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Biomedical subjects

S Bergmann

Publications and source records attributed to S Bergmann.

At least 19 recordsLinked to original sources

Analysis of the Candida albicans - specific T-cell response and oropharyngeal Candida colonization in a cohort of HIV-1-infected patients.

To investigate Candida epidemiology and immunologic correlates of protection in HIV-1 infected patients, we analyzed oral Candida colonization in correlation to the Candida-specific T-cell response measured by g-IFN ELISPOT using different Candida (C.) albicans strains. In 16/46 patients (13 asymptomatic, 3 with oral thrush), but in 0/28 controls, Candida (13 C. albicans, 1 C. lusitaniae, 1 C. krusei, 1 C. parapsilosis) was isolated. Candida specific T-cells were detected more frequently in controls (20/28) than in HIV-1+ subjects (16/46, p= 0.03). We observed a significant association of higher CD4 cell numbers with both detection of Candida specific T-cells and lack of oral Candida colonization, but there was no significant correlation of oral Candida colonization to the detection of Candida specific T-cells, viral load or antiretroviral therapy. Thus, local mucosal immunity seems to be more important in the pathogenesis of Candida colonization than circulating Candida specific T-cells. The pathogenic C. albicans strain K24122 was less frequently recognized by patients (6/46) than the laboratory adapted strain SC5314 (14/46, p= 0.03), whereas a similar recognition of both strains was observed in healthy controls. This indicates an impaired Candida-specific T-cell repertoire in HIV+ patients that could increase the risk of immune evasion by C. albicans.

AIDS-Related Opportunistic Infections↗

FTY720 for treatment of ischemia-reperfusion injury following complete renal ischemia in C57/BL6 mice.

BACKGROUND: Organ dysfunction followed by single-organ or even multiorgan failure due to ischemia-reperfusion injury (I/RI) is a common problem in liver and heart transplantation. Various approaches had been attempted to prevent this I/RI. One is the administration of FTY720, a synthetic structural analogue of sphingosine, which induces T-lymphocyte homing with consecutive lymphopenia. The purpose of this study was to evaluate the effect of intraoperative FTY720 administration following controlled bilateral kidney ischemia in comparison to steroid or placebo application. METHODS: Male c57BL6/J mice (n = 115; body weight 25 to 30 g) received either FTY720 (1 mg/kg body weight) or steroids or saline solution. Ischemia was applied for 30 or 60 minutes with subsequent follow-up for 48 hours. At termination all surviving animals were sacrificed. RESULTS: Following 30 minutes of ischemia, FTY720, but neither steroid nor vehicle treatment showed significant protective effects on long-term survival after controlled bilateral warm kidney ischemia. Fluorescein-activated cell sorting (FACS) analysis showed a significant T-lymphocyte depletion in peripheral blood after FTY720 treatment, which was not observed after steroid or vehicle treatment. CONCLUSION: The improved long-term survival shown in this study might be due to a protective effect of FTY720 to prevent I/RI, which may be mediated by the lymphocyte depletion shown in the FACS analysis.

Animals↗

Multicentre evaluation of performance of C-reactive protein analysis over a one-year period.

This communication deals with a longitudinal evaluation of C-reactive protein (CRP) analysis during a one-year period using a single lot of liquid control sera (3 levels) (BIOREF-CRP levels 1, 2 and 3) in different laboratories. A total of 652 sets of data were returned from 20 participating laboratories using 13 different reagent-measuring device combinations. The use of the control materials was defined in a standard operating procedure. Data was returned to the organizers on a monthly basis and questions could be asked or problems presented during the evaluation period. Although the performance of different reagents varied, the control materials were shown to be stable over the whole of the evaluation period when stored at 4-7 degrees C in a refrigerator/cold room. Typical problems were encountered, examples of which are presented here in graphical and tabular form.

C-Reactive Protein↗

Mechanism of the anti-inflammatory effect of colchicine in rheumatic diseases: a possible new outlook through microarray analysis.

OBJECTIVE: Colchicine is an alkaloid that is used to alleviate acute gout and to prevent acute attacks of familial Mediterranean fever (FMF). However, it is not beneficial when given during the occurrence of an acute episode of FMF. It is believed that colchicine exerts its anti-inflammatory effect through direct interaction with microtubules. We aim to study the molecular basis of colchicine action by analysing the effect of this drug on global gene expression of HUVEC (human umbilical vein endothelial cell line) cells. METHODS: HUVEC cells were exposed to various concentrations of colchicine and were harvested at different time points. Ribonucleic acid was extracted, amplified, reverse transcribed and hybridized to complementary deoxyribonucleic acid microarrrays containing more than 40,000 probes to human expressed sequence tags. This approach enabled us to have a global look at the transcriptional response induced by colchicine treatment. RESULTS: Colchicine changed the expression of many genes in HUVEC cells following exposure to a concentration of 100 ng/ml or higher. Following short exposure (30 or 120 min), colchicine affected genes known to be involved in the cell cycle and its regulation. However, change in expression of genes involved in neutrophil migration or other inflammatory processes were observed mainly after 12 to 24 h. CONCLUSIONS: The anti-inflammatory effect of colchicine may be mediated not only through direct interaction with microtubules but also through changes at the transcriptional level. This latter effect apparently requires a higher concentration and a longer time to occur. This can explain the observation that colchicine does not have an immediate effect when given during an acute attack of FMF.

Anti-Inflammatory Agents, Non-Steroidal↗

Inhibition of HIV-1-specific T-cells and increase of viral load during immunosuppressive treatment in an HIV-1 infected patient with Chlamydia trachomatis induced arthritis.

BACKGROUND: Studies in HIV-1 infected long-term non-progressors could demonstrate a strong HIV-1-specific CTL response, but it is difficult to prove that this strong CTL response actually is the cause of the efficient control of HIV-1 and not the consequence of low HIV-1 replication in these patients. OBJECTIVE: Studies of HIV-1-specific immunity and viral replication in patients undergoing immunosuppressive therapy provide important opportunities to understand the role of HIV-1-specific T-cells. RESULTS: In this report we describe an HLA B27 positive patient with normal CD4 counts and a low viral load of 200 copies/ml without antiretroviral therapy who exhibited a very strong HIV-1-specific CTL response. He had to be treated with steroids, NSAIDS and hydroxchloroquine because of a severe inflammatory reactive arthritis triggered by an acute Chlamydia trachomatis infection. Analysis of HIV-1 specific T-cells by gamma-IFN-ELISPOT revealed a high frequency of HIV-1 gag-specific CTL both in blood and synovial fluid, whereas gag-specific CD4-cells could be detected only in the peripheral blood. Further analysis revealed that the gag-specific T-cells were predominantly targeting the HLA B27-restricted CTL epitope KRWIILGLNK (KK10). Immunosuppressive therapy by prednisone was associated with a moderate increase of HIV-1 viremia and a decrease both in the number and in the gamma-IFN production of KK10-specific CTL indicating that inhibition of CTL function contributed to the increase of viral load. CONCLUSIONS: This study is suggesting that HIV-1 specific CTL play an important role in the control of HIV-1, at least in this patient. Inhibition of CTL function by immunosuppressive therapy with prednisone may enhance viral replication. In addition, we could demonstrate for the first time the migration of HIV-1 specific T-cells into the synovial fluid.

Adult↗

Subclinical inflammation is strongly related to insulin resistance but not to impaired insulin secretion in a high risk population for diabetes.

Subclinical inflammation was shown to be a strong predictor of cardiovascular events and was suggested to be a part of the metabolic syndrome (MS). The aim of the present study was to investigate the relationship of the inflammatory parameters-leukocyte count, C-reactive protein (CRP), and fibrinogen level-to insulin resistance and insulin secretion, as well as to other components of the MS in a population at risk for diabetes. A total of 396 subjects (142 men and 254 women) were analyzed from the follow-up of the Risk Factors in Impaired Glucose tolerance (IGT) for Atherosclerosis and Diabetes (RIAD) study, who were at risk for type 2 diabetes, such as family history of diabetes, obesity, and/or hyper/dyslipoproteinemia. Subjects under lipid-lowering treatment or with acute infections were not eligible. A variety of risk factors within the MS were examined: lipids, glycemic parameters, coagulation, insulin fractions. and microalbuminuria. CRP was determined by a highly sensitive method, using an immunological agglutination test, and fibrinogen was measured by the method of Clauss. Insulin resistance was evaluated by the homeostasis model assessment (HOMA) and insulin secretion by HOMA and by insulin areas under curve in an oral glucose tolerance test (OGTT), insulin increment at 30 mnutes of OGTT, and insulin increment/glucose increment at 30 minutes of OGTT. By univariate analysis, fibrinogen level (r = 0.180, P <.001), leukocyte count (r = 0.162, P =.001), and CRP (r = 0.251, P <.001) were all highly significantly correlated to insulin resistance, but not to insulin secretion. A significant rise was found for the majority of the components of the MS in quartiles of the examined inflammatory parameters. In multivariate analysis of all analyzed metabolic parameters, including age, sex, physical activity, and smoking, body mass index (BMI) was found a strong independent determinant of all inflammatory markers examined. Thus, in a population at risk for type 2 diabetes we demonstrate that subclinical inflammation underlies the metabolic syndrome, through association to one of its primary anomalies-insulin resistance, whereas no association was found to impaired insulin secretion.

Blood Glucose↗

Reduced ammonia emissions from slurry after self-acidification with organic supplements.

Ammonia volatilisation from field applied slurries causes environmental hazards and loss of fertilizer value. Acidification of slurry, usually with inorganic or organic acids has previously been used to reduce NH3 emissions. In this study, we present an alternative technique for the acidification of slurry, namely the use of fermentation by endogenous microbes to form organic acids from readily degradable organic compounds. In laboratory experiments, the addition of different sugars (sucrose in dosages of 0.003, 0.01, 0.03, 0.1 and 0.3 mol l(-1), glucose in dosages of 0.05 and 0.1 mol l(-1)) and organic residues (sugar beet residues in dosages of 33 and 330 g fresh weight l(-1), biowaste at 50 g fresh weight l(-1)) to cattle slurry resulted in a considerable decrease in pH, with a minimum pH of 4.7. A subsequent pH increase indicated that the organic acids were probably further degraded with a resultant loss of acidity in the slurry. In a field study, the NH3 emissions from untreated and acidified (pH = 6) slurries were compared after field application (20 m3 ha(-1)). During the first 20 hours, the acidified slurry showed NH3 emissions of less than 5% of the applied ammonia compared to a 26% loss from the untreated slurry. The total emissions of NH4+-N were 32% for acidified and 54% for untreated slurry. Easily degradable organic amendments therefore have the potential to effectively reduce NH3 emissions from slurries and may be an alternative for the use of acids.

Ammonia↗

Hyperthermia-induced nuclear translocation of transcription factor YB-1 leads to enhanced expression of multidrug resistance-related ABC transporters.

Genotoxic stress leads to nuclear translocation of the Y-box transcription factor YB-1 and enhanced expression of the multidrug resistance gene MDR1. Because hyperthermia is used for the treatment of colon cancer in combination with chemoradiotherapy, we investigated the influence of hyperthermia on YB-1 activity and the expression of multidrug resistance-related genes. Here we report that hyperthermia causes YB-1 translocation from the cytoplasm into the nucleus of human colon carcinoma cells HCT15 and HCT116. Nuclear translocation of YB-1 was associated with increased MDR1 and MRP1 gene activity, which is reflected in strong efflux pump activity. However, a combination of hyperthermia and drug treatment effectively reduced cell survival of the HCT15 and HCT116 cells. These results demonstrate that activation of MDR1 and MRP1 gene expression and increased efflux pump activity after hyperthermia were insufficient to cause an increase in drug resistance in colon cancer cell lines. The ability of hyperthermia to abrogate drug resistance in the presence of an increase in functional MDR proteins may provide an explanation for the efficacious results seen in the clinic in colon cancer patients treated with a combination of hyperthermia and chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Eight novel LDL receptor gene mutations among patients under LDL apheresis in Dresden and Leipzig.

LDL apheresis is highly efficient in reducing elevated plasma cholesterol. Due to strict indications only patients with severe, refractory hypercholesterolemia are treated with this method. Mutations in the LDL receptor gene are major genetic causes for severe hypercholesterolemia. Screening the entire gene in LDL apheresis patients from Saxony should determine whether an increased frequency of defined mutations is responsible for the atherogenic hypercholesterolemia in this group. 31 unrelated patients (15 male, 16 female, age 33-71 yrs.) were included in the analysis. The LDL-R gene was screened using SSCP and/or automated sequencing. The familial defective apolipoprotein B-100 (FDB) mutation was genotyped using established PCR techniques. Nineteen of 31 patients were carriers of an LDL-R mutation. Ten missense and two nonsense mutations, three insertions and two deletions were detected. The mutations C74S, C74R, T87M, 660delC, 662insCCCCG, 680insGGACAAATCTGA, 1428insC and 2167delG have not been previously described. One patient was compound heterozygous for two missense mutations. Two further patients were heterozygous for FDB. No mutations were found among controls. A genetic background for hypercholesterolemia in the LDL-R could be established in about 61% of the patients examined. Therefore, methods of DNA analysis allow to recognize and adequately treat a large portion of high-risk individuals at an early stage.

Adult↗

alpha-Enolase of Streptococcus pneumoniae is a plasmin(ogen)-binding protein displayed on the bacterial cell surface.

Binding of human plasminogen to Streptococcus pneumoniae and its subsequent activation promotes penetration of bacteria through reconstituted basement membranes. In this study, we have characterized a novel pneumococcal surface protein with a molecular mass of 47 kDa, designated Eno, which specifically binds human plasmin(ogen), exhibits alpha-enolase activity and is necessary for viability. Using enzyme assays, we have confirmed the alpha-enolase activity of both pneumococcal surface-displayed Eno and purified recombinant Eno protein. Immunoelectron microscopy indicated the presence of Eno in the cytoplasm as well as on the surface of encapsulated and unencapsulated pneumococci. Plasminogen-binding activity was demonstrated with whole pneumococcal cells and purified Eno protein. Binding of activated plasminogen was also shown for Eno; however, the affinity for plasmin is significantly reduced compared with plasminogen. Results from competitive inhibition assays indicate that binding is mediated through the lysine binding sites in plasmin(ogen). Carboxypeptidase B treatment and amino acid substitutions of the C-terminal lysyl residues of Eno indicated that the C-terminal lysine is pivotal for plasmin(ogen)-binding activity. Eno is ubiquitously distributed among pneumococcal serotypes, and binding experiments suggested the reassociation of secreted Eno to the bacterial cell surface. The reassociation was also confirmed by immunoelectron microscopy. The results suggest a mechanism of plasminogen activation for human pathogens that might contribute to their virulence potential in invasive infectious processes.

Amino Acid Sequence↗

Influence of psychosocial resources on the relationship between lifestyle and cardiovascular or mental health.

Among middle-aged women: The factor beta-lipoproteins is significantly influenced by cigarette smoking and by the intensity of physical activity at leisure time. The factor alpha-lipoproteins is not influenced by these lifestyle factors. The leukocyte count is higher among smokers. It is not significantly associated with other inflammation markers. The pre-diabetic risk profile is improved by physical activity at leisure time and by rigid eating behaviour in stressful situations. The physical activity at leisure time and a rigid eating behaviour in stressful situations play a positive role for mental health, too. Styles of coping with stress, action styles or sense of coherence do not influence the relationships between lifestyle factors and cardiovascular risk factors. Psychosocial resources intensify the relationships between lifestyle and mental health.

Adaptation, Psychological↗

Biosynthetic studies of the glycopeptide teicoplanin by (1)H and (13)C NMR.

The biosynthesis of the glycopeptide antibiotic teicoplanin was studied by growing a teicoplanin producing strain of Actinoplanes teichomyceticus (ATCC 31121) on glucose containing either 34.0% [1-(13)C]glucose or 9.7% [U-(13)C]glucose. The fractional enrichment pattern of teicoplanin produced in the medium containing [1-(13)C]glucose was obtained from a one-dimensional (13)C spectrum. The enrichment pattern showed characteristic peaks indicating that amino acids 3 and 7 are derived from acetate, whereas amino acids 1, 2, 4, 5, and 6 are derived from tyrosine. Multiplet structures in heteronuclear single quantum coherence spectra of teicoplanin produced in the medium containing [U-(13)C]glucose showed characteristic coupling patterns supporting these results. Fractional enrichment patterns and multiplet structures of the three sugars in teicoplanin showed that about 50% of the sugars have the same labeling pattern as the glucose substrate whereas the rest have a labeling pattern showing that they are reassembled, probably from precursors in the primary metabolism.

Actinomycetales↗

Lipids and stability of menopausal status in middle-aged women within two years.

In the whole population total cholesterol (TC) was unchanged within two years. The triglyceride (TG) level increased significantly, but HDLC increased too between 1996 and 1998. The increase of TG concentration was significantly in the stable group only, whereas the increase of HDLC concentration was observed in both groups. "Depressed mood" and "anxiety" seem to have a positive influence on the TC levels.

Female↗

Flow cytometric DNA quantification in immunophenotyped cells as a sensitive method for determination of aneuploid multiple myeloma cells in peripheral blood stem cell harvests and bone marrow after therapy.

The simultaneous measurement of DNA content and myeloma-related antigens (B-B4 or CD38) by flow cytometry is proposed as a method for the detection of aneuploid plasma cells in peripheral blood stem cell (PBSC) harvests and in bone marrow after therapy. In 30 patients with initially detected aneuploid myeloma cells we evaluated the bone marrow after therapy and in eight of these patients 23 PBSC harvests were analyzed. In 13 of 23 PBSC harvests aneuploid myeloma cells were detectable (range: 0.02-0.63%). In the bone marrow of the 30 patients aneuploid plasma cells were detectable in all samples after chemotherapy (range: 0.12-35.70%) and after autologous PBSC transplantation in two of three patients (0.21% and 0.03%). Furthermore the relationship between diploid and aneuploid plasma cells can be evaluated. In the PBSC harvests the percentage of aneuploid plasma cells is significantly lower than that of diploid plasma cells (P=0.006). In contrast, in bone marrow the aneuploid plasma cells are predominant in most patients even after therapy (24 of 30 patients; P=0.0055). In the case of initially detected aneuploid myeloma cells, a contamination with malignant cells can be estimated with a simple flow cytometric method in PBSC harvests and in bone marrow after therapy.

Aneuploidy↗

Even moderate cigarette smoking influences the pattern of circulating monocytes and the concentration of sICAM-1.

The pattern of circulating monocyte subtypes and the concentration of the soluble intercellular adhesion molecule-1 (ICAM-1) were compared in middle-aged female moderate smokers and lifetime non-smokers. Total leukocyte and monocyte counts were higher in smokers. The pattern of circulating monocytes of smokers was changed toward lower absolute counts of activated (CD16+/CD64+) monocytes and (CD16+/CD14+) monocyte-macrophages and higher counts of nonactivated monocytes. The serum concentration of soluble ICAM-1 was significantly higher in smokers than in non-smokers. It is supposed that even moderate cigarette smoking leads to an activation of the circulating monocytes and their increased adhesion to the endothelium.

Antigens, CD↗

Food supply abundant increase of serum selenium concentrations in middle-aged Dresden women between 1990 and 1996. DRECAN-Team. Dresden Cardiovascular Risk and Nutrition.

Serum selenium concentration was measured in middle-aged Dresden (East Germany) women in 1990 and 1996. In 1990, the serum concentration of selenium in middle-aged women was higher than in men living under the same environmental conditions (0.98 +/- 0.32 vs 0.82 +/- 0.19 micromol/l). In 1996, the serum concentration of selenium in middle-aged women was significantly higher than in 1990 (1.19 +/- 0.34 micromol/l). This increase seems to be caused by the changed foodstuff supply after the reunification of Germany. Selenium values did not correlate with age, blood pressure or daily energy intake. Moderate smoking and menopausal status did not influence the selenium levels. In 1990, the serum concentration of selenium was the highest in those women who consumed the lowest amounts of carbohydrates or fibers, or who had the highest consumption of meat, fresh fish or potatoes.

Adult↗

Oestrogen treatment of constitutional tall stature: a risk-benefit ratio.

Oestrogens are given in high doses for the treatment of tall stature in girls. The aim of this study was to obtain data considering efficiency, side effects, and acceptance of the treatment of 50 constitutionally tall girls treated with conjugated oestrogens (7.5-11.25 mg/day). The mean (SD) adult height predictions were 188.3 (4.4) cm and the achieved height was 5.2 (3.3) cm less than the predicted height. A greater reduction from final predicted height occurred when treatment was started at an early bone age (< 13.0 years) and with a remaining growth potential of greater than 10 cm. Even postmenarcheal girls, however, had a mean reduction of 4.8 (3.2) cm. The main side effects were considerable weight gain (> 10 kg), an increase in triglyceride concentrations (37.5% of the patients), and increased platelet aggregation (60% of the patients). Altogether 84.6% of the patients were satisfied with the treatment and 15.4% regretted having had it.

Child↗

[Characterization of viral hemorrhagic septicemia (VHS) virus isolates in trout].

Virus diseases of fish can seriously impair the economy of aquacultur. Control and prevention of fish diseases in the European Union (EU) are focussed on the viral haemorrhagic septicaemia (VHS) and the infectious haematopoeitic necrosis (IHN). The diagnosis of VHS and IHN is performed in the Federal Republic of Germany (FRG) on the basis of the legislation of the EU. Since 1994 we received an increasing number of VHS virus (VHSV) isolates which did not react with a commercially available anti-VHSV monoclonal antibody (MAb) in the indirect immuno fluorescence test. With our own MAb ID8, however, as well as with additional diagnostic methods these virus isolates could be identified. These isolates of rainbow trouts were designated as VHSV type "Wi". Electron microscopically all stages of rhabdovirus maturation could be detected. Morphologically the isolates were undistinguishable from other rhabdoviruses. By immuno electron microscopy using the MAb ID8 rhabdovirus nucleocapsid structures were demonstrated. The virulence of the new VHSV type Wi was not different from that of a VHSV isolate with conventional reaction patterns as well as of a VHSV laboratory strain.

Animals↗