Separation and mapping of multiple genes that control IgE level in Leishmania major infected mice

The strain BALB/cHeA (BALB/c) is a high producer, and STS/A (STS) a low producer of IgE after Leishmania major infection. We analyzed this strain difference using 20 recombinant congenic (RC) BALB/c-c-STS/Dem (CcS/Dem) strains that carry different random subsets of 12.5% of genes of the strain STS on the BALB/c background. Strains CcS-16 and -20 exhibit a high and a low IgE level, respectively. In their F(2) hybrids with BALB/c we mapped nine Leishmania major response (Lmr) loci. Two of them we previously found to influence IgE level in CcS-5. IgE production in CcS-16 is controlled by loci on chromosomes 2, 10, 16 and 18 and in CcS-20 by loci on chromosomes 1, 3, 4, 5 and 8. The STS alleles of loci on chromosomes 1, 4, 5, 8 and 10 were associated with a low, whereas the STS alleles on chromosomes 16 and 18 with a high IgE production. The loci on chromosomes 2 and 3 have no apparent individual effect, but interact with the loci on chromosomes 10 and 1, respectively. The loci on chromosomes 10 and 18 were mapped in the regions homologous with the human regions containing genes that control total serum IgE and intensity of infection by Schistosoma mansoni, suggesting that some Lmr loci may participate in the pathways influencing atopic reactions and responses to several parasites. The definition of genes controlling anti-parasite responses will permit a better understanding of pathways and genetic diversity underlying the disease phenotypes.     

Visualisation of the extent of damage in a rat spinal cord injury model using MR microsopy of the water diffusion tensor

Magnetic Resonance Diffusion Tensor Imaging (DTI) of the control and traumatic injured spinal cord of a rat in vitro is reported. Experiments were performed on excised spinal cords from 10 Wistar rats, using a home-built 6.4 T MR microscope. MRI and histopathological results were compared. Presented results show that DTI of the spinal cord, perfused with formalin 10 minutes after the injury, can detect changes in water diffusion in white matter (WM) and in gray matter (GM), in areas extending well beyond the region of direct impact. Histology of neurons of the GM shows changes that can be attributed to ischemia. This is in agreement with the observed decrease of diffusion in the injured regions, which may be attributed to the cytotoxic edema due to ischemia. However, the diffusion changes in highly anisotropic WM seem to be caused by a direct action of mechanical force of impact, which significantly distorts the nerve fibers.     

Dopamine, serotonin and noradrenaline changes in the striatum of C57BL mice following myelin oligodendrocyte glycoprotein (MOG) 35-55 and complete Freund adjuvant (CFA) administration.

Many data suggest involvement of inflammation in neurodegeneration. However, the exact mechanisms of this cooperation are poorly understood. We have previously shown that induction of inflammatory reaction, both before and after injury of the striatum, affects regeneration of dopaminergic neurons. In the present research we studied the role of inflammatory reaction in non-injured striatum. We used myelin oligodendrocyte glycoprotein (MOG) 35-55 in complete Freund's adjuvant (CFA) to elicit experimental autoimmune encephalomyelitis (EAE) mice model. As determined by HPLC, striatal dopamine (DA) and serotonin levels in mice treated with either MOG 35-55 in CFA or CFA alone were significantly higher compared to vehicle-treated controls on 13th day after induction. The ratio of homovanilic acid/dopamine (HVA/DA) and 3, 4 dihydroxyphenylacetic acid/dopamine (DOPAC/DA) were significantly lower in the MOG and CFA groups on 13th day, indicating decreased DA metabolism. Noradrenaline (NA) concentration did not differ between groups. Moreover, the striatal mRNA IL-1beta and TNF-alpha levels were elevated during induction phase of EAE in both groups, as determined by RT-PCR. Our data indicate regulatory connection between dopaminergic and immune systems.     

Polymerisationsauslösung mit substituierten ethanen, 2. Trennung der Oligomeren aus Methylmethacrylat und 1,1,2,2-Tetraphenyl-1,2-diphenoxyethan

The telechelics 1 from methyl methacrylate and 1,1,2,2-tetraphenyl-1,2-diphenoxyethane, can be separated by adsorption chromatography. The structure of the dimers and trimers was identified by ¹H NMR-spectroscopy. The free radical oligomerization is a process in which the syndiotactic structure is favoured above the isotactic one.     

Influence of exposure mode on vinyl chloride action

Rats were subjected to 4 h continuous or intermittent exposure to vinyl chloride (VC) at different time-weighted average concentrations (15, 50, 150, 500 and 15,000 mg/m³). Hepatic non-protein sulfhydryl content (NPSH) and excretion of thiodiglycolic acid (TdGA) in urine were determined. VC at concentrations from 50 mg/m³ to 15,000 mg/m³ caused a dose-dependent depression of NPSH, but no difference in the magnitude of this depression induced by continuous or intermittent exposure at the same average concentration of VC was noted. At average concentrations of 50 mg/m³ and 150 mg/m³, the urinary excretion of TdGA under continuous exposure did not differ from that under intermittent exposure, whereas at VC concentrations of 500 mg/m³ and 15,000 mg/m³ it was higher following continuous exposure.     

Methylation and Expression of FTO and PLAG1 Genes in Childhood Obesity: Insight into Anthropometric Parameters and Glucose–Lipid Metabolism

The occurrence of childhood obesity is influenced by both genetic and epigenetic factors. FTO (FTO alpha-ketoglutarate dependent dioxygenase) is a gene of well-established connection with adiposity, while a protooncogene PLAG1 (PLAG1 zinc finger) has been only recently linked to this condition. We performed a cross-sectional study on a cohort of 16 obese (aged 6.6–17.7) and 10 healthy (aged 11.4–16.9) children. The aim was to evaluate the relationship between methylation and expression of the aforementioned genes and the presence of obesity as well as alterations in anthropometric measurements (including waist circumference (WC), body fat (BF_kg) and body fat percent (BF_%)), metabolic parameters (lipid profile, blood glucose and insulin levels, presence of insulin resistance) and blood pressure. Expression and methylation were measured in peripheral blood mononuclear cells using a microarray technique and a method based on restriction enzymes, respectively. Multiple regression models were constructed to adjust for the possible influence of age and sex on the investigated associations. We showed significantly increased expression of the FTO gene in obese children and in patients with documented insulin resistance. Higher FTO expression was also associated with an increase in WC, BF_kg, and BF_% as well as higher fasting concentration of free fatty acids (FFA). FTO methylation correlated positively with WC and BF_kg. Increase in PLAG1 expression was associated with higher BF%. Our results indicate that the FTO gene is likely to play an important role in the development of childhood adiposity together with coexisting impairment of glucose-lipid metabolism.     

Effect of a cognitive behavioral intervention on reducing symptom severity during chemotherapy.

PURPOSE: To describe a randomized trial of a cognitive behavioral intervention on reducing symptom severity among patients diagnosed with solid tumors and undergoing a first course of chemotherapy and to determine whether the intervention had an additive or interactive effect on symptom severity in the presence of supportive care medications. PATIENTS AND METHODS: Patients (N = 237) were accrued from comprehensive and community cancer centers, interviewed, and randomly assigned to either the experimental intervention (n = 118) or conventional care (n = 119). A symptom severity index, based on summed severity scores across 15 symptoms, was the primary outcome. Each patient's site of cancer, stage at diagnosis, chemotherapy protocols, and use of supportive medications were learned from medical records. RESULTS: Groups were equivalent at baseline, and attrition by characteristics by group was not different. The proportion of patients not receiving chemotherapy at 10 and 20 weeks did not differ by group. At the 10- and 20-week observations, there was a significant interaction between the experimental group and baseline symptom severity. Patients in the experimental group who entered the trial with higher symptom severity reported significantly lower severity at 10 and 20 weeks. Controlling for chemotherapy treatment status at follow-up and supportive care medications did not alter the effect of the experimental intervention. CONCLUSION: Compared with conventional care alone, the experimental intervention was effective among patients who entered the trial with higher levels of symptom severity. Age, sex, site or stage of cancer, and supportive medications did not modify the effect of this cognitive behavioral intervention on symptom severity.     

Interleukin 12-based immunotherapy improves the antitumor effectiveness of a low-dose 5-Aza-2'-deoxycitidine treatment in L1210 leukemia and B16F10 melanoma models in mice.

PURPOSE: Recent findings indicating that many genes related to cancer development are silenced by an aberrant DNA methylation suggest that inhibitors of this process may be effective cancer therapeutics. In this study we investigated the efficacy of low-dose 5-aza-2'-deoxycitydine (DAC), a methylation inhibitor, with interleukin (IL) 12, one of the most potent cytokines with antitumor activity. Experimental Design: Mice inoculated with L1210 leukemia cells or with B16F10 melanoma cells were treated with 7 daily injections of low-dose DAC (0.2 mg/kg) and/or 7 daily doses of IL-12 (100 ng/dose). Scid/scid mice as well as monoclonal antibodies against CD4, CD8, and NK1.1 were used to investigate the mechanisms of the antitumor effects of the combination treatment. The activity of murine lymphocytes was measured with enzyme-linked immunospot and (51)Cr release assays. RESULTS: Treatment with DAC or IL-12 given alone produced moderate antitumor effects. In both tumor models combined treatment resulted in potentiated antitumor effects and produced 70% long-term survivors among mice inoculated with L1210 cells. The antitumor efficacy of combined treatment was abrogated in scid/scid mice, and after depletion of CD4(+) and CD8(+) T cells. Mice inoculated with B16F10 melanoma cells had significantly delayed tumor growth after combined treatment with DAC and IL-12. Strong antitumor effect correlated with a significant activation of lymph node-derived CD8(+) and CD4(+) cells. Transient neutropenia was observed in mice under treatment of DAC alone, but remarkably this effect was not potentiated by IL-12. CONCLUSIONS: This study provides the first evidence that antitumor effects of DAC can be strongly potentiated by IL-12 and could be beneficial in an effective low-dose-based antitumor therapy.