PubMed Health⌕ Search

Biomedical subjects

S Franke

Publications and source records attributed to S Franke.

At least 19 recordsLinked to original sources

Functional characterization of sphingolipid C4-hydroxylase genes from Arabidopsis thaliana.

In the genome of Arabidopsis thaliana, two genes were identified encoding isoenzymes for C4-hydroxylation of long chain bases (LCB) in plant sphingolipids. Both predicted proteins consist of 258 amino acid residues (77% identity) which show sequence similarity to di-iron-binding enzymes, such as Sur2p and Erg3p from yeast, involved in oxygen-dependent lipid modifications. Heterologous expression of these genes in a yeast sur2Delta-null mutant lacking C4-LCB hydroxylation resulted in the formation of D-ribo-C(18)- and -C(20)-phytosphinganine. The identity and stereochemical configuration of the isolated trihydroxybases was confirmed by electrospray ionization-mass spectroscopy, gas-liquid chromatography-mass spectrometry and 1H-nuclear magnetic resonance spectroscopy. These results represent the first functional identification of SUR2 genes from plants as well as from any organism other than yeast.

Arabidopsis↗

Lymphocyte predominance Hodgkin disease is characterized by recurrent genomic imbalances.

Single-cell polymerase chain reaction (PCR) has been used as a tool to demonstrate clonality and B-cell origin of Reed-Sternberg (RS) cells in Hodgkin disease (HD). An analogous approach was used to investigate genomic imbalances in a (cyto)genetically poorly characterized subentity: lymphocyte predominance Hodgkin disease (LPHD). Nineteen cases of LPHD were selected for a comparative genomic hybridization (CGH) study. CGH was performed with degenerate oligonucleotide primed-PCR (DOP-PCR)-amplified DNA from 4-5 microdissected CD20+ malignant cells. All analyzed cases revealed a high number of genomic imbalances (average 10.8 per case), involving all chromosomes but the excluded 19, 22, and Y, indicating a high complexity of LPHD. The majority of detected aberrations were recurrent. Gain of 1, 2q, 3, 4q, 5q, 6, 8q, 11q, 12q, and X, and loss of chromosome 17 were identified in 36.8% to 68.4% of the analyzed cases. Some of them have also been found in non-Hodgkin lymphoma (NHL), and possibly represent secondary changes associated with disease progression. Gain of 2q, 4q, 5q, 6, 11q, however, are much more rarely observed in NHL and could be more specifically associated with LPHD. Particularly interesting is a frequent overrepresentation of chromosome arm 6q, a region usually deleted in NHL. Rearrangement of the BCL6 gene (3q27) demonstrated by cytogenetics and fluorescence in situ hybridization in 2 cases in this study suggests its contribution in pathogenesis of LPHD. In conclusion, the data show a consistent occurrence of genomic alterations in LPHD and highlight genomic regions that might be relevant for development and/or progression of this lymphoma entity.

Adult↗

Secretion of cytokines by uroepithelial cells stimulated by Escherichia coli and Citrobacter spp.

Urinary tract epithelial cells (T 24/83) are able to express interleukin (IL)-6, IL-8, platelet-derived growth factor (PDGF) and tumour necrosis factor-alpha, but not IL-1 beta, IL-2, IL-4 and IL-10 in response to an infection with uropathogenic bacteria. The process of cytokine secretion is time dependent, with a significant increase in the cytokine activity after 60 min. The expression of virulence factors of the bacteria does not seem to play a role. The interaction between bacterial products (e.g. lipopolysaccharide) and/or bacterial adhesion mediated by adhesins and specific receptor molecules of cell surfaces may be responsible for the activity of mediator protein expression in the epithelial cells. The release of PDGF and IL-8 was found to be higher when due to Escherichia coli HB 101 (rough form) than that caused by other bacterial strains. Citrobacter CB 3009 provoked the highest level of IL-6. The PDGF level correlated significantly with IL-6 and IL-8 values (P<0.001). There was a significant correlation between the time-dependent release of IL-6 and IL-8 (P<0.05). In epithelial cytokine response to bacterial infection, the reaction of the epithelial cells may modify themselves (e.g. internalization of bacteria) and the immuno-regulatory processes that are caused by infection and responsible for parenchymal injury.

Citrobacter↗

[Embolization of aneurysma spurium of the superior gluteal artery].

While for the surgical treatment there are the transgluteal and the retroperitoneal approach, the alternative radiological modality is less invasive. It is performed by a from contralateral placed guidant-catheter in combination with a tracker catheter with the possibility of transcatheter embolization with liquid, particles or coils. The rate of success is high, complications are seldom and the hospital stay is short. Both modalities can and should be used complementary. In the case of an intractable acute hemorrhage transcatheter embolization should be used firstly.

Aged↗

Differences in the modulating potential of advanced glycation end product (AGE) peptides versus AGE proteins.

Differences in the modulating potential of advanced glycation end product (AGE) peptides versus AGE proteins. Advanced glycation end products (AGEs), identified as irreversible products of a complex reaction of carbonyl groups of reducing sugars with free protein amino groups, are characterized by resistance to proteolytic degradation. The incomplete digestion of AGEs results in low molecular weight AGEs accumulating in the blood of diabetic and uremic patients. We hypothesized that the accumulation of these compounds may contribute to the dysfunction and/or degeneration of tubular epithelial cells. Our study examined whether low-molecular-weight AGE peptides and high-molecular-weight AGE proteins affect the functional cellular properties of two tubular epithelial cell lines: immortalized human kidney tubular epithelial (IHKE) and immortalized rat renal proximal tubular cells (IRPTCs). Parameters of cellular damage and growth behavior were cell counting, analysis of the cellular metabolic activity (MTT assay), as well as cellular proliferation (3[H]-thymidine-incorporation). IHKE treated with bovine serum albumin-AGE (BSA-AGE 50) or BSA-AGE-Pep 50 revealed a decrease in cellular metabolic activity as compared with controls after 48 hours of incubation (73 +/- 9% for BSA-AGE 50 and 62 +/- 11% for BSA-AGE-Pep 50 vs. 89 +/- 8% for BSA Co 50). Low molecular weight BSA-AGE-Pep 50 induced a significantly greater cellular damage in IRPTCs as compared with high molecular weight BSA-AGE 50 after 144 hours of incubation (59 +/- 15% for BSA-AGE 50 vs. 31 +/- 13% for BSA-AGE-Pep 50). The decrease in metabolic activity correlated well with a decrease in cellular proliferation. The results suggest a higher toxic potential of low molecular weight AGE peptides compared with high molecular weight AGE proteins in IRPTC and IHKE. This may provide evidence that low molecular weight degradation products of AGE-modified proteins have an important risk potential.

Animals↗

Influence of dialysis modalities on serum AGE levels in end-stage renal disease patients.

BACKGROUND: The accumulation of advanced glycation end-products (AGEs) in end-stage renal disease (ESRD) influenced by dialysis modalities is of current interest. Highly permeable membranes in haemodialysis or haemofiltration should be able to eliminate circulating AGEs as well as their AGE precursors more efficiently. METHODS: In our study, 10 non-diabetic and 10 diabetic ESRD patients were on haemodialysis with low-flux membranes (LF) followed by a cross-over haemodialysis with high-flux or super-flux polysulfone membranes (HF, SF) for 6 months each. We measured the protein-bound pentosidine and free pentosidine serum levels by high-performance liquid chromatography (HPLC) as well as the serum AGE peptide, AGE-beta(2)-microglobulin and beta(2)-microglobulin concentrations, using ELISA assays. RESULTS: All parameters investigated were significantly higher in dialysis patients than in healthy subjects. The reduction rates during a single dialysis session were found to be higher using the SF than those obtained with the HF (free pentosidine 82.4+/-7.3 vs 76.6+/- 8.7%; AGE peptides 79.7+/-7.7 vs 62.3+/-14.7%; AGE-beta(2)-microglobulin 64.0+/-16.5 vs 45.4+/-17.7%; beta(2)-microglobulin 70.5+/-5.6 vs 58.2+/-6.0%). The protein-bound pentosidine levels remained constant over the respective dialysis sessions. In the 6-month treatment period with the SF, decreased pre-dialysis serum levels of protein-bound pentosidine, free pentosidine and AGE peptides were observed in non-diabetics and diabetics as compared with values obtained with the LF. The respective pre-dialysis AGE-beta(2)-microglobulin concentrations decreased insignificantly, whereas those of beta(2)-microglobulin were significantly lower. Using the HF dialyser, only moderate changes of the parameters measured were noted. CONCLUSION: Treatment with the biocompatible polysulfone SF dialyser seems to be better suited to lower serum AGE levels and to eliminate their precursors.

Adult↗

The AIDA autotransporter system is associated with F18 and stx2e in Escherichia coli isolates from pigs diagnosed with edema disease and postweaning diarrhea.

Pathogenic Escherichia coli strains are known to cause edema disease (ED) and postweaning diarrhea (PWD) in piglets. Although the exact mechanisms of pathogenicity that lead to ED-PWD remain to be elucidated, E. coli-borne Shiga-like toxin and adhesion-mediating virulence factors such as F18 adhesin or F4 fimbriae are believed to play a central role in ED-PWD. In light of these observations we investigated whether another E. coli adhesin, the plasmid-encoded AIDA (adhesin involved in diffuse adherence) might also be present in ED-PWD-causing E. coli isolates. For rapid screening for the AIDA system in large numbers of isolates, a multiplex PCR method along with a duplex Western blot procedure was developed. When screening 104 strains obtained from pigs with or without ED-PWD, we observed a high prevalence of the AIDA operon in porcine E. coli isolates, with over 25% of all strains being AIDA positive, and we could demonstrate a significant association of the intact AIDA gene (orfB) with ED-PWD, while defects in orfB were associated with the absence of disease. Although our data hint toward a contribution of AIDA to ED-PWD, further studies will be necessary since the presence of the AIDA genes was also associated with the presence of the Shiga-like toxin and F18 adhesin genes, two reported virulence factors for ED-PWD.

Adhesins, Escherichia coli↗

Cell transformation and genotoxicity induced by bis(2, 3-dichloro-1-propyl) ether.

Bis(dichloropropyl) ether isomers have been identified in a petrochemical plant effluent through a toxicity identification evaluation study in the United States. They have also been observed in the microgram per liter range along one of the largest rivers in Europe, the Elbe River. In the present investigation, the genotoxic and transforming activity of a bis(dichloropropyl) ether isomer, bis(2,3-dichloro-1-propyl) ether, was assayed in vitro. The results demonstrate that bis(2,3-dichloro-1-propyl) ether is a potent mutagen in Salmonella typhimurium strains TA 100, TA 1535, and to a lesser extent in strain TA 98, but only when tested in the presence of a metabolic activation system (S9 mix). We have also investigated the induction of micronuclei by bis(2,3-dichloro-1-propyl) ether in the metabolically competent cell line, MCL-5. A linear, dose-dependent increase in micronuclei was observed following exposure to bis(2,3-dichloro-1-propyl) ether. The DNA strand-breaking capacity of this chemical was assessed in the alkaline single-cell gel electrophoresis ("comet") assay with MCL-5 cells. Bis(2,3-dichloro-1-propyl) ether clearly induced DNA strand breaks in the 4.5-45.5 microg/ml dose range. The ether also induced malignant transformation in C3H/M2 mouse fibroblasts after metabolic activation (S9 mix). Thus, it must be suspected that bis(2, 3-dichloro-1-propyl) ether may possess a carcinogenic potential. Since the compound along with its isomers is present in considerable concentrations in surface water, their elimination is a matter of significant public concern.

Animals↗

Task-related variation of postpharyngeal and cuticular hydrocarbon compositions in the ant Myrmicaria eumenoides.

In the ant Myrmicaria eumenoides we investigated postpharyngeal and cuticular hydrocarbons. At eclosion the glands contained almost no hydrocarbons and there were no lipid inclusions in the glandular epithelium. During the first 3 weeks of adult life the amount of hydrocarbons in the gland increased until day 5, and then remained constant while the lipid content in the epithelium increased steadily. Intracolonial hydrocarbon compositions were not uniform. Compositions of post-pharyngeal and cuticular hydrocarbons in individual ants varied simultaneously, but in different manner depending on the tasks of the ant (brood-tenders, foragers, scouts). Variations on the cuticle were greater than in the gland, but they were strongly correlated. Independent of ants' age and task, cuticular hydrocarbon compositions were dominated by alkenes and alkadienes. Task-specific differences in cuticular compositions were mainly in the amount of alkenes (high in foragers) and alkadienes (high in brood-tenders). Variation of hydrocarbons was low in ants up to 10 weeks old. Thereafter, ants fell into two groups: (1) ants that did not change their hydrocarbons and remained in the nest, and (2) ants that changed their hydrocarbon compositions and became foragers. These results contribute to an ongoing discussion of the dynamic relationship between post-pharyngeal and cuticular hydrocarbons.

Age Factors↗

Immunochemical detection of imidazolone in uremia and rheumatoid arthritis.

The advanced glycation end-product imidazolone is formed by reaction of arginine with 3-deoxyglucosone (3-DG), a reactive intermediate of the Maillard reaction, whose formation is non-oxidative. Using an antibody specific to this 3-DG-derived AGE, we demonstrated the presence of imidazolone-modified proteins in vivo in the urine and dialysate of patients with chronic renal failure, in the synovial fluid of patients with rheumatoid arthritis, as well as in vitro in human serum and human serum albumin incubated with glucose. Furthermore, we could show that in uremic patients the dimeric form of beta(2)-microglobulin is more susceptible to imidazolone modification than the monomeric one. Thus, the immunochemical detection of imidazolone may be a good marker for 3-DG-derived AGE modification in vivo and in vitro permitting a differentiation between the oxidative and the non-oxidative pathway of AGE generation.

Adult↗

Naphthalene degradation and incorporation of naphthalene-derived carbon into biomass by the thermophile Bacillus thermoleovorans.

The thermophilic aerobic bacterium Bacillus thermoleovorans Hamburg 2 grows at 60 degrees C on naphthalene as the sole source of carbon and energy. In batch cultures, an effective substrate degradation was observed. The carbon balance, including naphthalene, metabolites, biomass, and CO(2), was determined by the application of [1-(13)C]naphthalene. The incorporation of naphthalene-derived carbon into the bulk biomass as well as into specified biomass fractions such as fatty acids and amino acids was confirmed by coupled gas chromatography-mass spectrometry (GC-MS) and isotope analyses. Metabolites were characterized by GC-MS; the established structures allow tracing the degradation pathway under thermophilic conditions. Apart from typical metabolites of naphthalene degradation known from mesophiles, intermediates such as 2, 3-dihydroxynaphthalene, 2-carboxycinnamic acid, and phthalic and benzoic acid were identified for the pathway of this bacterium. These compounds indicate that naphthalene degradation by the thermophilic B. thermoleovorans differs from the known pathways found for mesophilic bacteria.

Amino Acids↗

Enantiomeric composition of the polycyclic musks HHCB and AHTN in different aquatic species

Synthetic polycyclic musk fragrances are mainly represented by the compounds HHCB (Galaxolide(TM)) and AHTN (Tonalide(TM)). Because of their volume of use and their bioaccumulation potential, there is concern with respect to their environmental safety. HHCB and AHTN are chiral compounds, and gas chromatography using modified cyclodextrins as chiral stationary phases coupled to high-resolution mass spectrometry enabled enantioselective analysis even under unfavorable matrix conditions. The gas chromatographic elution order of (4S,7RS)- and (4R,7RS)-HHCB was assigned using synthetic (4S, 7RS)-HHCB. Fish and mussels reared in a pond associated with a municipal waste water treatment plant and semipermeable membrane devices exposed in the pond were analyzed for HHCB and AHTN. The highest lipid concentrations of HHCB and AHTN were observed in mussels (Dreissena polymorpha), tench (Tinca tinca), and crucian carp (Carassius carassius). Pronounced deviations in enantiomeric composition from racemic HHCB were observed in crucian carp and from racemic AHTN in tench. Correlations between lipid levels, enrichment, and enantioselective biotransformation of HHCB or AHTN were not seen. Selective biotransformation depended on both the compound and the species involved. The present study gives the first account of the enantiomeric composition of HHCB and AHTN in aquatic species. The lactone, 1,3,4,6,7,8-hexahydro-4,6,6,7,8, 8-hexamethylcyclopenta[g]-2-benzopyran-1-one, an oxidation product of HHCB, has been identified for the first time in environmental samples. Copyright 1999 Wiley-Liss, Inc.

Journal Article↗

Cross-reactivity and epitope analysis of Pru a 1, the major cherry allergen.

A high percentage of birch pollen allergic patients experiences food hypersensivity after ingestion of fresh fruits and vegetables. The cross-reactivity of the major allergens of sweet cherry (Pru a 1), apple (Mal d 1), pear (Pyr c 1), celery tuber (Api g 1) and carrot (Dau c 1) is due to structural similarities which are reflected by high amino acid sequence identities with Bet v 1a, the major birch pollen allergen. Apart from a strong cross-reactivity to Bet v 1a, IgE inhibition experiments with Mal d 1, Pru a 1 and Api g 1 demonstrated the presence of common and different epitopes among the tested food allergens. Secondary structure prediction of all investigated allergens indicated the presence of almost identical structural elements. In particular, the 'P-loop' region is a common domain of the pollen related food allergens and of pathogenesis related proteins. To identify the IgE binding epitopes, five overlapping recombinant Pru a 1 fragments representing the entire amino acid sequence with lengths of approximately 60-120 residues were investigated. Weak IgE binding capacity was measured exclusively with Pru a IF4 (1-120) by immunoblotting, whereas none of the fragments showed allergenicity in the rat basophil leukaemia cell mediator release assay. Site-directed mutagenesis experiments with Pru a 1 revealed that amino acid S112 is critical for IgE binding of almost all patients sera tested. This reduced IgE binding was also observed with a single point mutant of Bet v 1a (S112P) and thus indicated serine 112 as an essential residue for preserving the structure of a cross-reactive IgE epitope. Moreover, two Pru a 1 mutants with an altered 'P-loop' region, showed a lowered IgE binding capacity for IgE from a subgroup of allergic patients. The investigation of essential features for preserving cross-reactive IgE-epitopes provides the structural basis for understanding the clinically observed cross-allergenicity between pollen and fruits. Moreover, non-anaphylactic allergen fragments or variants derived from the IgE-inducing pollen allergens may serve as useful tools for a new strategy of specific immunotherapy.

Allergens↗

Relationship between soluble markers of immune activation and bone turnover in post-menopausal women with rheumatoid arthritis.

OBJECTIVE: Regarding interactions between pro-inflammatory cytokines and bone metabolism in rheumatoid arthritis (RA), we investigated the relationship between the serum levels of interleukin (IL)-1beta, IL-6, soluble interleukin-2 receptor (sIL-2r), C-reactive protein (CRP), the vitamin D metabolites 25-hydroxyvitamin D3 (25OHD3) and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], intact parathyroid hormone (iPTH) as well as serum and urinary parameters of bone turnover in 74 post-menopausal women with RA. RESULTS: SIL-2r correlated negatively with 1,25(OH)2D3 (P < 0.01), whereas IL-6 showed a positive correlation with urinary excretion of deoxypyridinoline collagen cross-links (P < 0.01). 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.01) were negatively related to CRP, whereas the urinary excretion of pyridinoline (P < 0.01) and deoxypyridinoline (P < 0.01)-collagen cross-links showed a positive correlation with CRP. 1,25(OH)2D3 (P < 0.01) and iPTH (P < 0.05) were positively related to bone alkaline phosphatase as a marker of osteoblast function. CONCLUSION: Our data indicate that IL-6 is a critical determinant of increased bone resorption in post-menopausal RA women with high disease activity and that serum levels of 1,25(OH)2D3 are inversely related to T-cell activation.

Aged↗