Expression of leukocyte integrins and tissue factor in mononuclear phagocytes

Histocompatible Fischer 344 and Lewis rats have been shown to differ on a wide variety of behavioral, chemical, and molecular measures. This investigation aimed to clarify strain differences in unconditioned motor behavior with respect to the amount and patterns of movements. Twenty female Fischer 344, Lewis, and Sprague-Dawley were tested in the Behavioral Pattern Monitor for 30 min. The locomotor activity and movement patterns, quantified by counts of photobeam breaks and the spatial scaling exponent, d, were assessed. The level of locomotor activity did not differ significantly between Fischer, Lewis, and Sprague-Dawley rats. In contrast, movement patterns differed significantly between the strains. Specifically, Sprague-Dawley rats exhibited significantly more straight movements than both Fischer and Lewis rats. Moreover, Lewis rats showed significantly more straight movements compared to Fischer rats during the first 10 min in the enclosures. Differences in movement patterns across strains may provide an important behavioral variable to further explore the genetic and developmental aspects of behavior.     

Host TIMP-1 overexpression confers resistance to experimental brain metastasis of a fibrosarcoma cell line

Within the tumor-stromal microenvironment a disrupted balance between matrix metalloproteinases (MMPs) and their inhibitors compromises the integrity of the extracellular matrix and promotes malignancy. Tissue inhibitors of metalloproteinases (TIMPs) have been linked to tumor suppression in studies of genetically altered tissue culture cells and in analyses of clinical specimens in situ. We generated transgenic mice as a model system to test the relationship between TIMP-1 levels in a host organ and susceptibility to experimentally targeted metastasis. Ectopically overexpressed TIMP-1 in the brain resulted in a tissue microenvironment with elevated protein levels of this natural MMP inhibitor. Metastatic challenge provided by lacZ-tagged fibrosarcoma cells permitted high-resolution analysis of metastatic load and pattern. We found that elevated host TIMP-1 imposed resistance to experimental metastasis of fibrosarcoma: In TIMP-1 overexpressing mice, brain metastases were significantly reduced by 75% compared to wild-type littermates. Our findings demonstrate that ectopic TIMP-1 expression efficiently exerts a suppressive effect on metastasizing tumor cells.     

Studies of structure-activity relationship of nitroxide free radicals and their precursors as modifiers against oxidative damage

The protective effects of stable nitroxides, as well as their hydroxylamine and amine precursors, have been tested in Chinese hamster V79 cells subjected to H2O2 exposure at fixed concentration or exposure to ionizing radiation. Cytotoxicity was evaluated by monitoring the viability of the cells assessed by the clonogenic assay. The compounds tested at fixed concentration varied in terms of ring size, oxidation state, and ring substituents. Electrochemical studies were carried out to measure the redox midpoint potentials. The studies show that in the case of protection against H2O2 exposure, the protection was determined by the ring size, oxidation state, and redox midpoint potentials. In general the protection factors followed the order nitroxides > hydroxylamines > amines. Both the six-membered ring nitroxides and substituted five-membered ring nitroxides were efficient protectors. For six-membered ring nitroxides, the compounds exhibiting the lowest midpoint potentials exhibited maximal protection. In the case of X-radiation, nitroxides were the most protective though some hydroxylamines were also efficient. The amines were in some cases found to sensitize the toxicity of aerobic radiation exposure. The protection observed by the nitroxides was not dependent on the ring size. However, the ring substituents had significant influence on the protection. Compounds containing a basic side chain were found to provide enhanced protection. The results in this study suggest that these compounds are novel antioxidants which can provide cytoprotection in mammalian cells against diverse types of oxidative insult and identify structural determinants optimal for protection against individual types of damage.     

U-insertion/deletion Edited Sequence Database

To study effort tolerance in elderly women with different physical activity backgrounds, 52 physically active (PA) and 42 sedentary control women (CO) aged 66-85 yr were assigned to perform cycle ergometer exercise to their volitional maximum. Oxygen uptake, respiratory exchange ratio (RER), heart rate, work power, and rate pressure product were measured to evaluate the severity of exercise. Plasma C-ANP (C-terminus of the atrial natriuretic peptide prohormone) and plasma N-ANP (N-terminus of the atrial natriuretic peptide prohormone) were analyzed as indicators of cardiac load. Eighty-one percent (N = 42) of the PA and 52% (N = 22) of CO performed the ergometer exercise. The mean peak oxygen uptake was 22.6 and 15.1 mL x kg(-1) x min(-1) among PA and CO, respectively. Twenty-two of the 42 PA and 19 of the 22 CO terminated the ergometer exercise before attaining the objective maximum. The most common reasons for termination were the subject's own wish, abnormal cardiovascular response, or lower limb tiredness. Both C-ANP and N-ANP increased after exercise. The increase in plasma C-ANP correlated significantly with a few physiological variables, whereas comparable associations with N-ANP were not found. It is concluded that inexperience of physical exertion and medical as well as physiological factors limit effort tolerance among elderly women. Differences in the response of C-ANP and N-ANP were found that are suggested to be due to differences in the postsecretory mechanisms between these hormones.     

Noninvasive detection of cerebral hypoperfusion and reversible ischemia from reductions in the magnetic resonance imaging relaxation time, T2

STUDY DESIGN: Consecutive case retrospective chart review. OBJECTIVES: First, to assess whether the number of' patients requiring a second cervical surgical intervention was changed as a result of using anterior cervical plate stabilization, and second, to determine the additional risks and/or benefits associated with the hardware implantation. SUMMARY OF BACKGROUND DATA: The optimal technique of performing stabilization, arthrodesis, and alignment of a cervical segment after discectomy with neural decompression in degenerative disease has yet to be determined. METHODS: The charts of 402 patients who had undergone an anterior cervical discectomy and arthrodesis for degenerative disease performed both with and without anterior cervical plate stabilization were reviewed, and reoperation data were compiled. The average follow-up time was 3.8 years (range, 1.5-9.4 years). RESULTS: Of 365 patients with 1- or 2-level cervical arthrodesis, 22 required a second surgical intervention (20 bone alone, 2 with anterior cervical plate stabilization). The Log-Rank test, which uses all patients and their total follow-up periods, was statistically significant favoring anterior cervical plate stabilization at one and two levels (P = 0.015). CONCLUSIONS: The addition of anterior cervical plate stabilization in one- and two-level cervical degenerative disease supplements the internal stabilization initially provided by the bone graft, and yields a lower reoperation rate.     

Partial isolation from intact cells of a cell surface-exposed lysophosphatidylinositol-phospholipase C

A novel cell surface phosphoinositide-cleaving phospholipase C (ecto-PLC) activity was isolated from cultured cells by exploiting its presumed external exposure. Biotinylation of intact cells followed by solubilization of the biotinylated proteins from a membrane fraction and recovery onto immobilized-avidin beads, allowed assay of this cell surface enzyme activity apart from the background of the substantial family of intracellular PLCs. Several cell lines of differing ecto-PLC expression were examined as well as cells stably transfected to overexpress the glycosylphosphatidylinositol (GP) anchored protein human placental alkaline phosphatase (PLAP) as a cell surface enzyme marker. The resulting bead preparations from ecto-PLC positive cells possessed calcium-dependent PLC activity with preference for lysophosphatidylinositol (lysaPI) rather than phosphatidylinositol (PI). The function of ecto-PLC of intact cells evidently is not to release GPI-anchored proteins at the cell surface, as no detectable Ca(2+)-dependent release of overexpressed PLAP from ecto-PLC-positive cells was observed. To investigate the cell surface linkage of the ecto-PLC itself, intact cells were treated with bacterial PI-PLC to cleave simple GPI anchors, but no decrease in ecto-PLC activity was observed. High ionic strength washes of biotinylated membranes prior to the generation of bead preparations did not substantially reduce the lysoPI-PLC activity. The results verify that the ecto-PLC is truly cell surface-exposed, and unlike other members of the PLC family that are thought to be peripheral membrane proteins, this novel lysoPI-PLC is most likely a true membrane protein.