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  • 1
    Keywords: DENDRITIC CELLS ; ESCHERICHIA-COLI ; NECROSIS-FACTOR-ALPHA ; EPITHELIAL-CELLS ; IMMUNE-RESPONSE ; MATRIX METALLOPROTEINASES ; CHEMOKINE RECEPTORS ; URINARY-TRACT-INFECTION ; BACTERIAL-INFECTION ; BASEMENT-MEMBRANES
    Abstract: The phagocytes of the innate immune system, macrophages and neutrophils, contribute to antibacterial defense, but their functional specialization and cooperation is unclear. Here, we report that three distinct phagocyte subsets play highly coordinated roles in bacterial urinary tract infection. Ly6C(-) macrophages acted as tissue-resident sentinels that attracted circulating neutrophils and Ly6C(+) macrophages. Such Ly6C(+) macrophages played a previously undescribed helper role: once recruited to the site of infection, they produced the cytokine TNF, which caused Ly6C(-) macrophages to secrete CXCL2. This chemokine activated matrix metalloproteinase-9 in neutrophils, allowing their entry into the uroepithelium to combat the bacteria. In summary, the sentinel macrophages elicit the powerful antibacterial functions of neutrophils only after confirmation by the helper macrophages, reminiscent of the licensing role of helper T cells in antiviral adaptive immunity. These findings identify helper macrophages and TNF as critical regulators in innate immunity against bacterial infections in epithelia.
    Type of Publication: Journal article published
    PubMed ID: 24485454
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  • 2
    ISSN: 1432-1041
    Keywords: cimetidine ; chronic haemodialysis ; pirenzepine ; uraemia ; parathormone ; plasma calcitonin ; secondary hyperparathyroidism
    Source: Springer Online Journal Archives 1860-2000
    Topics: Chemistry and Pharmacology , Medicine
    Notes: Summary The acute effects of intravenous injection of cimetidine and pirenzepine on plasma iPTH and CT were studied in seven patients on chronic haemodialysis and seven healthy controls. As expected, the resting iPTH and CT levels were significantly higher in patients on RDT than in the healthy subjects. Both drugs decreased to a similar extent the increased plasma iPTH in the patients, but neither was able entirely to normalize the elevated level. The CT concentration in the patients on haemodialysis was significantly decreased by cimetidine but was only moderately reduced by pirenzepine. As neither drug was able to normalize the elevated PTH level in patients on chronic dialysis, it can be assumed that neither used alone would improve signs and symptoms of secondary hyperparathyroidism.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    ISSN: 1433-8491
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-072X
    Keywords: Evolution ; Nif genes ; Nitrogen fixation ; Nitrogenase ; Nucleotide sequence ; Phylogeny ; Rhizobium ; 16S rRNA cataloguing
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract It was known that nitrogenase genes and proteins are well conserved even though they are present in a large variety of phylogenetically diverse nitrogen fixing bacteria. This has lead to the speculation, among others, that nitrogen fixation (nif) genes were spread by lateral gene transfer relatively late in evolution. Here we report an attempt to test this hypothesis. We had previously established the complete nucleotide sequences of the three nitrogenase genes from Bradyrhizobium japonicum, and have now analyzed their homologies (or the amino acid sequence homologies of their gene products) with corresponding genes (and proteins) from other nitrogen fixing bacteria. There was a considerable sequence conservation which certainly reflects the strict structural requirements of the nitrogenase iron-sulfur proteins for catalytic functioning. Despite this, the sequences were divergent enough to classify them into an evolutionary scheme that was conceptually not different from the phylogenetic positions, based on 16S rRNA homology, of the species or genera harboring these genes. Only the relation of nif genes of slow-growing rhizobia (to which B. japonicum belongs) and fast-growing rhizobia was unexpectedly distant. We have, therefore, performed oligonucleotide cataloguing of their 16S rRNA, and found that there was indeed only a similarity of S AB=0.53 between fast- and slowgrowing rhizobia. In conclusion, the results suggest that nif genes may have evolved to a large degree in a similar fashion as the bacteria which carry them. This interpretation would speak against the idea of a recent lateral distribution of nif genes among microorganisms.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-1440
    Keywords: Cimetidine ; Pirenzepine ; Parathyroid hormone ; Calcitonin ; Cimetidin ; Pirenzepin ; Parathormon-Calcitonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In letzter Zeit wurde über den Langzeiteffekt von Cimetidin, eines Histamin2-Rezeptorantagonisten, erhöhte PTH Serumkonzentrationen beim sekundären1 und primären Hyperparathyroidismus2 zu senken, berichtet. Dabei wurde auch eine Verbesserung des klinischen Bildes beobachtet. Wir haben die Wirkung von Cimetidin und Pirenzepin auf den Plasmaspiegel von PTH und CT bei Patienten mit sekundären Hyperparathyroidismus in einem Kurzzeitversuch geprüft. Eine signifikante Senkung der PTH Serumkonzentration wurde mit Cimetidin nach 30 min für die Dauer von 30 min gesehen. Mit Pirenzepin zeigte sich erst 60 min nach der Infusion ein 60 min lange anhaltender signifikanter Abfall der PTH Serumkonzentration. Der Calcitonin Serumspiegel war nur mit Cimetidin signifikant senkbar.
    Notes: Summary Long-term administration of cimetidine, a histamine2 receptor antagonist, has been reported to normalize elevated parathyroid hormone (PTH) concentrations in patients with secondary [1] and primary hyperparathyroidism [2] and even to improve the clinical symptoms. We have compared the effect of cimetidine and pirenzepine on PTH and calcitonin (CT) plasma levels in a short-term trial on patients with secondary hyperparathyroidism. After cimetidine a significant effect on PTH was seen within 30 min lasting 30 min and after pirenzepine, within 60 min and lasting 60 min. The effect on CT was only significant after cimetidine.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1476-5535
    Keywords: Keywords: biotin production; E. coli bio operon; Agrobacterium/Rhizobium HK4; limiting growth conditions
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Process Engineering, Biotechnology, Nutrition Technology
    Notes: E. coli biotin (bio) operon was modified to improve biotin production by host cells: (a) the divergently transcribed wild-type bio operon was re-organized into one transcriptional unit; (b) the wild-type bio promoter was replaced with a strong artificial (tac) promoter; (c) a potential stem loop structure between bioD and bioA was removed; and (d) the wild-type bioB ribosomal binding site (RBS) was replaced with an artificial RBS that resulted in improved bioB expression. The effects of the modifications on the bio operon were studied in E. coli by measuring biotin and dethiobiotin production, and bio gene expression with mini-cells and two-dimensional polyacrylamide gel electrophoresis. The modified E. coli bio operon was introduced into a broad host-range plasmid and used to transform Agrobacterium/Rhizobium HK4, which then produced 110 mg L−1 of biotin in a 2-L fermenter, growing on a defined medium with diaminononanoic acid as the starting material. Biotin production was not growth-phase dependent in this strain, and the rate of production remained high under limiting (maintenance) and zero growth conditions.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1750
    Keywords: Escherichia coli hemolysin ; Thrombin ; Human endothelial cells ; Adult respiratory distress syndrome ; Phosphodiesterases ; Endothelial permeability ; Rolipram
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The regulation of endothelial permeability is poorly understood. An increase in endothelial permeability in the pulmonary microvasculature, however, is critical in noncardiogenic pulmonary edema and other diffuse inflammatory reactions. In the present study thrombin and Escherichia coli hemolysin (HlyA), a membrane-perturbing bacterial exotoxin, were used to alter hydraulic permeability of porcine pulmonary artery and human endothelial cell monolayers. We also investigated the pharmacological approach of adenylyl cyclase activation/phosphodiesterase (PDE) inhibition to block endothelial hyperpermeability. Thrombin (1–5 units/ml) and H1yA (0.5–3 hemolytic units/ml) dose and time dependently (〉15 min) increased endothelial permeability. Forskolin, cholera toxin, and prostaglandin E1, which all stimulate adenylyl cyclase activity, abrogated this effect. One MM dibutyryl CAMP, a cell membrane-permeable CAMP analogue, was similarly active. Endothelial hyperpermeability was also reduced dose dependently by inhibitors of different PDE isoenzymes (motapizone, rolipram, and zardaverine, which block PDE3 and/or PDE4). The effectiveness of PDE inhibitors was increased in the presence of adenylyl cyclase activators. Analysis of cyclic nucleotide hydrolyzing PDE activity in lysates of human umbilical vein endothelial cells showed high activities of PDE isoenzymes 2, 3, and 4. Consistent with the functional data PDE3 and PDE4 were the major cAMP hydrolysis enzymes in intact endothelial cells. We conclude that the hyperpermeability of pulmonary endothelial monolayers, evoked by thrombin or H1yA, can be blocked by the simultaneous activation of adenylyl cyclase and inhibition of PDEs, especially of PDE3 and PDE4. The demonstration of PDE isoenzymes 2–4 in human endothelial cells will help optimize this therapeutic approach.
    Type of Medium: Electronic Resource
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  • 8
    Publication Date: 2018-06-05
    Description: Astrocytic hyperactivity is an important contributor to neuronal-glial network dysfunction in Alzheimer’s disease (AD). We have previously shown that astrocyte hyperactivity is mediated by signaling through the P2Y1 purinoreceptor (P2Y1R) pathway. Using the APPPS1 mouse model of AD, we here find that chronic intracerebroventricular infusion of P2Y1R inhibitors normalizes astroglial and neuronal network dysfunction, as measured by in vivo two-photon microscopy, augments structural synaptic integrity, and preserves hippocampal long-term potentiation. These effects occur independently from β-amyloid metabolism or plaque burden but are associated with a higher morphological complexity of periplaque reactive astrocytes, as well as reduced dystrophic neurite burden and greater plaque compaction. Importantly, APPPS1 mice chronically treated with P2Y1R antagonists, as well as APPPS1 mice carrying an astrocyte-specific genetic deletion (Ip3r2 –/– ) of signaling pathways downstream of P2Y1R activation, are protected from the decline of spatial learning and memory. In summary, our study establishes the restoration of network homoeostasis by P2Y1R inhibition as a novel treatment target in AD.
    Keywords: Neuroscience
    Print ISSN: 0022-1007
    Electronic ISSN: 1540-9538
    Topics: Medicine
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