Gene/Protein Disease Symptom Drug Enzyme Compound
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Protein crystals play a pivotal part in structural genomics, hence there is an urgent requirement for new and improved methodology to aid crystal growth. Considerable effort has been invested in the search of substances (nucleants) that will induce efficient nucleation of protein crystals in a controlled manner. To date, nucleation has been facilitated mainly by seeding, epitaxy, charged surfaces or mechanical means. A different approach is introduced here, involving the use of a mesoporous material that is likely to constrain protein molecules and thereby encourage them to aggregate in crystalline order. Large single crystals were obtained using porous silicon at conditions that are not sufficient for spontaneous nucleation, for five out of six proteins that were investigated. We propose that this success is due to the size distribution of pores in the specially designed porous silicon.
J Mol Biol 2001 Sep 28
PMID:Porous silicon: an effective nucleation-inducing material for protein crystallization. 1157 16

Si/SiO2 superlattices are recently under investigation to add optical functionality to silicon based microelectronics. In such superlattices quantum-confinement should drive Si to become a good light emitter. Emission properties can be further improved and controlled by placing the emitter in optical microcavities. In this paper emission properties of (Si/SiO2), superlattices grown by Low Pressure Chemical Vapour Deposition will be compared with the ones obtained by other growth techniques and the origin of the emission will be discussed. Emission properties can be further improved and controlled by placing the emitter in optical microcavities. Optical properties of microcavities produced with standard complementary metal-oxide-semiconductor techniques containing Si/SiO2 superlattices as light emitter will be reviewed and a comparison between properties estimated from calculations and experiments will be given.
Spectrochim Acta A Mol Biomol Spectrosc 2001 Sep 01
PMID:Photoluminescence from (Si/SiO2)n superlattices and their use as emitters in [SiO2/Si]n SiO2 [Si/SiO2]m microcavities. 1166 82

The formation of group V transition metal nitride films by means of rapid thermal processing (RTP) has been investigated. Here we focus on the nitridation of niobium films of 200-500 nm thickness in the temperature range from 500 to 1,100 degrees C under laminar flow of molecular nitrogen or ammonia. The nitride phases formed were characterized by X-ray diffraction (XRD). Secondary neutral mass spectrometry (SNMS) and transmission electron microscopy (TEM) in combination with electron energy loss spectroscopy (EELS) were carried out on samples of selected experiments to provide more detailed information about the initial stages of nitride formation and the microstructure of the films. A classical formation sequence of nitride phases was observed with increasing nitrogen content in the order: alpha-Nb(N) --> beta-Nb2N --> gamma-Nb4N3 --> delta'-NbN --> Nb5N6. Furthermore, oxide enriched regions were discovered inside the metal films. These turned out to be formed mainly in the nitride sequence between the a-alphaNb(N) and beta-Nb2N-phases at the Nb/SiO2 interface due to a reaction of the Nb with the SiO2 layer of the silicon substrates on which the films had been deposited. The SiO2 layer acts as diffusion barrier for nitrogen but also as source for oxygen, according to SNMS and TEM/EELS studies, resulting in the formation of Nb-oxides and/or oxynitrides at the Nb/SiO2 interface.
Spectrochim Acta A Mol Biomol Spectrosc 2001 Sep 01
PMID:Formation of niobium nitride by rapid thermal processing. 1166 87

Diatoms are unicellular photosynthetic eukaryotes that are thought to contribute as much as 25% of global primary productivity. In spite of their ecological importance in the worlds oceans, very little information is available at the molecular level about the novel aspects of their biology. Recent advances, such as the development of gene transfer protocols, are now allowing the genetic dissection of diatom biology. Notable examples are advances in understanding the genetic basis for the silica-based bioinorganic pattern formation of their cell walls and for elucidating key aspects of diatom ecophysiology. The potentiation of current research will allow an evaluation of the use of diatoms to construct submicrometre-scale silicon structures for the nanotechnology industry and will reveal the molecular secrets underlying their ecological success.
Cell Mol Life Sci 2001 Oct
PMID:Molecular insights into the novel aspects of diatom biology. 1170 92

Pulmonary inflammation increases nitric oxide (NO) production via inducible nitric oxide synthase (iNOS). This study was performed to determine some of the factors that affect the availability of the NOS substrate, L-arginine (L-arg), in the intact lung subjected to silica-induced inflammation. Nitrate production, as an index of NO production, was significantly greater in silica-exposed lungs (53.5 +/- 12.1 nmol/90 min) compared with controls (22.5 +/- 5.1 nmol/90 min, P < 0.05). This was accompanied by greater (P < 0.0001) 90-min [(3)H]L-arg uptake (62 +/- 3% control, 82 +/- 1% silica), a significantly (P < 0.005) increased permeability-surface area product for L-arg (0.28 +/- 0.05 ml/min control, 0.63 +/- 0.07 ml/min silica), and a significantly (P < 0.001) increased urea production (1.16 +/- 0.08 micromol/90 min control, 1.77 +/- 0.06 micromol/90 min silica). There was no difference in eNOS protein between groups and eNOS mRNA was not detectable in either group, whereas silica exposure resulted in the appearance of both iNOS protein and mRNA. Silica exposure increased CAT-1 and CAT-2 mRNA approximately 8-fold compared with controls. We conclude that the increase in NO production in silica-exposed lungs was associated with increased L-arg uptake from the vasculature, presumably resulting from increased CAT-1 and CAT-2, and by increased L-arg metabolism via arginase.
Am J Respir Cell Mol Biol 2002 Mar
PMID:L-Arginine uptake and metabolism following in vivo silica exposure in rat lungs. 1186 43

Following injection into the abdominal cavity of a C57BL/6 mouse, droplets of emulsified PDMS visible by light microscopy (diameter > or = 1 microm) disseminate to multiple organs of the animal. Because fibrinogen may facilitate dissemination, we compared histologically the accumulation of PDMS droplets in lymph nodes, lungs, spleen, liver, and left kidney of Fib +/+, Fib +/-, and Fib -/- mice of C57BL/6 background 35 and 75 days after intraperitoneal injection of an emulsion of the polymer. We also used ICP-AES to assess the accumulation of silicon in the lymph nodes, livers, and spleens of the animals. The emulsion droplets ranged in diameter from approximately 0.04 to approximately 80 microm. PDMS droplets visible by light microscopy were in all organs of both Fib +/+ mice and Fib +/- mice. In those animals, droplets were invariably either within or adjacent to inflammatory cells, predominantly macrophages. In contrast, PDMS droplets were visible in none of the organs of Fib -/- mice. Despite the absence of visible droplets in them, the lymph nodes, livers, and spleens of Fib -/- mice, like the corresponding organs of Fib +/+ and Fib +/- mice, contained measurable silicon after 35 and 75 days. The amount of silicon, however, was always greater in the organs of Fib +/+ and Fib +/- mice than in the organs of Fib -/- mice. We attribute the presence of silicon in organs that had no histologic evidence of droplets to diffusion of the very smallest droplets/soluble species of PDMS from the abdominal cavity. Taken together, our data and observations implicate a role for fibrinogen in the dissemination of larger PDMS droplets in vivo. We propose this role involves recognition of droplet-bound fibrinogen by macrophages and, perhaps, other inflammatory cells, and the subsequent fibrinogen-facilitated ingestion and/or extracellular movement of the droplets by those cells.
Exp Mol Pathol 2002 Apr
PMID:Distribution of silicon/e in tissues of mice of different fibrinogen genotypes following intraperitoneal administration of emulsified poly(dimethylsiloxane) [correction of poly(dimethysiloxane)]. 1189 Jul 25

The biological effect of a radiopharmaceutical depends heavily on the heterogeneity of the uptake in the various tissues. A comparative study of two radiopharmaceuticals should therefore include a comparison of the uptake patterns in different tissues. To eliminate the problems caused by variation in kinetics and tumour characteristics between individuals, such a comparison should be based on measured distributions of the radiopharmaceuticals in the same tissue sample. The excellent linearity between activity and counts in images obtained with a digital silicon strip detector allows such distributions to be derived from two autoradiographs acquired at different time points. This method was applied in a comparison of the uptake patterns of 153Sm-EDTMP and 89SrCl2 in sections obtained from a dog with spontaneous osteosarcoma, containing both tumour and normal bone tissues. As the areas of the section were larger than the detector area, the section had to be cut into smaller parts. Images of these were later merged by means of image processing techniques. There were significant differences in the uptake patterns of the two nuclides. In the primary tumour, the uptake of 153Sm was highly heterogeneous, while 89Sr was more uniformly distributed. In trabecular bone, the accumulation of 153Sm was higher than that of 89Sr. In solid cortical bone, 89Sr had the highest uptake.
Eur J Nucl Med Mol Imaging 2002 Feb
PMID:A method for measurement of the uptake patterns of two beta-emitting radionuclides in the same tissue section with a digital silicon detector: application to a study of 89SrCl2 and 153Sm-EDTMP in a dog with spontaneous osteosarcoma. 1227 28

Vascular endothelial growth factor (VEGF) and basic (b) fibroblast growth factor (FGF-2/bFGF) are involved in vascular development and angiogenesis. Pulmonary artery smooth muscle cells express VEGF and FGF-2 and are subjected to mechanical forces during pulsatile blood flow. The effect of stretch on growth factor expression in these cells is not well characterized. We investigated the effect of cyclic stretch on the expression of VEGF and FGF-2 in ovine pulmonary artery smooth muscle cells. Primary confluent cells from 6-wk-old lambs were cultured on flexible silicon membranes and subjected to cyclic biaxial stretch (1 Hz; 5-25% stretch; 4-48 h). Nonstretched cells served as controls. Expression of VEGF and FGF-2 was determined by Northern blot analysis. Cyclic stretch induced expression of both VEGF and FGF-2 mRNA in a time- and amplitude-dependent manner. Maximum expression was found at 24 h and 15% stretch (VEGF: 1.8-fold; FGF-2: 1.9-fold). These results demonstrate that mechanical stretch regulates VEGF and FGF-2 gene expression, which could play a role in pulmonary vascular development or in postnatal pulmonary artery function or disease.
Am J Physiol Lung Cell Mol Physiol 2002 May
PMID:Cyclic mechanical stretch induces VEGF and FGF-2 expression in pulmonary vascular smooth muscle cells. 1194 52

Phosphodiesterase (PDE) type 4 is the predominant PDE isozyme in polymorphonuclear leukocytes (PMN) and plays a key role in the regulation of PMN activation. The aim of this study was to examine the effect of a PDE type 4 inhibitor, rolipram, on the functional changes and the retention of PMN in the lung. In vitro, F-actin content and L-selectin and CD11b expression of PMN stimulated by N-formyl-Met-Leu-Phe were measured by flow cytometry. PMN deformability was evaluated using silicon microchannels. Rolipram reduced the increase of F-actin and CD11b but did not change the decrease of L-selectin. Rolipram inhibited the increase of the transit time of PMN through the microchannel. We evaluated the retention of PMN in the lung in vivo by infusing labeled blood into the vena cava and examining the recovery into aortic root samples in rabbits. Rolipram inhibited the retention of stimulated PMN in the lung. In conclusion, a PDE type 4 inhibitor, rolipram, reduces the retention of PMN in the lung by reducing deformability change and CD11b upregulation of PMN.
Am J Physiol Lung Cell Mol Physiol 2002 Jun
PMID:Phosphodiesterase type 4 inhibitor reduces the retention of polymorphonuclear leukocytes in the lung. 1200 95

We investigated immunopathogenic roles for apoptosis in acute murine silicosis. Intratracheal silica instillation induced pulmonary inflammation and enlarged thoracic lymph nodes. Lymphocytes from silica-exposed lymph nodes showed reduced mitogenic responses to T cell receptor (TCR) stimulation, and markedly increased activation-induced cell death, compared with control lymphocytes from saline-exposed lymph nodes. CD4(+) T cell death was mediated by Fas ligand, because CD4(+) T cells from Fas ligand-deficient gld mice did not undergo activation-induced apoptosis. Silica deposition also resulted in increased apoptosis associated with inflammatory infiltrates in lung parenchyma. In vivo treatment with caspase inhibitors reduced neutrophil accumulation, and alleviated inflammation in the lungs of silica-treated mice. These results suggest that silica-induced apoptosis plays an inflammatory role in the lung parenchyma, and creates immunologic abnormalities in regional lymph nodes, with pathogenic implications for the host.
Am J Respir Cell Mol Biol 2002 Jul
PMID:Apoptosis underlies immunopathogenic mechanisms in acute silicosis. 1209 Dec 49


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