Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0032285 (pneumonia)
 54,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Toxoids of protease and elastase of Pseudomonas aeruginosa were successfully prepared by treatment with 8% formalin plus 0.2 m lysine and by 4% formalin respectively. The two toxoids proved sufficiently potent to elicit high antibody titers as estimated by both the enzyme-neutralizing and passive hemagglutination tests. The effectiveness of immunizing minks with a single component-vaccine consisting of the common antigen (OEP) of P. aeruginosa or the protease toxoid (PT) or the elastase toxoid (ET) and with the two (PT and ET) or the three (OEP, PT and ET) component-mixed vaccines, on hemorrhagic pneumonia in minks due to the bacteria was investigated. Female Sapphire minks, 3.5 months old, were used in two experiments performed in 1975 and 1976. Minks were immunized three times in one month with a total of 1 mg of each of the three antigens in the case of a single component vaccine and with a total of 2 or 3 mg (equal amounts of each component) in the case of the two or three component vaccines. Two or three weeks after the last immunization, challenge exposure with strain No. 5 was carried out by intranasally inoculating an inoculum containing serial dilutions of 10(3) -10(10) of live bacteria. Summarizing the results of the two experiments, in the case of controls, nonimmunized minks and minks immunized with potassium aluminum sulfate (potash alum) alone, the LD50 values were approximately 10(3) -10(4) with no significant difference between the two. In the case of OEP-vaccinated minks, the LD50 value was about 10(6) and thus clearly differed from those of the controls. In minks immunized with the three-component-vaccine, however, the LD50 value was about 10(8) -10(9), which indicated that the three-component-mixed vaccine was remarkably more effective than the single OEP vaccine component. In minks immunized with either PT or ET or both, the LD50 values were about 10(8) -10(9). The effectiveness of the vaccine made with ET or PT alone is discussed in the text. The pathological findings of the minks which died or survived are described.
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PMID:Effectiveness of immunization with single and multi-component vaccines prepared from a common antigen (OEP), protease and elastase toxoids of Pseudomonas aeruginosa on protection against hemorrhagic pneumonia in mink due to P. aeruginosa. 10 98

The profile of the stimulant activity of a muramyl dipeptide (MDP) analog, N2-[(N-acetylmuramoyl)-L-alanyl-D-isoglutaminyl]-N6-stearoyl-L-lysine (MDP-Lys(L18), muroctasin) on the host resistance to infection was clarified through the following results. A comparative study of parent MDP and MDP-Lys(L18) in relation to the protection against infection with various pathogens revealed the same spectrum of antiinfectious activity, but a different potency: the greater strength of MDP-Lys(L18) was demonstrated both by the smaller influence of bacterial inoculum size on its activity and by the smaller minimal dosage required for inducing significant activity. The superiority of the oral application of MDP-Lys(L18) over MDP was also demonstrated. The protective activity of the compound was substantially influenced by the timing of treatment, the greatest activity being achieved by treatment 1 day before infection. Furthermore, treatment with MDP-Lys(L18) restored the depressed resistance induced by cyclophosphamide to systemic infection with E. coli in mice, and that induced by cortisone acetate to bacteremic pneumonia with P. aeruginosa in guinea pigs. The chemotherapeutic efficacy of antibiotics on E. coli infection was potentiated by combined use of MDP-Lys(L18) for normal mice and mice immunosuppressed with cyclophosphamide. From these findings, enhancement of the host resistance to infection by MDP-Lys(L18) may be an important aspect in the future evaluation of therapy for infection in immunocompromised patients. Finally, since the compound augmented 1. the function of polymorphonuclear leukocytes, such as chemotaxis, phagocytosis, and superoxide anion generating capacity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Stimulation of non-specific resistance to infection by muroctasin. 305 26

70 children aged 4 to 12 years with acute infection and inflammation of the respiratory tract (laryngitis, tracheitis, bronchitis, pneumonia) were enrolled in a double-blind investigation and randomised to treatment with nimesulide (50mg granules twice daily) or lysine-aspirin (360mg granules twice daily) for 5 days. The drugs were similarly effective in reducing cough, asthenia and dyspnoea, although nimesulide-treated patients experienced fewer gastrointestinal adverse events. These results confirm the efficacy of nimesulide in the treatment of respiratory inflammation and provide preliminary evidence of its value in children.
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PMID:Double-blind evaluation of nimesulide vs lysine-aspirin in the treatment of paediatric acute respiratory tract infections. 750 76

Carboxypeptidase M (CPM) cleaves the C-terminal arginine and lysine of peptides; it is expressed in the lung, especially on the plasma membrane of alveolar type I cells. Here, we report on CPM in human bronchoalveolar lavage (BAL) collected from 69 patients and analyzed for activity, cell number and type, and protein level. Seventy-six percent of CPM activity, measured at pH 7.5 with 5-dimethylamino-naphthalene-1-sulfonyl-alanyl-arginine (Dansyl-Ala-Arg) substrate, was immunoprecipitated with polyclonal antibody to purified human enzyme. In patients without active lung disease, CPM activity in BAL was 7.69 (+/- 2.12) nmol/h/mg protein, but in patients with acute pneumonia, it was 29.25 (+/- 4.06) (p < 0.01). In patients with Pneumocystis carinii pneumonia, CPM activity was elevated to 26.00 (+/- 4.85) (p < 0.01) and in patients with lung cancer, to 30.95 (+/- 4.12) (p < 0.01). The activity was not associated with the cellular elements of BAL. The highest specific activity was in the large aggregate fraction of surfactant, which also contained the highest concentration of phosphorus. Transmission electron microscopy of this fraction revealed the presence of typical lamellar bodies and tubular myelin structures. The high CPM activity may stem from its induction and release in acute lung disease. In addition, CPM may be a marker of infection with certain pathogens and an indicator of type I cell injury in parenchymal lung diseases.
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PMID:Carboxypeptidase M activity is increased in bronchoalveolar lavage in human lung disease. 763 39

Addressing diseases of a high burden with the most cost-effective interventions could do much to reduce disease in the population. We conducted a cost-effectiveness analysis of 40 health interventions in Guinea, a low-income country in sub-Saharan Africa, using local data. Interventions were selected from treatment protocols at health centres, first referral hospitals and national programmes in Guinea, based upon consultation with health care providers and government plans. For each intervention, we calculated the costs (comprising labour, drugs, supplies, equipment, and overhead) in relation to years of life saved, discounted at 3%. The results show that the per capita costs and effectiveness of any intervention vary considerably. Average costs show no clear pattern by level of care, but effectiveness is generally highest for curative hospital interventions. Several interventions have a cost-effectiveness of US$100 per year of life saved (LYS) or less, and address more than 5% of total years of life lost. These include health centre interventions such as: treatment of childhood pneumonia ($3/LYS); rehydration therapy for diarrhoea ($7/LYS); integrated management of childhood pneumonia, malaria and diarrhoea ($8/LYS); short-course treatment of tuberculosis ($12/LYS); treatment of childhood malaria ($13/LYS), and childhood vaccination ($25/LYS). Outreach programmes for impregnated bed nets against malaria cost $43/LYS. Maternal and perinatal diseases, have slightly less cost-effective interventions: integrated family planning, prenatal and delivery care at health centres ($109/LYS) or outreach programmes to provide prenatal and delivery care ($283/LYS). A minimum package of health services would cost approximately $13 per capita, and would address a large proportion (69%) of major causes of premature mortality. This minimum package would cost about three times the current public spending on health, suggesting that health spending needs to rise to achieve good health outcomes.
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PMID:The cost-effectiveness of forty health interventions in Guinea. 1018 95

Sepsis-induced nitric oxide (NO) overproduction has been implicated in a redistribution of flow from the pancreas making it vulnerable to ischemic injury in septic shock. To test this hypothesis in a remote injury model of normotensive sepsis, we induced Pseudomonas pneumonia in the rat and used intravital video microscopy (IVVM) of the pancreas to measure functional capillary density, capillary hemodynamics [red blood cell (RBC) velocity, lineal density, and supply rate], and lethal cellular damage (propidium iodine staining) at 6 and 24 h after the induction of pneumonia. With pneumonia, plasma nitrite/nitrate [NO2(-)/NO3(-)(NOx(-))] levels were doubled by 21 h (P < 0.05). To assess the effect of NO overproduction on microvascular perfusion, N6-(1-iminoethyl)-L-lysine (L-NIL) was administered to maintain NOx(-) levels at baseline. Pneumonia did cause a decrease in RBC velocity of 23% by 6 h, but by 24 h RBC velocity and supply rate had increased relative to sham by 22 and 38%, respectively (P < 0.05). L-NIL treatment demonstrated that this increase was due to NO overproduction. With pneumonia, there was no change in functional capillary density and only modest increases in cellular damage. We conclude that, in this normotensive pneumonia model of sepsis, NO overproduction was protective of microvascular perfusion in the pancreas.
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PMID:Effect of nitric oxide on capillary hemodynamics and cell injury in the pancreas during Pseudomonas pneumonia-induced sepsis. 1296 89

ExoT is a type III secreted effector protein found in almost all strains of Pseudomonas aeruginosa and is required for full virulence in an animal model of acute pneumonia. It is comprised of an N-terminal domain with GTPase activating protein (GAP) activity towards Rho family GTPases and a C-terminal ADP ribosyltransferase (ADPRT) domain with minimal activity towards a synthetic substrate in vitro. Consistent with its activity as a Rho family GTPase, ExoT has been shown to inhibit P. aeruginosa internalization into epithelial cells and macrophages, disrupt the actin cytoskeleton through a Rho-dependent pathway, and inhibit wound repair in a scrape model of injured epithelium. We have previously shown that mutation of the invariant arginine of the GAP domain to lysine (R149K) results in complete loss of GAP activity in vitro but only partially inhibits ExoT anti-internalization and cell rounding activity. We have constructed in-frame deletions and point mutations within the ADPRT domain in order to test whether this domain might account for the residual activity observed in ExoT GAP mutants. Deletion of a majority of the ADPRT domain (residues 234 to 438) or point mutations of the ADPRT catalytic site (residues 383 to 385) led to distinct changes in host cell morphology and substantially reduced the ability of ExoT to inhibit in vitro epithelial wound healing over a 24-h period. In contrast, only subtle effects on the efficiency of ExoT-induced bacterial internalization were observed in the ADPRT mutant forms. Expression of each domain individually in Saccharomyces cerevisiae was toxic, whereas expression of each of the catalytically inactive mutant domains was not. Collectively, these data demonstrate that the ADPRT domain of ExoT is active in vivo and contributes to the pathogenesis of P. aeruginosa infections.
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PMID:The ADP ribosyltransferase domain of Pseudomonas aeruginosa ExoT contributes to its biological activities. 1468 36

Aspergillus fumigatus is an important pathogen of the immunocompromised host, causing pneumonia and invasive disseminated disease with high mortality. In order to determine the importance of lysine biosynthesis for growth and pathogenicity, the A. fumigatus lysF gene, encoding a homologue of the A. nidulans homoaconitase LysF, was cloned and characterized. Cosmid cosGTM encoding lysF complemented a lysF mutant of Aspergillus nidulans. A. fumigatus lysF was deleted, resulting in a lysine-auxotroph. This phenotype was complemented to the wild-type by supplementation of the medium with both L-lysine and alpha-aminoadipic acid, or transformation using cosmid cosGTM. To study the virulence of the lysF deletion mutant of A. fumigatus, a low-dose intranasal mouse infection model of invasive aspergillosis was optimized for immunosuppressed BALB/c mice, allowing the application of an infection dose as low as 5 x 10(3) conidia per mouse. In this murine model, the Delta lysF mutant was avirulent, suggesting that lysine biosynthesis, or at least a functional homoaconitase, is important for survival of A. fumigatus in vivo and a potential target for antifungal drugs.
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PMID:Deletion of the Aspergillus fumigatus lysine biosynthesis gene lysF encoding homoaconitase leads to attenuated virulence in a low-dose mouse infection model of invasive aspergillosis. 1505 76

Pulmonary surfactant has two distinct functions within the lung: reduction of surface tension at the air-liquid interface and participation in innate host defense. Both functions are dependent on surfactant-associated proteins. Pseudomonas aeruginosa is primarily responsible for respiratory dysfunction and death in cystic fibrosis patients and is also a leading pathogen in nosocomial pneumonia. P. aeruginosa secretes a number of proteases that contribute to its virulence. We hypothesized that P. aeruginosa protease IV degrades surfactant proteins and results in a reduction in pulmonary surfactant host defense and biophysical functions. Protease IV was isolated from cultured supernatant of P. aeruginosa by gel chromatography. Incubation of cell-free bronchoalveolar lavage fluid with protease IV resulted in degradation of surfactant proteins (SP)-A, -D, and -B. SPs were degraded in a time- and dose-dependent fashion by protease IV, and degradation was inhibited by the trypsin-like serine protease inhibitor Nalpha-p-tosyl-L-lysine-chloromethyl ketone (TLCK). Degradation by protease IV inhibited SP-A- and SP-D-mediated bacterial aggregation and uptake by macrophages. Surfactant treated with protease IV was unable to reduce surface tension as effectively as untreated surfactant, and this effect was inhibited by TLCK. We speculate that protease IV may be an important contributing factor to the development and propagation of acute lung injury associated with P. aeruginosa via loss of surfactant function within the lung.
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PMID:Pseudomonas aeruginosa protease IV degrades surfactant proteins and inhibits surfactant host defense and biophysical functions. 1551 85

X-linked hyper-IgM syndrome (XHIM) is a rare primary immunodeficiency disorder caused by mutations of the gene encoding the CD40 ligand (CD40L). It is characterized by recurrent infections with markedly decreased serum IgG, IgA and IgE levels but normal or elevated IgM levels. We report the clinical manifestations and complete immune studies in the first family with molecularly proven XHIM in Taiwan. A 5-month-old boy presented with rapidly progressive pneumonia which responded poorly to antibiotics. High levels of IgM and very low levels of IgG, IgA, and IgE were noted in his plasma specimen: IgM, 128 mg/dl; IgG, 18 mg/dl; IgA, 4 mg/dl); IgE, 1 IU/ml. Whole blood flow cytometry when he was 21 months old showed that only a small percentage (0.48%) of his in vitro-activated CD4+ T cells expressed CD40L. When he was 3 years old, repeated flow cytometry showed essentially the same result (0.4%), compared with his father's CD40L expression of over 85%. The patient's mother had moderately decreased CD40L expression (74.4%). Hyper-IgM syndrome was confirmed by CD40L mutation analysis in the boy, which revealed a Lys 96 stop (nucleotide A307T) in exon 2 of CD40L, with a truncated protein resulting in the loss of the entire TNF domain. His mother was a carrier and apparently the individual in whom the mutation originated. Eleven other family members, including the patient's father, sister, and grandmother, and the mother's sisters and their children, all had normal results on CD40L mutation analysis. The patient has remained without significant bacterial infection on a regimen of monthly IVIG infusion and oral trimethoprim-sulfamethoxazole for Pneumocystis carinii pneumonia (PCP) prophylaxis, although he has had recurrent oral ulcers and neutropenia. Bone marrow transplantation is planned.
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PMID:De novo mutation causing X-linked hyper-IgM syndrome: a family study in Taiwan. 1599 75


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