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1.
Integrins and cardiovascular disease 总被引:2,自引:0,他引:2
Cardiovascular diseases involve abnormal cell-cell interactions leading to the development of atherosclerotic plaque, which when ruptured causes massive platelet activation and thrombus formation. Parts of a loose thrombus may detach to form an embolus, blocking circulation at a more distant point. The integrins are a family of adhesive cell receptors interacting with adhesive proteins or with counterreceptors on other cells. There is now solid evidence that the major integrin on platelets, the fibrinogen receptor α IIb β 3 , has an important role in several aspects of cardiovascular diseases and that its regulated inhibition leads to a reduction in incidence and mortality due to these disorders. The development of α IIb β 3 inhibitors is an important strategy of many pharmaceutical companies which foresee a large market for the treatment of acute conditions in surgery, the symptoms of chronic conditions and, it is hoped, maybe even the successful prophylaxis of these conditions. Although all the associated problems have not been solved, the undoubted improvements in patient care resulting from the first of these treatments in the clinic have stimulated further research on the role of integrins on other vascular cells in these processes and in the search for new inhibitors. Both the development of specific inhibitors and of mice with specific integrin subunit genes ablated have contributed to a better understanding of the function of integrins in development of the cardiovascular system. 相似文献
2.
K. J. Clemetson 《Cellular and molecular life sciences : CMLS》1998,54(6):499-501
Integrins are a family of adhesive receptors consisting of α- and β-subunits which attach cells together via adhesive protein ligands or bind cells to extracellular matrix. They are found on virtually all cell types and link the external ligand to the cytoskeleton of the cell. Integrins also act as signal transducers both from the outside of the cell to the interior and also inside-out. Their main functions are in recognition and in tight but regulated binding. The series of reviews presented here cover both basic aspects of integrin function, including signal transduction, snake disintegrins and structure and function of I-domains in some integrin α-subunits, as well as the role of integrins in diseases, cancer, inflammation and cardiovascular diseases. The search for suitable inhibitors of integrins for treatment of these diseases and future prospects for their use are also discussed. 相似文献
3.
Sánchez-Margalet V González-Yanes C Santos-Alvarez J Najib S 《Cellular and molecular life sciences : CMLS》1999,55(1):142-147
Insulin action is initiated by binding to its cognate receptor, which then triggers multiple cellular responses by activating
different signaling pathways. There is evidence that insulin receptor signaling may involve G protein activation in different
target cells. We have studied the activation of G proteins in rat hepatoma (HTC) cells. We found that insulin stimulated binding
of guanosine 5′-O-(3-thiotriphosphate) (GTP-γ-35S) to plasma membrane proteins of HTC cells, in a dose-dependent manner. This effect was completely blocked by pertussis toxin
treatment of the membranes, suggesting the involvement of G proteins of the Gα
i/Gα
o family. The expression of these Gα proteins was checked by Western blotting. Next, we used blocking antibodies to sort out the specific Gα protein activated by insulin stimulation. Anti-Gα
il,2 antibodies completely prevented insulin-stimulated GTP binding, whereas anti-Gα
o,i3 did not modify this effect of insulin on GTP binding. Moreover, we found physical association of the insulin receptor with
Gα
i1,2 by copurification studies. These results further support the involvement of a pertussis toxin-sensitive G protein in insulin
receptor signaling and provides some evidence of specific association and activation of Gα
i1,2 protein by insulin. These findings suggest that Gα
i1,2 proteins might be involved in insulin action.
Received 23 September 1998; received after revision 23 November 1998; accepted 25 November 1998 相似文献
4.
The human hair follicle is composed of different concentric compartments, which reflect different programmes of differentiation.
Using monoclonal antibodies against α2β1 and α3β1 integrins we demonstrated a shift in their expression, from a basolateral distribution in the basal cells of the lower outer
root sheath, to an apicolateral expression in the upper outer root sheath, as in epidermis. This shift takes place in a transition
zone, localized to the midpart of the follicle. The distinct basolateral distribution of α2β1 and α3β1 integrins in the lower portion of the outer root sheath coincides with the presence of basal cell protrusions and is probably
linked to the presence of the vitreous membrane which surrounds the bottom part of the anagen human hair follicle. Moreover,
we showed that the expression of α6β4 integrin is discontinuous along the hair follicle and coincides with that of laminin 5. Together these results establish
that within a given compartment – namely the outer root sheath – several domains can be clearly identified, which probably
reflect the onset of successive differentiation pathways along the hair follicle.
Received 17 January 1997; received after revision 18 February 1997; accepted 24 February 1997 相似文献
5.
The structure and function of heterotrimeric G protein subunits is known in considerable detail. Upon stimulation of a heptahelical
receptor by the appropriate agonists, the cognate G proteins undergo a cycle of activation and deactivation; the α-subunits and the βγ-dimers interact sequentially with several reaction partners (receptor, guanine nucleotides and effectors as well as regulatory
proteins) by exposing appropriate binding sites. For most of these domains, low molecular weight ligands have been identified
that either activate or inhibit signal transduction. These ligands include short peptides derived from receptors, G protein
subunits and effectors, mastoparan and related insect venoms, modified guanine nucleotides, suramin analogues and amphiphilic
cations. Because compounds that act on G proteins may be endowed with new forms of selectivity, we propose that G protein
subunits may therefore be considered as potential drug targets.
Received 18 September 1998; received after revision 6 November 1998; accepted 11 November 1998 相似文献
6.
Lau LF 《Cellular and molecular life sciences : CMLS》2011,68(19):3149-3163
CCN1 (CYR61) is a dynamically expressed, multifunctional matricellular protein that plays essential roles in cardiovascular
development during embryogenesis, and regulates inflammation, wound healing and fibrogenesis in the adult. Aberrant CCN1 expression
is associated with myriad pathologies, including various cancers and diseases associated with chronic inflammation. CCN1 promotes
diverse and sometimes opposing cellular responses, which can be ascribed, as least in part, to disparate activities mediated
through its direct binding to distinct integrins in different cell types and contexts. Accordingly, CCN1 promotes cell proliferation,
survival and angiogenesis by binding to integrin αvβ3, and induces apoptosis and senescence through integrin α6β1 and heparan sulfate proteoglycans. The ability of CCN1 to trigger the accumulation of a robust and sustained level of reactive
oxygen species underlies some of its unique activities as a matrix cell-adhesion molecule. Emerging studies suggest that CCN1
might be useful as a biomarker or therapeutic target in certain diseases. 相似文献
7.
M. V. Nogués M. Moussaoui E. Boix M. Vilanova M. Ribó C. M. Cuchillo 《Cellular and molecular life sciences : CMLS》1998,54(8):766-774
The enzymatic catalysis of polymeric substrates such as proteins, polysaccharides or nucleic acids requires precise alignment
between the enzyme and the substrate regions flanking the region occupying the active site. In the case of ribonucleases,
enzyme-substrate binding may be directed by electrostatic interactions between the phosphate groups of the RNA molecule and
basic amino acid residues on the enzyme. Specific interactions between the nitrogenated bases and particular amino acids in
the active site or adjacent positions may also take place. The substrate-binding subsites of ribonuclease A have been characterized
by structural and kinetic studies. In addition to the active site (p1 ), the role of other noncatalytic phosphate-binding subsites in the correct alignment of the polymeric substrate has been
proposed. p2 and p0 have been described as phosphate-binding subsites that bind the phosphate group adjacent to the 3′ side and 5′ side, respectively,
of the phosphate in the active site. In both cases, basic amino acids (Lys-7 and Arg-10 in p2 , and Lys-66 in p0 ) are involved in binding. However, these binding sites play different roles in the catalytic process of ribonuclease A.
The electrostatic interactions in p2 are important both in catalysis and in the endonuclease activity of the enzyme, whilst the p0 electrostatic interaction contributes only to binding of the RNA. 相似文献
8.
A. Zhang T. P.-O. Cheng X. Y. Wu B. T. Altura B. M. Altura 《Cellular and molecular life sciences : CMLS》1997,53(1):69-72
Effects of extracellular magnesium ions ([Mg2+]o ) on intracellular free Mg2+ ([Mg2+]i ) and its subcellular distribution in single fission yeast cells, Schizosaccharomyces pombe, were studied with digital-imaging microscopy and an Mg2+ fluorescent probe (mag-fura-2). Using 0.44 mM [Mg2+]o , [Mg2+]i in yeast cells was 0.91±0.08 mM. Elevation of [Mg2+]o to 1.97 mM induced rapid (within 5 min) increments in [Mg2+]i (2.18±0.11 mM). Lowering [Mg2+]o to 0.06 mM, however, exerted no significant effects on [Mg2+]i (0.93±0.14 mM), at least for periods of up to 30 min. Irrespective of the [Mg2+]o used, the subcellular distribution of [Mg2+]i remained hetero
geneous, i.e. where the sub-plasma membrane region >cytoplasm >nucleus. [Mg2+] in all three subcellular compartments increased significantly, two- to threefold, concomitant with [Mg2+]i when placed in 1.97 mM [Mg2+]o . We conclude that [Mg2+]i in fission yeast is maintained at a physiologic level when [Mg2+]o is low, but intracellular free Mg2+ rapidly rises when [Mg2+]o is elevated. Like most eukaryotic cells, yeast may have a Mg2+ transport system(s) which functions to maintain gradients of Mg2+ from the outside to inside the cell and among its subcellular compartments.
Received 18 April 1996; received after revision 4 July 1996; accepted 26 July 1996 相似文献
9.
M. Capdevila N. Cols N. Romero-Isart R. Gonzàlez-Duarte S. Atrian P. Gonzàlez-Duarte 《Cellular and molecular life sciences : CMLS》1997,53(8):681-688
Genetic engineering, coupled with spectro scopic analyses, has enabled the metal binding proper ties of the α and β subunits of mouse metallothionein 1 (MT) to be characterized. A heterologous expression system in E.coli has led to high yields of their pure zinc-complexed forms. The cadmium(II) binding properties of recombinant Zn4-αMT and Zn3-βMT have been studied by electronic absorption and circular dichroism. The former binds Cd(II) identically to α fragments obtained from mammalian organs, showing that the recombinant polypeptide behaves like the na tive protein. Titration
of Zn3-βMT with CdCl2 results in the formation of Cd3-βMT. The addition of excess Cd(II) leads to Cd4-βMT which, with the extra loading of Cd(II), unravels to give rise isodichroically to Cd9-βMT. The effect of cadmium-displaced Zn(II) ions and excess Cd(II) above the full metal occupancy of three has been studied
using Chelex-100. The Cd3-βMT species is stable in the presence of this strong metal-chelating agent.
Received 20 May 1997; received after revision 7 July 1997; accepted 9 July 1997 相似文献
10.
Simon S. Gerber Sofia Lejon Michael Locher Johann Schaller 《Cellular and molecular life sciences : CMLS》2010,67(9):1505-1518
The human α2-plasmin inhibitor (A2PI) possesses unique N- and C-terminal extensions that significantly influence its biological activities.
The C-terminal segment, A2PIC (Asn398-Lys452), contains six lysines thought to be involved in the binding to lysine-binding sites in the kringle domains of human plasminogen,
of which four (Lys422, Lys429, Lys436, Lys452) are completely and two (Lys406, Lys415) are partially conserved. Multiple Lys to Ala mutants of A2PIC were expressed in Escherichia coli and used in intrinsic fluorescence titrations with kringle domains K1, K4, K4 + 5, and K1 + 2 + 3 of human plasminogen. We
were able to identify the C-terminal Lys452 as the main binding partner in recombinant A2PIC (rA2PIC) constructs with isolated kringles. We could show a cooperative,
zipper-like enhancement of the interaction between C-terminal Lys452 and internal Lys436 of rA2PIC and isolated K1 + 2 + 3, whereas the other internal lysine residues contribute only to a minor extent to the binding
process. Sulfated Tyr445 in the unique C-terminal segment revealed no influence on the binding affinity to kringle domains. 相似文献
11.
R. M. H. Ravindranath M. H. Ravindranath M. C. Graves 《Cellular and molecular life sciences : CMLS》1997,53(9):750-758
IgM antibodies directed against neuronal gangliosides GM1 , GM2 , GD1a , GD1b and GT1b occur in normal individuals and their level significantly decreases with age. Patients with lower motor neuron disease (LMND)
produce high levels of these autoantibodies. AntiGM1 IgM is selectively augmented. In these patients, the CD5+ (B1) and CD5− (B2) subsets of B cells are not distinct entities
but range from those without detectable CD5 marker to those with high CD5+ expression. B1 B cells were sorted to homogeneity,
but B2 B cell cannot be isolated to homogeneity because of the presence of B1 cells with low CD5 expression. In short term
cultures both the subsets produced IgM antibodies, but the antibodies reacted better with desialylated GM1 than with GM1 . Cycloheximide (Cx) (0.35 mM) largely blocked IgM synthesis of the B1 B cells but inhibition of the B2 B cells was incomplete,
possibly due to shedding of cytophilic antibodies as well as to the presence of B1 phenotype with loss of CD5 expression.
CD5+ B cells may be involved in the production of antiglycolipid IgM.
Received 9 June 1997; received after revision 21 July 1997; accepted 28 July 1997 相似文献
12.
Three-dimensional structure of annexins 总被引:4,自引:0,他引:4
Annexins constitute a family of structurally related calcium- and phospholipid-binding proteins whose molecular structure
has been investigated in detail in the crystalline and membrane-bound form. Their polypeptide chain is folded into four or
eight α-helical domains of similar structure with a central hydrophilic pore. Bound to phospholipid membranes, the four-domain arrangement
of the annexin molecule is conserved. A peripheral binding mode has been well documented by electron microscopy and a variety
of other techniques. 相似文献
13.
E. Cohen-Hillel R. Mintz T. Meshel B.-Z. Garty A. Ben-Baruch 《Cellular and molecular life sciences : CMLS》2009,66(5):884-899
The chemokine CXCL8 is a powerful inducer of directional cell motility, primarily during inflammation. In this study, we found
that CXCL8 stimulation led to paxillin phosphorylation in normal neutrophils, and that both CXCL8 receptors (CXCR1 and CXCR2)
mediated CXCL8-induced paxillin phosphorylation. In CXCR2-transfected cells, the process depended on Gαi and Gαs coupling to CXCR2. Dominant negative (DN) paxillin increased CXCL8-induced adhesion and migration, indicating that endogenous
paxillin keeps migration at submaximal levels. Furthermore, using activating antibodies to β1 integrins, analyses with focal
adhesion kinase (FAK) DN variant (FRNK) and co-immunoprecipitations of FAK and paxillin, we found that β1 integrin ligation
cooperates with CXCL8-induced stimulation, leading to FAK activation and thereafter to FAK-mediated paxillin phosphorylation.
Our findings indicate that paxillin keeps directional motility at a restrained magnitude, and suggest that perturbations in
its activation may lead to chemotactic imbalance and to pathological conditions associated with excessive or reduced leukocyte
migration.
R. Mintz, T. Meshel: These authors contributed equally to this work.
Received 31 July 2008; received after revision 14 December 2008; accepted 16 December 2008 相似文献
14.
M. C. Marden L. Kiger C. Poyart S. J. Edelstein 《Cellular and molecular life sciences : CMLS》1998,54(12):1365-1384
While most researchers agree on the global features of cooperative ligand binding to haemoglobin (Hb), the internal mechanisms
remain open to debate. This is not due to inaccurate measurements, but is rather a consequence of the cooperative ligand binding
that decreases the equilibrium populations of the partially liganded states and makes observation of the transitions between
these substates more difficult. For example, the equilibrium population of the doubly liganded tetramers is typically less
than 5% of the total Hb. As a result many models with widely varying mechanisms may fit the oxygen equilibrium curve, but
may not be consistent with observations of other parameters, such as ligand-binding kinetics or subunit association equilibria.
The wide range of methods and models has led to divergent conclusions about the properties of specific substates. One notable
debate concerns the properties of the doubly liganded forms. The simple two-state model predicts a shift in the allosteric
equilibrium based on the number of ligands bound, but not on their distribution within the tetramer. From studies of dimer-tetramer
equilibria of various pure and hybrid forms, it was concluded that a tetramer with two ligands bound on the same α
β dimer (species 21, an asymmetric hybrid) shows an enhanced tetramer stability, similar to singly liganded Hb, relative to
the other three types of doubly liganded tetramers which resemble the triply liganded forms [Ackers et al. (1992), Science
255: 54–63]. The implications of this model and the relevant experiments will be reviewed here.
Received 27 April 1998; received after revision 17 July 1998; accepted 10 August 1998 相似文献
15.
C. S. Champion D. Kumar M. T. Rajan K. S. Jagannatha Rao M. A. Viswamitra 《Cellular and molecular life sciences : CMLS》1998,54(5):488-496
Spectroscopic study of the interactions of metal ions, Co, Mn, Mg and Al with d(GCCCATGGGC) and d(CCGGGCCCGG) revealed the
following. Metal ions Mn, Al and Mg at the lowest concentrations enhanced the t
m of oligomers, whereas Mn and Mg at higher concentrations decreased the t
m . Co enhanced the t
m of oligomers at higher concentrations. The studies have also indicated that Mn at lower concentrations displaced EtBr fluorescence,
Mg and Co at moderate concentrations and Al only at higher concentrations. Addition of Co, Mn, Mg and Al altered the bands
of the circulars dichroism (CD) spectra of the oligomers in a concentration-dependent manner. The CD spectra of d(GCCCATGGGC)
and d(CCGGGCCCGG) indicated B and Z forms of DNA, respectively, in contrast to the A form observed in the crystal structures.
Mg and Co at different ionic strength induced Z–B transition in d(CCGGGCCCGG), while Al at higher concentrations induced a
Z–A transition. Mn did not induce any transition. This is the first report to show that Al causes structural transitions in
sequence-specific oligomers and has strong binding ability with GC-rich euchromatin oligomers.
Received 22 December 1997; received after revision 16 March 1998; accepted 16 March 1998 相似文献
16.
Andrea Venerando Oriano Marin Giorgio Cozza Victor H. Bustos Stefania Sarno Lorenzo Alberto Pinna 《Cellular and molecular life sciences : CMLS》2010,67(7):1105-1118
The ability of three isoforms of protein kinase CK1 (α, γ1, and δ) to phosphorylate the N-terminal region of p53 has been assessed using either recombinant p53 or a synthetic peptide
reproducing its 1–28 sequence. Both substrates are readily phosphoylated by CK1δ and CK1α, but not by the γ isoform. Affinity
of full size p53 for CK1 is 3 orders of magnitude higher than that of its N-terminal peptide (K
m 0.82 μM vs 1.51 mM). The preferred target is S20, whose phosphorylation critically relies on E17, while S6 is unaffected
despite displaying the same consensus (E-x-x-S). Our data support the concept that non-primed phosphorylation of p53 by CK1
is an isoform-specific reaction preferentially affecting S20 by a mechanism which is grounded both on a local consensus and
on a remote docking site mapped to the K221RQK224 loop according to modeling and mutational analysis. 相似文献
17.
Muñoz U Bartolomé F Esteras N Bermejo-Pareja F Martín-Requero A 《Cellular and molecular life sciences : CMLS》2008,65(21):3507-3519
It has been proposed that neuroinflammation, among other factors, may trigger an aberrant neuronal cell cycle re-entry leading
to neuronal death. Cell cycle disturbances are also detectable in peripheral cells from Alzheimer’s disease (AD) patients.
We previously reported that the anti-inflammatory 15- deoxy-Δ12,14-prostaglandin J
2 (15d-PGJ
2) increased the cellular content of the cyclin-dependent kinase inhibitor p27, in lymphoblasts from AD patients. This work
aimed at elucidating the mechanisms of 15d-PGJ
2-induced p27 accumulation. Phosphorylation, half-life, and the nucleo-cytoplasmic traffic of p27 protein were altered by 15d-PGJ2
by mechanisms dependent on PI3K/Akt activity. 15d-PGJ
2 prevents the calmodulin-dependent Akt overactivation in AD lymphoblasts by blocking its binding to the 85-kDa regulatory
subunit of PI3K. These effects of 15d-PGJ
2 were not mimicked by 9,10-dihydro-15-deoxy-Δ12,14- prostaglandin J
2, suggesting that 15d-PGJ
2 acts independently of peroxisome proliferator-activated receptor γ activation and that the α,β-unsaturated carbonyl group
in the cyclopentenone ring of 15d-PGJ
2 is a requisite for the observed effects.
Received 14 July 2008; received after revision 2 September 2008; accepted 12 September 2008 相似文献
18.
H.-O. Ito T. Ueda Y. Hashimoto T. Imoto T. Koga 《Cellular and molecular life sciences : CMLS》1997,53(1):51-60
We previously generated a monoclonal antibody (mAb) against a putative pathogenic epitope on native type II collagen (CII)
for the induction of collagen-induced arthritis in mice (mAb1), and an anti-idiotypic mAb which appears to possess the internal
image of the CII epitope (mAb2). In the present study, the structural basis of the antigen/mAb1 and mAb1/mAb2 interactions
was examined. When partially SH-reduced mAb1 was analysed on Western blots, only fragments containing both heavy (H) and light
(L) chains were recognized by mAb2. When mAb2 was partially SH-reduced, only fragments containing both H and L chains were
recognized by mAb1. H and L chains were separated from mAb1 in a reduced, denatured condition, and each chain and a mixture
of the two were refolded. mAb2 reacted specifically to the renatured whole IgG molecule of mAb1, but not to the refolded L
or to H chains. Recombinant single chain Fv (scFv) generated from mAb1 and mAb2 had properties of the original mAbs, whereas
genetical
ly constructed chimeric scFvs, consisting of VH from mAb1 and an irrelevant VL , or VL of mAb1 and an irrelevant VH , did not react either to CII or to mAb2. Thus, interactions among CII, mAb1 and mAb2 appear to depend on quaternary structures
containing different protein subunits. These observations support the internal image property of the mAb2. In addition, this
dependency on quaternary structure for recognition of proteins may also be relevant to other protein-protein interactions.
Received 29 July 1996; received after revision 13 September 1996; accepted 18 October 1996 相似文献
19.
Signal regulation by family conspiracy 总被引:6,自引:0,他引:6
The signal regulating proteins (SIRPs) are a family of ubiquitously expressed transmembrane glycoproteins composed of two
subgroups: SIRPα and SIRPβ, containing more than ten members. SIRPα has been shown to inhibit signalling through a variety of receptors including receptor tyrosine kinases and cytokine receptors.
This function involves protein tyrosine kinases and is dependent on immunoreceptor tyrosine-based inhibition motifs which
recruit key protein tyrosine phosphatases to the membrane. Negative regulation by SIRPα may also involve its ligand, CD47, in a bi-directional signalling mechanism. The SIRPβ subtype has no cytoplasmic domain but instead associates with at least one other transmembrane protein (DAP-12, or KARAP).
DAP-12 possesses immunoreceptor tyrosine-based activation motifs within its cytoplasmic domain that are thought to link SIRPβ to activating machinery. SIRPα and SIRPβ thus have complementary roles in signal regulation and may conspire to tune the response to a stimulus.
Received 6 July 2000; revised 2 August 2000; accepted 5 August 2000 相似文献
20.
The superoxide-generating NADPH oxidase: structural aspects and activation mechanism 总被引:31,自引:0,他引:31
Vignais PV 《Cellular and molecular life sciences : CMLS》2002,59(9):1428-1459
Flavocytochrome b
558
is the catalytic core of the respiratory-burst oxidase, an enzyme complex that catalyzes the NADPH-dependent reduction of
O2 into the superoxide anion O2
- in phagocytic cells. Flavocytochrome b
558
is anchored in the plasma membrane. It is a heterodimer that consists of a large glycoprotein gp91phox (phox for phagocyte oxidase) (β subunit) and a small protein p22phox (α subunit). The other components of the respiratory-burst oxidase are water-soluble
proteins of cytosolic origin, namely p67phox, p47phox, p40phox and Rac. Upon cell stimulation, they assemble with the membrane-bound
flavocytochrome b
558
which becomes activated and generates O2
-. A defect in any of the genes encoding gp91phox, p22phox, p67phox or p47phox results in chronic granulomatous disease, a
genetic disorder characterized by severe and recurrent infections, illustrating the role of O2
- and the derived metabolites H2O2 and HOCl in host defense against invading microorganisms. The electron carriers, FAD and hemes b, and the binding site for NADPH are confined to the gp91phox subunit of flavocytochrome b
558
. The p22phox subunit serves as a docking site for the cytosolic phox proteins. This review provides an overview of current
knowledge on the structural organization of the O2
--generating flavocytochrome b
558
, its kinetics, its mechanism of activation and the regulation of its biosynthesis. Homologues of gp91phox, called Nox and
Duox, are present in a large variety of non-phagocytic cells. They exhibit modest O2
--generating oxidase activity, and some act as proton channels. Their role in various aspects of signal transduction is currently
under investigation and is briefly discussed.
Received 28 May 2002; received after revision 20 June 2002; accepted 24 June 2002 相似文献