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

The epidermal growth factor-seven transmembrane (EGF-TM7) family is a group of seven-span transmembrane receptors predominantly expressed by cells of the immune system. Family members CD97, EGF module-containing mucin-like receptor (EMR) 1, EMR2, EMR3, EMR4, and EGF-TM7-latrophilin-related protein are characterized by an extended extracellular region with a variable number of N-terminal EGF-like domains. EGF-TM7 receptors bind cellular ligands as demonstrated by the interaction of CD97 with decay accelerating factor (CD55) and dermatan sulfate. Investigating the effect of newly generated mAb on the migration of neutrophilic granulocytes, we here report for the first time in vivo data on the function of CD97. In dextran sulfate sodium-induced experimental colitis, we show that homing of adoptively transferred neutrophils to the colon was significantly delayed when cells were preincubated with CD97 mAb. The consequences of this defect in neutrophil migration for host defense are demonstrated in a murine model of Streptococcus pneumoniae-induced pneumonia. Mice treated with CD97 mAb to EGF domain 1 (1B2) and EGF domain 3 (1C5) displayed a reduced granulocytic inflammatory infiltrate at 20 h after inoculation. This was associated with a significantly enhanced outgrowth of bacteria in the lungs at 44 h and a strongly diminished survival. Together, these findings indicate an essential role for CD97 in the migration of neutrophils.
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PMID:The epidermal growth factor-seven transmembrane (EGF-TM7) receptor CD97 is required for neutrophil migration and host defense. 1470 87

Bacterial surface carbohydrates are important pathogenic factors in gram-negative pneumonia infections. Among these factors, O antigen has been reported to protect pathogens against complement-mediated killing. To examine further the role of O antigen, we insertionally inactivated the gene encoding a galactosyltransferase necessary for serotype O1 O-antigen synthesis (wbbO) from Klebsiella pneumoniae 43816. Analysis of the mutant lipopolysaccharide by sodium dodecyl sulfate-polyacrylamide gel electrophoresis confirmed the absence of O antigen. In vitro, there were no detectable differences between wild-type K. pneumoniae and the O-antigen-deficient mutant in regard to avid binding by murine complement C3 or resistance to serum- or whole-blood-mediated killing. Nevertheless, the 72-h 50% lethal dose of the wild-type strain was 30-fold greater than that of the mutant (2 x 10(3) versus 6 x 10(4) CFU) after intratracheal injection in ICR strain mice. Despite being less lethal, the mutant organism exhibited comparable intrapulmonary proliferation at 24 h compared to the level of the wild type. Whole-lung chemokine expression (CCL3 and CXCL2) and bronchoalveolar inflammatory cell content were also similar between the two infections. However, whereas the wild-type organism produced bacteremia within 24 h of infection in every instance, bacteremia was not seen in mutant-infected mice. These results suggest that during murine pneumonia caused by K. pneumoniae, O antigen contributes to lethality by increasing the propensity for bacteremia and not by significantly changing the early course of intrapulmonary infection.
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PMID:The Klebsiella pneumoniae O antigen contributes to bacteremia and lethality during murine pneumonia. 1497 47

Shuang-Huang-Lian (SHL) is a traditional Chinese formula containing Flos lonicerae, Radix scutellariae (RS) and Fructus forsythiae, and is commonly used for treating acute upper respiratory tract infection, acute bronchitis and light pneumonia. The aim of the present study is to compare the metabolites of baicalin in rats when orally administered with SHL and Radix scutellariae, and try to explore the principle of SHL compatibility. By using LC-MS(n) and HPLC-DAD, the metabolites of baicalin were analyzed from bile, urine and feces of rats dosed with SHL and RS. Our results showed significant difference of baicalin metabolism between RS and SHL. However, baicalein was found to be the main metabolites of baicalin in intestinal tract after oral administration of RS and SHL, glucuronide, glucoside and methylated products were also found in rat urine after administration of either RS or SHL. Meanwhile, several sulphates were found in rat urine after RS administration, but not found after SHL. Among the metabolites of the SHL, potentially there existed a isomerized baicalin and methylated product: 5,7-dihydroxy-6-methoxyisoflavone-7-O-beta-glucopyranuronoside, but without unidentified metabolite M3. Baicalein-6-O-beta-glucopyranuronoside-7-O-beta-glucopyranuronoside and baicalein-6-O-beta-glucose-7-O-beta-glucopyranuronoside were first reported by this study. The major metabolites of baicalin of RS and SHL in rat bile were the same, including baicalin-6-O-beta-glucopyranuronoside-7-O-beta-glucopyranuronoside, baicalin-6-beta-glucopyranuronoside and 6-O-methyl-baicalin-7-O-beta-glucopyranuronoside. Moreover, baicalein-6-O-beta-glucose-7-O-beta-glucopyranuronoside was also first found in rat bile by this study. Although baicalin-6-O-sulfate-7-O-beta-glucopyranuronoside was found in rat bile after RS administration, no sulphated products were found after oral administration of SHL. These differences of baicalin metabolism between RS and SHL indicated that compatibility of medicines could result in the differences of metabolites.
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PMID:Comparison of the metabolism of baicalin in rats orally administered with Radix scutellariae extract and Shuang-Huang-Lian extract. 1607 31

Mycoplasma hyopneumoniae is the causative agent of porcine enzootic pneumonia, a chronic and economically significant respiratory disease that affects swine production worldwide. M. hyopneumoniae adheres to and adversely affects the function of ciliated epithelial cells of the respiratory tract, and the cilium adhesin (Mhp183, P97) is intricately but not exclusively involved in this process. Although binding of pathogenic bacteria to glycosaminoglycans is a recognized step in pathogenesis, knowledge of glycosaminoglycan-binding proteins in M. hyopneumoniae is lacking. However, heparin and other sulfated polysaccharides are known to block the binding of M. hyopneumoniae to purified swine respiratory cilia. In this study, four regions within the cilium adhesin were examined for the ability to bind heparin. Cilium adhesin fragments comprising 653 amino acids of the N terminus and 301 amino acids of the C terminus (containing two repeat regions, R1 and R2) were cloned and expressed. These fragments bound heparin in a dose-dependent and saturable manner with physiologically significant binding affinities of 0.27 +/- 0.02 microM and 1.89 +/- 0.33 microM, respectively. Heparin binding of both fragments was strongly inhibited by the sulfated polysaccharides fucoidan and mucin but not by chondroitin sulfate B. When the C-terminal repeat regions R1 and R2 were cloned separately and expressed, heparin-binding activity was lost, suggesting that both regions are required for heparin binding. The ability of the cilium adhesin to bind heparin indicates that this molecule plays a multifunctional role in the adherence of M. hyopneumoniae to host respiratory surfaces and therefore has important implications with respect to the pathogenesis of this organism.
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PMID:Two domains within the Mycoplasma hyopneumoniae cilium adhesin bind heparin. 1636 4

The halophilous cyanobacterium Aphanothece halophytica releases large sums of single type sulfated exopolysaccharide in late logarithmic growth phase in culture. This polysaccharide contained sulfate up to 34.46% of the total moieties in the molecular. As a sulfated polysaccharide that can be biosynthesized in large quantities, however, its antiviral activity has not yet been reported. In this study, we examined effects of exopolysaccharide from A. halophytica Fremy (EPAH) on influenza virus A FM (H1N1) (FM1)-induced pneumonia and reduction in immunocompetence in mice. Previous and simultaneous treatment of EPAH at a dose of 60 mg/kg significantly inhibited pneumonia in FM1-infected mice by 30.4% and 26.7%, respectively. In post-treatment, EPAH displayed its most effective inhibition at a dose of 80 mg/kg with the inhibition rate at 18.69%. Simultaneous treatment of FM1-infected mice with EPAH showed effective improvement on reduction of lymphocyte number with its most effective dose at 60 mg/kg. FM1-infected mice simultaneously received EPAH at a dose of 40 mg/kg also acquired obvious enhancement on release of IL-2 on day 15, and those received EPAH at a dose of 60 mg/kg showed similar enhancement on day 10. Simultaneous treatment with EPAH indicated remarkable recovery or improvement of FM1-induced reduction of IL-1beta level and phagocytic capacity of RES. Simultaneous treatment with EPAH significantly resumed the cytolytic activity of natural killer cells in FM1-infected or CP treated mice at doses of 40 and 60 mg/kg. These results suggested that EPAH is an effective agent against FM1. The mechanisms of its action might be mediated, at least in part, by modulating the host immune system and the interaction positive charges in EPAH and negative charges FM1.
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PMID:Oral administration of exopolysaccharide from Aphanothece halophytica (Chroococcales) significantly inhibits influenza virus (H1N1)-induced pneumonia in mice. 1671 12

The data on preparation of liposome-entrapped gentamicin sulfate and cefoperazone and their investigation on albino mice with staphylococcal destructive pneumonia are presented. Comparative study of the efficacy of gentamicin sulfate and cefoperazone in free and liposome-entrapped forms showed that immobilization of the antibiotics in phospholipid vesicles provided a 2-fold increase of their efficacy.
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PMID:[Experimental study on the therapeutic effect of liposome-entrapped antibiotics in the treatment of destructive pneumonia]. 1701 6

Sanfilippo type B is an autosomal recessive mucopolysaccharidosis (MPS IIIB) caused by deficiency of N-acetyl-alpha-D-glucosaminidase, a lysosomal enzyme involved in the degradation of heparan sulfate. It is characterized by neurologic degeneration, behavioral problems, and mental decline. Somatic features are relatively mild and patients with this disorder can reach late adulthood. It is the most common subtype of MPS in the Netherlands and probably underdiagnosed in adult persons with mental retardation (MR). In order to increase knowledge on the adult phenotype and natural history in Sanfilippo type B, we present the clinical data of 20 patients with this disorder. Sixteen of them were followed for one to three decades. Six died between 28 and 69 years of age, mainly from pneumonia and cachexia; the surviving patients were 18-63 years old. Apart from the youngest, they had lost mobility at 36-68 years. Most had developed physical problems, in particular in the 4th-6th decade of life: cardiac disease (cardiomyopathy, atrial fibrillations), arthritis, skin blistering, swallowing difficulties requiring feeding by a gastrostomy tube, and seizures. The course of the disease was dominated in most of them by challenging behavioral problems with restlessness, extreme screaming and hitting, difficult to prevent or to treat pharmaceutically. Even in absence of knowledge of the history of an elderly patient with MR, the presence of behavioral problems should prompt metabolic investigation for MPS.
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PMID:Is Sanfilippo type B in your mind when you see adults with mental retardation and behavioral problems? 1764 47

This review, primarily for general readers, briefly presents experimental approaches to therapeutics of cancer, HIV/AIDS and various other diseases based on advances in glycobiology and glycochemistry. Experimental cancer and HIV/AIDS vaccines are being developed in attempts to overcome weak immunological responses to carbohydrate-rich surface antigens using carriers, adjuvants and novel carbohydrate antigen constructs. Current carbohydrate-based vaccines are used for typhus, pneumonia, meningitis; vaccines for anthrax, malaria and leishmaniasis are under development. The link between O-linked beta-N-acetylglucosamine glycosylation and protein phosphorylation in diseases including diabetes and Alzheimer's disease is also explored. Carbohydrate-associated drugs that are in current use or under development, such as heparan sulfate binders, lectins, acarbose, aminoglycosides, tamiflu and heparin, and technologies using carbohydrate and lectin microarrays that offer improved diagnostic and drug development possibilities, are described. Advances in carbohydrate synthesis, analysis and manipulation through the emerging fields of glycochemistry and glycobiology are providing new approaches to disease therapeutics.
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PMID:Carbohydrate-based experimental therapeutics for cancer, HIV/AIDS and other diseases. 1796 23

Vomiting after feeding is a symptom of gastroesophageal reflux (GER) and of eosinophilic esophagitis (EE), which are considered to be a cause of infant feeding disorder. The objective of the present study was to evaluate swallowing in children with feeding disorder manifested by vomiting after feeding. Using clinical and videofluoroscopic methods we studied the swallowing of 37 children with vomiting after feeding (mean age=15.4 months), and of 15 healthy children (mean age=20.5 months). In the videofluoroscopic examination the children swallowed a free volume of milk and 5 ml of mashed banana, both mixed with barium sulfate. We evaluated five swallows of liquid and five swallows of paste. The videofluoroscopic examination was recorded at 60 frames/s. Patients had difficulty during feeding, pneumonia, respiratory distress, otitis, and irritability more frequently than controls. During feeding, children with vomiting, choke were irritable, and refused food more frequently than controls, and during the videofluoroscopic examination the patients had more backward movement of the head than controls for both the liquid and paste boluses. There was no difference in the timing of oral swallowing transit, pharyngeal swallowing transit, or pharyngeal clearance between patients and controls. We conclude that children with vomiting after feeding may have difficulties in accepting feeding, although they have no alteration of oral and pharyngeal phases of swallowing.
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PMID:Evaluation of swallowing in children with vomiting after feeding. 1797 60

Klebsiella pneumoniae is both an opportunistic pathogen and a commensal organism. We have previously reported that K. pneumoniae strain IA565 (KpIA565) is non-pathogenic in a murine model of acute pneumonia. In this study, KpIA565 was inoculated into wild-type mice and found to stably colonize and persist in the nasal cavity and gastrointestinal tract of mice for up to 3weeks post-inoculation. Intranasal inoculation of wild-type or germ-free mice with KpIA565 resulted in similar bacterial levels in the nasal cavity, suggesting KpIA565 nasal colonization is independent of normal nasal microbiota. In contrast, KpIA565 gastrointestinal tract colonization was significantly higher in germ-free mice than in wild-type mice, indicating that members of the endogenous microbiota regulate KpIA565 colonization. In the presence of non-specific dextran sodium sulfate-induced inflammation, KpIA565 gastrointestinal tract colonization was significantly higher when compared to non-DSS treated mice. Interestingly, KpIA565 colonization was unaffected by Citrobacter rodentium-induced gastrointestinal tract inflammation. However, gastrointestinal tract colonization with K. pneumoniae strain IA565 had no impact on the inflammatory histopathology in either colitis model. This study is the first to identify and describe mechanisms influencing the growth and behavior of a murine commensal strain of K. pneumoniae.
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PMID:Host and microbiota factors that control Klebsiella pneumoniae mucosal colonization in mice. 1876 69


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