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Biomedical subjects

C Seidel

Publications and source records attributed to C Seidel.

At least 19 recordsLinked to original sources
PubMed2006

Selective nontemplated adsorption of organic molecules on nanofacets and the role of bonding patterns.

A key element of functionalizing nanocrystals with organic molecules is the nontemplated selective adsorption of different molecules on different facets. Here we report scanning-tunneling-microscopy images of perylene-3,4,9,10-tetracarboxylic-dianhydride and 2,5-dimethyl-N,N'-dicyanoquinonediimine on silver, demonstrating selective adsorption on different facets. We also report first-principles calculations that account for the data and show that bonding, which controls selectivity, occurs via the end atoms, while the molecule's midregion arches away from the substrate. The results are also consistent with data that have been interpreted in terms of bonding via the midregion.

Journal Article↗
PubMed2006

Role of lateral alkyl chains in modulation of molecular structures on metal surfaces.

We use low energy electron diffraction, scanning tunneling microscopy, first-principles density-functional theory, and molecular mechanics calculations to analyze the adsorption and growth of quinacridone derivatives (QA) with alkyl chains of 4 and 16 carbon atoms on a Ag(110) substrate. Surprisingly, we find that the alkyl chains determine the orientation of the molecular overlayers. While the interaction of QA and the Ag substrate is primarily due to chemical bonding of oxygen to the silver substrate, determining the molecular orientation and preferred adsorption site, the intermolecular arrangement can be adjusted via the length of alkyl chains. We are thus able to fabricate uniform QA films with very well controlled physical properties.

Journal Article↗
PubMed2006

Indole-3-acetic acid protein conjugates: novel players in auxin homeostasis.

Indole-3-acetic acid (IAA) is found in plants in both free and conjugated forms. Within the group of conjugated IAA there is a unique class of proteins and peptides where IAA is attached directly to the polypeptide structure as a prosthetic group. The first gene, IAP1, encoding for a protein with IAA as a prosthetic group, was cloned from bean (Phaseolus vulgaris). It was shown that the expression of IAP1 as a major IAA modified protein in bean seed (PvIAP1) was correlated to a developmental period of rapid growth during seed development. Moreover, this protein underwent rapid degradation during germination. Since further molecular analysis was difficult in bean, the IAP1 gene was transformed into Arabidopsis thaliana and Medicago truncatula. Expression of the bean IAP1 gene in both plant species under the control of its native promoter targeted protein expression to the seeds. In Arabidopsis no IAA was found to be attached to PvIAP1. These results show that there is specificity to protein modification by IAA and suggests that protein conjugation may be catalyzed by species specific enzymes. Furthermore, subcellular localization showed that in Arabidopsis PvIAP1 was predominantly associated with the microsomal fraction. In addition, a related protein and several smaller peptides that are conjugated to IAA were identified in Arabidopsis. Further research on this novel class of proteins from Arabidopsis will both advance our knowledge of IAA proteins and explore aspects of auxin homeostasis that were not fully revealed by studies of free IAA and lower molecular weight conjugates.

Arabidopsis↗
PubMed2005

Frequent promoter methylation of tumor-related genes in sporadic and men2-associated pheochromocytomas.

Hypermethylation of CpG island promoters is associated with transcriptional inactivation of tumor suppressor genes in neoplasia. Inactivation of p16 and Pten was related to the development of pheochromocytomas. In this report, we investigated the methylation status of the p16INK4a cell cycle inhibitor gene and other prominent tumor-related genes ( PTEN, RASSF1 A, CDH1, MSH2, MLH1, VHL, and TIMP3) in sporadic and multiple endocrine neoplasia type 2 (MEN2) pheochromocytomas by methylation-specific PCR. Hypermethylation was detected in 48 % of pheochromocytomas for RASSF1 A, 24 % for p16, 36 % for MSH2, 16 % for CDH1, and 8 % for PTEN. No VHL, MLH1, and TIMP3 methylation was observed. Interestingly, the frequency of p16 inactivation in familial tumors was higher (5 out of 12, 42 %) than in sporadic tumors (1 out of 13, 8 %; p = 0.047) and RASSF1 A inactivation was more common in the hereditary tumors (58 %) compared to the sporadic tumors (38 %). Combined methylation of RASSF1 A and p16 was found only in MEN2-related pheochromocytomas. Thus, a subset of hereditary pheochromocytomas displays preferential methylation of p16 and RASSF1 A.

Adrenal Gland Neoplasms↗
PubMed2005

The tumor suppressor RASSF1A in human carcinogenesis: an update.

Loss of heterozygosity of the small arm of chromosome 3 is one of the most common alterations in human cancer. Most notably, a segment in 3p21.3 is frequently lost in lung cancer and several other carcinomas. We and others have identified a novel Ras effector at this segment, which was termed Ras Association Domain family 1 (RASSF1A) gene. RASSF1 consists of two main variants (RASSF1A and RASSF1C), which are transcribed from distinct CpG island promoters. Aberrant methylation of the RASSF1A promoter region is one of the most frequent epigenetic inactivation events detected in human cancer and leads to silencing of RASSF1A. Hypermethylation of RASSF1A was commonly observed in primary tumors including lung, breast, pancreas, kidney, liver, cervix, nasopharyngeal, prostate, thyroid and other cancers. Moreover, RASSF1A methylation was frequently detected in body fluids including blood, urine, nipple aspirates, sputum and bronchial alveolar lavages. Inactivation of RASSF1A was associated with an advanced tumor stage (e.g. bladder, brain, prostate, gastric tumors) and poor prognosis (e.g. lung, sarcoma and breast cancer). Detection of aberrant RASSF1A methylation may serve as a diagnostic and prognostic marker. The functional analyses of RASSF1A reveal an involvement in apoptotic signaling, microtubule stabilization and mitotic progression. The tumor suppressor RASSF1A may act as a negative Ras effector inhibiting cell growth and inducing cell death. Thus, RASSF1A may represent an epigenetically inactivated bona fide tumor suppressor in human carcinogenesis.

Chromosomes, Human, Pair 3↗
PubMed2004

Mesenchymal stem cells inhibit the expression of CD25 (interleukin-2 receptor) and CD38 on phytohaemagglutinin-activated lymphocytes.

Mesenchymal stem cells (MSC) are immunomodulatory and inhibit lymphocyte proliferation. We studied surface expression of lymphocyte activation markers and secreted cytokines, when lymphocytes were activated in the presence of MSC. MSC suppressed the proliferation of phytohaemagglutinin (PHA)-stimulated CD3+, CD4+ and CD8+ lymphocytes. MSC significantly reduced the expression of activation markers CD25, CD38 and CD69 on PHA-stimulated lymphocytes. Mixed lymphocyte culture (MLC) supernatants containing MSC suppressed proliferation of MLC and PHA-stimulated lymphocytes dose-dependently. MSC secrete osteoprotegerin (OPG), but not hepatocyte growth factor (HGF) or transforming growth factor-beta (TGF-beta). Stromal-cell-derived factor-1 (SDF-1) is not expressed on the cell surface. A recent report suggested that T-cell suppression by MSC is mediated by HGF and TGF-beta. MSC suppression was not restored by the addition of neutralizing antibodies against SDF-1, OPG, HGF or TGF-beta, alone or in combination. Addition of guanosine to PHA-stimulated lymphocyte cultures containing MSC did not affect lymphocyte proliferation. The immunosuppressive effects of cyclosporine and MSC did not interfere, when present in the cultures of PHA-activated lymphocytes. In summary, human MSC suppress proliferation of both CD4+ and CD8+ lymphocyte and decrease the expression of activation markers.

ADP-ribosyl Cyclase↗
PubMed2003

[Amanita poisoning during pregnancy].

A pregnant woman at the 28th gestational week and three other members of the family had mushrooms for dinner. One of these mushrooms was an Amanita mushroom. The morning after, three of them suffered from nausea, vomiting and diarrhoea. The pregnant woman was admitted to hospital, and therapy with Penicillin and Silibinin was started immediately. Hepatic and renal blood parameters were observed repeatedly for early detecting of organ failure. Fetal lung maturation was forced by administration of betamethasone. After five days at the intensive care unit mother and unborn child were dismissed at normal physical condition.

Adult↗
PubMed2003

Non-linear osmotic brush regime: simulations and mean-field theory.

We investigate polyelectrolyte brushes in the osmotic regime using both theoretical analysis and molecular dynamics simulation techniques. In the simulations at moderate Bjerrum length, we observe that the brush height varies weakly with grafting density, in contrast to the accepted scaling law, which predicts a brush thickness independent of the grafting density. We show that such behavior can be explained by considering lateral electrostatic effects (within the non-linear Poisson-Boltzmann theory) combined with the coupling between lateral and longitudinal degrees of freedom due to the conserved polymer volume (which are neglected in scaling arguments). We also take the non-linear elasticity of polyelectrolyte chains into consideration, which makes significant effects as chains are almost fully stretched in the osmotic regime. It is shown that all these factors lead to a non-monotonic behavior for the brush height as a function of the grafting density. At large grafting densities, the brush height increases with increasing the grafting density due to the volume constraint. At small grafting densities, we obtain a re-stretching of the chains for decreasing grafting density, which is caused by lateral electrostatic contributions and is controlled by the counterion-condensation process around polyelectrolyte chains. These results are obtained assuming all counterions to be trapped within the brush, which is valid for sufficiently long chains of large charge fraction.

Journal Article↗
PubMed2003

Epigenetic inactivation of the Ras-association domain family 1 (RASSF1A) gene and its function in human carcinogenesis.

The Ras GTPases are a superfamily of molecular switches that regulate cellular proliferation and apoptosis in response to extra-cellular signals. The regulation of these pathways depends on the interaction of the GTPases with specific effectors. Recently, we have cloned and characterized a novel gene encoding a putative Ras effector: the Ras-association domain family 1 (RASSF1) gene. The RASSF1 gene is located in the chromosomal segment of 3p21.3. The high allelic loss in a variety of cancers suggested a crucial role of this region in tumorigenesis. At least two forms of RASSF1 are present in normal human cells. The RASSF1A isoform is highly epigenetically inactivated in lung, breast, ovarian, kidney, prostate, thyroid and several other carcinomas. Re-expression of RASSF1A reduced the growth of human cancer cells supporting a role for RASSF1 as a tumor suppressor gene. RASSF1A inactivation and K-ras activation are mutually exclusive events in the development of certain carcinomas. This observation could further pinpoint the function of RASSF1A as a negative effector of Ras in a pro-apoptotic signaling pathway. In malignant mesothelioma and gastric cancer RASSF1A methylation is associated with virus infection of SV40 and EBV, respectively, and suggests a causal relationship between viral infection and progressive RASSF1A methylation in carcinogenesis. Furthermore, a significant correlation between RASSF1A methylation and impaired lung cancer patient survival was reported, and RASSF1A silencing was correlated with several parameters of poor prognosis and advanced tumor stage (e.g. poor differentiation, aggressiveness, and invasion). Thus, RASSF1A methylation could serve as a useful marker for the prognosis of cancer patients and could become important in early detection of cancer.

Animals↗
PubMed2002

Equilibrium charge distribution on annealed polyelectrolytes.

Monte Carlo simulations are used to study the non-uniform equilibrium charge distribution along a single annealed polyelectrolyte chain under theta solvent conditions and with added salt. Within a range of the order of the Debye length charge accumulates at chain ends while a slight charge depletion appears in the central part of the chain. The simulation results are compared with theoretical predictions recently given by Castelnovo et al. In the parameter range where the theory can be applied we find almost perfect quantitative agreement.

Journal Article↗
PubMed2001

[Thalidomide--a dreaded drug with new indications].

BACKGROUND: Thalidomide was introduced as a non-toxic sleeping pill in 1957 and was prescribed in more than 20 countries. In 1961 the link between congenital limb defects and thalidomide use in pregnancy was proven, resulting in withdrawal of the drug. MATERIAL AND METHODS: On the basis of literature searches and personal experience we review the effects and use of thalidomide today. RESULTS: In vitro, thalidomide has immunoregulatory properties. This has lead to the administration of thalidomide in many immunological diseases. In 1964 it was discovered that thalidomide was effective against erythema nodosum leprosum. Thalidomide also has effect on aphthous stomatitis and Behçet's disease. The effect is more uncertain in graft-versus-host-disease, rheumatoid arthritis and Crohn's disease. Thalidomide reduces angiogenesis in experimental animals, and this has led to several studies of thalidomide as a possible anticancer drug. Advanced or resistant multiple myeloma may be a new target for thalidomide; at least 30% of these patients obtain response during treatment. Results indicate that patients with breast cancer and glioma do not benefit from treatment with thalidomide. INTERPRETATION: Thalidomide has proven to be effective in the treatment of erythema nodosum leprosum and aphthous stomatitis. It is also effective in advanced multiple myeloma, but not in other cancers.

Abnormalities, Drug-Induced↗
PubMed2001

Serum osteoprotegerin levels are reduced in patients with multiple myeloma with lytic bone disease.

Osteoprotegerin (OPG), the neutralizing decoy receptor for the osteoclast activator RANK ligand, was measured in serum taken from patients with multiple myeloma at the time of diagnosis. Median OPG was lower in the patients with myeloma (7.4 ng/mL; range, 2.6-80; n = 225) than in healthy age- and sex-matched controls (9.0 ng/mL; range 5.1-130; n = 40; P =.02). Importantly, OPG levels were associated with degree of radiographically assessed skeletal destruction (P =.01). The median OPG level in patients lacking osteolytic lesions was 9.1 ng/mL, as compared with 7.6 ng/mL and 7.0 ng/mL, respectively, in patients with minor or advanced osteolytic disease. Furthermore, OPG levels were associated with World Health Organization performance status (P =.003) and correlated to serum levels of carboxy-terminal propeptide of type I procollagen (PICP; P <.001) but not with clinical stage or survival. These findings suggest impaired OPG function in myeloma and give a rationale for OPG as a therapeutic agent against myeloma bone disease.

Adult↗
PubMed2001

Bone morphogenetic protein-4 inhibits proliferation and induces apoptosis of multiple myeloma cells.

Bone morphogenetic proteins (BMPs) can be isolated from organic bone matrix and are able to initiate de novo cartilage and bone formation. Here it is shown that BMP-4 inhibited DNA synthesis in a dose-dependent manner in 3 IL-6-dependent multiple myeloma (MM) cell lines (OH-2, IH-1, and ANBL-6). In contrast, no effect on DNA synthesis was observed in 3 IL-6-independent MM cell lines (JJN-3, U266, and RPMI 8226). BMP-4 induced cell cycle growth arrest in the G(0)/G(1) phase in OH-2 and ANBL-6 cells but not in IH-1 cells. BMP-4 induced apoptosis in OH-2 and IH-1 cells, but not significantly in ANBL-6 cells. Furthermore, BMP-4 induced apoptosis in freshly isolated MM cells from 4 of 13 patients. In the OH-2 and ANBL-6 cell lines and in a patient sample, immunoblotting showed that BMP-4 down-regulated IL-6-induced tyrosine phosphorylation of Stat3, suggesting a mechanism for the apparent antagonism between IL-6 and BMP-4. BMP-4 or analogues may be attractive therapeutic agents in MM because of possible beneficial effects on both tumor burden and bone disease.

Aged↗
PubMed2001

Roles of TNF-related apoptosis-inducing ligand in experimental autoimmune encephalomyelitis.

TRAIL, the TNF-related apoptosis-inducing ligand, induces apoptosis of tumor cells, but not normal cells; the roles of TRAIL in nontransformed tissues are unknown. Using a soluble TRAIL receptor, we examined the consequences of TRAIL blockade in an animal model of multiple sclerosis. We found that chronic TRAIL blockade in mice exacerbated experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein. The exacerbation was evidenced primarily by increases in disease score and degree of inflammation in the CNS. Interestingly, the degree of apoptosis of inflammatory cells in the CNS was not affected by TRAIL blockade, suggesting that TRAIL may not regulate apoptosis of inflammatory cells in experimental autoimmune encephalomyelitis. By contrast, myelin oligodendrocyte glycoprotein-specific Th1 and Th2 cell responses were significantly enhanced in animals treated with the soluble TRAIL receptor. Based on these observations, we conclude that unlike TNF, which promotes autoimmune inflammation, TRAIL inhibits autoimmune encephalomyelitis and prevents activation of autoreactive T cells.

Animals↗
PubMed2001

Elevated levels of osteoprotegerin (OPG) and hepatocyte growth factor (HGF) in rheumatoid arthritis.

Rheumatic diseases are often associated with changes in bone metabolism. Excessive production and release of cytokines and other growth factors due to inflammation, e.g. tumor necrosis factor-alpha (TNF-alpha), receptor activator of NF-kappaB ligand (RANKL), interleukins such as IL-1 and IL-6, may cause alterations in bone homeostasis leading to bone degradation. Other components such as osteoprotegerin (OPG) and possibly the ligand-receptor pair hepatocyte growth factor (HGF) and c-met may counteract this destruction, we have measured the levels of OPG, and HGF c-met, in serum, synovial fluid (SF), and cartilage from patients with rheumatoid arthritis (RA) and other arthritides. We found a) elevated levels of both OPG and HGF in SF from RA patients relative to arthritides of other causes, b) increased levels of both OPG and HGF in SF from seropositive RA patients (RA+) compared to seronegative RA patients (RA-), c) elevated levels or both OPG and HGF in serum from RA patients compared to healthy controls, d) no correlation between severity of inflammation and levels of OPG or HGF, and e) presence of HGF c-met in both cartilage and synovial tissue. The most significant elevations of OPG and HGF were found in patients with RA, the rheumatic disease most frequently associated with the development of secondary osteoporosis.

Adult↗
PubMed2001

The Cbk1p pathway is important for polarized cell growth and cell separation in Saccharomyces cerevisiae.

During the early stages of budding, cell wall remodeling and polarized secretion are concentrated at the bud tip (apical growth). The CBK1 gene, encoding a putative serine/threonine protein kinase, was identified in a screen designed to isolate mutations that affect apical growth. Analysis of cbk1Delta cells reveals that Cbk1p is required for efficient apical growth, proper mating projection morphology, bipolar bud site selection in diploid cells, and cell separation. Epitope-tagged Cbk1p localizes to both sides of the bud neck in late anaphase, just prior to cell separation. CBK1 and another gene, HYM1, were previously identified in a screen for genes involved in transcriptional repression and proposed to function in the same pathway. Deletion of HYM1 causes phenotypes similar to those observed in cbk1Delta cells and disrupts the bud neck localization of Cbk1p. Whole-genome transcriptional analysis of cbk1Delta suggests that the kinase regulates the expression of a number of genes with cell wall-related functions, including two genes required for efficient cell separation: the chitinase-encoding gene CTS1 and the glucanase-encoding gene SCW11. The Ace2p transcription factor is required for expression of CTS1 and has been shown to physically interact with Cbk1p. Analysis of ace2Delta cells reveals that Ace2p is required for cell separation but not for polarized growth. Our results suggest that Cbk1p and Hym1p function to regulate two distinct cell morphogenesis pathways: an ACE2-independent pathway that is required for efficient apical growth and mating projection formation and an ACE2-dependent pathway that is required for efficient cell separation following cytokinesis. Cbk1p is most closely related to the Neurospora crassa Cot-1; Schizosaccharomyces pombe Orb6; Caenorhabditis elegans, Drosophila, and human Ndr; and Drosophila and mammalian WARTS/LATS kinases. Many Cbk1-related kinases have been shown to regulate cellular morphology.

Amino Acid Sequence↗
PubMed2000

High levels of soluble syndecan-1 in myeloma-derived bone marrow: modulation of hepatocyte growth factor activity.

Syndecan-1 is a heparan sulfate proteoglycan expressed on the surface of, and actively shed by, myeloma cells. Hepatocyte growth factor (HGF) is a cytokine produced by myeloma cells. Previous studies have demonstrated elevated levels of syndecan-1 and HGF in the serum of patients with myeloma, both of negative prognostic value for the disease. Here we show that the median concentrations of syndecan-1 (900 ng/mL) and HGF (6 ng/mL) in the marrow compartment of patients with myeloma are highly elevated compared with healthy controls and controls with other diseases. We show that syndecan-1 isolated from the marrow of patients with myeloma seems to exist in an intact form, with glucosaminoglycan chains. Because HGF is a heparan-sulfate binding cytokine, we examined whether it interacted with soluble syndecan-1. In supernatants from myeloma cells in culture as well as in pleural effusions from patients with myeloma, HGF existed in a complex with soluble syndecan-1. Washing myeloma cells with purified soluble syndecan-1 could effectively displace HGF from the cell surface, suggesting that soluble syndecan-1 can act as a carrier for HGF in vivo. Finally, using a sensitive HGF bioassay (interleukin-11 production from the osteosarcoma cell line Saos-2) and intact syndecan-1 isolated from the U-266 myeloma cell line, we found that the presence of high concentrations of syndecan-1 (more than 3 microg/mL) inhibited the HGF effect, whereas lower concentrations potentiated it. HGF is only one of several heparin-binding cytokines associated with myeloma. These data indicate that soluble syndecan-1 may participate in the pathology of myeloma by modulating cytokine activity within the bone marrow.

Biopsy, Needle↗