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161.
162.
DeSimone JN Bengtsson U Wang X Lao XY Redpath JL Stanbridge EJ 《Radiation research》2003,159(1):72-85
Through a detailed study of cell cycle progression, protein expression, and kinase activity in gamma-irradiated synchronized cultures of human skin fibroblasts, distinct mechanisms of initiation and maintenance of G2-phase and subsequent G1-phase arrests have been elucidated. Normal and E6-expressing fibroblasts were used to examine the role of TP53 in these processes. While G2 arrest is correlated with decreased cyclin B1/CDC2 kinase activity, the mechanisms associated with initiation and maintenance of the arrest are quite different. Initiation of the transient arrest is TP53-independent and is due to inhibitory phosphorylation of CDC2 at Tyr15. Maintenance of the G2 arrest is dependent on TP53 and is due to decreased levels of cyclin B1 mRNA and a corresponding decline in cyclin B1 protein level. After transiently arresting in G2 phase, normal cells chronically arrest in the subsequent G1 phase while E6-expressing cells continue to cycle. The initiation of this TP53-dependent G1-phase arrest occurs despite the presence of substantial levels of cyclin D1/CDK4 and cyclin E/CDK2 kinase activities, hyperphosphoryated RB, and active E2F1. CDKN1A (also known as p21(WAF1/CIP1)) levels remain elevated during this period. Furthermore, CDKN1A-dependent inhibition of PCNA activity does not appear to be the mechanism for this early G1 arrest. Thus the inhibition of entry of irradiated cells into S phase does not appear to be related to DNA-bound PCNA complexed to CDKN1A. The mechanism of chronic G1 arrest involves the down-regulation of specific proteins with a resultant loss of cyclin E/CDK2 kinase activity. 相似文献
163.
Price DJ Campbell PG Sutton AG Grech ED Davies A Hall JA De Belder MA 《International journal of cardiovascular interventions》2001,4(1):15-20
BACKGROUND: The EPISTENT trial reported improved early outcomes with routine use of abciximab after coronary stenting. Increasing use of stents means that routine abciximab adds significantly to costs of percutaneous coronary intervention (PCI). This paper reports the results of a protocol encouraging restriction of abciximab therapy to high-risk patients only. METHODS: Data were collected prospectively over a 34-month period for patients undergoing PCI with stenting. In addition to those who fulfilled criteria for inclusion in the EPISTENT trial, patients treated in the setting of acute myocardial infarction (AMI) were studied. Demographic data, procedural details and early clinical outcomes were recorded. RESULTS: Of 808 patients studied, 601 fulfilled EPISTENT inclusion criteria and comprised 367 patients (45%) treated for stable angina and 234 (30%) treated for unstable or post-infarct angina. The additional 207 patients (25%) were treated during AMI. The 808 patients received a total of 981 stents. Abciximab was given in only 88 cases (10.9%). Major adverse clinical events occurred in 39 patients (4.8%). CONCLUSION: Selective use of abciximab for patients undergoing coronary stenting can be associated with outcomes equivalent to those reported for routine use, but with significant cost savings. 相似文献
164.
A rate-independent technique for analysis of nucleic acid sequences: evolutionary parsimony 总被引:24,自引:1,他引:23
The method of evolutionary parsimony--or operator invariants--is a
technique of nucleic acid sequence analysis related to parsimony analysis
and explicitly designed for determining evolutionary relationships among
four distantly related taxa. The method is independent of substitution
rates because it is derived from consideration of the group properties of
substitution operators rather than from an analysis of the probabilities of
substitution in branches of a tree. In both parsimony and evolutionary
parsimony, three patterns of nucleotide substitution are associated
one-to-one with the three topologically linked trees for four taxa. In
evolutionary parsimony, the three quantities are operator invariants. These
invariants are the remnants of substitutions that have occurred in the
interior branch of the tree and are analogous to the substitutions assigned
to the central branch by parsimony. The two invariants associated with the
incorrect trees must equal zero (statistically), whereas only the correct
tree can have a nonzero invariant. The chi 2-test is used to ascertain the
nonzero invariant and the statistically favored tree. Examples, obtained
using data calculated with evolutionary rates and branchings designed to
camouflage the true tree, show that the method accurately predicts the
tree, even when substitution rates differ greatly in neighboring peripheral
branches (conditions under which parsimony will consistently fail). As the
number of substitutions in peripheral branches becomes fewer, the parsimony
and the evolutionary-parsimony solutions converge. The method is robust and
easy to use.
相似文献
165.
166.
Direct measurement of translingual epithelial NaCl and KCl currents during the chorda tympani taste response. 总被引:1,自引:1,他引:0
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We have measured the NaCl or KCl currents under voltage clamp across the dorsal lingual epithelium of the rat and simultaneously the response of the taste nerves. Under short-circuit conditions a NaCl stimulus evoked an inward current (first current) that coincided with excitation of the chorda tympani. This was followed by a slower inward current (second current) that matched the kinetics of taste nerve adaptation. The peak first current and the coincident neural response satisfied the same saturating NaCl concentration dependence. Both first and second currents were partially blocked by amiloride as were the phasic and tonic components of the neural response. The NaCl-evoked second current was completely blocked by ouabain. Investigation of the NaCl-evoked current and the neural response over a range of clamped voltages showed that inward negative potentials enhanced the inward current and the neural response to 0.3 M NaCl. Sufficiently high inward positive potentials reversed the current, and made the neural response independent of further changes in voltage. Therefore, one of the NaCl taste transduction mechanisms is voltage dependent while the other is voltage independent. A KCl stimulus also evoked an inward short-circuit current, but this and the neural response were not amiloride-sensitive. The data indicate that neural adaptation to a NaCl stimulus, but not a KCl stimulus, is mediated by cell Na/K pumps. A model is proposed in which the connection between the NaCl-evoked second current and cell repolarization is demonstrated. 相似文献
167.
168.
Carbamoylphosphate synthetase (CPS) catalyzes the first committed step in
pyrimidine biosynthesis, arginine biosynthesis, or the urea cycle.
Organisms may contain either one generalized or two specific CPS enzymes,
and these enzymes may be heterodimeric (encoded by linked or unlinked
genes), monomeric, or part of a multifunctional protein. In order to help
elucidate the evolution of CPS, we have performed a comprehensive
phylogenetic analysis using the 21 available complete CPS sequences,
including a sequence from Sulfolobus solfataricus P2 which we report in
this paper. This is the first report of a complete CPS gene sequence from
an archaeon, and sequence analysis suggests that it encodes an enzyme
similar to heterodimeric CPSII. We confirm that internal similarity within
the synthetase domain of CPS is the result of an ancient gene duplication
that preceded the divergence of the Bacteria, Archaea, and Eukarya, and use
this internal duplication in phylogenetic tree construction to root the
tree of life. Our analysis indicates with high confidence that this
archaeal sequence is more closely related to those of Eukarya than to those
of Bacteria. In addition to this ancient duplication which created the
synthetase domain, our phylogenetic analysis reveals a complex history of
further gene duplications, fusions, and other events which have played an
integral part in the evolution of CPS.
相似文献
169.
Formation of enlarged mitochondria in a liver cell line in response to a synthetic glucocorticoid
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JA Berliner 《The Journal of cell biology》1975,64(3):711-716
For a number of years it has been recognized that glucocorticoids cause alterations in liver cell morphology (6, 9). Several investigators have shown that in liver in vivo mitochondria can be enlarged to many times their normal volume by treatment with cortisone (13, 15). There is a concomitant decrease in mitochondrial number, and the results of Kimberg and Loeb suggest that this is due to mitochondrial fusion (7). However, the exact mechanism whereby mitochondrial volume is altered and whether in fact cortisone is the direct causal agent are not known due to the complexity of studying these questions in a whole animal system. We have found that dexamethasone sodium phosphate (dex), a synthetic glucocorticoid, causes the formation of enlarged mitochondria in a liver cell line RLC-GAI, which grows in defined medium. In this paper we present our observations on the amount of enlargement that occurs after 5 days of treatment. The formation of enlarged mitochondria is reversible upon removal of the hormone from the medium, and we have attempted to determine whether "mitochondrial" or "nonmitochondrial" inhibitors are more effective in blocking the return of mitochondria to their normal size when the hormone is removed. 相似文献
170.
Jason Tri Roshini Asirvatham Christopher V. DeSimone Ammar M. Killu Alan M. Sugrue Scott H. Suddendorf Dorothy J. Ladewig Suraj Kapa Paul A. Friedman Christopher J. McLeod Samuel J. Asirvatham 《Indian pacing and electrophysiology journal》2018,18(6):195-200