Prostaglandin E1-initiated immune regulation during human mixed lymphocyte reaction

Prostaglandin E1 (PGE1) has therapeutic value for transplantations due to its microvascular activity. Interleukin (IL)-18, which is elevated in plasma during the acute rejection after organ transplantation, elicits the expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, CD40, and CD40 ligand (CD40L) on monocytes as well as the production of interferon (IFN)-gamma and IL-12 and proliferation of T-cells during the human mixed lymphocyte reaction (MLR) in an in vitro model of acute rejection. In contrast, PGE1 inhibits all the adhesion molecule expression, cytokine production and T-cell proliferation in the presence of IL-18. The effects of PGE1 depend on stimulation of the IP/EP2/EP4-receptor, and thus, PGE1 might have therapeutic potential for treating acute rejection due to its immune regulatory effect.     

Serotonin 2A receptor gene polymorphism and personality traits: no evidence for significant association

A number of studies have observed associations between the serotonin 2A (5-HT2A) receptor and mental disorders. Here, we investigated correlations between polymorphisms (-1438G/A and 102T/C) of the 5-HT2A gene and personality traits in healthy Japanese volunteers (n = 239). The personality traits were evaluated using the Revised NEO Personality Inventory (NEO PI-R). The -1438G/A and 102T/C were in complete linkage disequilibrium. There was a tendency for associations between the genotype and the scores for Agreeableness, Conscientiousness and Neuroticism of the NEO PI-R (P = 0.028, 0.039 and 0.062, respectively; analysis of variance, uncorrected for multiple testing). Subjects with the A/A of -1438G/A (or T/T of 102T/C) appeared to be lower in Neuroticism and higher in Conscientiousness than the rest of the subjects. However, the results were statistically non-significant after Bonferroni's correction for multiple testing of the five scales of the NEO PI-R. Thus, the present study provided no evidence for statistically significant associations between the 5-HT2A polymorphisms and the personality traits.     

No allelic association between Parkinson's disease and dopamine D2, D3, and D4 receptor gene polymorphisms

Parkinson's disease is thought to be caused by a combination of unknown environmental, genetic, and degenerative factors. Evidence from necropsy brain samples and pharmacokinetics suggests involvement of dopamine receptors in the pathogenesis or pathophysiology of Parkinson's disease. Genetic association studies between Parkinson's disease and dopamine D2, D3 and D4 receptor gene polymorphisms were conducted. The polymorphism was examined in 71 patients with Parkinson's disease and 90 controls. There were no significant differences between two groups in allele frequencies at the D2, D3, and D4 dopamine receptor loci. Our findings do not support the hypothesis that susceptibility to Parkinson's disease is associated with the dopamine receptor polymorphisms examined. © 1994 Wiley-Liss, Inc.     

Potentiation of vasopressin secretion by footshocks in rats

Effects of footshocks (FS) on antidiuretic hormone (vasopressin, VP) in the plasma were studied in rats. Continuously applied FS of 60 s period with 5 ms pulses at 50 Hz frequency significantly increased VP as well as adrenocorticotrophic hormone (ACTH) in the plasma in a time- and shock intensity-dependent manner. Contrarily, the 50 Hz FS of 2 s period as repeated intermittently at every 15 s for over the period of 2, 10, and 30 min were much less effective for increasing plasma VP, whereas these intermittent FS increased plasma ACTH to an extremely high level. During the inter-shock intervals of 13 s between successive two shock periods rats exhibited a "freezing" behavior. Hypertonic saline or urethane injected I.P. immediately after termination of the intermittent FS significantly increased VP as well as ACTH in the plasma. These data clearly indicate that FS potentiate VP secretion and suggest the possibility that emotional stress may suppress the noxious stimuli-induced VP secretion.     

Accumulation of somatic hypermutation and antigen-driven selection in rapidly cycling surface Ig+ germinal center (GC) B cells which occupy GC at a high frequency during the primary antihapten response in mice

Well-developed germinal centers (GC) contain rapidly dividing surface immunoglobulin-negative (sIg^-) B cells (centroblasts), and most of their progeny are sIg⁺ B cells (centrocytes) in a resting state. It has been predicted that somatic hypermutation occurs in centroblasts, whereas antigen-driven selection takes place in centrocytes. The present analysis indicates that murine GC B cells bearing sIg with specificity for an immunizing antigen are in a rapidly cycling state and increase exponentially in number to occupy spleen GC at high frequency during the 1st week after primary immunization; however, the number of these cells is significantly reduced in the 2nd week of immunization. During that period, these proliferating sIg⁺ GC B cells accumulate somatic hypermutations with nucleotide exchanges indicative of affinity maturation. These sIg⁺ GC B cells co-express B7-2, ICAM-1, and LFA-1, and have potent antigen-presenting activity which results in T cell activation in vitro. These observations indicate that the sIg⁺ GC B cells accumulate somatic hypermutations and undergo antigen-driven selection through proliferation, probably upon activation by T cells. This sIg⁺ GC B cell population may represent cell cycling centrocytes; however, the possibility that these may represent centroblasts undergoing re-expression of sIg could not be excluded.     

Thymosin alpha 1 exerts protective effect against the 5-FU induced bone marrow toxicity

Thymosin alpha 1 was shown to prevent the 5-fluorouracil(5-FU)-induced bone marrow toxicity in BDF1 mice, as determined by the cellularity, haemopoietic stem cells (CFU-s) and granulocyte-macrophage colony forming unit (GM-CFU). Furthermore, thymosin alpha 1 increased the levels of colony stimulating factor (CSF) in sera or in culture media of spleen cells derived from 5-FU-treated mice. The treatment of spleen cells with anti-Thy 1,2 antibody plus complement abolished completely the CSF production. The in vivo treatment of donor mice with anti-Thy 1,2 antibody following 5-FU abolished completely the capability of their bone marrow cells to save lethally irradiated recipients. Thymosin alpha 1 treatment prevented the damage by such combined treatment. The present study indicates that thymosin alpha 1 exerts its protective effect against the 5-FU-induced bone marrow toxicity, at least partially, through its effect on the maturation of immature T cells to functional T cells which produce various kinds of lymphokines including CSF.     

Gene-inducing program of human dendritic cells in response to BCG cell-wall skeleton (CWS), which reflects adjuvancy required for tumor immunotherapy

Adjuvants induce the expression of a number of genes in dendritic cells (DCs), which facilitate effective antigen-presentation and cytokine/chemokine liberation. It has been accepted that the toll-like receptor (TLR) family governs the adjuvant activity in DCs. An adjuvant with a long history is mycobacteria in an oil-in-water emulsion, namely Freund's complete adjuvant. Since the active center for the adjuvancy in mycobacteria is the cell-wall skeleton (CWS), we used the bacillus Calmette-Guerin cell-wall skeleton (BCG-CWS) to test DC maturation by GeneChip analysis. We identified the genes supporting an efficient DC response and output. Approximately 2000 genes were up-regulated by BCG-CWS stimulation. BCG-CWS-, peptidoglycan (PGN)- and lipopolysaccharide (LPS)-stimulation generally up-regulated some gene clusters including genes for inflammatory cytokines (TNF, IL1alpha, IL1beta, IL6, IL12 p40, IL23 p19, etc.), chemokines (CCL20, IL8, etc.), cell adhesion molecules (ICAM-1, etc.), apoptosis-related proteins (GADD45B, BCL2A1, etc.), metabolic enzymes (PTGS2, SOD2, etc.) and miscellaneous proteins (EHD1, TNFAIP6, etc.). LPS-stimulation, but not BCG-CWS- or PGN-stimulation, up-regulated the interferon-inducible antiviral proteins, including IFIT1, IFIT2, IFIT4, CXCL10, ISG15, OASL, IFITM1 and MX1. We also found that the BCG-CWS- or PGN-stimulation up-regulated CXCL5, MMP1, etc. We discussed their properties in association with TLRs and recently discovered TLR adapters.     

Dynamic imaging of the lungs using x-ray phase contrast

High quality real-time imaging of lungs in vivo presents considerable challenges. We demonstrate here that phase contrast x-ray imaging is capable of dynamically imaging the lungs. It retains many of the advantages of simple x-ray imaging, whilst also being able to map weakly absorbing soft tissues based on refractive index differences. Preliminary results reported herein show that this novel imaging technique can identify and locate airway liquid and allows lung aeration in newborn rabbit pups to be dynamically visualized.     

Effects of inorganic phosphate on cross-bridge behavior after photorelease of ATP in permeabilized cells of rat skeletal muscle

Effects of 20 mM inorganic phosphate on the cross-bridge behavior after photorelease of ATP from caged ATP was studied by X-ray diffraction in rat skinned psoas muscle fibers at 16 degrees C. In the first 30 ms after the photorelease, tension was similar in the presence and absence of phosphate. The tension development was then suppressed in the presence of phosphate. At 500 ms after the photolysis, it was lower by about 30% in the presence of phosphate. In the presence of phosphate, the intensity of the third meridional reflection from the thick filament at 1/14.4 nm(-1) increased more slowly and was 60% of the level without phosphate at 500 ms after the photolysis. The intensities of the equatorial (1,1) reflection and the actin layer-line at 1/36 nm(-1) decreased to a lower level in the presence of phosphate. These results suggest that phosphate does not affect dissociation of myosin heads from actin, but decreases the number of myosin heads in force-generating conformation and reduces tension. Phosphate may also shift the equilibrium between the detached and attached states towards the former.