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  • 1
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 540 (1988), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The application of cytokines for immunotherapy is frequently hampered by undesirable side effects. To avoid systemic effects, cytokines can be directly expressed in the target cells by using gene transfer. However, the uncontrolled cellular secretion of cytokines could still exert some undesirable bystander effects. Therefore, it is important to develop additional methods for a more restricted administration of cytokines. Recently, using the murine granulocyte–macrophage colony-stimulating factor (mGM-CSF), we have demonstrated that cytokines can be targeted to different subcellular compartments as stable and biologically active proteins. This model could be used as a method of highly restricted administration of cytokines. Here, as model for the proof of principle, we have used a cell line (DA-3) strictly dependent on mGM-CSF for growth and demonstrated that these cells acquired autonomous growth after gene modification with plasmids encoding either extracellular or intracellular forms of mGM-CSF. Cell lines expressing secreted forms of mGM-CSF displayed the highest rates of autonomous growth and released substantial amounts of mGM-CSF. However, cell lines expressing intracellular forms of mGM-CSF also acquired autonomous growth induced by a mechanism of restricted autocrine stimulation and did not release detectable mGM-CSF to the extracellular medium. Cocultivation experiments of DA-3 cell lines expressing intracellular mGM-CSF with unmodified cells showed that there was no activation of the bystander cells. Taken together, these results support the concept that genes encoding intracellular cytokines may be used to provide the desired effect of cytokines on the target cells while avoiding the side effects of their uncontrolled secretion.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The expression of the proliferation-associated nuclear antigen Ki-67 in peripheral blood mononuclear cells was studied in 30 patients with acute malarial illness and 11 healthy controls from Addis Ababa or Nazareth in Ethiopia. Seventeen patients had Plasmodium falciparum infections and 13 had Plasmodium vivax. Two-colour immunoenzymatic staining was developed in order to simultaneously detect the expression of the nuclear antigen Ki-67 and determine the surface phenotype of the cell. The median percentage of proliferating, Ki-67 positive lymphocytes was significantly higher in patients with acute P. falciparum (11.8%) and P. vivax (15.6%) illnesses compared to the controls (4.3%). The majority of Ki-67 positive cells were T cells (CD3+) while the relative increase of Ki-67 expressing cells was similar for both the CD4+ and CD8+ T-cell subsets. Our data show an increased number of activated cells driven to proliferation in the peripheral blood of patients during acute malaria illness.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    FEMS microbiology letters 89 (1992), S. 0 
    ISSN: 1574-6968
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology
    Notes: Abstract Three assays to measure antibodies against Staphylococcus aureus whole cells, lipase and staphylolysin were used to try to discriminate between complicated and uncomplicated S. aureus septicaemia. Sera were examined from 8 patients with S. aureus endocarditis, 23 patients with complicated S. aureus septicaemia, 12 patients with uncomplicated S. aureus septicaemia and 93 febrile non-septicaemic controls. No single assay could distinguish between complicated and uncomplicated S. aureus septicaemia. If the criterion for a positive result is defined as positive antibody level in the anti-lipase ELISA as well as in at least 1 of the other 2 assays, 10/31 patients with S. aureus endocarditis or complicated septicaemia were positive compared to 0/93 non-septicaemic patients and 0/12 patients with uncomplicated S. aureus septicaemia. Therefore, the combined use of serological assays in the diagnosis of complicated S. aureus septicaemia, one of which is the anti-lipase ELISA, is recommended.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 377 (1981), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 505 (1987), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1439-0973
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung 84 Patienten mit tiefen Atemwegsinfektionen wurden in einer randomisierten, doppelblind parallel geführten multizentrischen Studie mit Cefaclor oder Amoxicillin behandelt. Dabei wurde der Einfluß der Antibiotikatherapie auf die Kolonisationsresistenz untersucht. 40 Patienten erhielten Cefaclor, 44 Amoxicillin; die Dosierung betrug jeweils 250 mg dreimal täglich per os. Die Behandlung wurde sieben Tage lang durchgeführt. Vor, während und nach Antibiotikatherapie wurden Proben von Sputum, Abstriche aus dem Oropharynx und Stuhl entnommen. Die mikrobiologischen Untersuchungen dienten einerseits der Erregeridentifikation, andererseits der Verlaufskontrolle der Veränderungen der Mikroflora. Unter Cefaclor wurden 92,5%, unter Amoxicillin 88,4% der Patienten geheilt oder gebessert. Dieser Unterschied war nicht statistisch signifikant.Haemophilus influenzae, Branhamella catarrhalis undStreptococcus pneumoniae waren die häufigsten Erreger der Atemwegsinfektionen. In der Erregereradikationsrate unterschieden sich die beiden Therapien nicht. Unter Cefaclor traten keine wesentlichen Veränderungen der oropharyngealen Flora auf. Amoxicillin führte zu einer signifikanten Reduktion der Keimzahlen vonStreptococcus salivarius undVeillonella, die Enterobakterien nahmen in der oropharyngealen Mikroflora zu. Cefaclor führte zu einer signifikanten Verminderung der Keimzahlen von Streptokokken, Staphylokokken und anaeroben Kokken im Stuhl während Enterokokken, EnterobakterienBacteroides undCanadida albicans signifikant zunahmen. Auch Amoxicillin hatte zu Veränderungen der intestinalen Mikroflora mit Zunahme der Enterobakterien, anaerober grampositiver Stäbchen undBacteroides geführt. Stärkere Störungen der intestinalen Kolonisationsresistenz traten mit keiner der beiden Therapien auf.
    Notes: Summary Eighty-four patients with lower respiratory tract infections participated in a randomised double-blind parallel multicenter trial in order to compare the efficacy of cefaclor and amoxycillin as treatment for lower respiratory tract infections and their ability to influence colonization resistance. Cefaclor was given to 40 patients and amoxycillin to 44 patients perorally in doses of 250 mg t.i.d. for seven days in a double-blind fashion. Sputum, oropharyngeal and intestinal specimens were taken for microbial analysis to isolate the causative pathogen of the lower respiratory tract infection and to follow the microflora changes before, during and after antibiotic treatment. The clinical outcome showed 92.5% cured or improved patients on cefaclor versus 88.4% on amoxycillin. The difference in clinical outcome between the two treatment groups was not statistically significant. Among the pathogenic bacteria isolated,Haemophilus influenzae, Branhamella catarrhalis andStreptococcus pneumoniae dominated. There was no difference between the two treatments with regard to microbiological efficacy. Treatment with cefaclor did not cause any significant impact on the oropharyngeal microflora. Administration of amoxycillin caused a significant reduction of the number ofStreptococcus salivarius andVeillonella cocci, while an increase in number of enterobacteria was seen in the oropharyngeal microflora. In the intestinal flora, cefaclor significantly reduced the number of streptococci, staphylococci and anaerobic cocci, while the number of enterococci, enterobacteria, bacteroides andCandida albicans significantly increased. The intestinal microflora was partly influenced by amoxycillin treatment. Thus there was a significant increase in the number of enterobacteria, anaerobic gram-positive rods and bacteroides. In conclusion, none of these agents caused any major disturbances in the colonization resistance in patients with lower respiratory tract infections.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    European journal of clinical microbiology & infectious diseases 17 (1998), S. 873-876 
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The pharmacokinetics of meropenem were studied after single i.v. infusions of 15 mg meropenem/kg body weight in eight subjects with cystic fibrosis (CF) and eight healthy volunteers matched for age, sex, and weight. Significantly shorter terminal half-lives (mean, 0.74 h vs. 0.99 h) and mean residence times (mean, 1.09 h vs. 1.39 h) were noted in CF subjects. Plasma and renal clearances tended to be higher and distribution volumes smaller among the patients, but differences were not statistically significant. The results are consistent with the findings for many other beta-lactam agents used in CF patients. Assuming a MIC90 of 4 mg/l for meropenem against Pseudomonas aeruginosa, the time above the MIC was less than 3.3 h in six of the eight CF patients. This finding should be kept in mind when designing treatment regimens with meropenem in CF subjects.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1435-4373
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Deep-seated Candida infections are challenging to diagnose by noninvasive means, and new modalities are needed to improve the yield of such investigations. Reported here is a case of Candida tropicalis vertebral osteomyelitis complicating epidural catheterisation in a diabetic patient with complicated abdominal sepsis. The diagnosis was supported by detection of increased D-arabinitol/L-arabinitol ratios in urine samples, and failure of medical management was indicated by elevated D-arabinitol/L-arabinitol ratios, which later decreased to baseline with successful surgical debridement and prolonged antifungal therapy.
    Type of Medium: Electronic Resource
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