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Biomedical subjects

H Sprenger

Publications and source records attributed to H Sprenger.

At least 19 recordsLinked to original sources
PubMed2003

[Frequency distribution of dibucaine numbers in 24,830 patients].

PURPOSE: Atypical cholinesterase prolongs the duration of neuromuscular blocking drugs such as succinylcholine and mivacurium. Measuring the dibucaine number identifies patients who are at risk. This study shows the frequency distribution of dibucaine numbers routinely measured and discusses avoidable clinical problems and economic implications. METHODS: Dibucaine numbers were measured on a Hitachi 917-analyzer and all dibucaine numbers recorded over a period of 4 years were taken into consideration. Repeat observations were excluded. RESULTS: A total of 24,830 dibucaine numbers were analysed and numbers below 30 were found in 0.07% ( n=18) giving an incidence of 1:1,400. Dibucaine numbers from 30 to 70 were found in 1.23% ( n=306). On the basis of identification of the Dibucaine numbers we could avoid the administration of succinylcholine or mivacurium resulting in a cost reduction of 12,280 Euro offset against the total laboratory costs amounting to 10,470 Euro. CONCLUSIONS: An incidence of 1:1,400 of dibucaine numbers below 30 is higher than documented in the literature. Therefore, routine measurement of dibucaine number is a cost-effective method of identifying patients at increased risk of prolonged neuromuscular blockade due to atypical cholinesterase.

Anesthesia↗
PubMed2001

Defense against influenza A virus infection: essential role of the chemokine system.

Monocytes/macrophages are highly susceptible to an infection with influenza A virus. After infection, de novo virus protein synthesis is detectable but rapidly interrupted before completion of the first viral replication cycle. Within 24-48 hours the infected monocytes die by apoptosis. Before cell death, infected monocytes initiate a cell-specific immune response. This includes the transcription and subsequent release of TNF-alpha (tumor necrosis factor alpha), IL-1beta (Interleukin 1beta), IL-6, type I inferferons and CC chemokines. Enhanced cytokine mRNA expression is due to a prolonged mRNA stability and an augmented gene transcription. Activation of transcription factors such as NF-kappaB (nuclear factor kappaB) and AP-1 are involved in activation of cytokine mRNA transcription. Infection of monocytes with influenza A virus induces the selective expression of mononuclear leukocyte attracting chemokines, such as MCP-1 (monocyte chemotactic protein 1), MIP-1alpha (macrophage inflammatory protein 1alpha) and RANTES (regulated upon activation, normal T cell expressed and secreted). In striking contrast, the release of the neutrophil-specific chemokines IL-8 (interleukin 8) and GRO-alpha (growth stimulatory activity alpha) is entirely suppressed. This differentially regulated chemokine expression may explain the mononuclear cell infiltrate characteristic for virus-infected tissue. Thus, infection of monocytes/macrophages with influenza A virus primes for a rapid proinflammatory reaction and induces an enhanced immigration of mononuclear cells into infected tissue. Taken together, these mechanisms may prepare the infected host for a fast and virus-specific immune response.

Animals↗
PubMed2001

Increase of CCR1 and CCR5 expression and enhanced functional response to MIP-1 alpha during differentiation of human monocytes to macrophages.

Chemokines and their receptors regulate migration of leukocytes under normal and inflammatory conditions. In this study, we analyzed the CC chemokine receptor (CCR) expression of monocytes differentiating in vitro to macrophages. We observed a time-dependent change of expression and functional responsiveness of CCR1, CCR2, and CCR5 within 48 h. Whereas freshly harvested monocytes were strongly attracted by monocyte chemotactic protein 1 (MCP-1), a specific ligand for CCR2, only a weak response was observed to macrophage inflammatory protein 1alpha (MIP-1alpha), which binds to CCR1 and CCR5. In striking contrast, differentiated macrophages displayed a strong chemotactic response to MIP-1alpha and only a weak response to MCP-1. These findings were paralleled by intracellular calcium shifts. During the time course of monocyte to macrophage differentiation, mRNA levels and surface expression of CCR2 decreased, whereas that of CCR1 and CCR5 increased. The time-dependent switch from CCR2 on monocytes to CCR1 and CCR5 on mature macrophages reflects a functional change belonging to the differentiation process of monocytes to macrophages and may form the basis for a differential responsiveness of monocytes and macrophages to distinct sets of chemokines.

Calcium↗
PubMed2000

Differential desensitization of lipopolysaccharide-inducible chemokine gene expression in human monocytes and macrophages.

Bacterial lipopolysaccharide (LPS) has been shown to induce a wide variety of pro-inflammatory cytokines and chemokines. An initial challenge with minute amounts of LPS causes tolerance to later LPS effects which is characterized by a much lower or abrogated release of pro-inflammatory cytokines. To explore the relationship between the production of chemokines and the induction of LPS tolerance, we pretreated human monocytes with increasing LPS doses and thereafter restimulated with LPS. The re-expression of the CC chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES was substantially suppressed after pre-incubation with low LPS doses. In striking contrast, the re-expression of neutrophil-attracting IL-8 and melanoma growth stimulatory activity-alpha and of the monocyte-attracting monocyte chemotactic protein-1 remained high and was, in part, initially increased after restimulation with LPS. The corresponding gene expression pattern as determined by Northern blot analyses correlated closely with the release of chemokines and cytokines. Thus, a basic set of chemotactic mediators that are still produced by otherwise LPS-desensitized monocytes/macrophages may ensure the continuing recruitment of monocytes and neutrophils into an inflammatory process caused by gram-negative bacteria.

Cells, Cultured↗
PubMed2000

Selective induction of the monocyte-attracting chemokines MCP-1 and IP-10 in vesicular stomatitis virus-infected human monocytes.

It is characteristic of viral infections that monocytes/macrophages and lymphocytes infiltrate infected tissue, and neutrophils are absent. CC and non-ELR CXC chemokines predominantly attract mononuclear leukocytes, whereas the ELR motif-expressing CXC chemokines primarily act on neutrophils. To investigate the general role of chemokines in viral diseases, we determined their release and expression patterns after infection of human monocytes with vesicular stomatitis virus (VSV). Human monocytes were productively infected by VSV. Surprisingly, VSV did not induce the release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. In contrast, we found a strong induction of the CC chemokine monocyte chemotactic protein-1 (MCP-1) and the non-ELR CXC chemokine interferon-gamma (IFN-gamma) inducible protein-10 (IP-10) by VSV on the gene and protein level. The expression and release of the neutrophil chemoattractants IL-8 and growth-related oncogene-alpha (GRO-alpha) remained unaffected after VSV infection. Our results indicate that the typical monocyte and lymphocyte-dominated leukocyte infiltration of virus-infected tissue is based on a selective induction of mononuclear leukocyte-attracting chemokines.

Cells, Cultured↗
PubMed1999

Differential expression of monocyte chemotactic protein-1 (MCP-1) in transforming rat hepatic stellate cells.

BACKGROUNDS/AIMS: Hepatic stellate cells and infiltrating leukocytes play a key role in the pathogenesis of liver fibrosis. The chronic phase of liver inflammation is characterized by immigrating mononuclear cells. To understand the underlying mechanisms responsible for the attraction of mononuclear cells in the pathogenesis of liver fibrosis, we investigated the inducible production of chemotactic activities in hepatic stellate cells. METHODS: Cultured hepatic stellate cells of different transformation grades and after in vitro transformation to myofibroblast-like cells were stimulated with tumor necrosis factor-a or bacterial lipopolysaccharide. Mononuclear cell attracting chemotactic activities were evaluated by chemotaxis assays, ELISA, and Northern blot analysis. RESULTS: We observed a transformation grade-dependent differential responsiveness of hepatic stellate cells and myofibroblast-like cells. Monocyte chemotactic protein-1 was inducible by tumor necrosis factor-alpha in non-transformed hepatic stellate cells. In contrast, monocyte chemotactic protein-1 was not inducible by bacterial lipopolysaccharide until the cells were fully transformed into myofibroblast-like cells. Despite a delayed onset, the bacterial lipopolysaccharide-inducible monocyte chemotactic protein-1 expression did not depend on an endogenous production of tumor necrosis factor-alpha. CONCLUSIONS: Our results indicate that the tumor necrosis factor-alpha and bacterial lipopolysaccharide-inducible production of chemokines plays a central role in the pathogenesis of liver fibrosis. These data suggest that when hepatic stellate cells have been transformed to a myofibroblast-like cells phenotype, e.g. by chronic injury, the cells become more sensitive to bacterial lipopolysaccharide, which may potentiate the production of chemotactic and fibrogenic mediators. A strong secretion of monocyte chemotactic protein-1 may contribute to the maintenance of an inflammatory infiltrate dominated by mononuclear cells.

Animals↗
PubMed1999

Induction of cytokines and chemokines in human monocytes by Mycoplasma fermentans-derived lipoprotein MALP-2.

Bacterial infections are characterized by strong inflammatory reactions. The responsible mediators are often bacterially derived cell wall molecules, such as lipopolysaccharide or lipoteichoic acids, which typically stimulate monocytes and macrophages to release a wide variety of inflammatory cytokines and chemokines. Mycoplasmas, which lack a cell wall, may also stimulate monocytes very efficiently. This study was performed to identify mycoplasma-induced mediators. We investigated the induction of cytokines and chemokines in human monocytes exposed to the Mycoplasma fermentans-derived membrane component MALP-2 (macrophage-activating lipopeptide 2) by dose response and kinetic analysis. We found a rapid and strong MALP-2-inducible chemokine and cytokine gene expression which was followed by the release of chemokines and cytokines with peak levels after 12 to 20 h. MALP-2 induced the neutrophil-attracting CXC chemokines interleukin-8 (IL-8) and GRO-alpha as well as the mononuclear leukocyte-attracting CC chemokines MCP-1, MIP-1alpha, and MIP-1beta. Production of the proinflammatory cytokines tumor necrosis factor alpha and IL-6 started at the same time as chemokine release but required 10- to 100-fold-higher MALP-2 doses. The data show that the mycoplasma-derived lipopeptide MALP-2 represents a potent inducer of chemokines and cytokines which may, by the attraction and activation of neutrophils and mononuclear leukocytes, significantly contribute to the inflammatory response during mycoplasma infection.

Cells, Cultured↗
PubMed1998

Differential mononuclear leukocyte attracting chemokine production after stimulation with active and inactivated influenza A virus.

After influenza A virus infection of human monocytes, we found a rapid and marked release of the mononuclear cell attracting chemokines MCP-1, MIP-1 alpha, and IP-10, with corresponding gene expression patterns as determined by Northern blot analysis. In striking contrast, the expression and release of the neutrophil chemoattractant IL-8 was not inducible. To determine the underlying mechanisms responsible for the induction of this differential chemokine pattern, we stimulated monocytes with UV- and heat-inactivated (56 degrees C and 100 degrees C) influenza A virus. In comparison with fully infectious influenza A, 56 degrees C-inactivated virus induced a strong production of MCP-1, MIP-1 alpha, and IP-10, while the release of MIP-1 alpha and IP-10 was substantially lower after exposure to UV-inactivated virus. No chemokine expression was found after stimulation with 100 degrees C-inactivated influenza A virus. Our data indicate that, contingent upon the chemokine examined, the maximal induction depends on the unrestricted infectivity of the virus, the unaltered hemagglutinin molecule, or the intact viral RNA. This diversified chemokine production may enable the infected host to mount an efficient antiviral response against infective and noninfective virus particles.

Animals↗
PubMed1998

Time course of chemokines in the cerebrospinal fluid and serum during herpes simplex type 1 encephalitis.

Chemokines (chemoattractant cytokines) attract and activate specific leukocyte subsets. With regard to their expression by brain parenchymal cells, they may represent the key molecules that control leukocyte entry into the subarachnoid space. In order to evaluate the contribution of chemokines in vivo, we determined the levels of MCP-1, MIP-1alpha, RANTES, IL-8, as well as of the sIL-2R in three patients with proven herpes simplex encephalitis type 1 (HSE-1). CSF samples were drawn by a subarachnoid catheter system throughout the time course of hospitalisation. Results were compared to chemokine levels in serum drawn in parallel. The clinical status was documented by the Modified Barthel Index and correlated with chemokine levels in the CSF. The results were compared with the chemokine levels in the CSF of 17 control patients with normal CSF routine parameters. High chemokine levels were detectable in the CSF of all HSE-patients. MCP-1 peak levels were found at the time of admission, while maximal IL-8 levels occurred 4 to 8 h later. The levels of MIP-1alpha and RANTES were lower than those of MCP-1 with a maximum at the time of admission. In all patients the levels of the sIL-2R increased later in the time course, at 14 to 20 h after admission. When the levels of MCP-1 were compared with the clinical status by Modified Barthel Index, we found a high reciprocal correlation (r=-0.82). Routine CSF parameters, such as leukocytes, albumin and immunoglobulins did not correlate with the clinical status. Chemokine levels in serum were found to be close to the detection limits of the ELISA systems. Our data suggest that chemokines play an important role in the pathogenesis of HSE. They may be useful parameters to monitor the stage and severity of the disease. The late increase of sIL2-R levels may indicate the beginning of the reconstitution phase.

Cell Count↗
PubMed1998

Hypochlorite-modified LDL: chemotactic potential and chemokine induction in human monocytes.

Within blood vessels the accumulation of monocytes/macrophages at sites of modified lipoproteins is an important feature in atherosclerosis. Recently the presence of LDL and other proteins modified by hypochlorous acid (HOCl-LDL) was demonstrated in human atherosclerotic vessels and human inflammatory kidney disease by immunohistology and protein chemistry. Chemokines contribute to a specific and directed migration of inflammatory cells. IL-8 (alpha-chemokine) attracts mainly neutrophils and distinct T-cell subsets while MCP-1 (beta-chemokine) preferentially acts on monocytes/macrophages. In the present study it was postulated that HOCl-LDL may induce and amplify inflammatory reactions by the induction of chemokine synthesis in local monocytes. After exposure of human monocytes to HOCl-LDL, it was found that mRNA and protein of the chemokine IL-8 was strongly induced, while the chemokine MCP-1 was not. HOCl-LDL itself led to a chemotactic migration of neutrophils. A chemotactic response of human monocytes toward HOCl-LDL was not detectable. We propose that HOCl-LDL may represent a form of LDL modification in the atherosclerotic process which initiates leukocyte infiltration; these mononuclear cells have been observed in the early stages of atherosclerosis.

Arteriosclerosis↗
PubMed1997

Persistent long-term changes in lymphocyte subsets induced by polyclonal antibodies.

BACKGROUND: Clinicians are well aware of the short-term effects of immunosuppression by mono- or polyclonal antibodies. Little is known about long-term changes induced by these therapies. METHODS: Forty-three renal allograft recipients were selected according to their initial postoperative immunosuppression: (1) BI group=basic immunosuppression with steroids and cyclosporine, n=16; (2) ATG group=basic immunosuppression plus polyclonal antibody antithymocyte globulin (ATG), n=11; and (3) OKT3 group=basic immunosuppression plus monoclonal antibody OKT3, n=16 patients. At intervals of 6 months, the following parameters were measured prospectively: lymphocyte surface antigens (HLA-DR, CD3, CD4, CD8, CD16, CD19, CD56, and CD57); serum and urine neopterin; serum amyloid A; and indirect and direct tests for herpes viruses. RESULTS: The mean period of observation was 58.4 months. The most significant differences between the groups occurred for CD4+ and CD8+ T cells. The ratios of CD4+ to CD8+ cells (n=278 measurements) were significantly and persistently lower in the ATG group (P<0.001, Brown-Mood test). Five years after transplantation, the ATG group had a CD4+ to CD8+ cell ratio of x=0.6 versus x=1.7 in the OKT3 group and x=2.0 in the BI group. This inversion was due to a persistent depletion of the CD4+ cells and an increased regeneration of the CD8+ cells, in particular of the CD8+brightCD57+ subpopulation. Extent and duration of CD4+ depletion correlated with the cumulative ATG dose (r=0.7, P<0.05, Spearman rank correlation test). CONCLUSION: Therapy with polyclonal antibody ATG induces dose-dependent long-term changes in T-cell lymphocyte subsets, which persist over a period of years.

Adult↗
PubMed1997

Susceptibility of mononuclear phagocytes to influenza A virus infection and possible role in the antiviral response.

Among leukocytes, only monocytes and macrophages were found to be highly susceptible to an infection by influenza A virus. After infection, de novo viral protein synthesis was initiated but then interrupted after 4-6 h. Most macrophages died by apoptosis within 25-30 h. Before cell death, however, macrophages responded to influenza A virus with a high cytokine gene transcription and subsequent release of tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, interferon (IFN)-alpha/beta, and CC-chemokines. The basic mechanisms of virus-induced cytokine expression are still unknown and appear to involve transcription factors such as nuclear factor-kappaB and AP-1 which, however, were only activated for 2 h and declined below control values thereafter. After influenza A virus infection, only the mononuclear cell attracting CC-chemokines macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and RANTES were produced while the prototype neutrophil CXC-chemoattractants IL-8 and GRO-alpha were entirely suppressed. This selective induction of CC-chemokines may explain the preferential influx of mononuclear leukocytes into virus-infected tissue. Our data show that monocytes and macrophages represent a primary target for an influenza A virus infection. Thus, the mononuclear phagocyte response leads to a rapid proinflammatory reaction and an enhanced immigration of mononuclear leukocytes, which may condition the infected host for the subsequent virus antigen-specific defense.

Apoptosis↗
PubMed1997

Induction of neutrophil-attracting chemokines in transforming rat hepatic stellate cells.

BACKGROUND & AIMS: Hepatic stellate cells (HSCs) play a key role in the pathogenesis of liver fibrosis. Immigrating leukocytes can potentiate the progression of liver fibrosis by release of fibrogenic mediators and cytotoxic actions. The inducible production of neutrophil chemotactic activities in HSCs was investigated to understand the underlying mechanisms responsible for the attraction of leukocytes in the pathogenesis of liver fibrosis. METHODS: Cultured HSCs of different transformation grades and after transformation to myofibroblasts (MFBs) were stimulated with tumor necrosis factor (TNF)-alpha and lipopolysaccharide (LPS), respectively. Induced leukocyte chemotactic activities were evaluated by chemotaxis assays, enzyme-linked immunosorbent assay, and Northern blot analysis. RESULTS: A transformation grade-dependent differential responsiveness of HSCs and MFBs was observed. TNF-alpha-inducible production of chemotactic mediators increased substantially with advancing transformation. Only transformed MFBs were LPS responsive. Macrophage inflammatory protein 2 was identified as one of the inducible chemokines. CONCLUSIONS: The results suggest that chemokines play an important role in the pathogenesis of liver fibrosis. Proinflammatory cytokines can initiate the production of chemotactic activities. The more HSCs are transformed to MFBs, e.g., by chronic injury, the more sensitive the cells become to LPS, which may lead to a vicious circle of enhanced fibrogenic and chemotactic mediator production.

Animals↗
PubMed1997

Expression of transcription factor genes after influenza A virus infection.

Infection of human monocytes with influenza A virus induces a broad range of proinflammatory cytokines and mononuclear cell attracting chemokines before the infected cells undergo apoptosis. The underlying mechanisms by which the corresponding genes are transcriptionally initiated after virus infection are still poorly understood. Activation of NF-kappa B seems to play an important role in the regulation of many proinflammatory cytokine genes, but cannot be the only mechanism, since several cytokine genes lack respective binding sites in their promoter regions. Therefore, we additionally investigated other transcription factors of possible importance such as CREB, CTF, OTF-1, and OTF-2. To explore long-term regulatory mechanisms, we investigated the induction of transcription factors on the gene expression level which may be important to substitute for metabolized transcription factor proteins after their activation. We identified a cell-type-specific differential response: CREB, CTF, OTF-1, OFT-2, and NF-kappa B genes were strongly induced 1 to 4 hours after influenza A virus infection in the monocytic cell line Mono Mac 6, while in freshly prepared human monocytes no significant changes were detected. In infected monocytes, which die by apoptosis, the expression of CREB, CTF, and OTF-2 was rather suppressed 8 hours after infection. In conclusion, the long-term regulation of transcription factor gene expression in non-proliferating cells seems to be of minor importance after influenza infection since in apoptosisprone cells an immediate availability of transcription factor proteins is required.

Animals↗
PubMed1997

Borrelia burgdorferi induces chemokines in human monocytes.

Lyme disease is clinically and histologically characterized by strong inflammatory reactions that contrast the paucity of spirochetes at lesional sites, indicating that borreliae induce mechanisms that amplify the inflammatory response. To reveal the underlying mechanisms of chemoattraction and activation of responding leukocytes, we investigated the induction of chemokines in human monocytes exposed to Borrelia burgdorferi by a dose-response and kinetic analysis. Lipopolysaccharide (LPS) derived from Escherichia coli was used as a positive control stimulus. The release of the CXC chemokines interleukin-8 (IL-8) and GRO-alpha and the CC chemokines MIP-1alpha, MCP-1, and RANTES was determined by specific enzyme-linked immunosorbent assays, and the corresponding gene expression patterns were determined by Northern blot analysis. The results showed a rapid and strong borrelia-inducible gene expression which was followed by the release of chemokines with peak levels after 12 to 16 h. Spirochetes and LPS were comparably effective in stimulating IL-8, GRO-alpha, MCP-1, and RANTES expression, whereas MIP-1alpha production preceded and exceeded chemokine levels induced by LPS. Unlike other bacteria, the spirochetes themselves did not bear or release factors with intrinsic chemotactic activity for monocytes or neutrophils. Thus, B. burgdorferi appears to be a strong inducer of chemokines which may, by the attraction and activation of phagocytic leukocytes, significantly contribute to inflammation and tissue damage observed in Lyme disease.

Borrelia burgdorferi Group↗
PubMed1996

Selective induction of monocyte and not neutrophil-attracting chemokines after influenza A virus infection.

It is characteristic for virus infections that monocytes/macrophages and lymphocytes infiltrate infected tissue while neutrophils are absent. To understand the mechanisms selectively attracting mononuclear cells in viral diseases, we examined in an influenza A virus model the expression and regulation of chemokines as candidate molecules responsible for the immigration of leukocytes into inflamed tissue. After influenza A virus infection of human monocytes, a rapid expression of the mononuclear cell attracting CC-chemokine genes MIP-1, MCP-1, and RANTES occurred which was followed by the release of chemokine proteins. In striking contrast to CC-chemokines, the expression of the prototype neutrophil CXC-chemoattractants IL-8 and GRO-alpha was completely suppressed after influenza A infection. The release of other neutrophil chemotactic factors was excluded by microchemotaxis assays. These results suggest that the virus-specific induction of mononuclear cell-attracting chemokines accounts for the preferential influx of mononuclear leukocytes into virus-infected tissue.

Chemokine CCL2↗