The relationship between depression and aerobic capacity in hemodialysis patients

Depression and a reduction in the performance of pleasant activities have been reported in patients with end-stage renal disease receiving hemodialysis therapy. The purpose of this study was to examine the relationship between depression and the patients' capacity to engage in physical activity. The patients' VO2max, or maximal oxygen consumption, was found to be positively associated with three standardized self-report measures of depression in a sample of 15 patients receiving hemodialysis. The clinical and theoretical implications of this finding are considered.     

Temperature-sensitive membrane association of pp60src in tsNY68-infected cells correlates with increased tyrosine phosphorylation of membrane-associated proteins

Incubation of membrane vesicles from normal and Rous sarcoma virus-transformed chick embryo fibroblasts (CEF) with [gamma-32P]ATP resulted in the phosphorylation of a large number of proteins. The major differences observed between the membrane vesicles of untransformed and transformed cells were: (1) a 5- to 10-fold increase in the proportion of labeled phosphotyrosine in transformed vesicles and (2) the phosphorylation of pp60src in vesicles from transformed cells. Of the many proteins labeled in vitro, only pp60src was immunoprecipitated by TBR serum. Phosphorylation of the immunoprecipitated pp60src occurred on tyrosine in the 26-kDa carboxy-terminal Staphylococcus aureus V8 protease fragment. pp60src was not phosphorylated in vitro in membrane vesicles prepared from tsNY68-infected cells grown at the nonpermissive temperature. The proportion of labeled phosphotyrosine in membrane proteins from tsNY68-infected cells grown at the nonpermissive temperature was only slightly increased relative to that observed in membranes prepared from normal cells. Subcellular fractionation indicated that while pp60src was membrane associated in tsNY68-infected cells grown at the permissive temperature, pp60src was chiefly soluble in tsNY68-infected cells grown at the nonpermissive temperature. Temperature-sensitive membrane association of pp60src in tsNY68-infected cells was also observed by indirect immunofluorescence microscopy. When membranes were prepared from tsNY68-infected cells that had been downshifted from the nonpermissive to the permissive temperature, the reappearance of in vitro phosphorylated pp60src and the increase in the proportion of labeled phosphotyrosine in membrane vesicles correlated with the kinetics of src immune complex kinase reactivation and membrane association of pp60src.     

Dynamic properties of vestibular reflexes in the decerebrate cat

Summary Vestibulocollic (VCR) and vestibulo-ocular (VOR) reflexes were studied during angular rotation in the horizontal plane in precollicular decerebrate cats. Angular position was modulated by sinusoids or sums of sinusoids with frequencies ranging from 0.05 to 5 Hz.Reflex motor output was measured by recording electromyographic (EMG) activity of the lateral rectus and dorsal neck muscles and discharge of abducens motoneurons. Measured with respect to input angular acceleration VCR motor output displayed a second order lag at low frequencies, bringing mean EMG phase (–136 °) and gain slope (–35 dB/ decade) close to those of an angular position signal at 0.2 Hz. At higher frequencies the lag was counteracted by a second order lead bringing mean phase (–52 °) and gain slope (–5.6 dB/decade) back close to those of an angular acceleration signal at 3 Hz. By contrast, mean phase (–113 ° to –105 °) and gain slope (–21 to –28 dB/decade) of the VOR motor output remained close to those of an angular velocity signal across the entire frequency range.The data suggest that neural pathways producing the VCR receive selective input from irregular type horizontal semicircular canal afferents which provide one lag and one lead in the overall transfer function while the other lag and lead are produced by central pathways.Transaction of the medial longitudinal fasciculus (MLF), which eliminates all of the most direct (three neuron) arcs of the horizontal VCR, did not cause any detectable change in the horizontal VCR at either low or high frequencies. Reductions in overall gain occurred in some cases but these could be attributed to damage to axons outside the MLF. Less direct pathways, probably including vestibulo-reticulospinal pathways, are thus able to produce both the low-frequency, phase-lagging and high-frequency, phase-leading components of the horizontal VCR.Supported in part by NIH grants EY 02249, EY 00100, and NS 02619Recipient of NIH Fellowship NS 06030     

Eye movements and vestibular-nerve responses produced in the squirrel monkey by rotations about an earth-horizontal axis

Summary The eye movements produced by constant-speed rotations about an earth-horizontal axis (EHA) are similar in the alert squirrel monkey to those observed in other species. During EHA rotations, there are persistent eye movements, including a nonreversing nystagmus at lower rotation speeds and either a direction-reversing nystagmus or sinusoidal eye movements at higher rotation speeds. Horizontal eye movements are produced by barbecuespit (yaw) rotations, vertical eye movements by head-over-heels (pitch) rotations. The responses can be viewed as composed of a bias component, reflected in the nonreversing nature of the nystagmus, and a cyclic component, reflected in the periodic modulation of slow-phase eye velocity as head position varies. Vestibular-nerve recordings in the barbiturate-anesthetized monkey indicate that neither semicircular-canal nor otolith afferents give rise to a directionally specific dc signal which can account for the bias component. Apparently the appropriate dc signal has to be constructed centrally from a sinusoidal or ac peripheral input. The otolith organs are a likely source of this peripheral input, although contributions from the semicircular canals and from somatosensory receptors must also be considered. Our results suggest that the directional information required to distinguish rotation direction, rather than being contained in the discharge of individual otolith afferents, is encoded across a population of afferents. Possible sources of such information are the phase differences in the sinusoidal responses of otolith afferents differing in their functional polarization vectors.Supported by Grants NS 01330 from the National Institutes of Health and NGR-14-001-225 from the National Aeronautics and Space Administration     

Engineering of osteochondral tissue with bone marrow mesenchymal progenitor cells in a derivatized hyaluronan-gelatin composite sponge

The aim of this study was to investigate the potential of a composite matrix, containing esterified hyaluronic acid and gelatin, to facilitate the osteochondral differentiation of culture-expanded, bone marrow-derived mesenchymal progenitor cells. The cell loading characteristics and the effects of the matrix on cell differentiation were examined in vitro and in vivo. Empty and cell-loaded composites were cultivated for up to 28 days in a chemically defined medium with or without transforming growth factor-beta1 (TGF-beta1). A type II collagen-rich extracellular matrix was produced by cells loaded in the matrix and cultured in the presence of TGF-beta1. Empty and cell-loaded matrices were also implanted subcutaneously in immunodeficient mice. Three types of implant were used: empty (group I), cell-loaded matrices (Group II), and cell-loaded matrices cultured for 14 days in vitro in defined medium with TGF-beta1 (group III). No osteochondral differentiation was found in implanted empty matrices; however, the matrix supported osteochondrogenic cell differentiation in the cell-loaded implants. Preculture in vitro in a chondrogenic medium increased the percentage of osteochondral tissue found in the constructs after 3 weeks. These results indicate the potential use of this composite matrix for delivery of bone marrow-derived mesenchymal progenitor cells for the repair of chondral and osseous defects. The results also indicate that this composite matrix is useful for in vitro tissue engineering.     

Multiple pathways to tumor immunity and concomitant autoimmunity

Summary: The immune repertoire contains T cells and B cells that can recognize autologous cancer cells. This repertoire is directed against self, and in some cases altered self (mutations). Priming immune responses against self antigens can be difficult. Strategies are presented using altered self to elicit immunity against self in poorly immunogenic tumor models. Mechanisms underlying immunity to self antigens on cancer cells show that the immune system can use diverse strategies for cancer immunity, in both the immunization and the effector phases. CD4⁺ T cells are typically, but not always, required for immunization. The effector phase of tumor immunity can involve cytotoxic T cells, macrophages with activating Fc receptors, and/or killer domain molecules. This diversity in the effector phase is observed even when immunizing with conserved paralogs. A consequence of tumor immunity is potentially autoimmunity, which may be undesirable. Autoimmunity uses similar mechanisms as tumor immunity, but tumor immunity and autoimmunity can uncouple. These studies open up strategies for active immunization against cancer.