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91.
Seventeen patients with metastatic breast carcinoma were treated with a combination of 5-fluorouracil, methotrexate, vincristine, cyclophosphamide and prednisone. Six of the patients (35%) developed a syndrome consisting of fever, malaise, dyspnea, hypoxemia and bilateral pulmonary interstitial infiltrates from 41 to 148 days after institution of therapy. The syndrome varied from a mild to a life-threatening illness with recovery in 10 to 60 days. It is believed that these cases represent examples of methotrexate-induced pneumonitis. The high incidence of the syndrome in this patient group may be related to the concomitant administration of cyclophosphamide with methotrexate. The observations also suggest that patients with previous adrenalectomies may have pneumonitis with an especially severe and protracted course. 相似文献
92.
The molecular basis of cystathionine beta-synthase deficiency in Dutch patients with homocystinuria: effect of CBS genotype on biochemical and clinical phenotype and on response to treatment. 总被引:4,自引:0,他引:4
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L A Kluijtmans G H Boers J P Kraus L P van den Heuvel J R Cruysberg F J Trijbels H J Blom 《American journal of human genetics》1999,65(1):59-67
Homocystinuria due to cystathionine beta-synthase (CBS) deficiency, inherited as an autosomal recessive trait, is the most prevalent inborn error of methionine metabolism. Its diverse clinical expression may include ectopia lentis, skeletal abnormalities, mental retardation, and premature arteriosclerosis and thrombosis. This variability is likely caused by considerable genetic heterogeneity. We investigated the molecular basis of CBS deficiency in 29 Dutch patients from 21 unrelated pedigrees and studied the possibility of a genotype-phenotype relationship with regard to biochemical and clinical expression and response to homocysteine-lowering treatment. Clinical symptoms and biochemical parameters were recorded at diagnosis and during long-term follow-up. Of 10 different mutations detected in the CBS gene, 833T-->C (I278T) was predominant, present in 23 (55%) of 42 independent alleles. At diagnosis, homozygotes for this mutation (n=12) tended to have higher homocysteine levels than those seen in patients with other genotypes (n=17), but similar clinical manifestations. During follow-up, I278T homozygotes responded more efficiently to homocysteine-lowering treatment. After 378 patient-years of treatment, only 2 vascular events were recorded; without treatment, at least 30 would have been expected (P<.01). This intervention in Dutch patients significantly reduces the risk of cardiovascular disease and other sequelae of classical homocystinuria syndrome. 相似文献
93.
Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors.
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![点击此处可从《The EMBO journal》网站下载免费的PDF全文](/ch/ext_images/free.gif)
B Blom M H Heemskerk M C Verschuren J J van Dongen A P Stegmann A Q Bakker F Couwenberg P C Res H Spits 《The EMBO journal》1999,18(10):2793-2802
94.
Marti J. Anderson Carol E. Diebel Wilma M. Blom 《Journal of experimental marine biology and ecology》2005,320(1):35-56
The focus of this study was to measure natural spatial variability in the biodiversity of fauna inhabiting kelp holdfasts in northeastern New Zealand at several spatial scales: from meters up to hundreds of kilometers. We wished to test the hypothesis that multivariate variation and biodiversity would vary significantly at different spatial scales in different ways for the major phyla in the holdfast community (Arthropoda, Annelida, Mollusca and Bryozoa). Biodiversity was considered in terms of richness, total abundance, structural composition (as measured by the Bray-Curtis dissimilarity measure) and taxonomic breadth for each major phylum and for the assemblage as a whole. We also examined the effect of taxonomic resolution on multivariate patterns. Species richness and total abundance increased with increases in holdfast volume. Multivariate variation was greatest at the smallest spatial scale for all phyla, but different phyla showed different patterns of multivariate variation at different spatial scales. Variations among locations at the largest spatial scale were primarily due to differences in the composition and richness of bryozoans and molluscs. Location effects became less and less distinct with decreases in taxonomic resolution. There were very few significant differences in richness or abundance for holdfasts of a given volume, taxonomic breadth did not vary significantly across locations, nor did the proportional abundances of phyla. These consistencies across large spatial scales in the absence of environmental impacts and results from other studies suggest that holdfast communities in New Zealand systems would provide a useful model assemblage against which future impacts may be detected as changes in proportions of component phyla. In addition, high variability detected at small and large scales at the species level, especially for bryozoans and molluscs, suggest that these communities may also provide unique opportunities for studying and understanding sources and functions of marine biodiversity. 相似文献
95.
Motif decomposition of the phosphotyrosine proteome reveals a new N-terminal binding motif for SHIP2
Miller ML Hanke S Hinsby AM Friis C Brunak S Mann M Blom N 《Molecular & cellular proteomics : MCP》2008,7(1):181-192
Advances in mass spectrometry-based proteomics have yielded a substantial mapping of the tyrosine phosphoproteome and thus provided an important step toward a systematic analysis of intracellular signaling networks in higher eukaryotes. In this study we decomposed an uncharacterized proteomics data set of 481 unique phosphotyrosine (Tyr(P)) peptides by sequence similarity to known ligands of the Src homology 2 (SH2) and the phosphotyrosine binding (PTB) domains. From 20 clusters we extracted 16 known and four new interaction motifs. Using quantitative mass spectrometry we pulled down Tyr(P)-specific binding partners for peptides corresponding to the extracted motifs. We confirmed numerous previously known interaction motifs and found 15 new interactions mediated by phosphosites not previously known to bind SH2 or PTB. Remarkably, a novel hydrophobic N-terminal motif ((L/V/I)(L/V/I)pY) was identified and validated as a binding motif for the SH2 domain-containing inositol phosphatase SHIP2. Our decomposition of the in vivo Tyr(P) proteome furthermore suggests that two-thirds of the Tyr(P) sites mediate interaction, whereas the remaining third govern processes such as enzyme activation and nucleic acid binding. 相似文献
96.
The roles of MAPKs in disease 总被引:2,自引:0,他引:2
Lawrence MC Jivan A Shao C Duan L Goad D Zaganjor E Osborne J McGlynn K Stippec S Earnest S Chen W Cobb MH 《Cell research》2008,18(4):436-442
97.
Mohamad Bazzi Nicols E. Campione Per E. Ahlberg Henning Blom Benjamin P. Kear 《PLoS biology》2021,19(8)
Sharks (Selachimorpha) are iconic marine predators that have survived multiple mass extinctions over geologic time. Their prolific fossil record is represented mainly by isolated shed teeth, which provide the basis for reconstructing deep time diversity changes affecting different selachimorph clades. By contrast, corresponding shifts in shark ecology, as measured through morphological disparity, have received comparatively limited analytical attention. Here, we use a geometric morphometric approach to comprehensively examine tooth morphologies in multiple shark lineages traversing the catastrophic end-Cretaceous mass extinction—this event terminated the Mesozoic Era 66 million years ago. Our results show that selachimorphs maintained virtually static levels of dental disparity in most of their constituent clades across the Cretaceous–Paleogene interval. Nevertheless, selective extinctions did impact apex predator species characterized by triangular blade-like teeth. This is particularly evident among lamniforms, which included the dominant Cretaceous anacoracids. Conversely, other groups, such as carcharhiniforms and orectolobiforms, experienced disparity modifications, while heterodontiforms, hexanchiforms, squaliforms, squatiniforms, and †synechodontiforms were not overtly affected. Finally, while some lamniform lineages disappeared, others underwent postextinction disparity increases, especially odontaspidids, which are typified by narrow-cusped teeth adapted for feeding on fishes. Notably, this increase coincides with the early Paleogene radiation of teleosts as a possible prey source, and the geographic relocation of disparity sampling “hotspots,” perhaps indicating a regionally disjunct extinction recovery. Ultimately, our study reveals a complex morphological response to the end-Cretaceous mass extinction and highlights an event that influenced the evolution of modern sharks.Analysis of the tooth morphology of sharks across the end-Cretaceous mass extinction, 66 million years ago, shows that while generally unaffected, some apex predator shark lineages were selectively impacted; changing habitats and the differential survival of ‘fish-eating’ sharks also reveals responses to ecological cataclysm. 相似文献
98.
Martin Lee Miller Boumediene Soufi Carsten Jers Nikolaj Blom Boris Macek Ivan Mijakovic Dr. 《Proteomics》2009,9(1):116-125
There is ample evidence for the involvement of protein phosphorylation on serine/threonine/tyrosine in bacterial signaling and regulation, but very few exact phosphorylation sites have been experimentally determined. Recently, gel‐free high accuracy MS studies reported over 150 phosphorylation sites in two bacterial model organisms Bacillus subtilis and Escherichia coli. Interestingly, the analysis of these phosphorylation sites revealed that most of them are not characteristic for eukaryotic‐type protein kinases, which explains the poor performance of eukaryotic data‐trained phosphorylation predictors on bacterial systems. We used these large bacterial datasets and neural network algorithms to create the first bacteria‐specific protein phosphorylation predictor: NetPhosBac. With respect to predicting bacterial phosphorylation sites, NetPhosBac significantly outperformed all benchmark predictors. Moreover, NetPhosBac predictions of phosphorylation sites in E. coli proteins were experimentally verified on protein and site‐specific levels. In conclusion, NetPhosBac clearly illustrates the advantage of taxa‐specific predictors and we hope it will provide a useful asset to the microbiological community. 相似文献
99.
100.