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Biomedical subjects

C Niemann

Publications and source records attributed to C Niemann.

At least 19 recordsLinked to original sources
PubMed2005

Radiation-driven hydrodynamics of high- hohlraums on the national ignition facility.

The first hohlraum experiments on the National Ignition Facility (NIF) using the initial four laser beams tested radiation temperature limits imposed by plasma filling. For a variety of hohlraum sizes and pulse lengths, the measured x-ray flux shows signatures of filling that coincide with hard x-ray emission from plasma streaming out of the hohlraum. These observations agree with hydrodynamic simulations and with an analytical model that includes hydrodynamic and coronal radiative losses. The modeling predicts radiation temperature limits with full NIF (1.8 MJ), greater, and of longer duration than required for ignition hohlraums.

Journal Article↗
PubMed2005

Intensity limits for propagation of 0.527 microm laser beams through large-scale-length plasmas for inertial confinement fusion.

We have established the intensity limits for propagation of a frequency-doubled (2omega, 527 nm) high intensity interaction beam through an underdense large-scale-length plasma. We observe good beam transmission at laser intensities at or below 2x10(14) W/cm(2) and a strong reduction at intensities up to 10(15) W/cm(2) due to the onset of parametric scattering instabilities. We show that temporal beam smoothing by spectral dispersion allows a factor of 2 higher intensities while keeping the beam spray constant, which establishes frequency-doubled light as an option for ignition and burn in inertial confinement fusion experiments.

Journal Article↗
PubMed2004

Observation of the parametric two-ion decay instability with thomson scattering.

We present the first direct experimental observation of the parametric two-ion decay instability of ion-acoustic waves driven by a high intensity (5 x 10(15) W cm(-2)) laser beam in a laser produced high-Z plasma. Using two separate Thomson scattering diagnostics simultaneously, we directly measure the scattering from thermal ion-acoustic fluctuations, the primary ion waves that are driven to large amplitudes by the high intensity beam, and the two-ion decay products. The decay products are shown to be present only where the interaction takes place and their k spectrum is broad.

Journal Article↗
PubMed2004

Direct observation of the saturation of stimulated Brillouin scattering by ion-trapping-induced frequency shifts.

We report the first measurement of the saturation of stimulated Brillouin scattering (SBS) by an ion-trapping-induced frequency shift, which was achieved by directly measuring the amplitude and absolute frequency of SBS-driven ion-acoustic waves (IAW). A frequency shift of up to 30% and a simultaneous saturation of driven IAW and SBS reflectivity were observed. The scaling of the frequency shift with the IAW amplitude compares well with theoretical calculations. We have further measured fast 30 ps oscillations of the SBS-driven IAW amplitude induced by the frequency shift.

Journal Article↗
PubMed2004

Effect of nonlocal transport on heat-wave propagation.

We present the first direct measurements of spatially and temporally resolved temperature and density profiles produced by nonlocal transport in a laser plasma. Absolutely calibrated measurements have been performed by Rayleigh scattering and by resolving the ion-acoustic wave spectra across the plasma volume with Thomson scattering. We find that the electron temperature and density profiles disagree with flux-limited models, but are consistent with nonlocal transport modeling.

Journal Article↗
PubMed2003

Indian hedgehog and beta-catenin signaling: role in the sebaceous lineage of normal and neoplastic mammalian epidermis.

In mammalian epidermis, the level of beta-catenin signaling regulates lineage selection by stem cell progeny. High levels of beta-catenin stimulate formation of hair follicles, whereas low levels favor differentiation into interfollicular epidermis and sebocytes. In transgenic mouse epidermis, overexpression of beta-catenin leads to formation of hair follicle tumors, whereas overexpression of N-terminally truncated Lef1, which blocks beta-catenin signaling, results in spontaneous sebaceous tumors. Accompanying overexpression of beta-catenin is up-regulation of Sonic hedgehog (SHH) and its receptor, Patched (PTCH/Ptch). In DeltaNLef1 tumors Ptch mRNA is up-regulated in the absence of SHH. We now show that PTCH is up-regulated in both human and mouse sebaceous tumors and is accompanied by overexpression of Indian hedgehog (IHH). In normal sebaceous glands IHH is expressed in differentiated sebocytes and the transcription factor GLI1 is activated in sebocyte progenitors, suggesting a paracrine signaling mechanism. PTCH1 and IHH are up-regulated during human sebocyte differentiation in vitro and inhibition of hedgehog signaling inhibits growth and stimulates differentiation. Overexpression of DeltaNLef1 up-regulates IHH and stimulates proliferation of undifferentiated sebocytes. We present a model of the interactions between beta-catenin and hedgehog signaling in the epidermis in which SHH promotes proliferation of progenitors of the hair lineages whereas IHH stimulates proliferation of sebocyte precursors.

Animals↗
PubMed2000

Hepatocyte growth factor and neuregulin in mammary gland cell morphogenesis.

Organ culture and transplantation experiments in the early 1960s and 1970s have demonstrated that growth and morphogenesis of the epithelium of the mammary gland are controlled by mesenchymal-epithelial interactions. The identification of molecules that provide the essential signals exchanged in mesenchymal-epithelial interactions is an area of active research. Recent evidence suggests that morphogenic programs of epithelia can be triggered by mesenchymal factors that signal via tyrosine kinase receptors. This review concentrates on the effects of two mesenchymal factors, Hepatocyte Growth Factor/Scatter Factor and neuregulin, on morphogenesis and differentiation of mammary epithelial cells in vitro and signalling pathways involved during morphogenesis of mammary epithelial cells.

Animals↗
PubMed1998

Reconstitution of mammary gland development in vitro: requirement of c-met and c-erbB2 signaling for branching and alveolar morphogenesis.

We have established a cell culture system that reproduces morphogenic processes in the developing mammary gland. EpH4 mouse mammary epithelial cells cultured in matrigel form branched tubules in the presence of hepatocyte growth factor/scatter factor (HGF/SF), the ligand of the c-met tyrosine kinase receptor. In contrast, alveolar structures are formed in the presence of neuregulin, a ligand of c-erbB tyrosine kinase receptors. These distinct morphogenic responses can also be observed with selected human mammary carcinoma tissue in explant culture. HGF/SF-induced branching was abrogated by the PI3 kinase inhibitors wortmannin and LY294002. In contrast, neuregulin- induced alveolar morphogenesis was inhibited by the MAPK kinase inhibitor PD98059. The c-met-mediated response could also be evoked by transfection of a c-met specific substrate, Gab1, which can activate the PI3 kinase pathway. An activated hybrid receptor that contained the intracellular domain of c-erbB2 receptor suffices to induce alveolar morphogenesis, and was observed in the presence of tyrosine residues Y1028, Y1144, Y1201, and Y1226/27 in the substrate-binding domain of c-erbB2. Our data demonstrate that c-met and c-erbB2 signaling elicit distinct morphogenic programs in mammary epithelial cells: formation of branched tubules relies on a pathway involving PI3 kinase, whereas alveolar morphogenesis requires MAPK kinase.

Androstadienes↗
PubMed1997

Role of HGF/SF and c-Met in morphogenesis and metastasis of epithelial cells.

We have analysed the role of hepatocyte growth factor/scatter factor (HGF/SF) in the process of morphogenesis and metastasis of epithelial (carcinoma) cells. HGF/SF induces various morphogenic responses in epithelial cells that derive from different tissues when these are grown in three-dimensional gels, e.g. branching tubules in kidney, breast, and prostate epithelial cells, crypt-like structures with brush border in colon epithelial cells, and alveolar-like aggregates in lung and pancreas cells. Epithelial cells are thus able to form complex structures in vitro which resemble the structures formed in the organ they originate from. We also examined the response of human breast carcinoma cells to HGF/SF in vivo. MDA MB 435 cells transfected with HGF/SF were injected into the mammary fat pad of nude mice, where they form tumours which spontaneously metastasize to the lungs. We found that expression of HGF/SF promoted metastasis whereas expression of the cell adhesion molecule E-cadherin was inhibitory. Moreover, expression of E-cadherin reconstituted the ability of the cells to form complex structures in response to HGF/SF in vitro. These data demonstrate that the different responses to HGF/SF depend on the state of the epithelial cells: morphogenesis requires epithelial differentiation and cell polarity, whereas metastasis is observed when the cells have lost their epithelial characteristics. Moreover, we have recently identified Gab-1 as a direct-binding substrate of the c-Met receptor. Gab-1 binds to c-Met phosphorylated on tyrosine residues, but not to a number of other tyrosine kinases from different subfamilies. A newly identified proline-rich domain of Gab-1 is responsible for the binding to the bidentate docking site in c-Met. Expression of Gab-1 in epithelial cells is sufficient to induce c-Met-specific cellular responses which include the formation of branching tubules. Thus, Gab-1 seem to correspond to the substrate of the c-Met receptor tyrosine kinase that mediates the epithelial morphogenesis.

Animals↗
PubMed1997

A method for measuring capillary bleeding time in non-anaesthetized dogs: prolongation of the bleeding time by acetylsalicylic acid.

A reproducible standardized method for measuring capillary bleeding time (CBT) in dogs is presented. The skin was punctured at the toe from a forelimb of non-anaesthetized dogs parallel to the edge of the horny skin of the pad. Before the procedure, a cuff of a sphygmometer was placed above the antibrachium and a hyperaemie agent was applied to the shaved area. The normal CBT in non-anaesthetized dogs was 2.25 +/- 0.76 min (x +/- SD). After injection of acetylsalicylic acid (ASA) (20 mg/kg body weight), CBT was prolonged up to 25 min. Platelet aggregation in response to 10 micrograms collagen/ml was decreased in parallel after treatment with ASA.

Animals↗
PubMed1996

[Long-term results of surgical and conservative treatment of ruptures of the long biceps tendon].

INTRODUCTION: The therapeutic concept for rupture of the long biceps tendon continues to be controversially discussed. Various operative procedures compete with mostly unstructured conservative ones. QUESTION INVESTIGATED: a) Is operative therapy of the long biceps tendon rupture superior to the conservative treatment? b) For which group of patients should the operative or the conservative therapy be recommended? PATIENTS AND METHOD: The value of operative versus conservative therapy was examined based on a collective of 43 ruptures (39 patients), 31 operatively and twelve conservatively treated. The investigation comprised the following: 1) the subjective evaluation of the long-term result by the patient, 2) a thorough clinical examination including the function of the shoulder and the elbow joint and 3) an isokinetic force and endurance test on Cybex II. The results of the follow-up were evaluated by a score. RESULTS: It was found that very good but also poor results can be achieved with both operative and conservative therapy, the good results distinctly predominating in the operated collective. Statistically significant differences could not be detected because of the small number of cases and the relatively large variation range. Good results after conservative therapy require a differentiated rehabilitation program corresponding to the normal course followed after operative treatment. CONCLUSION: Since results tended to be better for the operated collective in our study, we recommend a surgical procedure for active younger patients. It seems to be of decisive importance to perform the operation as early as possible and to achieve optimal tension of the muscle by refixation of the tendon.

Adult↗
PubMed1995

Sequential requirement of hepatocyte growth factor and neuregulin in the morphogenesis and differentiation of the mammary gland.

We have examined the role of two mesenchymal ligands of epithelial tyrosine kinase receptors in mouse mammary gland morphogenesis. In organ cultures of mammary glands, hepatocyte growth factor (HGF, scatter factor) promoted branching of the ductal trees but inhibited the production of secretory proteins. Neuregulin (NRG, neu differentiation factor) stimulated lobulo-alveolar budding and the production of milk proteins. These functional effects are paralleled by the expression of the two factors in vivo: HGF is produced in mesenchymal cells during ductal branching in the virgin animal; NRG is expressed in the mesenchyme during lobulo-alveolar development at pregnancy. The receptors of HGF and NRG (c-met, c-erbB3, and c-erbB4), which are expressed in the epithelial cells, are not regulated. In organ culture, branching morphogenesis and lobulo-alveolar differentiation of the mammary gland could be abolished by blocking expression of endogenous HGF and NRG by the respective antisense oligonucleotides; in antisense oligonucleotide-treated glands, morphogenesis could again be induced by the addition of recombinant HGF and NRG. We thus show that two major postnatal morphogenic periods of mammary gland development are dependent on sequential mesenchymal-epithelial interactions mediated by HGF and NRG.

Animals↗
PubMed1992

Enzymatic synthesis of low molecular weight amyloses with modified terminal groups.

Low molecular weight amyloses with modified terminal groups were synthesized by cyclomaltohexaose (alpha-cyclodextrin) transfer using (1----4)-alpha-D-glucan: 4-alpha-D-(1----4)- alpha-D-glucopyranosyltransferase (cyclising) (EC 2.4.1.19) from Bacillus macerans. 4-Nitrophenyl alpha-malto-oligosaccharides d.p. 2-7 served as acceptors, and cyclomaltohexaose served as the donor. The reaction was optimized to obtain a majority of species of definite chain lengths in a range of d.p. 10-20, depending upon the chain length of the acceptor. The course of the coupling reactions, as well as the action of the enzyme in disproportionation, cyclisation, and hydrolysis of the products, were observed by h.p.l.c. analysis of the oligomer distributions. Using a 15-fold molar excess of cyclomaltohexaose and 0.5 units enzyme per mumol of acceptor at pH 5.2, the chromatograms revealed that the products of the coupling reaction were predominant during the first reaction period. By incubating the acceptors with the enzyme, but without the donor, the mechanism of disproportionation was elucidated as a transfer of malto-oligosaccharyl residues dependent upon the substrate chain length. The minimum chain length required for a direct cyclisation reaction was d.p. 7. The results were confirmed by separation and investigation of the products of hydrolysis and cyclisation, which were nonmodified alpha-malto-oligosaccharides and cyclomalto-oligosaccharides.

Amylose↗
PubMed1991

Rat adult hepatocytes in primary pure and mixed monolayer culture. Comparison of the maintenance of mixed function oxidase and conjugation pathways of drug metabolism.

The stabilities of several drug oxidation and conjugation pathways in adult rat hepatocytes were investigated in two systems: a primary pure culture lasting 3 days and a primary mixed culture (hepatocytes co-cultured with epithelial cells) lasting 10 days. The cytochrome P450 content in hepatocytes drastically declined within 48 hr in both culture systems. Cytochrome P450-dependent mixed function oxidase was measured by the O-dealkylation of ethoxyresorufin (EROD) and of pentoxyresorufin (PROD). UPD-glucuronosyl transferase (UDP-GT) activity was measured using 1-naphthol and morphine as substrates. In both culture systems, the activities of enzymes belonging to the 3-methylcholanthrene-inducible family, namely EROD and 1-naphthol UDP-GT, were much better maintained than those of PROD and morphine UDP-GT, which belong to the phenobarbitone-inducible family: in pure cultures, EROD and 1-naphthol UDP-GT activities declined to 60% of initial values within 3 days; in mixed cultures, EROD activity was stable throughout the 10 day culture period, whereas that of 1-naphthol UDP-GT was stable until day 4 but had declined to 70% of the initial value by day 8. In contrast, PROD and morphine UDP-GT activities declined to approx. 30% of the initial values within 2 days in both culture systems, and had dropped to approx. 10% of the initial value within 8 days in mixed culture. Reduced glutathione (GSH) levels fluctuated, but remained high throughout culture. GSH conjugation declined to 40% of initial values within 3 days in pure culture, whereas it remained relatively constant in mixed culture. Comparison of these two culture systems therefore showed that although the inclusion of epithelial cells did prolong hepatocyte viability, there was a change in relative enzyme activities in both systems, suggesting a shift towards a more de-differentiated drug metabolism pattern.

Animals↗
PubMed1991

Differentiation of species and strains among filamentous fungi by DNA fingerprinting.

We have analyzed 11 strains and clones, representing five species (Penicillium janthinellum, P. citrioviridae, P. chrysogenum, Aspergillus niger, Trichoderma harzianum) and three genera of filamentous fungi, for the presence of hypervariable loci in their genomes by hybridization with simple repeat oligonucleotides and the DNA of phage M13. The oligonucleotide probes (CT)8, (GTG)5 and (GACA)4, as well as M13 DNA, are informative probes for fingerprinting in all genera and species tested. The probe (GATA)4 produced informative fingerprints only with the genomic DNA of A. niger. There was no similarity between the fingerprints originating from fungi of different genera and also little similarity between the fingerprints of different species belonging to the same genus. Fingerprints of strains of the same species differed only slightly from each other. Fingerprints of clones originating from one strain were identical. The results indicate that DNA fingerprinting is a powerful method to differentiate species and strains of filamentous fungi.

Aspergillus niger↗