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991.
Leers MP Björklund V Björklund B Jörnvall H Nap M 《Cellular and molecular life sciences : CMLS》2002,59(8):1358-1365
We investigated the distribution and fate of apoptotic bodies during human development and in the adult, using an antibody
(M30) that recognizes a neo-epitope formed early in the apoptotic cascade by caspase cleavage of cytokeratin 18. In the fetus,
we found extensive accumulation of M30-positive, non-phagocytosed fragments in the red pulp of the spleen, subcutaneous and
submucosal vessels, the interstitium of the lung, and the glomerular mesangium of the kidneys. In the liver, M30-immunoreactive
fragments were found inside macrophages in the sinusoids. The number of these fragments and the intensity of the immunostaining
increased with the gestational age of the fetus. In the adult, M30-positive fragments were barely detectable in normal tissues.
However, many pathological situations, including both chronic degenerative processes and metastatic cancer, were associated
with accumulation of M30-positive fragments in the red pulp of the spleen. In the liver and kidney, no fragments could be
detected. Remarkably, 13 of the 16 patients with metastasized cancer showed pronounced accumulation of M30-positive fragments
containing hematoxylin-reactive material in the red pulp of the spleen. In the non-cancerous cases, such DNA-containing fragments
were only seen in 9 of 94 cases. The results show that when apoptotic activity is high, as during development in the fetus
or during metastasis and other pathological processes in the adult, the phagocytic clearance of apoptotic bodies can be overloaded.
These apoptotic fragments then accumulate in the spleen. The visual detection of apoptotic fragments is concluded to reflect
increased cell turnover.
Received 1 July 2002; accepted 1 July 2002 相似文献
992.
Strömberg P Svensson S Hedberg JJ Nordling E Höög JO 《Cellular and molecular life sciences : CMLS》2002,59(3):552-559
The human alcohol dehydrogenase system is comprised of multiple forms that catalyse the oxidation/reduction of a large variety of alcohols and aldehydes. A transition that results in an Ile308Val substitution was identified in the human ADH2 gene by single-strand conformation polymorphism analysis. Screening a Swedish population revealed that Val308 was the most frequent allele (73%), and site-directed mutagenesis was used to obtain both allelozymes, which were expressed in Escherichia coli for characterisation. Thermostability was assayed by activity measurements and circular dichroism spectroscopy. The results showed that the 308Val substitution decreases protein stability, as compared to the Ile308 variant, an effect also demonstrated during prolonged storage. Ethanol, octanol, 12-hydroxydodecanoic acid and all-trans retinol were used as model substrates and, generally, slightly higher Km values were observed with Val at position 308. Finally, homology modelling, from mouse ADH2, further supported the decreased stability of the Val308 variant and located position 308 in the subunit interface of the molecule and in the vicinity of the active-site pocket entrance. In conclusion, the Ile308Val substitution represents a novel functional polymorphism within the human alcohol dehydrogenase gene cluster that may affect the metabolism of ethanol and other substrates. 相似文献
993.
Screening for differentially expressed genes is a straightforward approach to study the molecular basis for changes in gene
expression. Differential display analysis has been used by investigators in diverse fields of research since it was developed.
Differential display has also been the approach of choice to investigate changes in gene expression in response to various
biological challenges in invertebrates. We review the application of differential display analysis of gene expression in invertebrates,
and provide a specific example using this technique for novel gene discovery in the nematode Caenorhabditis elegans. 相似文献
994.
Morphine 6 glucuronide stimulates nitric oxide release in mussel neural tissues: evidence for a morphine 6 glucuronide opiate receptor subtype 总被引:1,自引:0,他引:1
Mantione K Zhu W Rialas C Casares F Cadet P Franklin AL Tonnesen J Stefano GB 《Cellular and molecular life sciences : CMLS》2002,59(3):570-574
We have previously demonstrated that Mytilus edulis pedal ganglia contain opiate alkaloids, i.e., morphine and morphine 6 glucuronide (M6G), as well as mu opiate receptor subtype
fragments exhibiting high sequence similarity to those found in mammals. Now we demonstrate that M6G stimulates pedal ganglia
constitutive nitric oxide (NO) synthase (cNOS)-derived NO release at identical concentrations and to similar peak levels as
morphine. However, the classic opiate antagonist, naloxone, only blocked the ability of morphine to stimulate cNOS-derived
NO release and not that of M6G. CTOP, a mu-specific antagonist, blocked the ability of M6G to induce cNOS-derived NO release
as well as that of morphine, suggesting that a novel mu opiate receptor was present and selective toward M6G. In examining
a receptor displacement analysis, both opiate alkaloids displaced [3H]-dihydromorphine binding to the mu opiate receptor subtype. However, morphine exhibited a twofold higher affinity, again
suggesting that a novel mu opiate receptor may be present.
Received 1 November 2001; received after revision 1 February 2002; accepted 1 February 2002 相似文献
995.
Microbial cycling of volatile organic sulfur compounds 总被引:7,自引:0,他引:7
Lomans BP van der Drift C Pol A Op den Camp HJ 《Cellular and molecular life sciences : CMLS》2002,59(4):575-588
Microbial cycling of volatile organic sulfur compounds (VOSCs), especially dimethyl sulfide (DMS) and methanethiol (MT), is intensively studied because these compounds play an important role in the processes of global warming, acid precipitation, and the global sulfur cycle. VOSC concentrations in freshwater sediments are low due to the balance between the formation and degradation of these compounds. These reactions occur for the greater part at the oxic/anoxic interphase of sediment and water column. In contrast to marine ecosystems, where dimethylsulfoniopropionate is the main precursor of MT and DMS, in freshwater ecosystems, VOSCs are formed mainly by methylation of sulfide and to a lesser extent from the degradation of S-containing amino acids. One of the major routes for DMS and MT formation through sulfide methylation is anaerobic O-demethylation of methoxylated aromatic compounds. Inhibition studies have revealed that the major part of the endogenously produced MT and DMS is degraded anaerobically by methanogens. The major bacterial groups involved in formation and consumption of VOSCs are described. 相似文献
996.
Wabnitz H Bittner L de Castro AR Döhrmann R Gürtler P Laarmann T Laasch W Schulz J Swiderski A von Haeften K Möller T Faatz B Fateev A Feldhaus J Gerth C Hahn U Saldin E Schneidmiller E Sytchev K Tiedtke K Treusch R Yurkov M 《Nature》2002,420(6915):482-485
Intense radiation from lasers has opened up many new areas of research in physics and chemistry, and has revolutionized optical technology. So far, most work in the field of nonlinear processes has been restricted to infrared, visible and ultraviolet light, although progress in the development of X-ray lasers has been made recently. With the advent of a free-electron laser in the soft-X-ray regime below 100 nm wavelength, a new light source is now available for experiments with intense, short-wavelength radiation that could be used to obtain deeper insights into the structure of matter. Other free-electron sources with even shorter wavelengths are planned for the future. Here we present initial results from a study of the interaction of soft X-ray radiation, generated by a free-electron laser, with Xe atoms and clusters. We find that, whereas Xe atoms become only singly ionized by the absorption of single photons, absorption in clusters is strongly enhanced. On average, each atom in large clusters absorbs up to 400 eV, corresponding to 30 photons. We suggest that the clusters are heated up and electrons are emitted after acquiring sufficient energy. The clusters finally disintegrate completely by Coulomb explosion. 相似文献
997.
Numerous potentially functional but non-genic conserved sequences on human chromosome 21 总被引:28,自引:0,他引:28
Dermitzakis ET Reymond A Lyle R Scamuffa N Ucla C Deutsch S Stevenson BJ Flegel V Bucher P Jongeneel CV Antonarakis SE 《Nature》2002,420(6915):578-582
The use of comparative genomics to infer genome function relies on the understanding of how different components of the genome change over evolutionary time. The aim of such comparative analysis is to identify conserved, functionally transcribed sequences such as protein-coding genes and non-coding RNA genes, and other functional sequences such as regulatory regions, as well as other genomic features. Here, we have compared the entire human chromosome 21 with syntenic regions of the mouse genome, and have identified a large number of conserved blocks of unknown function. Although previous studies have made similar observations, it is unknown whether these conserved sequences are genes or not. Here we present an extensive experimental and computational analysis of human chromosome 21 in an effort to assign function to sequences conserved between human chromosome 21 (ref. 8) and the syntenic mouse regions. Our data support the presence of a large number of potentially functional non-genic sequences, probably regulatory and structural. The integration of the properties of the conserved components of human chromosome 21 to the rapidly accumulating functional data for this chromosome will improve considerably our understanding of the role of sequence conservation in mammalian genomes. 相似文献
998.
Inflammation and therapeutic vaccination in CNS diseases 总被引:20,自引:0,他引:20
The spectrum of inflammatory diseases of the central nervous system has been steadily expanding from classical autoimmune disorders such as multiple sclerosis to far more diverse diseases. Evidence now suggests that syndromes such as Alzheimer's disease and stroke have important inflammatory and immune components and may be amenable to treatment by anti-inflammatory and immunotherapeutic approaches. The notion of 'vaccinating' individuals against a neurodegenerative disorder such as Alzheimer's disease is a marked departure from classical thinking about mechanism and treatment, and yet therapeutic vaccines for both Alzheimer's disease and multiple sclerosis have been validated in animal models and are in the clinic. Such approaches, however, have the potential to induce unwanted inflammatory responses as well as to provide benefit. 相似文献
999.
1000.
Bennett IM Farfano HM Bogani F Primak A Liddell PA Otero L Sereno L Silber JJ Moore AL Moore TA Gust D 《Nature》2002,420(6914):398-401
Transport of calcium ions across membranes and against a thermodynamic gradient is essential to many biological processes, including muscle contraction, the citric acid cycle, glycogen metabolism, release of neurotransmitters, vision, biological signal transduction and immune response. Synthetic systems that transport metal ions across lipid or liquid membranes are well known, and in some cases light has been used to facilitate transport. Typically, a carrier molecule located in a symmetric membrane binds the ion from aqueous solution on one side and releases it on the other. The thermodynamic driving force is provided by an ion concentration difference between the two aqueous solutions, coupling to such a gradient in an auxiliary species, or photomodulation of the carrier by an asymmetric photon flux. Here we report a different approach, in which active transport is driven not by concentration gradients, but by light-induced electron transfer in a photoactive molecule that is asymmetrically disposed across a lipid bilayer. The system comprises a synthetic, light-driven transmembrane Ca2+ pump based on a redox-sensitive, lipophilic Ca2+-binding shuttle molecule whose function is powered by an intramembrane artificial photosynthetic reaction centre. The resulting structure transports calcium ions across the bilayer of a liposome to develop both a calcium ion concentration gradient and a membrane potential, expanding Mitchell's concept of a redox loop mechanism for protons to include divalent cations. Although the quantum yield is relatively low (approximately 1 per cent), the Ca2+ electrochemical potential developed is significant. 相似文献