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)

In the present study we observed that the Haemophilus influenzae type b (Hib) porin, among the different surface bacterial components, is involved in the pathophysiology of bacterial meningitis. This study demonstrates that inoculation of Hib porin into the fourth cerebral ventricle causes the simultaneous expression of interleukin-1alpha (IL-1alpha), tumor necrosis factor alpha (TNF-alpha), and macrophage inflammatory protein 2 (MIP-2) at 6 h after inoculation. At 24 h, the expression of MIP-2 decreases while the expression of IL-1alpha and TNF-alpha increases. The mRNA expression of IL-1alpha, TNF-alpha, and MIP-2 is correlated with injury to the blood-brain barrier as demonstrated by the appearance of serum proteins and leukocytes in cerebrospinal fluid and by the increase in brain water content.
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PMID:Haemophilus influenzae porin contributes to signaling of the inflammatory cascade in rat brain. 1111 9

The relationship between the antigen release from formulations in vitro and the antibody response after administration of water-in-oil-in-water (W/O/W) emulsion vaccines containing Haemophilus paragallinarum (Hpg) was studied in chickens. Increases of sorbitan sesquioleate volume in the formulation led to slower antigen release and tended to induce higher hemagglutination-inhibition (HI) antibody titers. In addition, the vaccines prepared with internal aqueous phase:oil phase:external aqueous phase (A:O:A) ratios of 3:4:3 and 3:3:4 also showed slower release of antigen and higher HI antibody titer compared with those of an A:O:A ratio of 3:2:5. Vaccines prepared with polyoxyethylene (POE)(10) hydrogenated castor oil or POE(40) hydrogenated castor oil instead of sorbitan sesquioleate showed higher release and lower antibody HI titers. As a result, HI antibody titers at 6 wk after vaccination were inversely related to antigen release, as determined by the release test. The correlation coefficient was 0.942. In infectious coryza W/O/W emulsion vaccines, the slow release of antigen from the formulation induced and maintained high HI antibody titers of Hpg.
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PMID:Relationship between antigen release and antibody response of infectious coryza water-in-oil-in-water emulsion vaccines. 1119 41

AS-924 is an oral prodrug of the antibiotic ceftizoxime (CTIZ), a parenteral use cephalosporin. This novel prodrug, produced by esterifying CTIZ with a lipophilic pivaloyloxymethyl (POM) group and introducing a water soluble L-alanyl group, is expected to increase the bioavailability and thereby, augment the antibacterial activity of CTIZ in vivo compared with existing prodrugs. To study the effect of the L-alanyl group in AS-924 on its bioavailability, the plasma concentration profiles of CTIZ in dogs were examined following the dosing of AS-924 and CTIZ-POM, in powder form, after pretreatment with the antacid ranitidine, and following the dosing of AS-924 after pretreatment with a gastrointestinal motility stimulant metoclopramide or suppressant scopolamine butylbromide. The absorption rate of AS-924 was constant under these different conditions due to its unique balance of lipophilicity and water solubility. CTIZ is as antibacterially active as pre-existing oral cephalosporins against Gram-positive clinical isolates, while being more active against all Gram-negative isolates-particularly Enterobacteriaceae and Haemophilus influenzae. A simulation model for the eradication profile of bacteria in computer programmed pharmacokinetic (PK) system was carried out to study the antibacterial action of CTIZ in human. CTIZ was proven to eradicate Streptococcus pneumoniae and H. influenzae effectively, while cefpodoxime (CPOD), the active moiety of CPOD proxetil, eradicated S. pneumoniae, but not H. influenzae. These results confirm that, AS-924 is a potent oral antibiotic and would be expected to be clinically effective and efficient.
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PMID:AS-924, a novel, orally active, bifunctional prodrug of ceftizoxime: physicochemical properties, oral absorption in animals, and antibacterial activity. 1171 Dec 61

The analgesic effects of four solutions administered intra-orally (25 and 50% sucrose solutions, hydrogenated glucose, and a sterile water placebo) were tested in groups of babies receiving routine DTP (diphtheria, tetanus, and pertussis) and HIB (Haemophilus influenzae type B) injections at the first, second, or third immunization. The duration of the baby's cry during 3 min following DTP and HIB injections was measured as main outcome. For all three immunization groups, the babies receiving the placebo generally spent most time crying. For both the DTP and HIB injections, the difference between 50% sucrose and placebo was most evident in the group receiving the 3rd immunization. Intra-oral administration of the 50% sucrose solution, compared to placebo, appeared to reduce the cry response to painful experiences in babies beyond the neonatal period.
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PMID:Intra-oral administration of sweet-tasting substances and infants' crying response to immunization: a randomized, placebo-controlled trial. 1193 21

Malnutrition, one of the world's greatest health problems, is a factor in the death of millions of children each year. Infection is the cause of death in over half these cases. Dietary deficiency, especially of protein, causes serious disturbances in the immune system. The mucus and cutaneous surfaces are the first affected. Studies of the respiratory mucus demonstrate frequent breaches which allow germs to penetrate. Antibodies are synthesized in reduced quantities, lymphocyte counts are often diminished, and reaction with infectious agents is poor. The phagocyte function of polynucleated cells is poor. Malnutrition is often associated with war, ignorance, poverty, and poor hygiene. Deficiencies of iron, vitamin A, and zinc may aggravate immune deficits. Ingestion of contaminated water is the main cause of diarrhea, which is very frequent among the malnourished and may be more serious than among adequately nourished individuals. Colibacillus and salmonella are most frequently isolated. Germs such as shigella, campylobacter, and rotavirus have the same incidence as in well nourished children. Pneumonia is responsible for 4 million deaths in children under 5 annually and is more common in the malnourished. The pathogenic agents may be pneumococci, Hemophilus, or staphylococci. Tuberculosis is also frequent, especially in zones with a prevalence of AIDS. Diagnosis of tuberculosis with cutaneous tests is difficult in the malnourished. Regardless of the pathogenic agent, pneumonia is more serious in the malnourished, and the need for treatment is more urgent. Urinary infections may occur in 10-25% of malnourished children vs. 2% of healthy children. The colibacillus is the most frequent cause. Specticemias, the most severe of infections, are not rare in the malnourished and are usually caused by Salmonella or the colibacillus. 20% of malnourished children are affected by infections acquired in the hospital. Among viral infections affecting them are measles and herpes. The fatality rate from measles may reach 25% in malnourished children. Parasitoses are frequent, but they do not seem to be more serious in malnourished children than in the general population. It is imperative in treating malnourished children to observe rigorous hygiene, use clean water, treat infections early, avoid hospital infections, and apply all available vaccines.
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PMID:[Infections in malnourished infants and children]. 1228 6

The periplasmic iron binding protein of pathogenic Gram-negative bacteria performs an essential role in iron acquisition from transferrin and other iron sources. Structural analysis of this protein from Haemophilus influenzae identified four amino acids that ligand the bound iron: His(9), Glu(57), Tyr(195), and Tyr(196). A phosphate provides an additional ligand, and the presence of a water molecule is required to complete the octahedral geometry for stable iron binding. We report the 1.14-A resolution crystal structure of the iron-loaded form of the H. influenzae periplasmic ferric ion binding protein (FbpA) mutant H9Q. This protein was produced in the periplasm of Escherichia coli and, after purification and conversion to the apo form, was iron-loaded. H9Q is able to bind ferric iron in an open conformation. A surprising finding in the present high resolution structure is the presence of EDTA located at the previously determined anion ternary binding site, where phosphate is located in the wild type holo and apo structures. EDTA contributes four of the six coordinating ligands for iron, with two Tyr residues, 195 and 196, completing the coordination. This is the first example of a metal binding protein with a bound metal.EDTA complex. The results suggest that FbpA may have the ability to bind and transport iron bound to biological chelators, in addition to bare ferric iron.
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PMID:High resolution structure of an alternate form of the ferric ion binding protein from Haemophilus influenzae. 1253 39

Bacteria continuously evolve their resistance mechanisms to antibiotics, either in community or in the hospital setting. Production of beta-lactamases is one of the oldest way to overcome antimicrobial agents activity, since it was first described in 1944 immediately after the penicillin discovery. Beta-lactamases are enzymes hydrolysing the beta-lactam nucleus of beta-lactam antibiotics by using two strategies: a nucleophilic attack of a serine residue or activating a water molecule via a Zn++. Cefuroxime is a injectable cephalosporin which can be also orally administered as a pro-drug named cefuroxime axetil. Cefuroxime has been classified as a second generation cephalosporin, even though the strict subgrouping of cephalosporins into classes is critically discussed by the Authors. Cefuroxime was the first beta-lactam with a higher stability to beta-lactamase hydrolysis due to its methoxy-imino side chain in position 7 of the cephem nucleus. Many of the clinically significant bacterial species producing beta-lactamases such as Haemophilus, Moraxella, Staphylococci and most Enterobacteriaceae then remain susceptible to cefuroxime. The more evoluted enzymes such as carbapenemases, extended-spectrum beta-lactamases or over-expressed cephalosporinases hydrolyse nearly all the beta-lactams antibiotics including cefuroxime. The available literature on the bacterial susceptibility to cefuroxime in Italy and use of cefuroxime in clinical settings where beta-lactamase producing bacteria could be involved has been analysed in the review. In conclusion, cefuroxime still represents a valid therapeutic option even in presence of most of the beta-lactamase producing bacteria.
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PMID:[Cefuroxime stability to beta-lactamases: clinical implications] 1270 98

In a phase I/II study, patients with solid metastatic MAGE-3-positive tumors, mainly melanoma, were vaccinated with recombinant MAGE-3 protein combined with the immunologic adjuvant AS02B comprised of MPL and QS21 in an oil-in-water emulsion. The recombinant MAGE-3 protein was made up of a partial sequence of the protein D (ProtD) antigen of Haemophilus influenzae fused to the MAGE-3 sequence. The vaccine was given intramuscularly at 3-week intervals. Patients whose tumors stabilized or regressed after 4 vaccinations received 2 additional vaccinations at 6-week intervals. MAGE-3 and ProtD antibody and cellular immune responses were monitored after vaccination. Ninety-six percent (23/24) of the patients vaccinated with MAGE-3 protein in AS02B adjuvant elicited a significant anti-MAGE-3 IgG antibody response after 4 vaccinations, and all developed anti-ProtD IgG antibodies. For the detection of T-cell activity, total peripheral blood mononuclear cells were restimulated in vitro with MAGE-3- or ProtD-loaded autologous mature dendritic cells. In 30% of the evaluable patients vaccinated with the adjuvanted recombinant protein, IFNgamma production was increased in response to MAGE-3, and 2 patients (14% of evaluable patients) had a concomitant increase in IL-5 production. In 37% and 43% of the patients, respectively, IFNgamma or IL-5 production was increased in response to ProtD. It is concluded that vaccination of advanced cancer patients with MAGE-3 self-antigen in AS02B adjuvant is able to elicit MAGE-3-specific antibody and a T-cell response.
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PMID:Immunologic analysis of a phase I/II study of vaccination with MAGE-3 protein combined with the AS02B adjuvant in patients with MAGE-3-positive tumors. 1477 84

Previous studies suggested that nontypeable Haemophilus influenzae (NTHI) can form biofilms during human and chinchilla middle ear infections. Microscopic analysis of a 5-day biofilm of NTHI strain 2019 grown in a continuous-flow chamber revealed that the biofilm had a diffuse matrix interlaced with multiple water channels. Our studies showed that biofilm production was significantly decreased when a chemically defined medium lacking N-acetylneuraminic acid (sialic acid) was used. Based on these observations, we examined mutations in seven NTHI strain 2019 genes involved in carbohydrate and lipooligosaccharide biosynthesis. NTHI strain 2019 with mutations in the genes encoding CMP-N-acetylneuraminic acid synthetase (siaB), one of the three NTHI sialyltransferases (siaA), and the undecaprenyl-phosphate alpha-N-acetylglucosaminyltransferase homolog (wecA) produced significantly smaller amounts of biofilm. NTHI strain 2019 with mutations in genes encoding phosphoglucomutase (pgm), UDP-galactose-4-epimerase, and two other NTHI sialyltransferases (lic3A and lsgB) produced biofilms that were equivalent to or larger than the biofilms produced by the parent strain. The biofilm formed by the NTHI strain 2019pgm mutant was studied with Maackia amurensis fluorescein isothiocyanate (FITC)-conjugated and Sambucus nigra tetramethyl rhodamine isocyanate (TRITC)-conjugated lectins. S. nigra TRITC-conjugated lectin bound to this biofilm, while M. amurensis FITC-conjugated lectin did not. S. nigra TRITC-conjugated lectin binding was inhibited by incubation with alpha2,6-neuraminyllactose and by pretreatment of the biofilm with Vibrio cholerae neuraminidase. Matrix-assisted laser desorption ionization-time of flight mass spectometry analysis of lipooligosaccharides isolated from a biofilm, the planktonic phase, and plate-grown organisms showed that the levels of most sialylated glycoforms were two- to fourfold greater when the lipooligosaccharide was derived from planktonic or biofilm organisms. Our data indicate that NTHI strain 2019 produces a biofilm containing alpha2,6-linked sialic acid and that the sialic acid content of the lipooligosaccharides increases concomitant with the transition of organisms to a biofilm form.
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PMID:Nontypeable Haemophilus influenzae strain 2019 produces a biofilm containing N-acetylneuraminic acid that may mimic sialylated O-linked glycans. 1521 70

To evaluate noninvasive measures of gene expression and tumor response in a gene-dependent enzyme prodrug therapy (GDEPT), a bifunctional fusion gene between Saccharomyces cerevisiae cytosine deaminase (CD) and Haemophilus influenzae uracil phosphoribosyltransferase (UPRT) was constructed. CD deaminates 5-fluorocytosine (5FC) to 5-fluorouracil (5FU), and UPRT subsequently converts 5FU to fluorouridine monophosphate, and both of these reactions can be monitored noninvasively in vitro and in vivo using 19F magnetic resonance spectroscopy (MRS). Following transient transfection the CD-UPRT fusion protein exhibited both UPRT and CD enzymatic activities as documented by 19F MRS. In addition, an increase in CD activity and thermal stability was witnessed for the fusion protein compared to native CD. Stable expression of CD-UPRT in 9L glioma cells increased both 5FC and 5FU sensitivity in vitro compared to CD-expressing and wild-type 9L cells. Noninvasive 19F MRS of both CD and UPRT gene function in vivo demonstrated that in animals bearing CD-expressing tumors there was limited conversion of 5FC to 5FU with no measurable accumulation of cytotoxic fluorinated nucleotides (F-nucs). In contrast, CD-UPRT-expressing tumors had increased CD gene activity with a threefold higher intratumoral accumulation of 5FU and significant generation of F-nucs. Finally, CD-UPRT yielded increased efficacy in an orthotopic animal model of high-grade glioma. More importantly, early changes in cellular water mobility, which are felt to reflect cellular death, as measured by diffusion-weighted MRI, were predictive of both durable response and increased animal survival. These results demonstrate the increased efficacy of the CD-UPRT GDEPT compared to CD alone both biochemically and in a preclinical model and validate both 19F MRS and diffusion-weighted MRI as tools to assess gene function and therapeutic efficacy.
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PMID:The use of 19F spectroscopy and diffusion-weighted MRI to evaluate differences in gene-dependent enzyme prodrug therapies. 1550 9


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