Porcine TCR CD3zeta-chain and eta-chain

Complete porcine CD3ζ-chain cDNA sequence was obtained for the first time, and its genomic nucleotide sequence was investigated from exon 2 down to CD3η-chain exon 8. The sequence of porcine CD3ζ-chain showed homologous amino acid sequence with human and murine counterparts, in contrast to CD3η-chain exon 8 with diversity among animals previously investigated. CD3η-chain peptide is an alternative splice form of CD3ζ-chain exon 7 splicing to CD3η-chain exon 8 instead of CD3ζ-chain exon 8. The genomic sequences revealed that the splice acceptor sequences of CD3η-chain exon 8 of all animals investigated to be completely uniform. Further, CD3η-chain exon 8 amino acid sequences retained the unique characters of having high proline (Pro) and positively charged amino acid content except for rats and mice. Although the biological role of CD3η-chain remains to be enigmatic, these evidences suggests the evolutional pressure to maintain its sequence.     

New algorithmic-based digital filter processing system for real-time continuous blood pressure measurement and analysis in conscious rats

A new algorithmic-based digital filter processing system for real-time continuous blood pressure (BP) measurement and analysis in freely-moving conscious rats has been developed. Real-time recognition of BP waveforms, real-time noise rejection and determination of representative waveform indexes (WIs) at indicated time points using digital filters and Smirnov's rejection test were realized with this system. Digital filters were applied for two different purposes: waveform segmentation and smoothing the calculations of representative WIs. Smirnov's rejection test was used for real-time noise rejection and yielded an accurate rejection rate of 99.99%. The result was that the digital filter processing and Smirnov's rejection test realized accurate real-time BP measurement and analysis in freely-moving conscious rats using a personal computer.     

The effect of available choices on ambiguity aversion: an examination of different types of ambiguity

Ellsberg's two-color problem, known as an example of ambiguity aversion, has generated a great deal of interest among many researchers. However, an unsettled question remains regarding the conditions that lead to heightened or diminished ambiguity aversion. We conducted a series of experiments, which required participants to choose between a clear and vague bet. Results showed that participants did not always prefer the clear bet, and the ratios of those who indicated ambiguity aversion varied depending on the types of ambiguity. Furthermore, ambiguity aversion consistently decreased when participants were allowed to choose the ambiguity task they would perform. These results were interpreted in terms of the pattern of second order probability distributions and illusion of control.     

Influence of polymorphisms in the genes for cytokines and glutathione S-transferase omega on sporadic Alzheimer's disease

We studied promoter region polymorphisms in the interleukin (IL)-1alpha, IL-1beta, IL-6, IL-10, tumor necrosis factor, and transforming growth factor (TGF)-beta1 genes in Japanese patients with Alzheimer's disease (AD) (n = 172) and normal controls (n = 163). We also examined an association of a polymorphism located in the glutathione S-transferase omega 1 (GSTO-1) gene region with AD patients. None of these genotypes or allele frequencies showed a significant difference between AD patients and controls. We also failed to detect any difference in the disease onset between each genotype of the seven polymorphisms. Although AD patients carrying high producer alleles of TGF-beta1 and IL-1beta or TGF-beta1 and IL-6 showed a tendency for an early onset of the disease, neither of these combined effects reached a significant level after multiple comparisons. Our findings suggest that genetic polymorphisms in the cytokines and GSTO do not play a major role in Japanese AD patients.     

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.     

Histamine downregulates CD14 expression via H2 receptors on human monocytes

Lipopolysaccharide (LPS) binds to LPS-binding protein (LBP) in plasma and is delivered to the cell surface receptor CD14 on human monocyte. LPS is transferred to the transmembrane signaling receptor toll-like receptor (TLR) 4. In the present study, the effect of histamine on the expression of CD14 on human monocytes was investigated. Histamine concentration- and time-dependently decreased the expression of cell surface CD14, whereas histamine did not decrease mRNA for CD14 nor increase soluble CD14 (sCD14). The inhibitory effects of histamine on CD14 expression were antagonized by H2-receptor antagonist, but not by H1 and H3/H4 antagonist. The effects of selective H2-receptor agonists, 4-methylhistamine and dimaprit, on CD14 expression mimicked that of histamine indicating that histamine regulated CD14 expression through the stimulation of H2-receptors. The pretreatment with histamine partially inhibited the LPS-induced TNF-alpha production in human peripheral blood mononuclear cells (PBMC). Such inhibition might be due to the down-regulation of CD14 expression on monocytes by histamine.     

Local adaptation and population differentiation at the interleukin 13 and interleukin 4 loci

A 25.6 kb region at chromosome 5q31, covering the entire human interleukin 13 (IL-13) and interleukin 4 (IL-4) genes, has been reported to be associated with bronchial asthma. We have examined nucleotide variations at this locus in African, European American, and Japanese populations, using 120 diallelic variants. A block of strong linkage disequilibrium (LD) (mid R:D'mid R:>0.7) spans a 10 kb region containing IL-4 in European American and Japanese populations, and is present but less clear in African samples. Two major haplotypes at IL-4 account for >80% of haplotypes in European Americans and Japanese. These haplotypes are common and quite diverged from each other and the ancestral haplotype, resulting in highly significant deviations from neutrality. F(ST) statistics show that European American and Japanese populations are unusually distinct at the IL-4 locus. The most common haplotype in the European American population is much less common in the Japanese population, and vice versa. This implies that natural selection has acted on IL-4 haplotypes differently in different populations. This selected variation at IL-4 may account for some genetic variance underlying susceptibility to asthma and other allergic diseases. The strong LD observed in the IL-4 region may allow more efficient disease-association studies using this locus.     

Early Transplant Arteriopathy in Kidney Transplantation

BackgroundEarly dysfunction of renal allografts may be associated with vascular injury, which raises the specter of active rejection processes that require medical intervention. In our practice, we have encountered patients who present with delayed graft function and demonstrate a unique pattern of endothelial cell injury that raises concern for rejection in their biopsy. Therefore, we sought to systematically determine the biopsy characteristics and outcome of these patients.MethodsDuring a 17-year period at the University of Washington in Seattle, United States, we identified 24 cases of a distinct arterial vasculopathy presenting in the first year posttransplantation. This early transplant arteriopathy (ETA) is characterized by endothelial cell swelling and intimal edema but without the intimal arteritis that defines vascular rejection.ResultsApproximately 1% of transplant biopsies during the study period showed ETA, almost all of which were in deceased donor organs (96%), and most presented with delayed graft function (54%) or increased serum creatinine (38%) soon after transplantation (median 13 days; range, 5-139). In this study, 77% of patients were managed expectantly, with only 2 patients (7.6%) subsequently developing acute vascular rejection. Except for 1 patient who died, all patients had functioning allografts at 1 year follow-up.ConclusionRecognizing ETA and distinguishing it from vascular rejection is important to prevent over-treatment because most patients appear to recover allograft function rapidly with expectant management.