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Rose Bengal adsorbed on microgranular cellulose: evidence on fluorescent dimers.

Rose Bengal adsorbed on microgranular cellulose was studied in the solid phase by total and diffuse reflectance and steady-state emission spectroscopy. A simple monomer-dimer equilibrium fitted reflectance data up to dye loadings of 4 x 10(-7) mol (g cellulose)(-1) and allowed calculation of monomer and dimer spectra. Further increase of dye loading resulted in the formation of higher aggregates. Observed emission and excitation spectra and quantum yields were corrected for reabsorption and reemission of luminescence, using a previously developed model, within the assumption that only monomers are luminescent [M. G. Lagorio, L. E. Dicelio, M. I. Litter and E. San Roman, J. Chem. Soc., Faraday Trans., 1998, 94, 419]. An apparent increase of fluorescence quantum yield with dye loading was found, which was attributed to the occurrence of dimer fluorescence. Extension of the model to two luminescent species (i.e. monomer and dimer) yielded constant fluorescence quantum yields for the monomer, phiM= 0.120 +/- 0.004, and for the dimer, phiD= 0.070 +/- 0.006. The monomer quantum yield is close to the value found for the same dye in basic ethanol. The presence of fluorescent dimers and calculated quantum yields are supported by analysis of the excitation spectra and other experimental evidence. The possible occurrence of non-radiative energy transfer and the effect of surface charge on the properties of the dimer are analyzed.

Journal Article↗

Refolding of Escherichia coli outer membrane protein F in detergent creates LPS-free trimers and asymmetric dimers.

The Escherichia coli OmpF (outer-membrane protein F; matrix porin) is a homotrimeric beta-barrel and a member of the bacterial porin superfamily. It is the best characterized porin protein, but has resisted attempts to refold it efficiently in vitro. In the present paper, we report the discovery of detergent-based folding conditions, including dodecylglucoside, which can create pure samples of trimeric OmpF. Whereas outer membrane LPS (lipopolysaccharide) is clearly required for in vivo folding, the artificially refolded and LPS-free trimer has properties identical with those of the outer-membrane-derived form. Thus LPS is not required either for in vitro folding or for structural integrity. Dimeric forms of OmpF have been observed in vivo and are proposed to be folding intermediates. In vitro, dimers occur transiently in refolding of trimeric OmpF and, in the presence of dodecylmaltoside, pure dimer can be prepared. This form has less beta-structure by CD and shows lower thermal stability than the trimer. Study of these proteins at the single-molecule level is possible because each OmpF subunit forms a distinct ion channel. Whereas each trimer contains three channels of equal conductance, each dimer always contains two distinct channel sizes. This provides clear evidence that the two otherwise identical monomers adopt different structures in the dimer and indicates that the asymmetric interaction, characteristic of C3 symmetry, is formed at the dimer stage. This asymmetric dimer may be generally relevant to the folding of oligomeric proteins with odd numbers of subunits such as aspartate transcarbamoylase.

Detergents↗

A kinetic and equilibrium study of ligand binding to the monomeric and dimeric haem-containing globins of two chitons.

The radular muscles of the amphineuran molluscs Amaurochiton glaucus and Sipharochiton pelliserpentis contain both a dimeric and a monomeric form of myoglobin. The dimeric form of the protein is composed of two polypeptide chains covalently linked to each other via one or more disulphide bonds. The dimeric protein shows co-operative O2-binding curves. Kinetic investigations indicate that CO binding is co-operative in the dimeric protein, subsequent to full photolysis, but mono-exponential following 10% photolysis. O2 recombination following part photolysis is mono-exponential in the dimeric form, whereas O2 dissociation kinetics indicates the presence of chain heterogeneity. The monomeric form of the protein exhibits mono-exponential time courses in all the experimental situations explored. Although the rate constants associated with the reactions of individual dimer and monomer molecular species are very different, the two species of chiton investigated show remarkably similar properties when compared with each other. All the reactions studied are pH-independent in the range pH 6-8. Amino acid analysis indicates that the monomeric units that combine to form the dimeric species are not identical with the naturally occurring monomeric form. A comparison is made between the chiton myoglobins and other similar O2-binding proteins.

Amino Acids↗

The usefulness of five D-dimer assays in the exclusion of deep venous thrombosis.

D-Dimer measurement is a promising tool in the exclusion of venous thrombosis. New d-dimer assays have been introduced, but need clinical validation. Our objective was to evaluate the clinical usefulness of four relatively new d-dimer assays and a classical ELISA in outpatients suspected for deep venous thrombosis. In 537 patients, participants in a large prospective management study using a clinical probability score and a d-dimer measurement (Tina-quant), additional samples were taken for d-dimer measurement using the Asserachrom ELISA, the VIDAS New, the STA-LIA and the Miniquant assay. Performances of each test were calculated using clinical data during a 3-month follow-up. Thrombosis was detected in 224 patients (42%). The area under the ROC curve was significantly higher for the Tina-quant as compared to the other assays. Using standard cut-off values, sensitivity, negative predictive value (NPV) and specificity of the Asserachrom were 97, 94 and 33%, respectively. For the VIDAS New, values were 100, 96 and 8%, respectively. The Tina-quant showed values of 99, 98 and 41%, respectively, and the STA-LIA 98, 95 and 32%. Values for the Miniquant were 95, 94 and 52%. The d-dimer assays in our study all show a high sensitivity and negative predictive value, but none of the assays reached an NPV of > 98% at standard cut-off values. d-Dimer assays with a low specificity still necessitate additional diagnostic tests in the majority of the patients.

Diagnosis, Differential↗

Fibrin D-dimer in thrombogenic disorders.

Measurement of D-dimer (fibrin degradation product) is important for determining not only the activation of fibrinolysis but also the severity of a hypercoagulable state. However, fibrin degradation products are in variable, and the reactivity to cross-linked fibrin degradation products produced during fibrin degradation differs depending on the kind of antibody used against D-dimer. In patients with disseminated intravascular coagulation or earthquake-induced mental and physical stress and in patients after percutaneous transluminal coronary angioplasty, all of which are associated with acute fibrin formation and degradation, some discrepancies between two methods of D-dimer detection, automated latex agglutination assay (LPIA) and enzyme-linked immunosorbent assay (Stago), were found. No discrepancies in persistent fibrin formation and degradation were found among the healthy elderly, patients with lacunar stroke, and patients with coronary artery disease, almost all of whom had levels under 5.0 microg/mL, as determined by both methods. Evidence of persistently increased intravascular coagulation and fibrin turnover in patients with atherosclerotic disease was found. The cleavage of cross-linked fibrin by plasmin results in a production of fibrin degradation products, mostly contained D-dimer domains. Although the clinical utility of D-dimer can be achieved by their detection with specific antibodies, measurement of D-dimer as high-molecular-weight fragments may be useful to determine whether patients will undergo further fibrin degradation. When intermediate products of the degradation process need to be assessed, D-dimer level measurement by LPIA may serve as a suitable marker for ongoing fibrinolysis.

Adult↗

A density-functional theory investigation of 3-nitro-1,2,4-triazole-5-one dimers and crystal.

Density-functional method with different basis sets was applied to the study of the highly efficient and low sensitive explosive 3-nitro-1,2,4-triazole-5-one (NTO) in both gaseous dimer and its bulk state. The binding energies have been corrected for the basis set superposition errors. Six stable dimers (II-VII) were located. The corrected binding energy of the most stable dimer VII is predicted to be -53.66 kJ/mol at the B3LYP/6-311++G(**) level. It was found that the structures of the more stable dimers (V-VII) are through the hydrogen bonding interaction between the carbonyl oxygen and the azole hydrogen of 3-nitro-1,2,4-triazole-5-one. The changes of Gibbs free energies (DeltaG) in the processes from the monomer to the dimers at 298.15 K are 8.51, 0.90, 0.35, -8.74, -10.67, and -11.06 kJ/mol for dimers from II to VII, respectively. Dimers V-VII, possessing cyclic structures, can be spontaneously produced from the isolated monomer at room temperature. The lattice energy is -156.14 kJ/mol, and this value becomes to -150.43 kJ/mol when a 50% correction of the basis set superposition error was adopted. The frontier bands are quite flat. Judged from the value of band gap of 4.0 eV, it may be predicted that 3-nitro-1,2,4-triazole-5-one is an insulator. Most atoms in NTO, with the exception of C(5) atom and the nitro atoms, make up the upper valence bands. In contrast, the lower conduction bands mainly consist of the nitro N and O atoms. The population of the C-NO(2) bond is much less than those of the other bonds and the detonation may be initiated by the breakdown of this bond.

Journal Article↗

Plasmon hybridization in nanoshell dimers.

We extend the plasmon hybridization method to investigate the plasmon modes of metallic nanoshell dimers. The formalism is also generalized to include the effects of dielectric backgrounds. It is shown that the presence of dielectrics shifts the plasmon resonances of the individual nanoparticles to lower energies and screens their interaction in the dimer configuration. The net result is a redshift of dimer energies compared to the system without dielectrics and a weaker dependence of the dimer plasmon energies on dimer separation. We calculate the plasmon energies and optical absorption of nanoshell dimers as a function of dimer separation. The results are in excellent agreement with the results of finite difference time domain simulations.

Journal Article↗

Vibrational coupling in carboxylic acid dimers.

The vibrational level splitting in the ground electronic state of carboxylic acid dimers mediated by the doubly hydrogen-bonded networks are investigated using pure and mixed dimers of benzoic acid with formic acid as molecular prototypes. Within the 0-2000-cm(-1) range, the frequencies for the fundamental and combination vibrations of the two dimers are experimentally measured by using dispersed fluorescence spectroscopy in a supersonic jet expansion. Density-functional-theory calculations predict that most of the dimer vibrations are essentially in-phase and out-of-phase combinations of the monomer modes, and many of such combinations show significantly large splitting in vibrational frequencies. The infrared spectrum of the jet-cooled benzoic acid dimer, reported recently by Bakker et al. [J. Chem. Phys. 119, 11180 (2003)], has been used along with the dispersed fluorescence spectra to analyze the coupled g-u vibrational levels. Assignments of the dispersed fluorescence spectra of the mixed dimer are suggested by comparing the vibronic features with those in the homodimer spectrum and the predictions of density-functional-theory calculation. The fluorescence spectra measured by excitations of the low-lying single vibronic levels of the mixed dimer reveal that the hydrogen-bond vibrations are extensively mixed with the ring modes in the S1 surface.

Journal Article↗

Optical coherence and theoretical study of the excitation dynamics of a highly symmetric cyclophane-linked oligophenylenevinylene dimer.

Optoelectronic properties of a polyphenylenevinylene-based oligomer and its paracylophane-linked dimer are studied using a variety of experimental and theoretical techniques. Despite the symmetrical structure and redshifted absorption of the dimer versus the monomer, an exciton picture is not the most appropriate. Electronic structure calculations establish changes in charge density upon optical excitation and show localized excitations that cannot be accounted for by a simple Frenkel exciton model. Visible frequency pump-probe anisotropy measurements suggest that the dimer should be considered as a three-level system with a fast, approximately 130 fs, internal conversion from the higher to lower energy excited electronic state. Signatures of nuclear relaxation processes are compared for electric field-resolved transient grating and two-dimensional photon echo spectra. These measurements reveal that nuclear relaxation occurs on similar time scales for the monomer and dimer. The connection between the spectral phase of four-wave mixing signals and the time dependent width of a nuclear wave packet is discussed. Semiempirical electronic structure and metropolis Monte Carlo calculations show that the dominant line broadening mechanisms for the monomer and dimer are associated with inter-ring torsional coordinates. Together, the theoretical calculations and electric field-resolved four-wave mixing experiments suggest that while the structure of dimer is more rigid than that of monomer, the difference in their rigidities is not sufficient to slow down excited state relaxation of dimer with respect to the monomer.

Journal Article↗

Infrared spectra of the CF3I dimer: a concurrent application of matrix-isolation spectroscopy and cavity ring-down spectroscopy.

We have observed infrared spectra of the CF(3)I dimer produced in a supersonic jet by matrix-isolation Fourier transform infrared spectroscopy and infrared cavity ring-down (IR-CRD) spectroscopy. In the matrix-isolation experiments, the dimer was isolated in an Ar matrix by the pulse-deposition method. The recorded spectral range covers the symmetric (nu(1)) and doubly degenerate (nu(4)) C-F stretching regions. From the concentration dependence of the matrix-isolation spectra we have assigned one dimer band for each fundamental region. It was not easy to identify the dimer band for the nu(4) band because of the multiplet feature of the monomeric nu(4) band caused by the site symmetry breaking. The spectra of (CF(3)I)(2) in the nu(4) band region were thus also measured in the gas phase by IR-CRD spectroscopy, where we detected two dimer bands. Comparing the observed band positions with the results of quantum chemical calculations, we have assigned the observed dimer bands to the head-to-head isomer. The structure of (CF(3)I)(2) and its photochemical implications are discussed, in comparison with methyl iodide dimer reported previously [Ito et al., Chem. Phys. Lett. 343, 185 (2001)].

Journal Article↗

D-dimer and calf circumference in the evaluation of outpatient deep venous thrombosis.

OBJECTIVE: Duplex ultrasonography (DU) is the primary method for diagnosis of deep venous thrombosis (DVT) but is relatively expensive and not always readily available. Attempts to exclude the diagnosis of DVT with D-dimer or clinical criteria independently have been unsuccessful. The goal of our study was to evaluate a second-generation rapid quantitative D-dimer and simple clinical parameters for screening of outpatients for DVT. PATIENTS AND METHODS: Patients undergoing DU of the lower extremities for suspected DVT were prospectively evaluated. Patients undergoing lower extremity venous ultrasound scan for suspected pulmonary embolism or already on anticoagulant therapy were excluded from the study. Data were analyzed to assess the optimal combination of characteristics to include and exclude proximal DVT. RESULTS: One hundred fifty-six outpatients met inclusion criteria and were enrolled in the study. Elevated levels of D-dimer of 0.5 ng/mL or more were noted in 21 of 22 patients diagnosed with DVT, yielding a sensitivity of 95% and negative predictive value of 99%. Subjective symptoms of swelling or pain were present in 94% of all outpatients. Asymmetric calf swelling of more than 2.0 cm was noted in 14 of 22 patients (64%) with proximal DVT compared with 22 of 134 patients (16%) without DVT (P <.003). No single clinical history variable was significant on multivariate analysis. All outpatients with proximal DVT had either leg swelling of more than 2 cm or a positive D-dimer. CONCLUSION: A combination of a second-generation quantitative D-dimer and calf measurement provides an easy and effective means of excluding proximal DVT when screening outpatients. Patients with calf circumference 2.0 cm or less and a negative D-dimer may undergo nonemergent DU. Patients with a positive D-dimer or asymmetrical calf swelling of more than 2.0 cm alone or in combination should undergo emergent DU.

Female↗

Effect of interchain disulfide bond on hapten binding properties of light chain dimer of protein 315.

The hapten binding characteristics of the covalent light chain dimer, derived from the murine IgA secreted by plasmacytoma MOPC-315, to two nitroaromatic compounds, epsilon-N-(2,4-dinitrophenyl)-L-lysine and 4-(alpha-N-alanine)-m-nitrobenz-2-oxa-1,3-diazole, were investigated by differential spectroscopic titrations. The binding curves for both haptens were found to display sigmoidity similar to that reported earlier for the reduced and alkylated dimer held together by noncovalent bonds only. However, the presence of the interchain disulfide bond in the covalent dimer was found to cause marked changes in its binding properties. The data, like those obtained for the noncovalent dimer, fit the allosteric model of Monod, Wyman, and Changeux in which binding of the first hapten to the dimer causes a conversion of both sites of the protein molecule from a lower to a higher affinity conformation. However, the binding parameters show that both the affinity and the positive cooperativity in the interaction between haptens and the covalent dimer are significantly enhanced. The differences in the parameters of the binding and of the allosteric transition caused by the presence of the interchain disulfide bond demonstrate the existence of longitudinal interactions in immunoglobulin derivatives. These properties of the light chain dimer make it a potential model for the receptors present on thymus-derived lymphocytes.

Allosteric Regulation↗

Assembly of the functional membrane attack complex of human complement: formation of disulfide-linked C9 dimers.

The 158,000 Mr protein, previously designated C5c, present in fully assembled complement (C) membrane attack complexes (MC5b-9) has been identified as a disulfide-bonded dimer of C9. This conclusion was based on the observations that: (i) a portion of the 125I-radiolabeled precursor C9 incorporated into MC5b-9 complexes comigrated with the 158,000 Mr protein band in NaDodSO4/polyacrylamide slab gels; (ii) monospecific antisera produced against native C9 and the 158,000 Mr protein immunologically crossreacted with monomeric native C9 by double immunodiffusion and with monomeric C9 and the 158,000 Mr protein on immunoreplication procedures; and (iii) two-dimensional NaDodSO4/polyacrylamide slab gel electrophoresis, in which the second dimension was conducted under reducing conditions, revealed that the 158,000 Mr protein contained two identical 71,000 Mr subunits which comigrated with monomeric C9. Molar ratio estimates indicated that 1 mol of C5b, C9 dimer, C6, C7, and C8 and 3-4 mol of C9 monomer were present per MC5b-9 complex. Each fully assembled membrane-bound MC5b-9 complex would therefore have a calculated Mr of 982,000. The presence of C9 dimers in the hemolytically active 29S dimeric form of the MC5b-9 complex and the absence of C9 dimers in the hemolytically inactive 23S monomeric form of the fluid phase SC5b-9 complex strongly suggest an important role for C9 dimer formation in MC5b-9 complex structure and function. The most probable function of C9 dimers would be the formation of intercomplex disulfide crosslinks which would provide a mechanism to stabilize the assembly of MC5b-9 into aggregates of increasing size on the target membrane surface which would thus be responsible for the observed pore size heterogeneity of functional C lesions.

Animals↗

Evidence for interstrand quadruplex formation in the dimerization of human immunodeficiency virus 1 genomic RNA.

Retroviruses package two homologous single-stranded RNA genomes within a gag protein-RNA complex. In mature virion particles, the two RNA strands are thought to associate primarily through direct RNA-RNA interactions, although the structural basis for this stable association is unknown. We now report that a 127-nucleotide (nt) HIV-1NL4-3 RNA fragment (positions 732-858) encompassing the 5' end of the gag gene dimerizes spontaneously under high ionic strength conditions in the absence of any protein cofactor. The HIV-1 RNA dimer is dramatically and specifically stabilized by the monovalent cation potassium. Thermal dissociation of the dimer occurs at 80 degrees C in 100 mM K+ (5 mM Mg2+) but at significantly lower temperatures in the presence of either smaller or larger monovalent cations (100 mM Li+, 40 degrees C; 100 mM Na+, 55 degrees C; 100 mM Cs+, 30 degrees C). Deletion analyses of the 3' end of the 127-nt fragment reveal that an HIV-1 RNA fragment as short as 94 nt (732-825) can dimerize spontaneously, but a further 9-base deletion of the purine-rich sequence, GGGGGAGAA from positions 817 through 825, eliminates dimerization. These experimental results support a model in which HIV-1 RNA dimerizes by forming an interstrand quadruple helix stabilized by guanine (and/or purine)-base tetrads in analogy to the well-known dimerization of telomeric DNA. We speculate that this structure may also mediate the association of genomic HIV-1 RNA in vivo, revealing how RNA itself can achieve the self-recognition required for subsequent genetic recombination.

Base Sequence↗

Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer.

Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To understand the structure-activity relationships of human iNOS, we constitutively expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector. These cells are deficient in de novo H4B biosynthesis and the role of H4B in the expression and assembly of active iNOS in an intact cell system could be studied. In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1 and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis correlated with an increase in intracellular H4B but no increase in iNOS protein. Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from H4B-deficient cells exhibited little iNOS activity but acquired activity during a 60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis activity was associated with conversion of monomers into dimeric iNOS during the incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B plays a critical role in promoting dimerization in intact cells. This reveals a post-translational mechanism by which intracellular H4B can regulate iNOS expression.

3T3 Cells↗

Dimerization regulates the enzymatic activity of Escherichia coli outer membrane phospholipase A.

The outer membrane phospholipase A (OMPLA) of Escherichia coli is present in a dormant state in the cell envelope. The enzyme is activated by various processes, which have in common that they perturb the outer membrane. Kinetic experiments, chemical cross-linking, and analytical ultracentrifugation were carried out with purified, detergent-solubilized OMPLA to understand the underlying mechanism that results in activation. Under conditions in which the enzyme displayed full activity, OMPLA was dimeric. High detergent concentrations or very dilute protein concentrations resulted in low specific activity of the enzyme, and under those conditions the enzyme was monomeric. The cofactor Ca2+ was required for dimerization. Covalent modification of the active site serine with hexadecylsulfonylfluoride resulted in stabilization of the dimeric form and a loss of the absolute calcium requirement for dimerization. The results of these experiments provide evidence for dimerization as the molecular mechanism by which the enzymatic activity of OMPLA is regulated. This dimerization probably plays a role in vivo as well. Data from chemical cross-linking on whole cells indicate that OMPLA is present in the outer membrane as a monomer and that activation of the enzyme induces dimerization concurrent with the appearance of enzymatic activity.

Detergents↗

Ligand linked assembly of Scapharca dimeric hemoglobin.

The assembly of Scapharca dimeric hemoglobin as a function of ligation has been explored by analytical gel chromatography, sedimentation equilibrium, and oxygen binding experiments to test the proposal that its cooperativity is based on quaternary enhancement. This hypothesis predicts that the liganded form would be assembled more tightly into a dimer than the unliganded form and that dissociation would lead to lower oxygen affinity. Our experiments demonstrate that although the dimeric interface is quite tight in this hemoglobin, dissociation can be clearly detected in the liganded states with monomer to dimer association constants in the range of 10(8) M-1 for the CO-liganded state and lower association constants measured in the oxygenated state. In contrast, the deoxy dimer shows no detectable dissociation by analytical ultracentrifugation. Thus, the more highly hydrated deoxy interface of this dimer is also the more tightly assembled. Equilibrium oxygen binding experiments reveal an increase in oxygen affinity and decrease in cooperativity as the concentration is lowered (in the muM range). These experiments unambiguously refute the hypothesis of quaternary enhancement and indicate that, as in the case of human hemoglobin and other allosteric proteins, quaternary constraint underlies cooperativity in Scapharca dimeric hemoglobin.

Animals↗

Clinical evaluation of a diagnostic strategy for deep venous thrombosis with exclusion by low plasma levels of fibrin degradation product D-dimer.

Clinical research studies have indicated the possibility of diagnostic strategies for deep venous thrombosis (DVT), strategies which include a step where the diagnosis is excluded by low or undetectable plasma levels of fibrin degradation product D-dimer. In collaboration with two local hospitals in Sweden, three implementations of such a strategy are evaluated in this study. Procedures 1, 2 and 3 differed in the method for D-dimer determination, i.e. latex agglutination, immunofiltration and both, respectively. The evaluated procedures were performed in parallel and compared with the current procedure in the different hospitals. At both hospitals, the current procedure stipulated mandatory phlebography and laboratory analysis of acute coagulation status and routine haematology with report-back time of 2 h. Within the 2 h the hospitals' clinical chemistry laboratories also determined plasma D-dimer by the two methods. Of 180 patients enrolled in the study, phlebography was successful in 155 and unsuccessful in 25. The phlebographies revealed 47 proximal DVT, 13 distal DVT and 95 no DVT. With Procedure 1, 53 patients (29%) were excluded in the D-dimer step. For these patients, 47 successful phlebographies revealed one proximal DVT and two distal DVT. With Procedure 2, 71 patients (39%) were excluded. For these patients, 65 successful phlebographies revealed two proximal DVT and four distal DVT. With Procedure 3, 44 patients (24%) were excluded. For these patients, 41 successful phlebographies revealed two distal DVT. The negative predictive values of the D-dimer exclusion step, with 95% confidence intervals given within parentheses, were 96% (88-100%), 91% (84-98%) and 95% (89-100%) for Procedures 1, 2 and 3, respectively. The evaluation demonstrated that the diagnostic potential of D-dimer revealed in research studies can be achieved in clinical practice. The study also indicated that the positive diagnostic value of high levels of D-dimer may be of use in finalizing the diagnosis in the 14% of patients for whom phlebography is unsuccessful.

Enzyme-Linked Immunosorbent Assay↗