ABSTRACTDendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of p... more ABSTRACTDendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 (also known as UBD), which localises to aggresomes, structures that are similar to DALIS. FAT10 is conjugated to substrate proteins and serves as a signal for their rapid and irreversible degradation by the 26S proteasome similar to, yet independently of ubiquitin, thereby contributing to antigen presentation. Here, we have investigated whether FAT10 is involved in the formation and turnover of DALIS, and whether proteins accumulating in DALIS can be modified through conjunction to FAT10 (FAT10ylated). We found that FAT10 localises to DALIS in maturing DCs and that this localisation occurs independent...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2017
Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) impro... more Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) improved ICU, hospital and 28-day survival in Intensive Care Units (ICU) with low levels of antibiotic resistance. Yet, it is unclear whether the effect differs between medical and surgical ICU patients. In an individual patient data meta-analysis we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16,528 hospital admissions and 17,884 ICU-admissions for complete case analysis. Compared to standard care or placebo the pooled adjusted odds ratios (aOR) for hospital mortality was 0·82 (95% Confidence Interval [CI] 0·72 - 0·93) for SDD and 0·84 (95%-CI 0·73 - 0·...
... WA Krueger · M. Trick · TH Schroeder · KE Unertl ... Unsere Daten zeigen, dass die Verwen-dun... more ... WA Krueger · M. Trick · TH Schroeder · KE Unertl ... Unsere Daten zeigen, dass die Verwen-dung von Prüfgasen mit Analysenzertifi-kat eine technisch einfach realisierbare Möglichkeit bietet, die Kalibrierung selbst-ständig mit hoher Präzision bei vertret-barem Arbeitsaufwand ...
We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infe... more We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and strati- fied according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 � 400
Enterococci are a common cause of serious infections, especially in newborns, severely immunocomp... more Enterococci are a common cause of serious infections, especially in newborns, severely immunocompromised patients, and patients requiring intensive care. To characterize enterococcal surface antigens that are targets of opsonic antibodies, rabbits were immunized with various gentamicin-killed Enterococcus faecalis strains, and immune sera were tested in an opsonophagocytic assay against a selection of clinical isolates. Serum raised against one strain killed the homologous strain (12030) at a dilution of 1:5,120 and mediated opsonic killing of 33% of all strains tested. In addition, this serum killed two (28%) of seven vancomycin-resistant Enterococcus faecium strains. Adsorption of sera with the homologous strain eliminated killing activity. The adsorbing antigens were resistant to treatment with proteinase K and to boiling for 1 h, but were susceptible to treatment with sodium periodate, indicating that the antigen inducing opsonic activity is a polysaccharide. Antibodies in immun...
Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, wh... more Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, which might help to prevent inflammatory injury to the organism. However, if host defense mechanisms are affected similarly, the ability to eliminate bacteria might be reduced. We hypothesized that local anesthetics have time-dependent effects on phagocytosis of S. aureus, oxidative burst, and CD11b expression by human neutrophils. To test this hypothesis, we reanalyzed data from a previous study. Blood samples from 11 healthy volunteers were incubated with lidocaine (1,846 mumol/L), bupivacaine (770 mumol/L) or ropivacaine (801 mumol/L) for 30 minutes. Thereafter, bacteria were added, either fluorescently labeled for determination of phagocytosis, or unstained for determination of oxidative burst and CD11b expression. After an additional incubation for 0, 10, 30, or 60 minutes, phagocytosis was stopped and neutrophils were stained with monoclonal antibodies for flow cytometric analysis. Data were analyzed by analysis of variance for repeated measurements. Lidocaine and bupivacaine inhibited neutrophil functions in a time-dependent manner (P < .05). Prolonged local anesthetic exposure reduced the fraction of ingesting neutrophils by 20% +/- 12% (mean +/- SD) and 7% +/- 7%, bacterial uptake by 19% +/- 16% and 14% +/- 12%, oxidative burst by 29% +/- 23% and 28% +/- 25%, and CD11b expression by 66% +/- 24% and 25% +/- 21% for lidocaine and bupivacaine, respectively. Ropivacaine exerted a time-dependent effect on CD11b expression only (24% +/- 34%; P < .05). Our results indicate that in a whole blood model, time-dependent effects of local anesthetics affect key neutrophil functions necessary for bacterial elimination. However, these effects only occur at concentrations that are unlikely to be routinely attained in the clinical setting, and concern about interfering with the host defense is likely unwarranted.
Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the pr... more Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response. Therapeutic effectiveness was documented microbiologically and by the simultaneous measurement of linezolid levels in serum and cerebrospinal fluid.
ABSTRACTDendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of p... more ABSTRACTDendritic cell (DC) aggresome-like induced structures (DALIS) are protein aggregates of polyubiquitylated proteins that form transiently during DC maturation. DALIS scatter randomly throughout the cytosol and serve as antigen storage sites synchronising DC maturation and antigen presentation. Maturation of DCs is accompanied by the induction of the ubiquitin-like modifier FAT10 (also known as UBD), which localises to aggresomes, structures that are similar to DALIS. FAT10 is conjugated to substrate proteins and serves as a signal for their rapid and irreversible degradation by the 26S proteasome similar to, yet independently of ubiquitin, thereby contributing to antigen presentation. Here, we have investigated whether FAT10 is involved in the formation and turnover of DALIS, and whether proteins accumulating in DALIS can be modified through conjunction to FAT10 (FAT10ylated). We found that FAT10 localises to DALIS in maturing DCs and that this localisation occurs independent...
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2017
Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) impro... more Selective Digestive Decontamination (SDD) and Selective Oropharyngeal Decontamination (SOD) improved ICU, hospital and 28-day survival in Intensive Care Units (ICU) with low levels of antibiotic resistance. Yet, it is unclear whether the effect differs between medical and surgical ICU patients. In an individual patient data meta-analysis we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16,528 hospital admissions and 17,884 ICU-admissions for complete case analysis. Compared to standard care or placebo the pooled adjusted odds ratios (aOR) for hospital mortality was 0·82 (95% Confidence Interval [CI] 0·72 - 0·93) for SDD and 0·84 (95%-CI 0·73 - 0·...
... WA Krueger · M. Trick · TH Schroeder · KE Unertl ... Unsere Daten zeigen, dass die Verwen-dun... more ... WA Krueger · M. Trick · TH Schroeder · KE Unertl ... Unsere Daten zeigen, dass die Verwen-dung von Prüfgasen mit Analysenzertifi-kat eine technisch einfach realisierbare Möglichkeit bietet, die Kalibrierung selbst-ständig mit hoher Präzision bei vertret-barem Arbeitsaufwand ...
We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infe... more We prospectively studied the impact of an antibiotic prophylaxis regimen on the incidence of infections, organ dysfunctions, and mortality in a predominantly surgical and trauma intensive care unit (ICU) population. A total of 546 patients were enrolled and strati- fied according to Acute Physiology and Chronic Health Evaluation (APACHE)-II scores. They were then randomized to receive either 2 � 400
Enterococci are a common cause of serious infections, especially in newborns, severely immunocomp... more Enterococci are a common cause of serious infections, especially in newborns, severely immunocompromised patients, and patients requiring intensive care. To characterize enterococcal surface antigens that are targets of opsonic antibodies, rabbits were immunized with various gentamicin-killed Enterococcus faecalis strains, and immune sera were tested in an opsonophagocytic assay against a selection of clinical isolates. Serum raised against one strain killed the homologous strain (12030) at a dilution of 1:5,120 and mediated opsonic killing of 33% of all strains tested. In addition, this serum killed two (28%) of seven vancomycin-resistant Enterococcus faecium strains. Adsorption of sera with the homologous strain eliminated killing activity. The adsorbing antigens were resistant to treatment with proteinase K and to boiling for 1 h, but were susceptible to treatment with sodium periodate, indicating that the antigen inducing opsonic activity is a polysaccharide. Antibodies in immun...
Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, wh... more Local anesthetics have been shown to modulate neutrophil functions in a time-dependent manner, which might help to prevent inflammatory injury to the organism. However, if host defense mechanisms are affected similarly, the ability to eliminate bacteria might be reduced. We hypothesized that local anesthetics have time-dependent effects on phagocytosis of S. aureus, oxidative burst, and CD11b expression by human neutrophils. To test this hypothesis, we reanalyzed data from a previous study. Blood samples from 11 healthy volunteers were incubated with lidocaine (1,846 mumol/L), bupivacaine (770 mumol/L) or ropivacaine (801 mumol/L) for 30 minutes. Thereafter, bacteria were added, either fluorescently labeled for determination of phagocytosis, or unstained for determination of oxidative burst and CD11b expression. After an additional incubation for 0, 10, 30, or 60 minutes, phagocytosis was stopped and neutrophils were stained with monoclonal antibodies for flow cytometric analysis. Data were analyzed by analysis of variance for repeated measurements. Lidocaine and bupivacaine inhibited neutrophil functions in a time-dependent manner (P < .05). Prolonged local anesthetic exposure reduced the fraction of ingesting neutrophils by 20% +/- 12% (mean +/- SD) and 7% +/- 7%, bacterial uptake by 19% +/- 16% and 14% +/- 12%, oxidative burst by 29% +/- 23% and 28% +/- 25%, and CD11b expression by 66% +/- 24% and 25% +/- 21% for lidocaine and bupivacaine, respectively. Ropivacaine exerted a time-dependent effect on CD11b expression only (24% +/- 34%; P < .05). Our results indicate that in a whole blood model, time-dependent effects of local anesthetics affect key neutrophil functions necessary for bacterial elimination. However, these effects only occur at concentrations that are unlikely to be routinely attained in the clinical setting, and concern about interfering with the host defense is likely unwarranted.
Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the pr... more Methicillin-resistant Staphylococcus epidermidis (MRSE) can cause nosocomial meningitis in the presence of prosthetic devices. Vancomycin is the treatment of choice, but its penetration into the cerebrospinal fluid is poor, especially in cases without severe meningeal inflammation. We successfully used linezolid to treat a case of posttraumatic MRSE meningitis with a low-level inflammatory response. Therapeutic effectiveness was documented microbiologically and by the simultaneous measurement of linezolid levels in serum and cerebrospinal fluid.
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