Interleukin-4 and -13 inhibit tumor necrosis factor-alpha mRNA translational activation in lipopolysaccharide-induced mouse macrophages

The production of tumor necrosis factor-alpha (TNF-alpha) by lipopolysaccharide (LPS)-stimulated macrophages can be markedly inhibited by the two closely related cytokines, interleukin (IL)-4 and IL-13. To investigate the molecular mechanism of this inhibition, we analyzed the effect of the two cytokines on TNF-alpha production and TNF-alpha mRNA accumulation in the mouse macrophage cell lines RAW 264.7 and J774 stimulated by LPS. Whereas LPS-induced TNF-alpha production is strongly suppressed by both cytokines, TNF-alpha mRNA accumulation is not significantly affected, indicating that IL-4 and IL-13 induce a translational repression of TNF-alpha mRNA. Transfection of reporter gene constructs containing different regions of the TNF-alpha gene revealed that the inhibitory action of IL-4 and IL-13 is mediated by the UA-rich sequence present in the TNF-alpha mRNA 3'-untranslated region.     

Penicilloyl peptides are recognized as T cell antigenic determinants in penicillin allergy

Although hapten immune responses have been intensively studied in the mouse, very little is known about hapten determinants involved in human allergic reactions. Penicillins, as chemically reactive compounds of low molecular weight, constitute typical examples of hapten allergens for humans. Penicillins become immunogenic only after covalent binding to carrier proteins and in this form frequently induced IgE-mediated allergic reactions in patients subjected to antibiotic treatment. However, our previous data strongly indicated that penicillins also form part of the epitopes contacting the antigen receptors of beta lactam-specific T cells in allergic individuals. We have therefore investigated the molecular constraints involved in the T cell immune response to penicillin G (Pen G). Designer peptides containing a DRB1*0401-binding motif and covalently modified with Pen G via a lysine epsilon-amino group were found to induce proliferation of Pen G-specific T cell clones. A precise positioning of the hapten molecule on the peptide backbone was required for optimal T cell recognition. Furthermore, we extended these observations from our designer peptides to show that a peptide sequence derived from a natural DRB1*1101-binding peptide modified in vitro with Pen G, also acquired antigenic properties. Our data for the first time provide insight into the manner in which allergenic haptens are recognized by human T cells involved in allergic reactions to drugs and suggest possible mechanisms leading to the onset of these adverse immune responses.     

A truncated poisson regression model with applications to occurrence of adenomatous polyps

Adenomatous polyps are considered as the dominant precursor lesion of colorectal cancer. A phase III colorectal cancer prevention trial, conducted by the Arizona Cancer Center, concerns the ability of wheat bran fibre supplement to reduce the recurrence of adenomatous polyps. All participants in the study are to have had colorectal polyps detected and removed during a baseline (qualifying) colonoscopy within three months prior to enrolment. In this paper, our interest focuses on occurrence of adenomatous polyps at the baseline colonoscopy. We use a truncated Poisson model to fit these types of data. We develop a regression model to assess the effects of explanatory factors on the positive counting variable. We fit truncated Poisson parameters by a log-linear regression model and estimate regression parameters by the maximum likelihood procedure. Finally, we apply it to the baseline colonoscopy data from the Wheat Bran Fiber study.     

The T cell-directed CC chemokine TARC is a highly specific biological ligand for CC chemokine receptor 4

Thymus and activation-regulated chemokine (TARC) is a recently identified CC chemokine that is expressed constitutively in thymus and transiently in stimulated peripheral blood mononuclear cells. TARC functions as a selective chemoattractant for T cells that express a class of receptors binding TARC with high affinity and specificity. To identify the receptor for TARC, we produced TARC as a fusion protein with secreted alkaline phosphatase (SEAP) and used it for specific binding. By stably transfecting five orphan receptors and five known CC chemokine receptors (CCR1 to -5) into K562 cells, we found that TARC-SEAP bound selectively to cells expressing CCR4. TARC-SEAP also bound to K562 cells stably expressing CCR4 with a high affinity (Kd = 0.5 nM). Only TARC and not five other CC chemokines (MCP-1 (monocyte chemoattractant protein-1), RANTES (regulated upon activation, normal T cells expressed and secreted), MIP-1alpha (macrophage inflammatory protein-1alpha), MIP-1beta, and LARC (liver and activation-regulated chemokine)) competed with TARC-SEAP for binding to CCR4. TARC but not RANTES or MIP-1alpha induced migration and calcium mobilization in 293/EBNA-1 cells stably expressing CCR4. K562 cells stably expressing CCR4 also responded to TARC in a calcium mobilization assay. Northern blot analysis revealed that CCR4 mRNA was expressed strongly in human T cell lines and peripheral blood T cells but not in B cells, natural killer cells, monocytes, or granulocytes. Taken together, TARC is a specific functional ligand for CCR4, and CCR4 is the specific receptor for TARC selectively expressed on T cells.     

Effect of ecabet sodium on Helicobacter pylori adhesion to gastric epithelial cells

STUDY OBJECTIVES: To determine the rates of alcohol-related morbidity and mortality in a cohort of intoxicated ED patients 5 years after presentation and to compare them with those of non-intoxicated ED patients. METHODS: The study group comprised 150 consecutive ED patients who presented with intoxication (blood alcohol level higher than 100 mg/dL) in June 1986 and 50 control patients matched for age, sex, ED arrival time, and date. The setting was an urban university hospital ED. Morbidity and mortality over a 5-year follow-up period were measured using hospital ED and admission records from all state Level I trauma centers and computerized statewide databases. RESULTS: The 5-year mortality rate among alcohol-intoxicated patients was 2.4 times that of the comparison group (95% confidence interval, .3 to 18.9). The 5-year death rate among intoxicated patients aged 40 to 69 years was especially high (19%). Thirty-seven percent of the intoxicated patients made at least one alcohol-related ED revisit during the follow-up period, compared with 6% of the comparison group (P < .001). Intoxicated patients were more likely to revisit EDs because of suicidal behavior or domestic violence (P = .001). Admission to an alcohol detoxification unit during the follow-up period occurred in 24% of the intoxicated patients, compared with 10% of the sober controls (P = .03). At least one arrest for drunk driving occurred in 47% of the intoxicated group; the rate was lower, but still substantial, in the comparison group (20%, P < .001). CONCLUSION: A single alcohol-related ED visit is an important predictor of continued problem drinking, alcohol-impaired driving and, possibly, premature death.     

Surface leakage currents in SiN/sub x/ passivated AlGaN/GaN HFETs

A novel guarded surface leakage test structure is used to isolate the surface and bulk leakage contributions to gate current in AlGaN/GaN HFETs. Passivation with various recipes of SiN/sub x/ always resulted in the commonly observed increase in gate leakage, which was found to be dominated by bulk leakage through the AlGaN. However, high temperature deposited SiN/sub x/ recipes gave a 1-2 orders reduction in surface leakage, whereas low temperature deposition gave an increase. Gate lag measurements were found to correlate closely with the surface leakage component, giving direct evidence that the key device problem of current slump is associated with current flow at the AlGaN surface.     

Formation of glass synthesized by sol-gel technology

The process of glass synthesis by the sol-gel method is studied using analysis of EPR spectra. The gelation process and formation of xerogels are considered depending on the temperature-time parameters and the type of initial components. It is established that the glass phase starts to be formed at 800°C. __________ Translated from Steklo i Keramika, No. 8, pp. 9–13, August, 2006.