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)     

Magnetic Relaxation of Solid and Liquid 3He Confined Inside a Silver Sinter

We present T ₁ measurements performed in liquid and solid ³ He confined in sintered silver. In the liquid case, we find a close to linear relationship between T ₁ and the applied magnetic field, similar to other (non metallic) systems, and up to higher frequencies (corresponding to 11 T) than previously reported. In the solid, the relaxation rate is found to increase spectacularly at large polarizations, which may indicate a polarization dependence of the exchange motion. Now atNow at     

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)     

EMS1 gene expression in primary breast cancer: relationship to cyclin D1 and oestrogen receptor expression and patient survival

The EMS1 and CCND1 genes at chromosome 11q13 are amplified in about 15% of primary breast cancers but appear to confer different phenotypes in ER positive and ER negative tumours. Since there are no published data on EMS1 expression in large series of breast cancers we examined the relationship of EMS1 expression with EMS1 gene copy number and expression of mRNAs for cyclin D1 and ER. In a subset of 129 patients, where matched tumour RNA and DNA was available, EMS1 mRNA overexpression was associated predominantly with gene amplification (P = 0.0061), whereas cyclin D1 mRNA overexpression was not (P = 0.3142). In a more extensive series of 351 breast cancers, there was no correlation between cyclin D1 and EMS1 expression in the EMS1 and cyclin D1 overexpressors (P = 0.3503). Although an association between EMS1 mRNA expression and ER positivity was evident (P = 0.0232), when the samples were divided into quartiles of EMS1 or cyclin D1 mRNA expression, the increase in the proportion of ER positive tumours in the ascending EMS1 mRNA quartiles was not statistically significant (P = 0.0951). In marked contrast there was a significant stepwise increase in ER positivity in ascending quartiles of cyclin D1 mRNA (P = 0.030). A potential explanation for this difference was provided by the observation that in ER positive breast cancer cells oestradiol treatment resulted in increased cyclin D1 gene expression but was without effect on EMS1. The relationship between EMS1 expression and clinical outcome was examined in a subset of 234 patients with median follow-up of 74 months. High EMS1 expression was associated with age > 50 years (P = 0.0001), postmenopausal status (P = 0.0008), lymph node negativity (P = 0.019) and an apparent trend for worse prognosis in the ER negative subgroup. These data demonstrate that overexpression of EMS1 mRNA is largely due to EMS1 gene amplification, is independent of cyclin D1 and ER expression and, in contrast to cyclin D1, is not regulated by oestrogen. Independent overexpression of these genes may confer different phenotypes and disease outcomes in breast cancer as has been inferred from recent studies of EMS1 and CCND1 gene amplification.     

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.