Interleukin-12 induces relapse in experimental allergic encephalomyelitis in the Lewis rat

Acute, monophasic experimental allergic encephalomyelitis (EAE) in the Lewis rat shows pathological similarities to the human disease multiple sclerosis (MS). Rats that recover from EAE are essentially resistant to disease reinduction, unlike MS in which relapses are frequently associated with common bacterial and viral infections. As macrophage-derived interleukin (IL)-12 is a critical component of innate resistance to bacterial infection and appears to directly activate encephalitogenic T cells in vivo, the ability of this cytokine to reinduce paralysis in EAE was examined. Paralytic disease was exacerbated by intraperitoneal IL-12 administration and could be reinduced up to 1 week after recovery from the primary clinical episode. Concomitant with worsening of initial clinical signs and relapse was an increase in the ratio of macrophages to T cells in brain stem perivascular cuffs and the expression of inducible nitric oxide synthase in cells with both macrophage and microglial morphology. These findings suggest that IL-12 may contribute to macrophage-mediated disease exacerbation and relapse in patients with MS.     

Neutrophil attractant protein-1 and monocyte chemoattractant protein-1 in human serum. Effects of intravenous lipopolysaccharide on free attractants, specific IgG autoantibodies and immune complexes

We recently found that normal human sera contain IgG antibodies against two chemoattractants, neutrophil attractant protein-1 (NAP-1/IL-8) and monocyte chemoattractant protein-1 (MCP-1), as well as immune complexes of these proteins. Intravenously administered LPS was reported to cause a sharp rise in serum NAP-1 concentration. Our study was designed to determine if LPS also caused an increase in MCP-1 and to measure associated changes in concentrations of antibody and immune complex. LPS caused a rise to peak within 2 to 3 h in serum concentrations of free NAP-1 and MCP-1, followed by an almost equally rapid fall toward base-line levels by about 5 h postinjection. MCP-1 concentration in sera from the 11 subjects rose to a peak of 330 +/- 52 pM. The peak value for NAP-1 was 80 +/- 11 pM. In 10 of the 11 subjects, free IgG autoantibody to MCP-1 decreased from a mean pre-LPS value of 1820 +/- 660 pM to a mean low of 53% of the respective initial values. Corresponding data for IgG anti-NAP-1 were a pre-LPS concentration of 216 +/- 7 pM, which decreased to a mean low of 44% of the respective initial values. The finding in some subjects of a rapid rise in free antibody after the nadir suggests the possibility of acute regulation of autoantibody secretion rates. Although the results suggested that LPS-induced chemoattractant combined with free antibody, serum concentrations of MCP-1-IgG or NAP-1-IgG did not increase, which points to an as yet unknown mechanism for trapping and elimination of the immune complexes.     

Editor’s column: Generational shifts.

This issue begins the journal's second year as an APA divisional journal. In this column, the editor presents a brief review of the history of the division, and discusses trends, or shifts, in the division's focus. Prior to 1972, the first phase saw the development of rudimentary theories of consultation emerging in the clinical, educational, and business fields. In the second phase, consultation theories were elaborated and tuned to specific application areas. Competition and some hostility developed between these groups which limited cooperation and collaboration. In the emerging third phase, the editor expects increased respect, cooperation and collaboration to emerge as the next generation of consultants become influential. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of an enhanced natural radioactivity on mammal fertility

Male and female mice of the BALB/c strain were placed on the floor of a hut built at a site of the Permian Basin of Lodève (Southwest France) where the dose rate of γ radiation amounts to about 10 mrad/h. In previous experiments such high natural radioactivity was shown to induce point mutations in plant material as well as chromosome aberrations in somatic cells of experimental mammals. Controls were kept near the radioactive site under comparable conditions. After the exposure period, the animals were mated in our laboratory, with control mice of the same strain.Due to the high radiosensitivity of mouse oocytes, the fertility of the exposed females was drastically reduced in spite of the fact that the dose received did not exceed 13.8 rad. The fertility of the males exposed to 13 rad, 15 rad or to 45 rad was increased above the control values but was reduced for the animals receiving 63 rad. Analysis of the results show that the differences in fertility are mainly due to a decrease in the number of sterile pairs when males have been exposed to doses upto 45 rad and to an inverse effect when animals received 63 rad. Since histology and weight of the testes suggest that the germ cell population was normal, one has to conclude that the variations in fertility result from physiological effects.     

Loglinear models: A way to study main effects and interactions for multidimensional contingency tables with categorical data.

Until recently, behavioral researchers failed to examine categorical data based on multidimensional data in a unified whole because of the complex arithmetic such procedures entail. With the appearance of the loglinear model and user-friendly computer software, the problems associated with the analysis of multifaceted contingency tables no longer exist. In this article, we describe the loglinear model and apply it to categorical data cross-tabulated on four dimensions. We define contrasts similar to those of the analysis of variance and describe post hoc and planned comparison strategies. We illustrate hypothesis testing and model building for categorical data, and provide guidelines for performing an analysis on frequency data by using the loglinear model. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Biochemical studies of the mechanism of action of the Cdc42-GTPase-activating protein

The small GTP-binding proteins Rac, Rho, and Cdc42 were shown to mediate a variety of signaling pathways including cytoskeletal rearrangements, cell-cycle progression, and transformation. Key to the proper function of these GTP-binding proteins is an efficient shut-off mechanism that ensures the decay of the signal. Regulatory proteins termed GAPs (GTPase-activating proteins) enhance the intrinsic GTP hydrolysis of the GTP-binding proteins, thereby ensuring signal termination. We have used site-specific mutagenesis to elucidate the limit domain for GAP activity in Cdc42-GAP, and show that in addition to the known GAP-homology domain (three conserved boxes), a C-terminal region outside that domain is also essential for GAP activity. In addition, we have replaced the conserved arginine (Arg305), which was suggested by structural studies to be a key catalytic residue, with an alanine and found that the R305A Cdc42-GAP mutant has a greatly diminished catalytic capacity but is still able to bind Cdc42 with high affinity. Thus, a key catalytic role for this residue is confirmed. However, we also present evidence for the involvement of an additional residue(s), since the R305A Cdc42-GAP mutant still exhibits measurable activity. Some of this residual activity might result from a neighboring arginine, since a double mutant R305A/R306A shows a further decrease in catalytic activity.     

Effect of vacuum-packaged frozen storage, after cooking, on the phospholipids of Hereford and Bison

Changes in the neutral lipid (NL), phospholipid (PL) and their fatty acid (FA) profiles in lean samples of cooked and cooked, vacuum-packaged, frozen (28 days) Hereford and Bison L. dorsi muscle were analyzed. Samples from Herefords contained more saturated fatty acids (SFA) in the neutral lipid fraction than Bison. Storage decreased the C_18:2, C_18:3, C_20:1 and C_20:4 content of the NL. Bison samples contained more total PL and phosphatidylethanolamine (PE) than Hereford. Storage decreased the content of the least polar of the PL which were eluted in the solvent front (fraction 1), phosphatidylinositol (PI), phosphatidylserine (PS), PE and sphingomyelin (SPH). In the combined PL fraction, there were no differences in the FA profile of Bison and Hereford. Storage resulted in a decrease in the content of C_18:2, C_20:4, unsaturated fatty acid (UFA) and polyunsaturated fatty acid (PUFA) in the combined PL fraction. In the PE fraction, Bison samples contained more C_20:4 and PUFA than Hereford. Storage had no effect on the FA profile of PE. The LPC fraction of Bison samples contained more saturated SFA, UFA and PUFA than Hereford, and with storage these FA decreased. Cooked frozen storage also decreased SFA, UFA and PUFA in PC/LPE.     

Inference rules using local contexts

We construct equivalent localized versions of a formula, adding assumptions simultaneously to various locations, where the particular location determines what is added. Inference rules that take advantage of localized formulas are presented for sequent calculi in which the left hand side of sequents can be used to accumulate the background assumptions (or contexts) of assertions. The intended application is to the automatic generation of tractable justifying lemmas for substitution operations for interactive proof development systems, especially those concerned with mathematical topics where manipulation of deeply embedded terms is desirable.     

A formal approach to specifying assembly operations

Experience has proved that exploiting robots for assembly tasks is much more difficult than manufacturing engineers had expected and many attempts at implementing robotic assembly have failed. Our research has led us to believe that a formal approach to specifying the steps required for assembly would be of great benefit in developing the required software for a specific task, and in adaptively controlling and monitoring the execution of robotic assembly steps. The US National Bureau of Standards has developed a formal system, called ABC (for Assembly By Constraints) for specifying the steps required for assembly. The system is based on the reduction in the degrees of freedom of objects as they are assembled. Using this basic concept, we have developed 14 primitive operations which can be used to completely specify assembly steps for a large class of problems. This paper initially outlines the historical development of the system, then describes two pieces of software developed to allow easy definition of assembly tasks using the ABC system, and finally presents two practical examples.     

Adsorption of dissolved organics from industrial effluents on to activated carbon

Industrial effluents usually include multicomponent organic solutes. The optimum pH for adsorption of a specific industrial effluent on activated carbon should be determined experimentally because, in general, more than one mechanism is involved. A series of experiments was conducted to establish the influence of the initial hydrogen ion concentration on carbon adsorption of organic solutes. For these studies, powdered activated carbon was used, and the water systems studied included both single component pure organic compounds as well as multicomponent organic wastes. Results indicate that the pH effect upon the effectiveness of carbon adsorption mainly depends upon the nature of the adsorbed substance. In general, the degree of ionisation is the controlling factor for adsorption of ionic organic solutes on activated carbon. Adsorption reaches a maximum at the point of least ionisation of the adsorbate. As the organic compounds become more complex (i.e. longer hydrocarbon chains, higher molecular weights, increased branching), the electrical adsorption forces between activated carbon and ionic organic solutes will govern. Anionic surfactants meet with decreased electronegative repulsive forces at low pH levels, which increase the effectiveness of carbon adsorption. However, the adsorption of a cationic surfactant is increased by an increase in the electronegative carbon surface at high pH levels. When ionic organic solutes become much more complex, like a polymer, the effects of both ionisation and electrical adsorption forces become less important. Instead, the adsorption rate will be controlled by the extent of hydrolysis caused by the pH adjustment. For non-ionic organic solutes, chemical reaction(s) between the adsorbate and the added chemical (acid or base) for pH adjustment is an important controlling factor. Again, hydrolysis is responsible for the breakdown of larger size molecules to smaller sizes. Then an increase in adsorption rate with decreasing molecular weight of adsorbate is expected.