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- Trainer, P J, et al.
(författare)
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Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant.
- 2000
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Ingår i: The New England journal of medicine. - 0028-4793. ; 342:16, s. 1171-7
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Tidskriftsartikel (refereegranskat)abstract
- Patients with acromegaly are currently treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone.We conducted a 12-week, randomized, double-blind study of three daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly.The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score fortotal symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P< or =0.05). The incidence of adverse effects was similar in all groups.On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement.
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| 4. |
- Edwards, N.V., et al.
(författare)
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Optical characterization of wide bandgap semiconductors
- 2000
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Ingår i: Thin Solid Films. - 0040-6090 .- 1879-2731. ; 364:1, s. 98-106
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Tidskriftsartikel (refereegranskat)abstract
- Our work primarily concerns the characterization of wide-gap III-V nitride semiconductors, nondestructively and at variable temperature, with spectroscopic ellipsometry (SE) and reflectometry in the spectral range from 1.5 to 6 eV. In the case of GaN, there are three main concerns associated with such data: (a) the quantification of the dispersion of the index of refraction with energy, (b) the removal of surface overlayers in real-time, and (c) the determination of the variation of valence bands with biaxial stress and the quantification of residual stress in thin films. The SE and reflectance capabilities provide (1) broadband spectra from 1.5 to 6 eV, which yield information about (a) below the bandgap and (b) above it, and (2) high resolution spectra (less than 1 meV at 3.4 eV) in the vicinity of the gap (3.3-3.6 eV), which enables (c). Here we will discuss issues concerning the relation of (c) to GaN material and growth parameters, though similar data for other wide bandgap materials will be discussed where relevant. Specifically, optimal heterostructure design for potential valence band engineering applications will be discussed in the context of trends in residual stress as a function of film thickness, growth temperature and substrate orientation for GaN/AlN/6H-SiC heterostructures. Standard heterostructures are mostly compressive for samples less than about 0.7 µm thick, are tensile up to about 2 µm and then abruptly become less tensile with stress values near 1 kbar thereafter. Additionally, these trends can be circumvented for moderately thick (approximately 2 µm) GaN layers (normally>2 kbar, tensile) by the introduction of a `buried interface' approach, namely, a strain mediating layer (SML) above the standard high-temperature AlN buffer layer designed to yield a range of compressive stresses from 0 to 2 kbar. The strain characteristics but also the growth rates of subsequently deposited nitride layers can be modulated by changing the growth parameters of the SML. This is achieved by in situ techniques during crystal growth without degrading the optical and structural properties of the deposited layer, as confirmed by XRD, SEM, PL, and AFM data taken on the overlying GaN layers. These results are interpreted in terms of coefficient of thermal expansion data for the layers and data concerning the planarization of GaN layers and growth behavior in non-(0001) directions.
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- van der Lely, A J, et al.
(författare)
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Long-term treatment of acromegaly with pegvisomant, a growth hormone receptor antagonist.
- 2001
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Ingår i: Lancet (London, England). - 0140-6736. ; 358:9295, s. 1754-9
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Tidskriftsartikel (refereegranskat)abstract
- Pegvisomant is a new growth hormone receptor antagonist that improves symptoms and normalises insulin-like growth factor-1 (IGF-1) in a high proportion of patients with acromegaly treated for up to 12 weeks. We assessed the effects of pegvisomant in 160 patients with acromegaly treated for an average of 425 days.Treatment efficacy was assessed by measuring changes in tumour volume by magnetic resonance imaging, and serum growth hormone and IGF-1 concentrations in 152 patients who received pegvisomant by daily subcutaneous injection for up to 18 months. The safety analysis included 160 patients some of whom received weekly injections and are excluded from the efficacy analysis.Mean serum IGF-1 concentrations fell by at least 50%: 467 mg/L (SE 24), 526 mg/L (29), and 523 mg/L (40) in patients treated for 6, 12 and 18 months, respectively (p<0.001), whereas growth hormone increased by 12.5 mg/L (2.1), 12.5 mg/L (3.0), and 14.2 mg/L (5.7) (p<0.001). Of the patients treated for 12 months or more, 87 of 90 (97%) achieved a normal serum IGF-1 concentration. In patients withdrawn from pegvisomant (n=45), serum growth hormone concentrations were 8.0 mg/L (2.5) at baseline, rose to 15.2 mg/L (2.4) on drug, and fell back within 30 days of withdrawal to 8.3 mg/L (2.7). Antibodies to growth hormone were detected in 27 (16.9%) of patients, but no tachyphylaxis was seen. Serum insulin and glucose concentrations were significantly decreased (p<0.05). Two patients experienced progressive growth of their pituitary tumours, and two other patients had increased alanine and asparate aminotransferase concentrations requiring withdrawal from treatment. Mean pituitary tumour volume in 131 patients followed for a mean of 11.46 months (0.70) decreased by 0.033 cm(3) (0.057; p=0.353).Pegvisomant is an effective medical treatment for acromegaly.
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| 6. |
- Aguilar, A., et al.
(författare)
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Double photodetachment from the Cl[-]ion
- 2004
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Ingår i: Physical Review A - Atomic, Molecular, and Optical Physics. - 2469-9926 .- 2469-9934. ; 69:2
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Tidskriftsartikel (refereegranskat)abstract
- The correlated process involving the photodetachment of two electrons from the [Formula Presented] ion has been investigated over the photon energy range 20–45 eV. In the experiment, a beam of photons from the Advanced Light Source (ALS) was collinearly merged with a counterpropagating beam of [Formula Presented] ions from a sputter ion source. The [Formula Presented] ions produced in the interaction region were detected, and the normalized signal was used to monitor the relative cross section for the reaction. An absolute scale for the cross section was established by measuring the spatial overlap of the two beams and by determining the efficiency for collection and detection of the [Formula Presented] ions. The overall magnitude and shape of the measured cross section for this process agrees well with an R-matrix calculation. The calculation identifies the dominant mechanism leading to the production of the [Formula Presented] ion as being a direct nonresonant process involving the ejection of a pair of electrons from the valence shell. Less important is the indirect nonresonant process that involves the production and decay of core-excited and doubly excited states of the Cl atom in an intermediate step. Direct and indirect resonant mechanisms involving the excitation of a single [Formula Presented] core electron or more than one valence electron of the [Formula Presented] ion were found to be insignificant in the energy range studied.
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| 8. |
- Dunsby, C., et al.
(författare)
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An electronically tunable ultrafast laser source applied to fluorescence imaging and fluorescence lifetime imaging microscopy
- 2004
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Ingår i: Journal of Physics D. - : IOP Publishing. - 0022-3727 .- 1361-6463. ; 37:23, s. 3296-3303
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Tidskriftsartikel (refereegranskat)abstract
- Fluorescence imaging is used widely in microscopy and macroscopic imaging applications for fields ranging from biomedicine to materials science. A critical component for any fluorescence imaging system is the excitation source. Traditionally, wide-field systems use filtered thermal or arc-generated white light sources, while point scanning confocal microscope systems require spatially coherent (point-like) laser sources. Unfortunately, the limited range of visible wavelengths available from conventional laser sources constrains the design and usefulness of fluorescent probes in confocal microscopy. A 'hands-off' laser-like source, electronically tunable across the visible spectrum, would be invaluable for fluorescence imaging and provide new opportunities, e.g. automated excitation fingerprinting and in situ measurement of excitation cross-sections. Yet more information can be obtained using fluorescence lifetime imaging (FLIM), which requires that the light source be pulsed or rapidly modulated. We show how a white light continuum, generated by injecting femtosecond optical radiation into a micro-structured optical fibre, coupled with a simple prism-based tunable filter arrangement, can fulfil all these roles as a continuously electronically tunable (435-1150 nm) visible ultrafast light source in confocal, wide-field and FLIM systems.
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| 9. |
- Eleme, K., et al.
(författare)
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Cell surface organization of stress-inducible proteins ULBP and MICA that stimulate human NK cells and T cells via NKG2D
- 2004
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 199:7, s. 1005-1010
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Tidskriftsartikel (refereegranskat)abstract
- Cell surface proteins major histocompatibility complex (MHC) class I-related chain A (MICA) and UL16-binding proteins (ULBP) 1, 2, and 3 are up-regulated upon infection or tumor transformation and can activate human natural killer (NK) cells. Patches of cross-linked raft resident ganglioside GM1 colocalized with ULBP1, 2, 3, or MICA, but not CD45. Thus, ULBPs and MICA are expressed in lipid rafts at the cell surface. Western blotting revealed that glycosylphosphatidylinositol (GPI)-anchored ULBP3 but not transmembrane MICA, MHC class I protein, or transferrin receptor, accumulated in detergent-resistant membranes containing GM1. Thus, MICA may have a weaker association with lipid rafts than ULBP3, yet both proteins accumulate at an activating human N-K cell immune synapse. Target cell lipid rafts marked by green fluorescent protein-tagged GPI also accumulate with ULBP3 at some synapses. Electron microscopy reveals constitutive clusters of ULBP at the cell surface. Regarding a specific molecular basis for the organization of these proteins, ULBP1, 2, and 3 and MICA are lipid modified. ULBP1, 2, and 3 are GPI anchored, and we demonstrate here that MICA is S-acylated. Finally, expression of a truncated form of MICA that lacks the putative site for S-acylation and the cytoplasmic tall can be expressed at the cell surface, but is unable to activate NK cells.
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