Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “TROPOLONES”

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 649 records · Page 36Linked to original sources
PubMed1989

Value of blood-pool subtraction in cardiac indium-111-labeled platelet imaging.

Blood-pool subtraction has been proposed to enhance 111In-labeled platelet imaging of intracardiac thrombi. We tested the accuracy of labeled platelet imaging, with and without blood-pool subtraction, in ten subjects with cardiac thrombi of varying age, eight with endocarditis being treated with antimicrobial therapy and ten normal controls. Imaging was performed early after labeled platelet injection (24 hr or less) and late (48 hr or more). Blood-pool subtraction was carried out. All images were graded subjectively by four experienced, "blinded" readers. Detection accuracy was measured by the sensitivity at three fixed levels of specificity estimated from receiver operator characteristic curve analysis and tested by three-way analysis of variance. Detection accuracy was generally improved on delayed images. Blood-pool subtraction did not improve accuracy. Although blood-pool subtraction increased detection sensitivity, this was offset by decreased specificity. For this population studied, blood-pool subtraction did not improve subjective detection of abnormal platelet deposition by 111In platelet imaging.

Adult↗
PubMed1989

Cytoplasmic microtubules in human neutrophil degranulation: reversible inhibition by the colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1- one.

The colchicine analogue 2-methoxy-5-(2',3',4'-trimethoxyphenyl)-2,4,6-cycloheptatrien-1-on e (MTC) was found to inhibit concanavalin A- and formyl-methionyl-leucyl-phenylalanine-stimulated human neutrophil degranulation and to depolymerize the microtubule network at low concentrations. The inhibitory capacity of MTC for neutrophil degranulation was similar to that of nocodazole and taxol. The mechanistically distinct actions of these three drugs on microtubules support the notion that microtubules are required for neutrophil enzyme release in response to different stimuli. MTC affected both degranulation and microtubule integrity rapidly and reversibly, after only a 5-min preincubation. At these short periods of incubation, colchicine irreversibly affected neutrophil degranulation only at concentrations in the millimolar range and behaved similarly to its microtubule-inactive analogue lumicolchicine. At longer times of incubation (30-60 min), low concentrations of both MTC and colchicine induced a drastic shortening and depolymerization of microtubules, preserving the microtubule-organizing center, but only MTC was able to completely inhibit the secretory response of neutrophils. These results suggest that the colchicine effect on neutrophil degranulation is not specifically mediated by its action on the microtubule network of these cells. In contrast, the specific and reversible effects of the colchicine analogue MTC suggest that it may be a useful agent with which to study the role of microtubules in this cellular function.

Cell Degranulation↗
PubMed1988

Comparison of purified indium-111 granulocytes and indium-111 mixed leukocytes for imaging of infections.

Several methods have been proposed for the separation and labeling of white blood cells for the diagnosis of suspected infection. We retrospectively compared 105 patients imaged with 111In purified granulocytes (GRAN) to 106 patients imaged with 111In mixed leukocytes (MIX). We found that in acute infection the sensitivity of GRAN and MIX were both high and not statistically different. In chronic infections the sensitivities were lower than for acute infections. Again, there was no significant difference between GRAN and MIX with the borderline significant exception of MIX being superior to GRAN in chronic soft tissue infections (p = 0.06). We then had independent observers blindly grade the degree of lesion visualization. We found that delayed images visualized the lesions better than early images (p = 0.0001) and acute infection was better visualized than chronic infection (p = 0.03). We concluded that, in routine clinical practice, MIX is probably the agent of choice for three reasons: (a) easier preparation, (b) comparable sensitivity in acute infection and, (c) borderline superior sensitivity in chronic infection.

Acute Disease↗
PubMed1987

A fluorescence stopped flow study of the competition and displacement kinetics of podophyllotoxin and the colchicine analog 2-methoxy-5-(2',3',4'-trimethoxyphenyl) tropone on tubulin.

The colchicine analog 2-methoxy-5-(2',3',4'-trimethoxyphenol) tropone (AC) was used as a fluorescent probe to study the binding kinetics of podophyllotoxin at high concentrations. The observed pseudo-first order rate constant showed a linear concentration dependence up to 1 mM. The bimolecular rate constant (195 M-1 s-1 at 15 degrees C) and the activation energy (57 kJ/mol) correspond perfectly with those previously determined in the submicromolar range (Cortese, F., Bhattacharyya, B., and Wolf, J. (1977) J. Biol. Chem. 252, 1134-1140). Displacement kinetics of bound AC by podophyllotoxin, allow the determination of the dissociation rate constants for AC. By studying the temperature dependence, and combining with the binding rate constants previously determined (Engelborghs, Y., and Fitzgerald, T.J. (1986) Ann. N.Y. Acad. Sci. 466, 709-717) a full characterization of the kinetic pathway is possible. This is shown to differ considerably from the pathway of colchicine binding.

Animals↗
PubMed1984

Binding to tubulin of the colchicine analog 2-methoxy-5-(2', 3', 4'-trimethoxyphenyl)tropone. Thermodynamic and kinetic aspects.

The thermodynamics and kinetics of the binding to tubulin of the colchicine analog 2-methoxy-5-(2', 3', 4'-trimethoxyphenyl) tropone (termed AC because it lacks the B-ring of colchicine) have been characterized by fluorescence techniques. The fluorescence of AC is weak in aqueous solution and is enhanced 250-fold upon binding to tubulin. The following thermodynamic values were obtained for the interaction at 37 degrees C: K = 3.5 X 10(5) M-1; delta G0 = -7.9 kcal/mol; delta H0 = -6.8 kcal/mol; delta S0 = 3.6 entropy units. The AC-tubulin complex is 1-2 kcal/mol less stable than the colchicine-tubulin complex. The change in fluorescence of AC was employed to measure the kinetics of the association process, and quenching of protein fluorescence was used to measure both association and dissociation. The association process, like that of colchicine, could be resolved into a major fast phase and a minor slow phase. The apparent second order rate constant for the fast phase was found to be 5.2 X 10(4) M-1 S-1 at 37 degrees C, and the activation energy was 13 kcal/mol. This activation energy is 7-11 kcal/mol less than that for the binding of colchicine to tubulin. The difference in activation energies can most easily be rationalized by a mechanism involving a tubulin-induced conformational change in the ligand ( Detrich , H. W., III, Williams, R. C., Jr., Macdonald, T. L., Wilson, L., and Puett , D. (1981) Biochemistry 20, 5999-6005). Such a change would be expected to have a small activation energy in AC because it possesses a freely rotating single bond in place of the B-ring of colchicine.

Animals↗
PubMed1981

Role of B-ring of colchicine in its binding to tubulin.

The chemical specificity of the colchicine-binding site of tubulin is less stringent for the presence of the B-ring than the A- and C-rings of colchicine, Colchicine analogues with modifications in the B-ring bind to tubulin at the same site as colchicine. Analogues with smaller or no substituents in the B-ring bind tubulin remarkably faster than colchicine. Thus, a compound without the B-ring [2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone] binds tubulin even at 4 degrees C and the binding is almost instantaneous at 37 degrees C. Colcemid and 2-methoxy-5-(2',3',4'-trimethoxyphenyl)tropone bind reversibly to tubulin, whereas colchicine and desacetamidocolchicine bind almost irreversibly, suggesting that the size of the B-ring moiety of colchicine is not related to the reversibility of binding. We conclude that although the presence of the B-ring of colchicine does not appear to be an essential prerequisite for the drug-tubulin interaction, the B-ring substituents play an important role in determining the binding properties of colchicine to tubulin.

Animals↗
PubMed1995

Mushroom tyrosinase has an ascorbate oxidase activity.

The reaction between mushroom tyrosinase and L-ascorbic acid was studied by oxymetric assays and evidence pointing to ascorbate oxidase activity of this enzyme has been obtained. The activity is clearly linear to enzyme concentration and the Michaelis constant for L-ascorbic acid has a value of 2.69 +/- 0.11 mM. Maximum activity is obtained at pH 7.5. A possible reaction mechanism, which is based on the different enzymatic forms of tyrosinase, is also presented.

Ascorbate Oxidase↗
PubMed1994

Indium-111-labeled leukocytes for the detection of infection: current status.

Several chelates are available for leukocyte labeling. Studies indicate that cells labeled with any of the chelates have a sensitivity for infection of 90% to 95% when imaged at 24 hours postinjection. The sensitivity of 111In-labeled leukocytes at earlier imaging times is more controversial. There has been concern about the utility of labeled leukocytes in musculoskeletal infection. Recent leukocyte studies show a high sensitivity for infected prostheses, even though these infections are often walled off and do not cause systemic symptoms. However, leukocytes frequently miss osteomyelitis of the spine for reasons that are not known. Although some investigators do not recommend the use of 111In-labeled leukocytes in chronic infections, we have found a high sensitivity for infections that are 2 or more weeks old. Autopsy studies from the preantibiotic era indicate that bacterial infections with common organisms have high levels of neutrophil infiltration for months. Labeled lymphocytes from mixed-cell preparations also may play a role in detecting these inflammatory sites. Questions have been raised about the effect of antibiotic therapy on leukocyte sensitivity. Antibiotics do not appear to have a significant effect on scan sensitivity. By reducing the number of bacteria at an inflammatory site, antibiotics reduce the amount of chemotactic inhibitors. In addition, some antibiotics have been shown to directly stimulate leukocyte chemotaxis. Other factors that can theoretically reduce leukocyte function, including hemodialysis, hyperalimentation, hyperglycemia, and steroids, do not appear to reduce labeled leukocyte sensitivity for infection. The specificity of leukocyte uptake is reduced in the gastrointestinal tract and lungs. In these sites, uptake correlates with infection or the true cause of the patients' fever in only 10% to 50% of cases.

Chronic Disease↗