[Large cell lymphoepithelioma-like carcinoma of the lung]. / Carcinoma anaplásico tipo linfoepitelioma de pulmón.

Lymphoepithelioma-like carcinoma of the lung is a rare tumor that is considered a subtype of undifferentiated large cell carcinoma with abundant invasion by lymphocytes. Although initially described as a tumor occurring in the nasopharynx, this type of carcinoma has since been seen in many other organs. We report the case of a 59-year-old male smoker diagnosed with lymphoepithelioma-like carcinoma.

Beyond prejudice as simple antipathy: hostile and benevolent sexism across cultures.

The authors argue that complementary hostile and benevolent components of sexism exist across cultures. Male dominance creates hostile sexism (HS), but men's dependence on women fosters benevolent sexism (BS)--subjectively positive attitudes that put women on a pedestal but reinforce their subordination. Research with 15,000 men and women in 19 nations showed that (a) HS and BS are coherent constructs that correlate positively across nations, but (b) HS predicts the ascription of negative and BS the ascription of positive traits to women, (c) relative to men, women are more likely to reject HS than BS, especially when overall levels of sexism in a culture are high, and (d) national averages on BS and HS predict gender inequality across nations. These results challenge prevailing notions of prejudice as an antipathy in that BS (an affectionate, patronizing ideology) reflects inequality and is a cross-culturally pervasive complement to HS.

Do sequence repeats play an equivalent role in the choline-binding module of pneumococcal LytA amidase?

LytA amidase breaks down the N-acetylmuramoyl-l-alanine bonds in the peptidoglycan backbone of Streptococcus pneumoniae. Its polypeptide chain has two modules: the NH(2)-terminal module, responsible for the catalytic activity, and the COOH-terminal module, constructed by six tandem repeats of 20 or 21 amino acids (p1-p6) and a short COOH-terminal tail. The polypeptide chain must contain at least four repeats to efficiently anchor the autolysin to the choline residues of the cell wall. Nevertheless, the catalytic efficiency decreases by 90% upon deletion of the final tail. The structural implications of deleting step by step the two last (p5 and p6) repeats and the final COOH-tail and their effects on choline-amidase interactions have been examined by comparing four truncated mutants with LytA amidase by means of different techniques. Removal of this region has minor effects on secondary structure content but significantly affects the stability of native conformations. The last 11 amino acids and the p5 repeat stabilize the COOH-terminal module; each increases the module transition temperature by about 6 degrees C. Moreover, the p5 motif also seems to participate, in a choline-dependent way, in the stabilization of the NH(2)-terminal module. The effects of choline binding on the thermal stability profile of the mutant lacking the p5 repeat might reflect a cooperative pathway providing molecular communication between the choline-binding module and the NH(2)-terminal region. The three sequence motives favor the choline-amidase interaction, but the tail is an essential factor in the monomer <--> dimer self-association equilibrium of LytA and its regulation by choline. The final tail is required for preferential interaction of choline with LytA dimers and for the existence of different sets of choline-binding sites. The p6 repeat scarcely affects the amidase stability but could provide the proper three-dimensional orientation of the final tail.

Conformational features and thermal stability of bovine seminal plasma protein PDC-109 oligomers and phosphorylcholine-bound complexes.

At ejaculation, PDC-109, the major heparin-binding protein of bull seminal plasma, binds to the phosphorylcholine group of sperm lipids and modulates capacitation promoted by glycosaminoglycans during sperm residence in the female genital tract. Combination of size-exclusion chromatography, analytical ultracentrifugation, circular dichroism, Fourier-transform infrared spectroscopy, and differential scanning calorimetry has allowed us to biophysically characterize PDC-109 and its interaction with phosphorylcholine. PDC-109 can be regarded as a polydisperse molecule whose aggregation state can be modulated by the solute composition of its solution environment. Dissociation of PDC-109 oligomers occurs upon increasing the concentration of either NaCl, EDTA, CaCl2, or phosphorylcholine, suggesting that both ionic and hydrophobic interactions are responsible for the aggregation tendency of PDC-109 monomers. Dissociation processes are accompanied by exposure of peptide bonds to the solvent, changes in the environment of tyrosine and tryptophan residues, and a slight increase in the turn content at the expense of non-regular structure. Analysis of the heat-induced denaturation of PDC-109 oligomers revealed two melting transitions at about 36 degrees C (irreversible) and 55 degrees C (partially reversible) characterized by calorimetric enthalpy changes of 42 kJ/mol and 217 kJ/mol, respectively. These transitions could be assigned to the dissociation of oligomers and to the cooperative unfolding of PDC-109 monomers, respectively. The modulation of the aggregation state of PDC-109 by its molecular environment and by phosphorylcholine binding suggests possible mechanisms for capacitation mediated by the seminal plasma protein.

Structural organization of the major autolysin from Streptococcus pneumoniae.

LytA amidase is the best known bacterial autolysin. It breaks down the N-acetylmuramoyl-L-alanine bonds in the peptidoglycan backbone of Streptococcus pneumoniae and requires the presence of choline residues in the cell-wall teichoic acids for activity. Genetic experiments have supported the hypothesis that its 36-kDa chain has evolved by the fusion of two independent modules: the NH2-terminal module, responsible for the catalytic activity, and the COOH-terminal module, involved in the attachment to the cell wall. The structural organization of LytA amidase and of its isolated COOH-terminal module (C-LytA) and the variations induced by choline binding have been examined by differential scanning calorimetry and analytical ultracentrifugation. Deconvolution of calorimetric curves have revealed a folding of the polypeptide chain in several independent or quasi-independent cooperative domains. Elementary transitions in C-LytA are close but not identical to those assigned to the COOH-terminal module in the complete amidase, particularly in the absence of choline. These results indicate that the NH2-terminal region of the protein is important for attaining the native tertiary fold of the COOH terminus. Analytical ultracentrifugation studies have shown that LytA exhibits a monomer <--> dimer association equilibrium, through the COOH-terminal part of the molecule. Dimerization is regulated by choline interaction and involves the preferential binding of two molecules of choline per dimer. Sedimentation velocity experiments give frictional ratios of 1.1 for C-LytA monomer and 1.4 for C-LytA and LytA dimers; values that deviated from that of globular rigid particles. When considered together, present results give evidence that LytA amidase might be described as an elongated molecule consisting of at least four domains per subunit (two per module) designated here in as N1, N2, C1, and C2. Intersubunit cooperative interactions through the C2 domain in LytA dimer occur under all experimental conditions, while C-LytA requires the saturation of low affinity choline binding sites. The relevance of the structural features deduced here for LytA amidase is examined in connection with its biological function.

Molecular characterization of the human platelet integrin GPIIb/IIIa and its constituent glycoproteins.

Human platelet plasma membrane glycoproteins IIb (GPIIb) and IIIa (GPIIIa) form a Ca(2+)-dependent heterodimer, the integrin GPIIb/IIIa, which serves as the receptor for fibrinogen and other adhesive proteins at the surface of activated platelets. Below the critical micellar concentration of Triton X100 (TtX), the three glycoproteins do not bind appreciably to TtX and form association products of large size. The size-exclusion chromatographic patterns of GPIIb, GPIIIa and GPIIb/IIIa have been obtained at 0.2% TtX, and the molecular properties of the association products and monomer fractions have been determined by analysis of the detergent bound to the glycoproteins, laser-light scattering, sedimentation velocity, and electron microscopy (TEM). The monomer of the GPIIb-TtX complex was identified by the molecular mass (M) of the glycoprotein moiety (125 +/- 15 kDa), the molecular size (9.5 +/- 1.5 nm x 11 +/- 1.5 nm) and globular shape observed by TEM. It has a molecular mass (M*) of 197 +/- 20 kDa, a sedimentation coefficient s degrees 20* of 5.8 +/- 0.1 S, a Stokes radius R s* of 6.8 +/- 0.4 nm, and a frictional ratio f*/fmin* of 1.7 +/- 0.14. The (GPIIb)n-TtX complexes are disulphide-bonded size-heterogeneous association products of GPIIb, tetramers being the smallest species found. GPIIIa has a greater propensity to self-associate than GPIIb, this tendency being lower below 1 mg GPIIIa/ml, 0.1 mM Ca2+, pH 9.0. The (GPIIIa)n-TtX complexes are noncovalent size-heterogeneous association products of GPIIIa, tetramers being the smallest form observed. The monomer of the GPIIIa-TtX complex was identified by the 103 +/- 15 kDa M determined for the glycoprotein moiety, and the 9 +/- 1.5 nm x 10 +/- 1.5 nm size and globular shape observed by TEM. It has a M* of 136 +/- 15 kDa, a s degrees 20* of 3.9 +/- 0.3 S, a Rs* of 6.4 +/- 0.5 nm, a f*/fmin* of 1.9 +/- 0.3, and, when stored at pH 7.4, has a certain tendency to form filamentous association products (20-70 nm x 2-5 nm), as observed by TEM. The GPIIb/IIIa-TtX complex in 0.2% TtX/0.1 mM Ca2+ elutes as a single monomeric fraction, as deduced from the 210 +/- 15 kDa M determined for its glycoprotein moiety and the 12 +/- 1.5 nm x 14 +/- 1.5 nm size of the globular forms observed by TEM.(ABSTRACT TRUNCATED AT 400 WORDS)

Molecular characterization of human platelet glycoproteins IIIa and IIb and the subunits of the latter.

Sedimentation equilibrium and low-angle laser-light scattering were used to determine the molar mass of the glycoprotein moieties in the complexes of sodium dodecyl sulphate with the human platelet membrane glycoproteins IIb (GPIIb), IIIa (GPIIIa), and the alpha (GPIIb alpha) and beta (GPIIb beta) subunits of GPIIb. The values obtained by both procedures, except those for GPIIb, agree within experimental error with those calculated from their chemical composition: GPIIb alpha (114,000 g mol-1), GPIIb beta (22,200 g mol-1), and GPIIIa (91,500 g mol-1). The molar mass of GPIIb determined by light scattering (142,000 g mol-1 and sedimentation equilibrium at different solvent densities (134,000 g mol-1) also agree, within experimental error, with the values calculated either from its chemical composition (136,500 g mol-1) or from the sum of the molar masses of its subunits. However the molar mass determined by sedimentation equilibrium at constant solvent density, is consistently underestimated (116,000 g mol-1). High-performance size-exclusion chromatography in sodium dodecyl sulphate solutions overestimates the molar mass of these glycoproteins and their Stokes radii, and therefore the maximal frictional ratios derived from them.

Physicochemical studies on tryptic digestion of bovine fibrinogen.

The high molecular weight fragments observed during tryptic digestion of bovine fibrinogen and the variation of their relative proportion with time has been studied. Separation of the different molecular species was carried out by gel filtration and the molecular weights of the isolated fragments were determined by sedimentation equilibrium and from their electrophoretic mobilities in sodium dodecylsulfate-polyacrylamide gels. The fibrinogen is degraded by trypsin into distinct fragments, with molecular weights of 270 000, 170 000, 90 000 and 50 000 accompanied by a series of smaller fragments whose properties were not investigated. The relative proportion of the components was estimated from area measurements on scans of the stained gels obtained after electrophoresis in the presence of sodium dodecylsulfate. The relative concentration and the molecular weight of each component established its molar concentration in each of the digestion mixtures obtained after varying incubation times (1-60 min). These data were used for a kinetic analysis of the process. The kinetic model derived on the basis of the trinodular model of fibrinogen (see Appendix) gave a very good representation of all the experimental results.