib-TT elicited a 160-fold increase of Hib antibodies to a geometric mean concentration of 39.0 micrograms of Ab/ml after the first injection. These levels rose approximately 2-fold following 2 additional injections to 71.7 micrograms/ml and declined to 10.7 micrograms/ml at the 6-month sampling.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Studies on Pneumococcus vaccine alone or mixed with DTP and on Pneumococcus type 6B and Haemophilus influenzae type b capsular polysaccharide-tetanus toxoid conjugates in two- to five-year-old children with sickle cell anemia. 233 98

In the past decade, significant progress has been made in understanding structure-function relationships of the new quinolones, which have a N-1-substituted, 1,4-dihydro-4-oxo-pyridine-3-carboxylic acid moiety as the basic nucleus. Modification of the groups affixed to positions C-6, C-7, and C-8 has made a major change in the antimicrobial activity, pharmacokinetic, and metabolic properties of the quinolones as have changes in the moieties affixed to the N-1 nitrogen. The new quinolones have a carboxyl group at position 3 and a keto group at C-4. The presence of a fluorine atom at C-6 enhances the deoxyribonucleic acid (DNA) gyrase inhibitory activity as well as the ability of the compounds to inhibit staphylococci. Position C-7 has been one of the most modified sites. Addition of a piperazinyl group markedly increased gram-positive activity, primarily antistaphylococcal activity; lowered the minimal inhibitory concentrations against Enterobacteriaceae, Haemophilus spp., and Neisseria spp.; and added activity against Pseudomonas aeruginosa compared with nalidixic acid. Methyl derivatives of the piperazine group or of the pyrroles have longer half-lives than do unsubstituted moieties. At the N-1 position, a cyclopropyl group appears to be most potent with respect to minimal inhibitory concentrations against Enterobacteriaceae and Pseudomonas. Ofloxacin is unique in that it has an oxygen substituted at C-8 with the substituent part of the ring system formed by fusion to the N-1 position. This has produced excellent in vitro activity against gram-positive species comparable with that of ciprofloxacin, excellent activity against the Enterobacteriaceae, and antipseudomonal activity superior to agents with an ethyl substitution at position N-1. The oxazine ring of ofloxacin provides excellent oral absorption with virtually 95 percent bioavailability; this modification also has prevented metabolism and has provided a long half-life of seven to eight hours.
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PMID:Chemical evolution of the fluoroquinolone antimicrobial agents. 255 62

Saliva is the main source of urea in the human mouth and may be responsible for the predilection of ureolytic bacteria for certain tooth sites. As a test of this hypothesis, the ureolytic bacteria, Haemophilus parainfluenzae, Actinomyces naeslundii, Actinomyces viscosus and coagulase-negative oral staphylococci, were enumerated in supragingival plaque from various sites in each of 10 subjects. The sites sampled included the maxillary and mandibular incisors (chosen because the lower incisors are more exposed to the submandibular-sublingual secretion than the upper) and the maxillary and mandibular molars (the upper molars being closer to the source of parotid saliva). After dispersion of the plaque samples in saline, subsamples of each suspension were plated on appropriate selective media and other subsamples were taken for nitrogen analysis to measure the amount of plaque sampled. H. parainfluenzae that used urea was present in the largest numbers, A. viscosus was next and A. naeslundii and coagulase-negative staphylococci were least. The staphylococci and H. parainfluenzae were more numerous from mandibular than from maxillary incisors and from maxillary than mandibular molars, a pattern which suggests that salivary access favours their selection. The numbers of A. viscosus and A. naeslundii were not related to salivary access: A. viscosus was most numerous from the maxillary incisors, possibly because this site is normally the most acidic of the four studied and A. viscosus is strongly acidogenic and aciduric; the incidence of A. naeslundii had no relationship with site.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Incidence of selected ureolytic bacteria in human dental plaque from sites with differing salivary access. 261 Jun 14

Certain cell-free filtrates from broth cultures of Pseudomonas aeruginosa, Hemophilus influenzae and Streptococcus pneumoniae stimulate secretion of glycoconjugates by explants of guinea pig trachea. The stimulatory effect is not related to toxicity or damage to the respiratory mucosa, as well as could be determined by ultrastructural examination of the explants after exposure. Bacteria isolated from patients with a history of chronic obstructive lung disease (P aeruginosa from cystic fibrosis, H influenzae, and S pneumoniae from chronic bronchitis) do not demonstrate increased frequency of positive strains or greater stimulation of secretion than organisms isolated from other individuals. At least three stimulatory substances are found in cell-free filtrates of P aeruginosa. They appear to be proteins of molecular weight 60,000-100,000 as determined by gel filtration. Within the crude filtrate, they are relatively stable to heat, proteolysis, and storage at 4 C and in liquid nitrogen. The stimulatory activity is not lost upon subculture of the bacteria. When isolated from the filtrate by column chromatography, they become labile to heat and trypsin. Isolated active fractions show proteolytic activity coinciding with mucin-stimulating capacity, suggesting a relationship with Pseudomonas proteases. Stimulatory substances released by S pneumoniae and H influenzae appear to be different from those elaborated by Pseudomonas. They are extremely labile to heat and storage, and the capacity to stimulate secretion is lost on subculture. Preliminary gel filtration indicates the S pneumoniae stimulatory substance(s) is in a molecular weight range of 100,000-300,000 daltons, while that of H influenzae is between 50,000 and 200,000. The results suggest bacteria which chronically infect or colonize respiratory airways of individuals suffering from obstructive lung disease can elaborate extracellular product(s) capable of stimulating secretion of mucin. Thus, the bacteria themselves may contribute to local manifestations and, ultimately, to the pathogenesis of obstructive disease.
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PMID:Bacteria associated with obstructive pulmonary disease elaborate extracellular products that stimulate mucin secretion by explants of guinea pig airways. 309 81

A series of erythromycin A-derived semisynthetic antibiotics, featuring incorporation of a basic nitrogen atom into a ring expanded (15-membered) macrocyclic lactone, have been prepared and biologically evaluated. Semisynthetic modifications focused upon (1) varied substitution at the macrocyclic ring nitrogen and (2) epimerization or amine substitution at the C-4'' hydroxyl site within the cladinose sugar. In general, the new azalides exhibit improved Gram-negative potency, expanding the spectrum of erythromycin A to fully include Haemophilus influenzae and Neisseria gonorrhoeae. When compared to erythromycin A, the azalides exhibit substantially increased half-life and area-under-the-curve values in all species studied. The overall in vitro/in vivo performance of N-methyl, C-4'' epimers 3a and 9; and C-4'' amine 11 identify these compounds as the most interesting erythromycin A-superior agents. Compound 3a has been advanced to clinical study.
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PMID:Synthesis, in vitro and in vivo activity of novel 9-deoxo-9a-AZA-9a-homoerythromycin A derivatives; a new class of macrolide antibiotics, the azalides. 313 3

Ciprofloxacin is a new quinolone antimicrobial agent with activity against a broad spectrum of gram-negative and gram-positive organisms, including Pseudomonas aeruginosa and methicillin-resistant strains of staphylococci. The efficacy and safety results of 80 clinical studies of the oral form of ciprofloxacin are reported. Drug safety was assessed in 2236 courses in 2203 adult patients treated primarily in the United States. Data from 1676 courses were suitable for analysis of drug efficacy. The unit dose for most patients ranged from 250 mg to 750 mg (median, 500 mg), usually given every 12 hours. The duration of treatment ranged from 3 to 231 days (median, 10 days). Predominant among 1722 infections were those of the urinary tract (43%), skin structures (29%), and respiratory tract (19%); the remainder were bone and joint infections (5%), bacteremias (2%), and intra-abdominal (1%), gastrointestinal (1%), and pelvic infections (less than 1%). Signs and symptoms of infection resolved in 79% of all cases; a further 15% improved, and 5% failed to improve. Pathogens were eradicated in 89% of urinary tract infections and persisted in 5%; 80% of patients still had sterile urine at the 3-to 6-week follow-up. In 81% of nonurinary tract infections, pathogens were eradicated; they persisted in 11%, and superinfection occurred in less than 5%. After treatment, 89% of the 2253 causative organisms were eradicated and 2% were reduced to clinically insignificant counts; 8% persisted. Of 411 isolates of P. aeruginosa, 77% were eradicated, as were 97% of 421 Escherichia coli and 80% of 248 Staphylococcus aureus isolates. Also eradicated were 95% of 166 Klebsiella, 96% of 139 Proteus mirabilis, 100% of 20 other Proteus, 94% of 123 Enterobacter, 100% of 68 Haemophilus influenzae, 96% of 49 Citrobacter, 89% of 45 Serratia, 95% of 41 Streptococcus pneumoniae, 91% of 43 Salmonella, 100% of 38 Morganella morganii, and 100% of 35 Providencia isolates. Adverse reactions were judged probably or possibly drug-related in 14.8% of courses; drug treatment had to be stopped prematurely in 3.5%. The most frequent reactions were gastrointestinal complaints (chiefly nausea, diarrhea, and vomiting), metabolic disorders (elevated SGOT, SGPT, serum creatinine, or blood urea nitrogen), and nervous system effects (dizziness, light-headedness, restlessness, tremor, and headache). Crystalluria, judged to be related to ciprofloxacin, occurred in two patients.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A survey of clinical experience with ciprofloxacin, a new quinolone antimicrobial. 336 Sep 68

Conjugates were prepared by carbodiimide-mediated coupling of adipic acid hydrazide derivatives of Haemophilus influenzae type b (Hib), Escherichia coli K100, and pneumococcal 6A (Pn6A) polysaccharides with tetanus toxoid (TT), as an example of a "useful" carrier, and horseshoe crab hemocyanin (HCH), as an example of a "nonsense" carrier. These conjugates were injected into NIH mice, and their serum antibody responses to the polysaccharides and proteins were characterized. As originally reported, Hib conjugates increased the immunogenicity of the capsular polysaccharide and elicited greater than the estimated protective levels of anti-Hib antibodies in most recipients after one injection and in all after the third injection (Schneerson et al., J. Exp. Med. 152:361-376, 1980). Both Hib conjugates induced similar anti-Hib responses. The K100-HCH conjugate was more immunogenic than the K100-TT conjugate and elicited anti-Hib responses similar to the Hib conjugates after the third injection. Simultaneous injection of the K100 and the Hib conjugates did not enhance the anti-Hib response. The Pn6A-TT conjugate induced low levels of anti-Hib antibodies; when injected simultaneously with the Hib conjugates, the anti-Hib response was enhanced, as all mice responded after the first injection and with higher levels of anti-Hib than observed with the Hib conjugates alone (P < 0.05). The Pn6A conjugates were not as immunogenic as the Hib conjugates. Pn6A-TT was more effective than was Pn6A-HCH; it elicited anti-Pn6A (>100 ng of antibody nitrogen per ml) in 6 of 10 mice after the third injection. The addition of the Hib-HCH conjugate to the Pn6A-TT conjugate increased the anti-Pn6A response with a higher geometric mean antibody titer, and 9 of 10 mice responded after the third injection. A preparation of diphtheria toxoid, TT, and pertussis vaccine increased the anti-Hib antibody levels after the first injection only in mice receiving Hib-TT, but not in mice receiving Hib-HCH, suggesting that additional carrier protein (TT) enhanced the anti-polysaccharide response. Simultaneous injection of Hib and Pn6A conjugates with the same or different carriers resulted in an enhanced serum antibody response to each polysaccharide. The anti-tetanus toxin response reached protective levels (>0.01 U/ml) in most mice after the first injection and in all mice after the second and third injections of TT conjugates. A progressive increase in the anti-HCH response with each additional injection was noted in animals receiving HCH conjugates. Animals receiving the diphtheria toxoid-TT-pertussis vaccine preparation responded with a greater increase in anti-carrier antibody than those receiving the conjugates alone. This method of synthesis provided conjugates capable of inducing protective levels of antibodies to both the polysaccharides and carrier proteins.
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PMID:Further studies on the immunogenicity of Haemophilus influenzae type b and pneumococcal type 6A polysaccharide-protein conjugates. 660 Oct 61


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