Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Dimerization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,693 records · Page 94Linked to original sources

Carboxylated zinc-phthalocyanines--II. Dimerization and singlet molecular oxygen sensitization in hexadecyltrimethylammonium bromide micelles.

The dimerization of the diamide of zinc-tetracarboxyphthalocyanine was studied spectroscopically in hexadecyltrimethylammonium bromide (CTAB) micelles at surfactant concentrations from 0.026 to 0.1 M and dye concentrations between 0.1 and 10 microM. The apparent dimerization constant in CTAB 0.1 M is 8.6 x 10(5) M-1, while the intramicellar dimerization constant is 1.8 x 10(3). The dimer absorption spectrum was also obtained. Singlet molecular oxygen sensitization was studied by steady state photolysis using 1,3-diphenylisobenzofurane as scavenger in 0.1 M CTAB. The usual sensitization mechanism is extended to include dimer reactions. Singlet molecular oxygen sensitization yields for monomer and dimer in the micelles are 0.7 and 0.1, respectively. With the reported values it is possible to calculate the average yield of singlet molecular oxygen production at any surfactant and dye concentrations.

Cetrimonium↗

Modulation of the dimerization of a transcriptional antiterminator protein by phosphorylation.

The transcriptional antiterminator protein BglG inhibits transcription termination of the bgl operon in Escherichia coli when it is in the nonphosphorylated state. The BglG protein is now shown to exist in two configurations, an active, dimeric nonphosphorylated form and an inactive, monomeric phosphorylated form. The migration of BglG on native polyacrylamide gels was consistent with it existing as a dimer when nonphosphorylated and as a monomer when phosphorylated. Only the nonphosphorylated dimer was found to bind to the target RNA. When the dimerization domain of the lambda repressor was replaced with BglG, the resulting chimera behaved like an intact lambda repressor in its ability to repress lambda gene expression, which suggests that BglG dimerizes in vivo. Repression by the lambda-BglG hybrid was significantly reduced by BglF, the BglG kinase, an effect that was relieved by conditions that stimulate dephosphorylation of BglG by BglF. These results suggest that the phosphorylation and the dephosphorylation of BglG regulate its activity by controlling its dimeric state.

Bacterial Proteins↗

Dimerization of human growth hormone by zinc.

Size-exclusion chromatography and sedimentation equilbrium studies demonstrated that zinc ion (Zn2+) induced the dimerization of human growth hormone (hGH). Scatchard analysis of 65Zn2+ binding to hGH showed that two Zn2+ ions associate per dimer of hGH in a cooperative fashion. Cobalt (II) can substitute for Zn2+ in the hormone dimer and gives a visible spectrum characteristic of cobalt coordinated in a tetrahedral fashion by oxygen- and nitrogen-containing ligands. Replacement of potential Zn2+ ligands (His18, His21, and Glu174) in hGH with alanine weakened both Zn2+ binding and hGH dimer formation. The Zn(2+)-hGH dimer was more stable than monomeric hGH to denaturation in guanidine-HCl. Formation of a Zn(2+)-hGH dimeric complex may be important for storage of hGH in secretory granules.

Amino Acid Sequence↗

Repair of pyrimidine dimer damage induced in yeast by ultraviolet light.

Crude extracts from ultraviolet (UV)-irradiated yeast cells compete with UV-irradiated transforming deoxyribonucleic acid (DNA) for photoreactivating enzyme. The amount of competition is taken as a measure of the level of cyclobutyl pyrimidine dimers in the yeast DNA. A calibration of the competition using UV-irradiated calf thymus DNA indicates that an incident UV dose (1,500 ergs/mm(2)) yielding 1% survivors of wild-type cells produces between 2.5 x 10(4) to 5 x 10(4) dimers per cell. Wild-type cells irradiated in the exponential phase of growth remove or alter more than 90% of the dimers within 220 min after irradiation. Pyrimidine dimers induced in stationary-phase wild-type cells appear to remain in the DNA; however, with incubation, they become less photoreactivable in vivo, although remaining photoreactivable in vitro. In contrast, exponentially growing or stationary-phase UV-sensitive cells (rad2-17) show almost no detectable alteration of dimers. We conclude that the UV-sensitive cells lack an early step in the repair of UV-induced pyrimidine dimers.

Animals↗

Pyrimidine dimer excision in surviving and nonsurviving cells of ultraviolet-irradiated cultures of Escherichia coli.

We compared dimer excision in viable and nonviable cells fractions separated from Escherichia coli B/r cultures exposed to ultraviolet (UV) irradiation. For cells grown on minimal medium with glycerol as a carbon source, both fractions from the irradiated (20 J/m2, 5% survival) culture excised 60 to 70% of the thymine dimers from prelabeled DNA within 120 min. This percentage was, within experimental error, the same as that obtained from unseparated cultures. When isolated viable and nonviable populations were given a second UV exposure (20 J/m2) both types of cells were again able to excise dimers. The UV survival curve for the isolated viable population indicates that these cells are no more sensitive to radiation than exponentially growing cells not previously exposed to UV. The extent of dimer excision after UV irradiation was also the same in viable and nonviable cells separated from cultures grown on a glucose minimal medium in which both populations excised about 85% of the dimers within 120 min. These results show that the extent of removal of pyrimidine dimer from deoxyribonucleic acid is not precisely correlated with survival of repair-competent bacterial cells after exposure to UV light.

DNA Repair↗

Plasmid dependence of Pseudomonas sp. strain NK87 enzymes that degrade 6-aminohexanoate-cyclic dimer.

A bacterial strain, Pseudomonas sp. strain NK87, that can use 6-aminohexanoate-cyclic dimer as the sole source of carbon and nitrogen was newly isolated from wastewater of a factory which produces nylon-6. Two responsible enzymes, 6-aminohexanoate-cyclic-dimer hydrolase (P-EI) and 6-aminohexanoate-dimer hydrolase (P-EII), were found in the NK87 strain, as is the case with Flavobacterium sp. strain KI72, another 6-aminohexanoate-cyclic-dimer-metabolizing bacterium (H. Okada, S. Negoro, H. Kimura, and S. Nakamura, Nature [London] 306:203-206, 1983). The P-EI enzyme is immunologically identical to the 6-aminohexanoate-cyclic-dimer hydrolase of KI72 (F-EI). However, antiserum against the 6-aminohexanoate-dimer hydrolase purified from KI72 (F-EII) did not react with cell extracts of NK87, indicating that the F-EII and P-EII enzymes are immunologically different. Restriction endonuclease analyses show that the NK87 strain harbors at least six plasmids ranging in size from 20 to 80 kilobase pairs (kbp). The P-EI and P-EII genes were cloned in Escherichia coli. Both the P-EI and F-EI probes strongly hybridized with a 23-kbp plasmid in Southern hybridization analyses. The P-EII probe hybridized specifically with an 80-kbp plasmid, but the F-EII probe hybridized with none of the plasmids harbored in NK87. These results indicate that the P-EI gene and P-EII gene are encoded on the 23-kbp and 80-kbp plasmids, respectively.

Amidohydrolases↗

Structure and formation of circular dimers of simian virus 40 DNA.

Most of the viral DNA extracted from simian virus 40 (SV40)-infected African green monkey kidney cells consists of circular molecules about 5.3 kilobases in contour length. However, about 1% of the viral DNA was found to occur as closed circular dimers that appeared to be formed, preferentially, late in infection. The monomeric units of dimers were organized in a head-to-tail, tandem arrangement; moreover, the monomeric units were not defective; i.e., they lacked deletions or other rearrangements. After infections with dimer DNA, nondefective monomers were formed. These findings suggest that dimers are not intermediates in the production of defective SV40 genomes. The majority of the dimers formed in mixed infections with two mutants were homodimers, but about 5% of the circular dimers were heterodimers and must have arisen by intermolecular recombination.

Cell Line↗

High-molecular-weight RNAs of AKR, NZB, and wild mouse viruses and avian reticuloendotheliosis virus all have similar dimer structures.

Several 50 to 70S tumor viral RNAs have previously been shown by electron microscopy to be dimers, with the two monomer subunits joined near their 5' ends. Five additional naturally occurring type C RNA tumor viruses have now been examined: AKR, and endogenous murine ecotropic virus; NZB, an endogenous murine xenotropic virus; and ecotropic and an amphotropic virus isolated from a wild mouse; and the avian reticuloendotheliosis virus (REV). All five 50 to 70S RNAs have similar 5'-to-5' dimer structures. Therefore, the observations support the hypothesis that the dimer linkage is a structural feature common to all type C mammalian viruses. REV is the first example of an avian virus with a clear 5'-to 5' dimer linkage. All of the mammalian viral RNAs, but not REV, showed symmetrically placed loops in each subunit of the dimer. Possible molecular structures and biological functions of the dimer linkages and loops are discussed.

AKR murine leukemia virus↗

Human immunodeficiency virus type 1 and type 2 protease monomers are functionally interchangeable in the dimeric enzymes.

Human immunodeficiency virus type 1 (HIV-1) and HIV-2 proteases are dimers of identical subunits. We made a construct for the expression of recombinant one-chain HIV-2 protease dimer, which, like the previously described one-chain HIV-1 protease dimer, is fully active. The constructs for the one-chain dimers of HIV-1 and HIV-2 proteases were modified to produce hybrid one-chain dimers consisting of both HIV-1 and HIV-2 protease monomers. Although the monomers share only 47.5% sequence identity, the hybrid one-chain dimers are fully active, suggesting that the folding of both HIV-1 and HIV-2 protease monomers is functionally similar.

Base Sequence↗

Evaluation of the Simplify D-dimer assay as a screening test for the diagnosis of deep vein thrombosis in an emergency department.

OBJECTIVES: To evaluate the use in an emergency department of a new D-dimer assay (Simplify D-dimer) as a screening test for deep vein thrombosis (DVT). METHODS: 187 outpatients with clinical features suspicious of acute DVT were entered into this study. A Simplify D-dimer test was performed in the emergency department on all patients. A SimpliRED D-dimer test and a semi-automated latex agglutination assay (Auto-D-dimer 700 on a Thromboscreen 400C analyser) were performed in the haematology laboratory. All patients were investigated with contrast venography to confirm or exclude the diagnosis of DVT. RESULTS: The Simplify test had a sensitivity of 94.1% and a negative predictive value (NPV) of 94.8%. These results compared favourably with the SimpliRED test (sensitivity 74.5%, NPV 89.7%) and the latex agglutination assay (sensitivity 90.2%, NPV 92.2%). This increased sensitivity was at the cost of a lower specificity, the specificity of the three d-dimer tests being Simplify 40.4%, SimpliRED 83.1%, and latex agglutination 43.4%. CONCLUSIONS: Simplify proved to be a rapid and easy to use test and may be useful for use in the emergency department as part of a diagnostic algorithm for deep vein thrombosis. Further larger scale studies are needed.

Acute Disease↗

Second trimester screening for Down's syndrome using maternal serum dimeric inhibin A.

OBJECTIVES: To determine the second trimester Down's syndrome screening performance of maternal serum dimeric inhibin A, both alone and in combination with existing serum markers. SETTING: A case-control set of serum samples from patients with Down's syndrome (52) and subjects with matched unaffected pregnancies obtained in a previous cohort study before second trimester amniocentesis and karyotyping. The amniocenteses were performed for reasons other than a positive serum screening test result. METHODS: For each serum from a Down's syndrome pregnancy, five serum samples from pregnancies with a normal karyotype were matched for recruitment centre, gestational age, maternal age, and date of amniocentesis. A specific form of inhibin (dimeric inhibin A) was measured using monoclonal antibodies. Measurements of alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin and its free beta subunit were already available. Screening performance was modelled using distribution variables of the analytes coupled with the 1993 age distribution of pregnant women in the United States. RESULTS: The median dimeric inhibin A level was 2.10 times higher in Down's syndrome pregnancies. When dimeric inhibin A was combined with maternal age and three other serum markers (alpha fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin) the Down's syndrome detection rate increased to 75% (from 66%) at a 5% false positive rate. If dimeric inhibin A could be added for less than $31 (ranging from $16 to $39 depending on the detection rate, markers chosen, and method of dating), the cost of detecting each Down's syndrome pregnancy and the number of procedure related fetal losses would both be reduced. CONCLUSIONS: The addition of dimeric inhibin A to prenatal screening programmes for Down's syndrome should be considered, or possibly it could be substituted for an existing serum marker. One barrier to implementation in the United States, however, is the unavailability of kits with Food and Drug Administration approval.

Case-Control Studies↗

[Diagnostic utility of D-dimer measurement in patients with clinical suspect of pulmonary thromboembolism in the setting of an Internal Medicine Department].

BACKGROUND: The diagnosis of pulmonary thromboembolism (PTE) may be a challenge in many cases, particularly among the elderly patients. OBJECTIVE: To establish the diagnostic utility of D-dimer measurement by a rapid semi-quantitative immunoassay (NycoCard, D-Dimer, normal value < or =0.3 mg/l) in a series of patients with suspected PTE admitted to an Internal Medicine Department. METHODS: Retrospective review of 48 patients admitted to our Department with the clinical suspect of PTE and D-dimer assay, in whom a lung ventilation/perfusion scan was conclusive (high or normal/very low/low probability of PTE). RESULTS: The median age of patients was 67.4 years and 79.2% were older than 60 years. For the diagnosis of PTE, the values of sensitivity, specificity, positive predictive value, and negative predictive value were 95.2%, 55.5%, 62.5% and 93.7%, respectively. When patients with potential confounding factors in the measurement of D-dimer (surgery and/or trauma in the 2 previous weeks, or neoplasm) were excluded, similar results were obtained. CONCLUSIONS: When a normal D-dimer (< or =0.3 mg/l) measurement by a rapid semi-quantitative immunoassay (NycoCard) is obtained, the presence of PTE is very unlikely. An increased D-dimer should lead to additional complementary tests to confirm or rule out PTE. These results apply for patients aged over 60 years and are not influenced by potential confounding factors.

Aged↗

A model for the harmonisation of test results of different quantitative D-dimer methods.

The numerical test results of different D-dimer assays vary widely. Because of the complexity of the analyte of target as well as the variability in specificity of different D-dimer assays, only harmonisation of the test results seems to be feasible. The use of a single conversion factor does not take into account for several methods the lack of commutability between test results and consensus values at different D-dimer levels. This is probably related to the mutually different response of methods to high and low levels. We therefore designed a harmonisation model based on the transformation of a method-specific regression line to a reference regression line. We used the data for the measurement of a set of plasma samples with different D-dimer levels by 353 different laboratories using 7 of the most frequently used quantitative D-dimer methods. For each method we calculated the method-specific consensus value for each sample. The overall median value was also estimated. Per method linear regression was applied throughout the method-specific consensus values using the amount of patient pooled plasma added to the different plasma samples as the independent variable. The line through the overall median values of all 7 methods was used as the reference line. Harmonisation between the methods was obtained by transformation of the method-specific regression line to the reference line. This harmonisation resulted in a reduction of the variability between the method-specific consensus values from about 75% to about 5.5%. Clinical validation of this concept had shown significant improvement of the test result comparability. We conclude that this model is a feasible approach in the harmonisation of D-dimer methods. If the harmonisation procedure is included in the calibration procedure by the manufacturers, customers will automatically obtain harmonised test results.

Biomarkers↗

C-reactive protein, fibrin D-dimer, and risk of ischemic heart disease: the Caerphilly and Speedwell studies.

BACKGROUND: There is increasing interest in the predictive value of C-reactive protein (CRP) and fibrin D-dimer in the prediction of ischemic heart disease (IHD). We assessed their joint and independent associations with IHD in a large combined analysis of 2 population cohorts. METHODS AND RESULTS: Men aged 49 to 66 years from the general populations of Caerphilly and Speedwell were studied between 1982 and 1988 and re-examined for new IHD events at fixed intervals of approximately 105 months (Caerphilly) and 75 months (Speedwell). 3213 men had CRP and D-dimer measured at baseline and 351 (11%) had a new IHD event. Mean levels of CRP and D-dimer were significantly higher among men in whom IHD developed. The relative odds of IHD in men in the top 20% of the distribution of CRP was 2.97 (95% CI, 2.04, 4.32) and for D-dimer was 2.40 (95% CI, 1.69, 3.40); CRP and D-dimer had additive effects on risk of IHD. Multivariate analysis reduced the size of the relative odds, which remained significant for D-dimer. CONCLUSIONS: Both inflammatory and thrombogenic markers are important (and potentially additive) predictors of coronary risk.

Aged↗

D-dimer predicts early clinical progression in ischemic stroke: confirmation using routine clinical assays.

BACKGROUND AND PURPOSE: Plasma d-dimer levels, measured using a research laboratory assay, independently predict progressing ischemic stroke. We wished to confirm these findings using commercially available assays and to provide data to allow the design of intervention studies. METHODS: We studied 219 consecutive acute ischemic stroke admissions of whom 54 (25%) met criteria for progressing stroke. RESULTS: There were strong correlations between d-dimer results as measured by the Biopool AB, MDA and VIDAS assays; correlation coefficients r=0.91 to 0.94; all P<0.001. In binary logistic regression analyses, d-dimer, as measured by the 3 different assays, was an independent predictor of progressing stroke (odds ratios, 1.87 to 2.45; all P<0.001). This confirms the results of our original analysis (Biopool AB) using 2 commercial d-dimer assays, demonstrating the potential usefulness of d-dimer in providing early prognostic information after ischemic stroke in different clinical settings. We also provide information on the performance of the 3 assays in predicting progressing stroke at a variety of cutoff values. CONCLUSIONS: Ischemic stroke patients at high risk of early progression can be identified using commercial d-dimer measurements. This could allow selection of high-risk patients for inclusion in randomized trials of early antithrombotic treatments.

Brain Ischemia↗

Ruling out acute deep vein thrombosis by ELISA plasma D-dimer assay versus ultrasound in inpatients more than 70 years old.

In geriatric care, deep-vein thrombosis (DVT) is mostly diagnosed by noninvasive techniques. The objectives of this prospective study were: (1) to evaluate the power of ELISA plasma D-dimer assay versus ultrasound (US) in ruling out acute DVT of the lower limbs in symptomatic geriatric inpatients, and (2) to determine the most effective D-dimer cutoff value over the age of 70 years. Over a 10-month period, inpatients with suspected lower limb DVT simultaneously underwent US examination and ELISA plasma D-dimer assay. Noninclusion criteria were comorbid conditions able to modify the D-dimer level. Data were processed by receiver operating characteristic (ROC) curve analysis. In total, 150 patients (125 women, 25 men), average age 86.3 years (range 70-101) were included. A diagnosis of lower limb DVT was established in 53 patients (35.3%). With a 500 ng/mL D-dimer cutoff conventional value, DVT was ruled out in only five patients (3.3%), whereas a 750 ng/mL value ruled out DVT in 19 patients (12.7%) with a sensitivity of 98.1%, and a negative predictive value of 95.0%. The only false negative corresponded to a patient with a 15-mm thrombus in the distal calf. In inpatients above 70, an ELISA plasma D-dimer value smaller than 750 ng/mL is a rapid reliable noninvasive means to rule out lower limb DVT, if color flow Doppler ultrasound is not available on site.

Aged↗

A highly sensitive ELISA D-dimer increases testing but not diagnosis of pulmonary embolism.

OBJECTIVES: To determine the effect of introducing a rapid enzyme-linked immunosorbent assay (ELISA) D-dimer on the percentage of emergency department (ED) patients evaluated for pulmonary embolism (PE), the use of associated laboratory testing, pulmonary vascular imaging, and the diagnoses of PE. METHODS: Patients evaluated for PE during three 120-day periods were enrolled: immediately before (period 1), immediately after (period 2), and one year after the introduction of a rapid ELISA D-dimer in the hospital. The frequency of ED patients evaluated for PE with any test, with D-dimer testing, and with pulmonary vascular imaging and the frequency of PE diagnosis during each time period were determined. RESULTS: The percentage of patients evaluated for PE nearly doubled; from 1.36% (328/24,101) in period 1 to 2.58% (654/25,318) in period 2 and 2.42% (583/24,093) in period 3. The percentage of patients who underwent D-dimer testing increased more than fourfold; from 0.39% (93/24,101) in period 1 to 1.83% (464/25,318) in period 2 and 1.77% (427/24,093) in period 3. The percentage of patients who underwent pulmonary vascular imaging increased from 1.02% (247/24,101) in period 1 to 1.36% (344/25,318) in period 2 and to 1.39% (334/24,093) in period 3. There was no difference in the percentage of patients diagnosed as having PE in period 1 (0.20% [47/24,101]), period 2 (0.27% [69/25,318]), and period 3 (0.24% [58/24,093]). CONCLUSIONS: In the study's academic ED, introduction of ELISA D-dimer testing was accompanied by an increase in PE evaluations, D-dimer testing, and pulmonary vascular imaging; there was no observed change in the rate of PE diagnosis.

Emergency Service, Hospital↗

The metabolic clearance, distribution, and degradation of dimeric and monomeric growth hormone (GH): implications for the pattern of circulating GH forms.

The ratio of oligomeric (big) to monomeric (little) human (h)GH forms in plasma exceeds that in the pituitary gland severalfold. To investigate whether delayed metabolic clearance of oligomers could explain this discrepancy, we measured MCR, distribution volumes, and degradation rates of radio-labeled hGH22K dimer, hGH20K dimer, hGH22K monomer, and hGH20K monomer in the rat. Hormones were injected as a bolus, and disappearance from plasma was followed by immunoprecipitation and trichloroacetic acid precipitation. MCRs of the dimers were significantly lower than those of the corresponding monomers (5-fold in the case of hGH22K, and 2-fold in the case of hGH20K). Both dimers were also degraded at slower rates than the monomers. Distribution volumes for the dimers, although somewhat smaller, were not statistically different from those for the monomers and were consistent with distribution in the extracellular space. We conclude that hGH dimers are relatively protected from degradation and hence cleared more slowly from the blood than hGH monomers. This may lead to their accumulation in the circulation relative to their monomeric counterparts, which may explain their high proportion in plasma as compared to pituitary.

Animals↗