Hostility, cultural orientation, and casual blood pressure readings in African Americans.

Evidence suggests that hostility correlates with blood pressure levels in African-American samples. However, some studies have reported an inverse relationship, while others have found the relationship between blood pressure and hostility to be positive. Other literature suggests health outcomes in general, and blood pressure in particular, are related to cultural orientation in African-American samples. In the present study, six casual measures of blood pressure and heart rate in a sample of 90 African-American college students were aggregated and correlated with measures of hostility and cultural orientation. Correlational and regression analyses revealed a weak positive relationship between hostility and systolic blood pressure. The relationships between the cardiovascular measures and cultural orientation were more consistent. The tendency to embrace mainstream Euro-American values, such as materialism, individuality, and competitiveness, was associated with more rapid heart rate and higher diastolic blood pressure levels for both men and women. The relationship between systolic blood pressure and cultural orientation emerged for men only. The findings encourage further research into the relationship between personality variables and cardiovascular activity in African-American samples.

New magnetic resonance imaging techniques for the detection of breast cancer.

The importance of contrast agents in enhancing diagnoses from magnetic resonance images has been established in numerous cases. However, the development of a potent tissue-specific contrast agent, as a sensitive probe for early detection and investigation of the physiological characteristics of a tumor, has not yet been realized in MR imaging (MRI). In nuclear scintigraphy the technique has been demonstrated; however, the poor spacial resolution inherent to the modality and the substantial dose of radioactivity administered to the patient has hindered its widespread use. This article will review the different classes of contrast agents in MRI, with special focus on the strategies involved in the development of targeted tissue-specific MRI contrast agents for the early detection of breast cancer. The features of a new class of contrast agents for targeted MR imaging will be described. Gadolinium-containing melanin polymers (GMP's) have been synthesized as MR contrast agents in our laboratory. These GMP's demonstrate significantly higher relaxivities than any other paramagnetic contrast agents reported; consequently, they are extremely effective contrast enhancing, imaging agents by themselves. The successful coupling of these potent GMP's to a monoclonal antibody specific for breast carcinoma, the 323/A3 monoclonal antibody, suggests that in vivo tissue-specific MR imaging, at the receptor level, will become feasible in the near future.

Method to improve the accuracy of membrane osmometry measures of protein molecular weight.

Membrane osmometry provides a simple method to determine protein molecular weight but accuracy is limited by nonideal behavior. Recent studies (Fullerton et al., Biochem. Cell Biol., in press) show that non-ideal osmotic response of protein solutions is described by the empirical equation, Msv/M(s) = RT rho/A(s) x 1/II+I, where M(s) = mass of solute, Msv = mass of solvent, R = the Universal gas constant, T = absolute temperature, rho = solvent density, A(s) = solute molecular mass, II = osmotic pressure, and I = the nonideality parameter. This linear relation is used in this paper to demonstrate that measurement of molecular weight from the slope simplifies such measures and improves the accuracy relative to classical methods. The molecular weight of bovine serum albumin is measured with error less than 0.9%. The single dimensionless non-ideality parameter, I = 4.05 + 0.07, describes non-ideal curvature in the typical IIV = nRT diagram better than the customary second power viral expansion requiring 3 fitting constants. Analysis of eight data sets on four proteins from the literature shows that molecular weight calculated from the slope of the new equation agrees with chemical molecular weight within an RMS error of only 1.9%.

Photoaffinity labeling of tubulin with (2-nitro-4-azidophenyl)deacetylcolchicine: direct evidence for two colchicine binding sites.

A new photoaffinity analogue of colchicine, (2-nitro-4-azidophenyl)deacetylcolchicine (NAPDAC), bound to two classes of sites on bovine renal tubulin and photolabeled both the alpha- and beta-subunits. The apparent Ki for the photoaffinity analogue was 1.40 +/- 0.17 microM (mean +/- SD, n = 3) as measured by competition with [3H] colchicine. Values of the apparent KdS for the two sites, as measured by the direct binding of the [3H]NAPDAC to tubulin, were 0.48 +/- 0.11 microM and 11.6 +/- 3.5 microM (mean +/- SD, n = 6), and the corresponding stoichiometries of binding of the two sites were 0.25 +/- 0.06 and 1.3 +/- 0.4 mol/mol of tubulin (mean +/- SD, n = 6). NAPDAC was a potent inhibitor of microtubule formation as detected by electron microscopy. When tubulin was photolabeled with NAPDAC at 25 degrees C, 15 +/- 3 mol % (mean +/- SD, n = 6) of the [3H]NAPDAC was covalently bound to the alpha-subunit, and 67 +/- 9 mol % (mean +/- SD, n = 6) was covalently bound to the beta-subunit. Since NAPDAC is a mixture of two interconvertible diastereomers, the photoincorporation of each was also examined. One diastereomer photolabeled both alpha- and beta-tubulin; however, the other did not significantly photolabel either subunit. Tubulin photolabeled with NAPDAC (1:1 mole ratio) exhibited a 23% decrease in colchicine binding. Preblocking and prephotolysis experiments with colchicine, NAPDAC, or ANPAH-CLC [Williams et al. (1985) J. Biol. Chem. 260, 13794-13802] provided evidence for conformational changes in tubulin upon colchicine binding. Peptide maps of [3H]NAPDAC-labeled alpha- and beta-tubulin, using Staphylococcus aureus V8 protease, demonstrated the presence of NAPDAC in one peptide of the alpha-subunit and in five peptides of the beta-subunit as detected by autoradiography. NAPDAC provides the first direct evidence for two colchicine binding sites on tubulin.

A photoaffinity derivative of colchicine: 6'-(4'-azido-2'-nitrophenylamino)hexanoyldeacetylcolchicine. Photolabeling and location of the colchicine-binding site on the alpha-subunit of tubulin.

A photoaffinity analog of colchicine, 6-(4'-azido-2'-nitrophenylamino)hexanoyldeacetylcolchicine, was synthesized by reacting deacetylcolchicine or [3H]deacetylcochicine with N-succinimidyl-6-(4'-azido-2'-nitrophenylamino)hexanoate. Homogeneity of the photoaffinity analog was established by thin-layer chromatography and high-pressure liquid chromatography. The structure of the photoaffinity analog was determined by 1H and 13C NMR, infrared and ultraviolet-visible spectroscopies, and elemental analysis. Binding of 6-(4'-azido-2'-nitrophenylamino)hexanoyldeacetylcolchicine to bovine renal tubulin was measured by competition with [3H]colchicine. The value of the apparent Ki for the photoaffinity analog was 0.28 microM in the concentration range of 0.8-1.2 microM of the analog. A value of 0.50 microM for the apparent Kd was measured by the direct binding of the tritiated photoaffinity analog to tubulin. The analog is slightly more potent an inhibitor of microtubule formation than colchicine. The photoaffinity analog reacted with renal tubulin upon irradiation with a mercury lamp equipped with a 420-nm cutoff filter. Spectral and radiochemical analyses of the tubulin after photolysis and dialysis have demonstrated a stoichiometric incorporation of the photoaffinity analog in the alpha-subunit of the tubulin. Covalent labeling of tubulin with the photoaffinity analog decreases the extent of [3H]colchicine binding by more than 90%.