Dynamic infrared linear dichroism (DIRLD) measurements of films of a thermo-plastic polyester/polyurethane random copolymer (Estane 5703, B. F. Goodrich) are reported. Step-scan Fourier transform infrared (FT-IR) is used for dynamic measurements, and a photoelastic modulator (PEM) is used to create broadband polarization modulation as the carrier frequency for the strain modulation. A novel modulation/demodulation strategy has been employed that simplifies the triple-modulation experiment into a double-modulation experiment; the theory is thoroughly discussed. Both static and dynamic dichroic absorption difference spectra have been measured on the prestretched polymer film. The results are of high signal-to-noise ratio (SNR) and clearly indicate the static and dynamic orientation of the transition dipole moments due to the tensile deformation. The dynamic orientation responses are primarily in phase with the perturbation. The orientation magnitudes of the infrared absorption bands are quantified and compared, and the orientations of the hard and soft domains are differentiated. To assist in the interpretation of the dynamically measured data, we also describe a static linear dichroic measurement using a wire-grid polarizer and FT-IR in the rapid-scan mode for a sample incrementally drawn until the point of breaking. The orientation functions of selected bands have been calculated, and the static results agree with the dynamic data, indicating the dependency of the dynamic orientation response on the preorientation state.

The ␣ 2 integrin subunit cytoplasmic domain is necessary for epidermal growth factor (EGF)-stimulated chemotactic migration and insulin-dependent entry into Sphase of mammary epithelial cells adherent to type I collagen. Truncation mutants revealed that the seven amino acids, KYEKMTK, in addition to the GFFKR motif were sufficient for these functions. Mutation of tyrosine 1134 to alanine inhibited the ability of the cells to phosphorylate p38 MAPK and to migrate in response to EGF but had only a modest effect on the ability of the cells to induce sustained phosphorylation of the ERK MAPK, to up-regulate cyclin E and cdk2 expression, and to enter S-phase when adherent to type I collagen. Conversely, mutation of the lysine 1136 inhibited the ability of the cells to increase cyclin E and cdk2 expression, to maintain long term phosphorylation of the ERK MAPK, and to enter S-phase but had no effect on the ability of the cells to phosphorylate the p38 MAPK or to migrate on type I collagen in response to EGF. Methionine 1137 was essential for both migration and entry into S-phase. Thus, distinctly different structural elements of the ␣ 2 integrin cytoplasmic domain are required to engage the signaling pathways leading to cell migration or cell cycle progression.The integrin family of heterodimeric cell surface adhesion receptors not only mediates adhesion to the extracellular matrix and other cells, but also serves to integrate signals from the outside to the inside of the cell (1-5). Signals from growth factor receptors acting in combination with signals from integrins are necessary to regulate complex cellular processes such as migration and proliferation. Adhesion to the extracellular matrix via integrins is required for growth factors to induce robust activation of both the extracellular signal-regulated kinase (ERK) 1 and c-Jun NH 2 -terminal kinase mitogen-activated protein kinase (JNK) cascades, which leads to progression through the G 1 phase of the cell cycle (6 -11). During chemotactic migration integrin ligation not only provides the adhesion necessary for traction on the extracellular matrix but also activates intracellular signaling molecules such as Rac, Cdc42, and p38 MAPK (12, 13).The ␣ 1 ␤ 1 and ␣ 2 ␤ 1 integrins are expressed on the surface of many cell types where they serve as receptors for collagens and/or laminins (14 -17). Studies by several groups, including our own, have shown that although the ␣ 1 ␤ 1 and ␣ 2 ␤ 1 integrins have similarities in ligand binding, they mediate different functions and are not redundant adhesive receptors (9, 10, 18 -23). Recent studies employing wild type, truncated, and chimeric ␣ 2 integrin subunits indicate that the unique phenotypic influences of the ␣ 2 ␤ 1 integrin on cell proliferation and migration on collagenous substrates are mediated through the cytoplasmic domain of the ␣ 2 subunit (13, 24). These findings suggested that certain residues present in the ␣ 2 integrin cytoplasmic domain not present in the ␣ 1 cytoplasmic domain might be responsible for medi...

We reasoned that a prospective assessment of glucocorticoid withdrawal in subjects with asthma would provide insight into the basis for flares of the disease. We therefore enrolled 25 subjects with moderate persistent asthma and treated them for 30 days with inhaled fluticasone propionate (1,760 microg/day) followed by a withdrawal period that lasted until peak expiratory airflow decreased by 25% and FEV(1) by 15% or 6 weeks elapsed. After glucocorticoid withdrawal, 13 of 25 subjects reached the target, whereas 12 subjects did not. The number of eosinophils in bronchial biopsies was increased by glucocorticoid withdrawal in both groups, but increases in airway T cells were found in only those with exacerbation. T-cell accumulation was a reflection of similar increases in both CD4(+) and CD8(+) T cells and was accompanied by increased expression of chemokine CCL5 (regulated upon activation, normal T cell expressed and secreted) in the airway epithelium without activation of the transcription factor nuclear factor-kappaB. The pattern of glucocorticoid-sensitive inflammation during an asthma exacerbation is more reminiscent of an antiviral response than an eosinophil-predominant response to allergen and implies an independent role for airway T cells in mediating asthma flares and in determining glucocorticoid efficacy in the treatment of this disease.

By combining FTIR data of plasticized Estane (a polyester polyurethane copolymer) subjected to mechanical deformation with spectral differences as a function of added plasticizer, insight into the physical role of plasticization is gained. For Estane, the orientation functions and dichroic difference data show that, in static stretching, the soft domains reach orientation saturation before the hard domains. With added plasticizer, hydrogen bonding to the hard segments is disrupted and the glass transition of the soft domain decreases, indicating that plasticizer remains solubilized in the soft domain. On the time scale of the static experiment, plasticization diminishes the ability of both domains to reorient, while the plasticizer itself does not orient. With added plasticizer, neither domain reaches orientation saturation during the prestretching process, and dynamic distortion results in a similar response from both domains. Bimodal bands in the dynamic data indicate that the strain applied on a rapid time scale (20 Hz) allows resolution of the components of differently oriented bands.