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Biomedical subjects

C Dietrich

Publications and source records attributed to C Dietrich.

At least 19 recordsLinked to original sources
PubMed2006

Targeting the EGF/VEGF-R system by tyrosine-kinase inhibitors--a novel antiproliferative/antiangiogenic strategy in thyroid cancer.

AIM: In thyroid cancer (TC), endothelial growth factor (EGF) has been associated with dedifferentiation, tumor cell proliferation, and angiogenesis. Vascular endothelial growth factor (VEGF) has been documented to be the main stimulator of angiogenesis in the thyroid gland. Patients with undifferentiated thyroid cancer are in desperate need of new therapeutic strategies because common protocols of therapy usually fail. The aim of this study, therefore, was to evaluate two tyrosine-kinase inhibitors (TKI, ZD 1839 gefitinib and ZD 6474 vandetanib), directed against the EGF/VEGF receptor for possible antitumor therapy in thyroid cancer. METHODS: EGF/VEGF-R was documented in anaplastic (Hth74, C643), follicular (FTC133), and papillary (TPC1) thyroid cancer cell lines by Western blot analysis. The antiproliferative effect of two TKI (0.1-10 microM) on thyroid cancer cell lines in vitro was quantified by MTT assay, the antiangiogenic effect by assessing secretion of VEGF by enzyme-linked immunosorbent assay (R&D Systems). ZD 1839 is mainly directed against EGF-R and ZD 6474 against VEGF-R (AstraZeneca, UK), single applications and combinations of compounds were evaluated. RESULTS: EGF-R and VEGF-R as well as the phosphorylated receptor were documented in all of the cell lines. Administration of ZD1839 led to an up to 90% reduction of cell number in Hth74, 80% in C643, 50% in FTC133, and 90% in TPC1 (p < 0.05). ZD1839 induced a decrease of VEGF secretion between 30% in C643 and 90% in Hth74. Administration of ZD6474 led to an up to 95% reduction of cell number in Hth74, 85% in C643, 90% in FTC133, and 90% in TPC1 (p < 0.05). The ZD6474 induced decrease of VEGF secretion ranged between 20% (FTC133) and 60% (TPC1). Combinations of IC50 concentrations of TKI showed synergistic effects, resulting in additional inhibition of proliferation between 50 and 90% compared to single drug administration. CONCLUSION: The EGF/EGF-R system resembles a powerful VEGF-stimulating pathway in all histiotypes of TC and can be inhibited by TKI. TKI directed against EGF-R as well as VEGF-R inhibit tumor cell proliferation and VEGF secretion in vitro. Combinations of TKI are more effective than strategies using single agents. It is suggested that targeting EGF-R/VEGF-R-mediated pathways may have therapeutic potential in some undifferentiated thyroid cancers.

Carcinoma↗
PubMed2006

Clinical findings and a therapeutic trial in the first patient with beta-ureidopropionase deficiency.

The clinical, neurophysiological and neuroradiological work-up as well as the results of a specific treatment trial are presented of the first patient diagnosed with beta-ureidopropionase deficiency (E.C. 3.5.1.6, McKusick 606673). The patient presented with an early-onset dystonic movement disorder, severe developmental delay with marked impairment of visual responsiveness in combination with severely delayed myelination in magnetic resonance imaging studies. In addition, there were partial optic atrophy, pigmentary retinopathy and mild cerebellar hypoplasia. The enzyme defect was expected to lead to intracerebral deficiency of beta-alanine which seems to be a neuromodulator at inhibitory synapses. Therefore, a therapeutic trial with supplementation of beta-alanine was undertaken over 1.5 years with no convincing clinical improvement.

Amidohydrolases↗
PubMed2004

Presence of dendritic cells, T lymphocytes, macrophages, B lymphocytes and glandular tissue in the human fetal larynx.

OBJECTIVE: The laryngeal mucosa starts to be exposed to infectious agents immediately after birth. The course of laryngeal infections in young children differs significantly from that in adults. The first line of defense encountered by an inhaled infectious agent is the mucosa-associated immune system, which includes immunocompetent cells and secretory components. The cellular elements are partially organized in a typical morphological pattern known as mucosa-associated lymphoid tissue (MALT). Differences in the ability of young children and adults to react to a laryngeal infection raise the questions of whether and to what extent immunocompetent cells are already present in the larynx at birth. These questions were investigated in this study. MATERIAL AND METHODS: Dendritic cells, T lymphocytes, B lymphocytes, macrophages and glands were examined and detected in an (immuno-)histological study of 8 fetal larynges (14th-22nd week of gestation). RESULTS: Immunocompetent cells and glands were present mainly in the epi- and subglottic regions and ventricular folds, whereas the glottis was largely spared. The pattern of distribution was scattered and no organized MALT was seen. CONCLUSION: Essential cell populations of a mucosa-associated immune system for the initiation of an immune response may exist in the human larynx at birth.

Antibodies, Monoclonal↗
PubMed2003

3/2 harmonic generation by femtosecond laser pulses in steep-gradient plasmas.

The onset of an electron parametric instability and 3/2 harmonic generation in variable-scale-length plasmas on solid surfaces using femtosecond pulses is observed. With the intensity approaching 10(18) W/cm(2), the instability threshold is already reached at plasma scale lengths of the order of the laser wavelength. A well-collimated harmonic emission with unusually broad spectrum is obtained.

Journal Article↗
PubMed2002

2,3,7,8-tetrachlorodibenzo-p-dioxin-dependent release from contact inhibition in WB-F344 cells: involvement of cyclin A.

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is the most potent tumor promoter ever tested in rodents. Although it is known that most of TCDD actions are mediated by binding to the aryl hydrocarbon receptor (AhR), the mechanisms leading to tumor promotion still remain to be elucidated. Loss of contact inhibition is one characteristic hallmark in tumorigenesis. In rat liver epithelial WB-F344 cells, TCDD induces a release from contact inhibition, which is manifested by a twofold increase in cell number when TCDD (1 nM for 48 h) is added to confluent cells in the presence of serum, but not when given to exponentially growing or subconfluent, serum-deprived WB-F344 cells. Loss of G1 arrest was also shown by flow cytometric analysis. We demonstrate that TCDD treatment significantly increases cyclin D2 and cyclin A protein levels and show by immunofluorescence that these proteins accumulate in the nucleus. Although TCDD treatment leads to a strong increase in cyclin D2/cdk4 and cyclin A/cdk2 complex formation, we could only detect an elevation of cyclin A/cdk2 activity. In accordance with a lack of elevated cdk4 activity, no decrease in the amount of hypophosphorylated retinoblastoma protein could be shown after TCDD treatment. The importance of increased cyclin A/cdk2 activity for TCDD-dependent release from contact inhibition was shown by the fact that the cdk2/cdc2-specific inhibitor olomoucine (25 microM) abolished TCDD response. These data indicate cyclin A-dependent loss of G1 arrest after TCDD treatment mainly downstream of the retinoblastoma protein.

Animals↗
PubMed2002

Oxidation-resistant gold-55 clusters.

Gold nanoparticles ranging in diameter from 1 to 8 nanometers were prepared on top of silicon wafers in order to study the size dependence of their oxidation behavior when exposed to atomic oxygen. X-ray photoelectron spectroscopy showed a maximum oxidation resistance for "magic-number" clusters containing 55 gold atoms. This inertness is not related to electron confinement leading to a size-induced metal-to-insulator transition, but rather seems to be linked to the closed-shell structure of such magic clusters. The result additionally suggests that gold-55 clusters may act as especially effective oxidation catalysts, such as for oxidizing carbon monoxide.

Journal Article↗
PubMed2001

Femtosecond x-ray measurement of ultrafast melting and large acoustic transients.

Time-resolved x-ray diffraction with ultrashort ( approximately 300 fs), multi-keV x-ray pulses has been used to study the femtosecond laser-induced solid-to-liquid phase transition in a thin crystalline layer of germanium. Nonthermal melting is observed to take place within 300-500 fs. Following ultrafast melting we observe strong acoustic perturbations evolving on a picosecond time scale.

Journal Article↗
PubMed2001

Partitioning of Thy-1, GM1, and cross-linked phospholipid analogs into lipid rafts reconstituted in supported model membrane monolayers.

As shown earlier, raft-like domains resembling those thought to be present in natural cell membranes can be formed in supported planar lipid monolayers. These liquid-ordered domains coexist with a liquid-disordered phase and form in monolayers prepared both from synthetic lipid mixtures and lipid extracts of the brush border membrane of mouse kidney cells. The domains are detergent-resistant and are highly enriched in the glycosphingolipid GM1. In this work, the properties of these raft-like domains are further explored and compared with properties thought to be central to raft function in plasma membranes. First, it is shown that domain formation and disruption critically depends on the cholesterol density and can be controlled reversibly by treating the monolayers with the cholesterol-sequestering reagent methyl-beta-cyclodextrin. Second, the glycosylphosphatidylinositol-anchored cell-surface protein Thy-1 significantly partitions into the raft-like domains. The extent of this partitioning is reduced when the monolayers contain GM1, indicating that different molecules can compete for domain occupation. Third, the partitioning of a saturated phospholipid analog into the raft phase is dramatically increased (15% to 65%) after cross-linking with antibodies, whereas the distribution of a doubly unsaturated phospholipid analog is not significantly affected by cross-linking (approximately 10%). This result demonstrates that cross-linking, a process known to be important for certain cell-signaling processes, can selectively translocate molecules to liquid-ordered domains.

Antibodies↗
PubMed2001

Involvement of protein kinase Cdelta in contact-dependent inhibition of growth in human and murine fibroblasts.

There is evidence that protein kinase C delta (PKCdelta) is a tumor suppressor, although its physiological role has not been elucidated so far. Since important anti-proliferative signals are mediated by cell-cell contacts we studied whether PKCdelta is involved in contact-dependent inhibition of growth in human (FH109) and murine (NIH3T3) fibroblasts. Cell-cell contacts were imitated by the addition of glutardialdehyde-fixed cells to sparsely seeded fibroblasts. Downregulation of the PKC isoforms alpha, delta, epsilon, and mu after prolonged treatment with 12-O-tetradecanoylphorbol-13-acetate (TPA, 0.1 microM) resulted in a significant release from contact-inhibition in FH109 cells. Bryostatin 1 selectively prevented TPA-induced PKCdelta-downregulation and reversed TPA-induced release from contact-inhibition arguing for a role of PKCdelta in contact-inhibition. In accordance, the PKCdelta specific inhibitor Rottlerin (1 microM) totally abolished contact-inhibition. Interestingly, immunofluorescence revealed a rapid translocation of PKCdelta to the nucleus when cultures reached confluence with a peak in early-mid G1 phase. Nuclear translocation of PKCdelta in response to cell-cell contacts could also be demonstrated after subcellular fractionation by Western blotting and by measuring PKCdelta-activity after immunoprecipitation. Transient transfection of NIH3T3 cells with a dominant negative mutant of PKCdelta induced a transformed phenotype. We conclude that PKCdelta is involved in contact-dependent inhibition of growth.

3T3 Cells↗
PubMed2001

Rottlerin induces a transformed phenotype in human keratinocytes.

PKCdelta plays a fundamental role in cell cycle control. Consistent with its proposed tumour suppressor function, ras transfection of the human keratinocyte cell line HaCaT results in a loss of PKCdelta expression mediated by TGFalpha (Exp. Cell Res., 219, 299, 1995). To get more insight into the role of PKCdelta in keratinocytes, we investigated the effects of Rottlerin, a specific inhibitor of protein kinase Cdelta, in HaCaT cells. After Rottlerin treatment, HaCaT cells lost their cobble-stone morphology and displayed a spindle-shaped, fibroblastic phenotype. Additionally, the establishment of cell-cell contacts was prevented. This was caused by an internalization of E-cadherin and beta-catenin as assessed by immunofluorescence. A similar phenotype was observed in the presence of a neutralizing anti-E-cadherin antibody. Rottlerin-treated HaCaT cells proliferated like transformed cells in a three-dimensional cell culture system. We therefore conclude that PKCdelta is involved in mediating cell-cell contacts via E-cadherin and hence regulates differentiation in HaCaT cells.

Acetophenones↗
PubMed2001

[Diagnostic imaging in liver cirrhosis].

For the diagnosis of liver cirrhosis ultrasound, computed tomography, magnetic resonance imaging, and angiography are recommended as imaging modalities. Ultrasound of the liver is used as a screening imaging tool in cases of patients suspicious for diffuse liver disease and is helpful in the term of follow-up examinations. Computed tomography is mainly performed to clarify the presence of liver disease detected by ultrasound. In this context, accurate examination of the vascular structures of the liver as well as extrahepatic situation, is of the essence. Diagnosis of diffuse liver disease and characterization of morphologic changes is improved using contrast-enhanced MR imaging with liver specific contrast media. Combined magnetic resonance imaging can provide comprehensive evaluation of cirrhosis. An improved detection rate and characterization of regenerating nodules can be achieved compared to imaging modalities such as ultrasound and computed tomography. MR imaging can be performed in a one-stop-technique using unenhanced and liver-specific-contrast-enhanced sequence protocols to evaluate the liver parenchyma itself, MR cholangiography to verify the bile duct system, and MR angiography to specify the vascular situation. This technique is the optimal protocol for diagnostic imaging in patients suffering from liver cirrhosis and the method of choice to reach the final diagnosis.

Diagnostic Imaging↗
PubMed2001

Lipid rafts reconstituted in model membranes.

One key tenet of the raft hypothesis is that the formation of glycosphingolipid- and cholesterol-rich lipid domains can be driven solely by characteristic lipid-lipid interactions, suggesting that rafts ought to form in model membranes composed of appropriate lipids. In fact, domains with raft-like properties were found to coexist with fluid lipid regions in both planar supported lipid layers and in giant unilamellar vesicles (GUVs) formed from 1) equimolar mixtures of phospholipid-cholesterol-sphingomyelin or 2) natural lipids extracted from brush border membranes that are rich in sphingomyelin and cholesterol. Employing headgroup-labeled fluorescent phospholipid analogs in planar supported lipid layers, domains typically several microns in diameter were observed by fluorescence microscopy at room temperature (24 degrees C) whereas non-raft mixtures (PC-cholesterol) appeared homogeneous. Both raft and non-raft domains were fluid-like, although diffusion was slower in raft domains, and the probe could exchange between the two phases. Consistent with the raft hypothesis, GM1, a glycosphingolipid (GSL), was highly enriched in the more ordered domains and resistant to detergent extraction, which disrupted the GSL-depleted phase. To exclude the possibility that the domain structure was an artifact caused by the lipid layer support, GUVs were formed from the synthetic and natural lipid mixtures, in which the probe, LAURDAN, was incorporated. The emission spectrum of LAURDAN was examined by two-photon fluorescence microscopy, which allowed identification of regions with high or low order of lipid acyl chain alignment. In GUVs formed from the raft lipid mixture or from brush border membrane lipids an array of more ordered and less ordered domains that were in register in both monolayers could reversibly be formed and disrupted upon cooling and heating. Overall, the notion that in biomembranes selected lipids could laterally aggregate to form more ordered, detergent-resistant lipid rafts into which glycosphingolipids partition is strongly supported by this study.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed2001

Transmural drainage of cystic peripancreatic lesions with a new large-channel echo endoscope.

BACKGROUND AND STUDY AIMS: The availability of a new large-channel echo endoscope led us to develop a new needle-stent device for endoscopic puncture and drainage of pancreatogenic cystic lesions. The purpose of this study was to examine whether endoscopic ultrasound (EUS)-guided one-step 10-F puncture and drainage with the new equipment could be feasible and successful. The use of the technique and the short-term outcome in our first four patients are described and discussed. PATIENTS AND METHODS: Cystic lesions were drained using the new technique in four patients. All the patients had symptomatic peripancreatic lesions, one with intrahepatic and one with intrasplenic extension. Punctures were carried out using a new echo endoscope with a 3.7 mm working channel and an Albarran lever. The 10-F transmural stents were placed over a 1 mm stainless steel needle and a 6-F Teflon catheter using a special assembly designed for controlled one-step placement and stent release. RESULTS: Puncture and drainage were technically successful in two patients. In one patient, the 10-F component failed to pass the cystic wall. Drainage was successful in the same session using a 7-F one-step device. In one patient, no stent was placed, but the 1 mm needle was used for diagnostic tissue sampling during the procedure because of the suspicious cyst morphology. Surgical resection revealed a ganglioneuroma. CONCLUSIONS: The new echo endoscope allows endoscopic interventions for peripancreatic cystic lesions under excellent endoscopic and EUS control. The Albarran lever was reliable and helpful for optimal direction of the needle. The new echo endoscope combined with special needle-stent devices was effective and safe for diagnosis and therapy in the first four cystic lesions. Cystic tumors must always be considered as a differential diagnosis in patients with apparently pancreatitis-induced cystic lesions.

Adult↗
PubMed2001

Flagellum of Legionella pneumophila positively affects the early phase of infection of eukaryotic host cells.

Legionella pneumophila, the etiologic agent of Legionnaires' disease, contains a single, monopolar flagellum which is composed of one major subunit, the FlaA protein. To evaluate the role of the flagellum in the pathogenesis and ecology of Legionella, the flaA gene of L. pneumophila Corby was mutagenized by introduction of a kanamycin resistance cassette. Immunoblots with antiflagellin-specific polyclonal antiserum, electron microscopy, and motility assays confirmed that the specific flagellar mutant L. pneumophila Corby KH3 was nonflagellated. The redelivery of the intact flaA gene into the chromosome (L. pneumophila Corby CD10) completely restored flagellation and motility. Coculture studies showed that the invasion efficiency of the flaA mutant was moderately reduced in amoebae and severely reduced in HL-60 cells. In contrast, adhesion and the intracellular rate of replication remained unaffected. Taking these results together, we have demonstrated that the flagellum of L. pneumophila positively affects the establishment of infection by facilitating the encounter of the host cell as well as by enhancing the invasion capacity.

Acanthamoeba↗
PubMed2000

Cloning and characterization of a Legionella pneumophila-specific gene encoding a member of the LysR family of transcriptional regulators.

Flagellin gene regulation in Legionella pneumophila is modulated by various environmental factors. The expression of the virulent phenotype seems to be linked genetically to flagellum expression. To better understand the mechanisms of flagellin gene expression in L. pneumophila (Lp), we screened a pool of plasmids from a L. pneumophila Corby genomic library for the ability to prevent or reduce luciferase activity in the Escherichia coli strain YK410, which harbours a Lp-pflaA-luxAB fusion. We cloned a DNA fragment encoding the N-terminal part of a protein with significant similarity to members of the LysR family of transcriptional regulators (LTTRs). The entire gene, cloned by inverse PCR, was named flaR. It encodes a protein of 302 amino acids, and computer-assisted analysis of the amino acid sequence revealed a helix-turn-helix motif located near the N-terminus of the protein. The FlaR protein exhibits 21-31% identity to various LTTRs. Furthermore, gel retardation experiments indicate that the FlaR protein is able to bind to its own promoter region and, to a lesser extent, to the flaA promoter of L. pneumophila. The flaR promoter region contains putative LysR binding motifs and two putative Fur boxes. Taken together, these results indicate that FlaR is a DNA-binding protein which belongs to the LTTR family. Southern analysis with a L. pneumophila Corby-specific flaR probe revealed homologous genes in various L. pneumophila strains, but not in the 12 nonpneumophila strains tested so far.

Amino Acid Sequence↗
PubMed2000

Pretransitional effects in dimyristoylphosphatidylcholine vesicle membranes: optical dynamometry study.

We used micron-sized latex spheres to probe the phase state and the viscoelastic properties of dimyristoylphosphatidylcholine (DMPC) bilayers as a function of temperature. One or two particles were manipulated and stuck to a DMPC giant vesicle by means of an optical trap. Above the fluid-gel main transition temperature, T(m) congruent with 23.4 degrees C, the particles could move on the surface of the vesicle, spontaneously (Brownian motion) or driven by an external force, either gravity or the laser beam's radiation pressure. From the analysis of the particle motions, we deduced the values of the membrane hydrodynamic shear viscosity, eta(s), and found that it would increase considerably near T(m). Below T(m), the long-distance motion of the particles was blocked. We performed experiments with two particles stuck on the membrane. By optical dynamometry, we measured the elastic resistance of the membrane to a variation in the interparticle distance and found that it would decrease considerably (down to zero) when the temperature was increased to T(m). We propose an interpretation relating the elastic response to the membrane curvature modulus, k(C). In this scheme, the two-bead dynamometry experiments provide a direct measurement of k(C) in the P'(beta) phase of lipid bilayers.

Biophysical Phenomena↗
PubMed2000

Endocervical curettage when colposcopic examination is satisfactory and normal.

OBJECTIVE: To estimate the incidence of endocervical dysplasia in women with cervical cytology of atypical squamous cells of undetermined significance (ASCUS) or low-grade squamous intraepithelial lesion (SIL) who have a satisfactory and normal colposcopic examination. METHODS: An electronic colposcopy database was reviewed and women with satisfactory colposcopic examinations and original cervical cytology of ASCUS on two consecutive Papanicolaou smears, ASCUS favor SIL, or low-grade SIL were selected. Exclusion criteria were pregnancy, insufficient endocervical curettage (ECC), or colposcopic examination that showed an abnormality that required cervical biopsy. Subjects also were excluded if they were postmenopausal or had surgical or ablative therapy for cervical dysplasia within the past year. A computerized review of 2517 patient records found 860 that met the search criteria. A manual review of those records using the exclusion criteria isolated a study group of 159 women. RESULTS: Four of 159 subjects (2.5%, 95% confidence interval [CI] 0.69, 6.3) had dysplastic cells in endocervical curettings. In these four, the ECC specimens had benign endocervical cells and separate fragments of squamous cells with mild dysplasia. In three women, loop electrosurgical excision procedures showed mild dysplasia limited to the transformation zone. The fourth subject was believed to have contamination from an unrecognized ectocervical lesion and was treated conservatively. A repeat ECC found benign endocervical cells. Involvement of the endocervix by dyplasia was excluded in all but one of 159 patients (0.63%, 95% CI 0.02, 3.5). CONCLUSION: Incidence of endocervical dysplasia was extremely low in women with cervical cytology of consecutive ASCUS, ASCUS favor SIL, or low-grade SIL who have a satisfactory and normal colposcopic examination. Our findings suggest that endocervical curettage might be safely avoided in those women.

Cervix Uteri↗