Assessment of response style in combat veterans seeking compensation for posttraumatic stress disorder

This study examined response styles of veterans seeking compensation for PTSD (N = 204). Veterans were classified as having a valid or overreporting response style based on their scores on three MMPI-2 validity scales that measure overreporting F, F(p), F-K. Sixteen percent of veterans had valid scores on all three scales. The number of veterans classified as having an overreporting response style differed depending on which scale was used. This finding highlights the importance of using multiple validity scales to measure response style. Veterans who were and were not classified as overreporters were compared on measures of combat exposure, PTSD, and depression.     

Microtubules in mammalian erythroblasts. Are marginal bands present?

Summary The purpose of this study was to determine if marginal bands, such as those present in mature nucleated red blood cells of other non-mammalian vertebrates and in primitive mammalian erythrocytes are present in definitive mammalian erythroblasts. In a small number of erythroblasts examined from mouse spleen, a bundle of 5–8 microtubules could be seen. These microtubules appeared similar to those previously identified by others as marginal band microtubules in liver and marrow erythroblasts. However, it was difficult to distinguish these bundles from remnants of mitotic spindle microtubules, or bundles of microtubules which extend to the midbody, a structure which is seen quite frequently in sections of erythroid cells. Triton extraction, a process which renders cytoskeletal elements such as microtubules more visible, also failed to confirm the presence of conventional marginal bands in these cells. It is suggested that use of the term marginal band be restricted to those cases in which it can be unequivocally demonstrated that a bundle of microtubules encircles the perimeter of the cell.     

Development of a recombinant HSP110-HER-2/neu vaccine using the chaperoning properties of HSP110

Several studies have shown that when purified from a tumor, certain heat shock proteins (HSPs) can function as effective vaccines against the same tumor by virtue of their ability to bind tumor-specific peptides. However, only a small fraction of the associated peptides would be expected to be immunogenic, in addition to which, the clinical application of this vaccine requires the availability of a surgical specimen of sufficient quantity for purification of the HSP. The present study describes a new approach for the development of natural HSP vaccines that do not have these limitations. This approach uses a recombinant HSP that is noncovalently bound to a recombinant tumor protein antigen by heat shock. HSP110 has been selected for this purpose, because it has been shown to be a highly efficient molecular chaperone in binding to large protein substrates. We show that a "natural chaperone complex" between HSP110 and the intracellular domain (ICD) of human epidermal growth factor receptor 2 protein (HER-2)/neu is formed by heat shock. This HSP110-ICD vaccine elicited both CD8(+) and CD4(+) T-cell responses against ICD as determined by an antigen-specific IFN-gamma production in an enzyme-linked immunospot assay (ELISPOT). In vivo depletion studies revealed that the CD8(+) T-cell response was independent of CD4(+) T-cell help. The HSP110-ICD complex also significantly enhanced ICD-specific antibody responses relative to that seen with ICD alone. No CD8(+) T cell or antibody response was detected against HSP110. The use of recombinant HSP110 to form natural chaperone complexes with large protein antigens represents a new and powerful approach for the design of protein-targeted cancer vaccines.     

Recombinant CD40 ligand therapy has significant antitumor effects on CD40-positive ovarian tumor xenografts grown in SCID mice and demonstrates an augmented effect with cisplatin

CD40 is a member of the tumor necrosis factor receptor family and was first identified with a monoclonal antibody raised against bladder carcinoma. Recombinant human CD40L has been shown previously to have a direct antitumor effect on an ovarian cancer cell line and ovarian carcinoma cells isolated from ascites fluid. We show here that rhuCD40L inhibits the growth of several ovarian adenocarcinomas derived from surgical specimens and grown as xenografts in severe combined immunodeficient mice. Two 14-day treatment cycles were more effective than one. This effect is apparently not mediated by natural killer cells, because blocking natural killer cell activity by antiasialo GM-1 did not diminish this effect. In addition to suppression of tumor growth, treatment with rhuCD40L resulted in an increased expression of FasL, an increase in apoptosis, and histological changes including increased fibrosis and areas of tumor destruction. Using this model, we examined the efficacy of rhuCD40L in combination with chemotherapeutic agents. The antitumor effect of rhuCD40L in combination with 4 mg/kg cisplatin (CDDP) was increased over the effect of CDDP alone. Furthermore, rhuCD40L increased the efficacy of a suboptimal dose of CDDP (2mg/kg) such that it matched that of high-dose CDDP alone. These data suggest a role for rhuCD40L therapy in combination with platinum based regimens for primary treatment of epithelial ovarian tumors.     

A regional analysis of alpha-spectrin in the isolated Mauthner neuron and in isolated axons of the goldfish and rabbit

Isolated dendrites, somata, and desheathed axons of the goldfish Mauthner neuron (M-cell), in addition to other isolated myelin sheath-free axons of the goldfish spinal cord and of rabbit lumbar ventral roots, were shown by immunochemical and immunofluorescence techniques to contain alpha-spectrin (fodrin). alpha-Spectrin appeared to be organized as a randomly distributed reticular network, localized to the surface of isolated neuronal cellular structures. In addition, alpha-spectrin was also distributed nonrandomly at specialized cellular sites. These sites included synaptic junctions and morphologically differentiated nodes of Ranvier (i.e., rabbit axons, but not goldfish axons). At the latter sites, it is possible to demonstrate that alpha-spectrin is co-localized with F-actin, as indicated by a striking correspondence of fluorescent images due to double labeling, using the indirect immunofluorescence technique with alpha-spectrin antiserum, and direct binding of F-actin by rhodamine-conjugated palloidin. However, the spectrin-actin network at synaptic junctions appears to be distributed over the entire area of junctional contact and is not just restricted to postsynaptic densities. The possibility of a duality of roles of spectrin in membrane-related motile and anchorage functions is discussed.     

Heterogeneity of spectrin distribution among avian muscle fiber types

Muscle spectrin has been examined in avian fast, slow, and mixed muscles using the techniques of immunofluorescence microscopy and immunoautoradiography. By immunofluorescence, fibers of the fast-twitch pectoralis major (PM) are seen to contain alpha-spectrin antigen primarily at the sarcolemma, while in the slow-tonic anterior latissimus dorsi (ALD), alpha-spectrin antigen is found in high concentrations throughout the sarcoplasm as well as being present in association with the sarcolemma. In mixed (fast- and slow-twitch) muscles of the leg, two populations of fibers can be distinguished: those which resemble the fibers of the PM and another group which displays interior staining similar to the fibers of the ALD. Histochemical staining for actomyosin ATPase reveals that the fibers of mixed muscles which contain the most spectrin antigen correspond to the slow-twitch fibers. Supportive data were obtained using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoautoradiography. In slow muscle, an approximate threefold increase in alpha-spectrin concentration relative to other proteins is evident. These results suggest that the distribution of alpha-spectrin may be modified by the physiological state of the myofiber.     

Thermal regulation of dendritic cell activation and migration from skin explants.

Dendritic cells (DCs) in the skin rapidly take up antigen and migrate out of the skin to draining lymph nodes for antigen presentation. As a result, these cells play an important role in generating specific immune responses against infectious agents that enter the skin and against antigens delivered as vaccines. Previous efforts revealed that fever-like elevations in body temperature enhance antigen-dependent immune responses initiated at the site of the skin and stimulate the migration of epidermal DCs to draining lymph nodes. Collectively, these data have led to the hypothesis that the activation of epidermal DCs is sensitive to physiological thermal stimuli. In this study, ear skin explants derived from BALB/c mice were either maintained at 37 degrees C or incubated at 40 degrees C for the first 6.5 h before being placed at 37 degrees C. This heating protocol altered the density and morphology of the epidermal DCs in a manner suggestive of an increased kinetics of activation-associated DC migration. Flow cytometric analysis of the emigrated cells also indicated that mild heating enhanced the migration kinetics of DCs and increased the DC expression of MHC class II and the activation marker CD86. Importantly, these migrated cells displayed higher stimulatory capacity in a mixed lymphocyte reaction compared to those of controls. Overall, these results suggest that mild thermal stimuli can enhance DC activation and function and that strategic applications of heat could enhance the potency of vaccines consisting of relatively weak antigens, such as cancer vaccines.